Luteinizing hormone-follicle stimulating hormone ratio as biological predictor of post-partum depression.

PubMed

Ramachandran Pillai, R; Sharon, Leena; Premkumar, Nancy R; Kattimani, Shivanand; Sagili, Haritha; Rajendiran, Soundravally

2017-01-01

Post-partum depression (PPD) is the common adverse outcome of child bearing which affects the wellbeing of both mother and newborn and has long-term effects. Hence, reliable potential biological tests for early detection of PPD are essential. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) were associated with depressive disorders and the present study estimated the levels of serum FSH, LH in postpartum depression and explored them as predictive biomarkers in the development of PPD. In this nested case control study done at a tertiary care hospital in South India, 450 postpartum women were screened at 6th week post-delivery for PPD. Socio-demographic and clinical data were recorded and depressive symptoms were assessed using Edinburgh Postnatal Depression Scale (EPDS). Out of 450 subjects screened, 100 women with depressive symptoms were categorized as cases and 100 controls were selected from the remaining subjects matching for age and BMI with cases. Serum levels of FSH and LH were measured using direct competitive immunoassay by chemiluminescene technology. Serum LH/FSH ratio was found to be significantly (p=0.02) low in PPD women when compared to normal postpartum subjects. We also found a significant negative correlation between LH/FSH ratio and EPDS scores. Based on the receiver operating characteristic curve, the optimal cut-off value for serum of LH/FSH levels in predicting postpartum depression was estimated to be 0.22mlU/mL with an AUC of 0.598 (95%CI, 0.291-0.859). Our study demonstrated that low LH/FSH ratio after delivery was associated with increased risk for the development of PPD. Low LH/FSH ratio at six-week post delivery can be used as a robust biochemical predictor of post-partum depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Mucuna pruriens improves male fertility by its action on the hypothalamus-pituitary-gonadal axis.

PubMed

Shukla, Kamla Kant; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem; Shankhwar, Satya Narain; Rajender, Singh; Jaiswar, Shyam Pyari

2009-12-01

To understand the mechanism of action of Mucuna pruriens in the treatment of male infertility. Prospective study. Departments of Biochemistry, Urology, and Obstetrics and Gynecology, C.S.M. Medical University, Lucknow, India. Seventy-five normal healthy fertile men (controls) and 75 men undergoing infertility screening. High-performance liquid chromatography assay for quantitation of dopa, adrenaline, and noradrenaline in seminal plasma and blood. Estimation by RIA of hormonal parameters in blood plasma, namely T, LH, FSH, and PRL. Before and after treatment, serum T, LH, FSH, PRL, dopamine, adrenaline, and noradrenaline in seminal and blood plasma were measured. Decreased sperm count and motility were seen in infertile subjects. Serum T and LH levels, as well as seminal plasma and blood levels of dopamine, adrenaline, and noradrenaline were also decreased in all groups of infertile men. This was accompanied by significantly increased serum FSH and PRL levels in oligozoospermic subjects. Treatment with M. pruriens significantly improved T, LH, dopamine, adrenaline, and noradrenaline levels in infertile men and reduced levels of FSH and PRL. Sperm count and motility were significantly recovered in infertile men after treatment. Treatment with M. pruriens regulates steroidogenesis and improves semen quality in infertile men.

Daily testosterone and gonadotropin levels are similar in azoospermic and nonazoospermic normal men administered weekly testosterone: implications for male contraceptive development.

PubMed

Amory, J K; Anawalt, B D; Bremner, W J; Matsumoto, A M

2001-01-01

Weekly intramuscular administration of testosterone esters such as testosterone enanthate (TE) suppresses gonadotropins and spermatogenesis and has been studied as a male contraceptive. For unknown reasons, however, some men fail to achieve azoospermia with such regimens. We hypothesized that either 1) daily circulating serum fluoroimmunoreactive gonadotropins were higher or testosterone levels were lower during the weekly injection interval, or 2) monthly circulating bioactive gonadotropin levels were higher in nonazoospermic men. We therefore analyzed daily testosterone and fluoroimmunoreactive gonadotropin levels as well as pooled monthly bioactive and fluoroimmunoreactive gonadotropin levels in normal men receiving chronic TE injections and correlated these levels with sperm production. After a 3-month control period, 51 normal men were randomly assigned to receive intramuscular TE at 25 mg (n = 10), 50 mg (n = 9), 100 mg (n = 10), 300 mg (n = 10), or placebo (n = 12) weekly for 6 months. After 5 months of testosterone administration, morning testosterone and fluoroimmunoreactive follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured daily for a 1-week period between TE injections. In addition, fluoroimmunoreactive and bioactive FSH and LH levels were measured in pooled monthly blood samples drawn just before the next TE injection. In the 100-mg and 300-mg TE groups, mean monthly fluoroimmunoreactive FSH and LH levels were suppressed by 86%-97%, bioactive FSH and LH levels by 62%-80%, and roughly half the subjects became azoospermic. In the 1-week period of month 6, daily testosterone levels between TE injections were within the normal range in men receiving placebo, or 25 or 50 mg of weekly TE, but were significantly elevated in men receiving 100 or 300 mg of weekly TE. At no point during treatment, however, were there significant differences in daily testosterone or fluoroimmunoreactive gonadotropin levels, or monthly bioactive gonadotropin levels between men achieving azoospermia and those with persistent spermatogenesis. This study, therefore, demonstrates that neither monthly nor daily differences in serum testosterone, or fluoroimmunoreactive or bioactive gonadotropins explain why some men fail to completely suppress their sperm counts to zero with weekly TE administration. Innate differences in the testicle's ability to maintain spermatogenesis in a low-gonadotropin environment may explain persistent spermatogenesis in some men treated with androgen-based contraceptive regimens.

Comparative morphophysiological evaluation of the testis of adult Wistar rats fed low protein-energy diet and dosed with aqueous extracts of Cuscuta australis.

PubMed

Ozegbe, P C; Omirinde, J O

2012-12-18

Cuscuta australis (C. australis) seed and stem are historically used by the local population as dietary supplement for the management of infertility. This study, therefore, evaluated the effect of orally administered aqueous extracts of C. australis seed and stem, 300 mg/kg body weight/day for seven days, on the testis of the adult Wistar rat fed either low or normal protein-energy diets. The control group received water. The relative weight of the testis was non-significantly increased (p>0.05) in the Low Protein-energy diet-Water-treated (LPWA), Low Protein-energy diet-Seed-treated (LPSE) and Normal Protein-energy diet-Seed-treated (NPSE) groups relative to the Normal Protein-energy diet-Water-treated (NPWA). The weight of the testis was also non-significantly increased (p˃0.05) in the Low Protein-energy diet-Stem-treated (LPST), but decreased in the Normal Protein-energy diet-Stem-treated (NPST), relative to LPWA and NPWA. Heights of germinal epithelium were significantly decreased (p<0.05) in the LPWA, LPSE and LPST relative to the NPWA, NPSE and NPST. Diet significantly influenced (p<0.001) the effect of stem extract on the height of germinal epithelium. The NPSE, LPSE, NPST, LPST and LPWA showed significantly decreased (p<0.001) plasma levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) relative to NPWA. The LPWA, LPSE and NPST also showed significantly decreased (p<0.001) levels of testosterone relative to NPWA and LPST. Diet significantly influenced (p<0.001) the effect of seed on the level of LH. Seed-diet interactions significantly affected the levels of FSH (p<0.001) and LH (p<0.05), but not testosterone. Diet significantly influenced (p<0.001) the effects of stem extract on the levels of FSH, LH and testosterone. Stem-diet interactions significantly affected (p<0.001) the levels of FSH, LH and testosterone. Our data suggest that the aqueous extract of C. australis stem is more potent than the seed extract and that dietary protein-energy intake may influence the efficacy of orally administered aqueous extracts of C. australis.

Assessment of ovarian reserve in euthyroid adolescents with Hashimoto thyroiditis.

PubMed

Pirgon, Ozgur; Sivrice, Cigdem; Demirtas, Hakan; Dundar, Bumin

2016-01-01

We aimed to investigate the ovarian function and reserve in euthyroid adolescents (TSH < 2.5 mIU/L) diagnosed with Hashimoto thyroiditis (HT). This case-control study included 30 adolescent girls (mean age 15.1 ± 1.4 years) newly diagnosed as HT with presence of high thyroid antibodies with gland heterogeneity in ultrasound and age-matched 30 healthy female subjects. Anti-ovarian antibody (AOAb), LH/FSH ratio, estradiol, anti-mullerian hormone (AMH), inhibin-B, total testosterone, antral follicle count, ovarian volumes and uterine length were measured. The clinical, laboratory, and ultrasound data of the HT and control groups were compared. There were no significant differences between the girls with HT and healthy controls in relation to LH/FSH ratio, estradiol and inhibin-B levels. AOAb (p = 0.02), AMH (p = 0.007) and total testosterone levels were higher in HT group than the control group (p = 0.03). AOAb level was found to be positively correlated with LH/FSH ratio (p = 0.03), AMH (p = 0.01) and inhibin-B (p < 0.001) in HT group. This study demonstrated that the adolescent girls diagnosed with autoimmune thyroiditis had normal ovarian reserve based on measurements of AMH, inhibin B, FSH, LH/FSH ratio, estradiol and antral follicle counts.

Patients with 47, XXX karyotype who experienced premature ovarian failure (POF): two case reports.

PubMed

Sugawara, Nobuo; Maeda, Machiko; Manome, Tomomi; Nagai, Rie; Araki, Yasuhisa

2013-10-01

Pubertal onset and sexual development are usually normal in 47, XXX individuals; however, we report two cases of premature ovarian failure (POF) in infertile women with trisomy X. Chromosome analysis was conducted with G-banding and fluorescence in situ hybridization using X- and Y-bearing probe. Hormonal administration was primarily Kaufmann's treatment or long-term estradiol treatment, followed by withdrawal bleeding from estrogen and progesterone. Two patients with trisomy X, aged 31 (patient 1) and 27 years (patient 2), were diagnosed with POF due to hypergonadotropic hypogonadism. Their ovaries were small. Patient 1 had a FSH level of 44.6 mIU/ml and patient 2 had a FSH level of 74.6 mIU/ml. In patient 1, with Kaufmann's treatment, the FSH decreased to 13.5 mIU/ml; however, follicle growth did not occur following HMG stimulation. In patient 2, FSH did not decrease despite Kaufmann's treatment; therefore, she was given a GnRH agonist and her FSH level decreased to 7.1 mIU/ml. However, her ovaries never responded to HMG stimulation. We report on two patients with a 47, XXX karyotype who became infertile due to POF. We recommend that when a patient is diagnosed with trisomy X, the possibility of POF must be strongly considered.

Flavonoid-enriched extract from Hippophae rhamnoides seed reduces high fat diet induced obesity, hypertriglyceridemia, and hepatic triglyceride accumulation in C57BL/6 mice.

PubMed

Yang, Xin; Wang, Qian; Pang, Zeng-Run; Pan, Meng-Ran; Zhang, Wen

2017-12-01

Flavonoid-enriched extract from Hippophae rhamnoides L. (Elaeagnaceae) seed (FSH) has shown beneficial effects in anti-hypertension and lowering cholesterol level. However, evidence for its efficacy in treating obesity is limited. We sought to determine if FSH can reduce body weight and regulate lipid metabolism disorder in high fat diet (HFD)-induced obese mouse model, and to investigate potential molecular targets involved. C57BL/6 mice were fed with HFD for 8 weeks to induce obesity. The modeled mice were divided into four groups and treated with vehicle, rosiglitazone (2 mg/kg), low (100 mg/kg) and high (300 mg/kg) dose of FSH, respectively. Normal control was also used. The treatments were administered orally for 9 weeks. We measured the effect of FSH on regulating body weight, various liver and serum parameters, and molecular targets that are key to lipid metabolism. FSH administration at 100 and 300 mg/kg significantly reduced body weight gain by 33.06 and 43.51%, respectively. Additionally, triglyceride concentration in serum and liver were decreased by 15.67 and 49.56%, individually, after FSH (300 mg/kg) treatment. Upon FSH (100 and 300 mg/kg) treatment, PPARα mRNA expression was upregulated in liver (1.24- and 1.42-fold) and in adipose tissue (1.66- and 1.72-fold). Furthermore, FSH downregulated PPARγ protein level both in liver and adipose tissue. Moreover, FSH inhibited macrophage infiltration into adipose tissues, and downregulated TNFα mRNA expression in adipose tissue (38.01-47.70%). This effect was mediated via regulation of PPARγ and PPARα gene expression, and suppression of adipose tissue inflammation.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions

PubMed Central

Mitrofanova, Lubov B.; Konovalov, Petr V.; Krylova, Julia S.; Polyakova, Victoria O.; Kvetnoy, Igor M.

2017-01-01

Introduction plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. Objective To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. Materials and methods We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. Results We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). Conclusion Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment. PMID:28418929

Ovulation disorders: part I anovulation associated with estrogen deficiency.

PubMed

Check, J H

2007-01-01

To describe the diagnosis and treatment of anovulatory disorders associated with estrogen deficiency. Anovulation with estrogen deficiency was divided into two types: association with low vs. high serum gonadotropin levels. Treatments included bromocriptine or cabergoline for hyperprolactinemia and gonadotropins for normal prolactin levels. When gonadotropins were low, lowering the elevated serum FSH to restore down-regulated FSH receptors in the few remaining follicles with either ethinyl estradiol or GnRH agonists or antagonists was used. High serum FSH was followed by either close observation for spontaneous follicular maturation or low dose gonadotropin stimulation. Progesterone supplementation, especially by vaginal use, was given in the luteal phase. Though success in ovulation induction and pregnancies was greater in women with low FSH than high FSH, pregnancies following ovulation induction were nevertheless achieved even in women in apparent menopause. The use of ethinyl estradiol as opposed to other estrogen drugs has the advantage of not being able to be measured by most serum assays for estradiol allowing the physician to detect endogenous follicular development and thus determining when follicular maturation has been achieved. Even in the presence of marked diminished ovarian egg reserve, eggs from chronically younger women are superior in quality to women aged > or = 45.

Occurrence of FSH, inhibin and other hypothalamic-pituitary-intestinal hormones in normal fertility, subfertility, and tumors of human testes.

PubMed

Mehta, M K; Garde, S V; Sheth, A R

1995-01-01

To compare the distribution of peptide hormones in presumably normal human testicular tissues and specimens exhibiting any of five pathologies. Biopsies from patients having testicular malfunctions were prepared as sections and specifically immunohistochemically stained for inhibin, FSH, serotonin, AUP, and oxytocin. Immunocytochemical studies revealed the presence of various hypophysial-pituitary-intestinal hormones, viz., FSH, inhibin, arginine vasopressin (AVP), calcitonin, serotonin, oxytocin, adrenocorticotropin (ACTH), gastrin, secretin, and somatostatin in human testicular biopsies exhibiting normal spermatogenesis, Sertoli-cell-only syndrome, spermatogenic arrest, Leydig cell hyperplasia, Leydig cell tumor, and seminoma. Intensity of immunostaining for all peptides except FSH was stronger in cases of subfertile as compared to normal testis. Intensity of immunostaining with inhibin was maximum in Leydig cell tumor. These regulatory peptides may be involved in the pathophysiology of the testes.

The time course of follicle-stimulating hormone suppression by recombinant human inhibin A in the adult male rhesus monkey (Macaca mulatta).

PubMed

Ramaswamy, S; Pohl, C R; McNeilly, A S; Winters, S J; Plant, T M

1998-08-01

In higher primates, FSH secretion appears to be regulated by a control system consistent with that described by the classical inhibin hypothesis. The purpose of the present experiment was to examine the time course of inhibin's action to suppress FSH secretion in the intact adult male rhesus monkey. To this end, five adult males implanted with indwelling venous catheters and exhibiting typical episodic patterns of LH and testosterone (T) secretion received a 4-day i.v. infusion of recombinant human (rh) inhibin A (832 ng/h x kg) followed, after a 4-week interval, by vehicle infusion of similar duration. Changes in circulating FSH concentrations during the inhibin and vehicle infusions were determined using a sensitive homologous macaque RIA, whereas enzyme-linked immunosorbent assays were employed to track inhibin A, inhibin B, and inhibin pro-alpha-C levels during the experiment. Normal pulsatile activity in the hypothalamic-pituitary-Leydig cell axis was confirmed by monitoring changes in circulating concentrations of LH and T in 12-h windows of sequential blood collection (1200-2400 h; every 20 min) before, during, and after the rh inhibin A and vehicle infusions. Although infusion of rh inhibin A, which led to a 12 ng/ml square wave increment in circulating levels of this inhibin dimer, produced a marked decline in circulating FSH concentrations, significant suppression of the secretion of this gonadotropin was not manifest until 54 h after initiation of the infusion. Despite the marked decline in FSH secretion during the last 24 h of the 4-day infusion of recombinant hormone, circulating inhibin B and pro-alpha-C concentrations were maintained at preinfusion control levels (1 ng/ml). The finding that imposition of an exaggerated circulating inhibin signal led to suppression of FSH secretion in the male monkey only after 2 days of exposure to the hormone indicates that in this species the feedback action of testicular inhibin on FSH secretion is heavily lagged. Moreover, as the decrease in FSH did not lead to changes in native inhibin secretion, it seems reasonable to propose that the FSH-inhibin feedback loop that governs testicular function in higher primates operates with considerable hysteresis at both the pituitary and gonadal levels. The failure of dramatically elevated inhibin A levels to influence the pulsatile secretion of LH in the monkey reinforces the idea that in this species the pituitary action of testicular inhibin is specific for FSH and does not involve modulation of GnRH receptor levels.

Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation

PubMed Central

Yu, Chunxiao; Zhang, Xu; Zhang, Haiqing; Guan, Qingbo; Zhao, Jiajun; Xu, Jin

2015-01-01

Objective The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. Methods We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). Results 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. Conclusions The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro. PMID:26241313

Follicle-Stimulating Hormone Increases the Risk of Postmenopausal Osteoporosis by Stimulating Osteoclast Differentiation.

PubMed

Wang, Jie; Zhang, Wenwen; Yu, Chunxiao; Zhang, Xu; Zhang, Haiqing; Guan, Qingbo; Zhao, Jiajun; Xu, Jin

2015-01-01

The objectives of this study were to observe the changes in follicle-stimulating hormone (FSH) and bone mineral density (BMD) in postmenopausal women, to research the relationship between FSH and postmenopausal osteoporosis, and to observe the effects of FSH on osteoclast differentiation in RAW264.7 cells. We analyzed 248 postmenopausal women with normal bone metabolism. A radioimmunoassay (RIA) was used to detect serum FSH, luteinizing hormone (LH), and estradiol (E2). Dual-energy X-ray absorptiometry was used to measure forearm BMD. Then, we analyzed the age-related changes in serum FSH, LH and E2. Additionally, FSH serum concentrations were compared between a group of postmenopausal women with osteoporosis and a control group. Osteoclasts were induced from RAW264.7 cells in vitro by receptor activator of nuclear factor kappa B ligand (RANKL), and these cells were treated with 0, 5, 10, and 20 ng/ml FSH. After the osteoclasts matured, tartrate-resistant acid phosphatase (TRAP) staining was used to identify osteoclasts, and the mRNA expression levels of genes involved in osteoclastic phenotypes and function, such as receptor activator of NF-κB (Rank), Trap, matrix metalloproteinase-9 (Mmp-9) and Cathepsin K, were detected in different groups using real-time PCR (polymerase chain reaction). 1. FSH serum concentrations in postmenopausal women with osteoporosis increased notably compared with the control group. 2. RANKL induced RAW264.7 cell differentiation into mature osteoclasts in vitro. 3. FSH increased mRNA expression of genes involved in osteoclastic phenotypes and function, such as Rank, Trap, Mmp-9 and Cathepsin K, in a dose-dependent manner. The circulating concentration of FSH may play an important role in the acceleration of bone loss in postmenopausal women. FSH increases osteoclastogenesis in vitro.

Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem.

PubMed

Huber, Malin; Hadziosmanovic, Nermin; Berglund, Lars; Holte, Jan

2013-11-01

To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns. Retrospective cross-sectional study. University-affiliated private center. The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist-recombinant FSH protocol). None. The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome. OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield. The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The use of Data Mining in the categorization of patients with Azoospermia.

PubMed

Mikos, Themistoklis; Maglaveras, Nikolaos; Pantazis, Konstantinos; Goulis, Dimitrios G; Bontis, John N; Papadimas, John

2005-01-01

Data Mining is a relatively new field of Medical Informatics. The aim of this study was to compare Data Mining diagnosis with clinical diagnosis by applying a Data Miner (DM) to a clinical dataset of infertile men with azoospermia. One hundred and forty-seven azoospermic men were clinically classified into four groups: a) obstructive azoospermia (n=63), b) non-obstructive azoospermia (n=71), c) hypergonadotropic hypogonadism (n=2), and d) hypogonadotropic hypogonadism (n=11). The DM (IBM's DB2/Intelligent Miner for Data 6.1) was asked to reproduce a four-cluster model. DM formed four groups of patients: a) eugonadal men with normal testicular volume and normal FSH levels (n=86), b) eugonadal men with significantly reduced testicular volume (median 6.5 cm3) and very high FSH levels (n=29), c) eugonadal men with moderately reduced testicular volume (median 14.5 cm3) and raised FSH levels (n=20), and d) hypogonadal men (n=12). Overall DM concordance rate in hypogonadal men was 92%, in obstructive azoospermia 73%, and in non-obstructive azoospermia 69%. Data Mining produces clinically meaningful results but different from those of the clinical diagnosis. It is possible that the use of large sets of structured and formalised data and continuous evaluation of DM results will generate a useful methodology for the Clinician.

Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells

PubMed Central

Fortin, Jérôme; Boehm, Ulrich; Weinstein, Michael B.; Graff, Jonathan M.; Bernard, Daniel J.

2014-01-01

The activin/inhibin system regulates follicle-stimulating hormone (FSH) synthesis and release by pituitary gonadotrope cells in mammals. In vitro cell line data suggest that activins stimulate FSH β-subunit (Fshb) transcription via complexes containing the receptor-regulated SMAD proteins SMAD2 and SMAD3. Here, we used a Cre-loxP approach to determine the necessity for SMAD2 and/or SMAD3 in FSH synthesis in vivo. Surprisingly, mice with conditional mutations in both Smad2 and Smad3 specifically in gonadotrope cells are fertile and produce FSH at quantitatively normal levels. Notably, however, we discovered that the recombined Smad3 allele produces a transcript that encodes the entirety of the SMAD3 C-terminal Mad homology 2 (MH2) domain. This protein behaves similarly to full-length SMAD3 in Fshb transcriptional assays. As the truncated protein lacks the N-terminal Mad homology 1 (MH1) domain, these results show that SMAD3 DNA-binding activity as well as SMAD2 are dispensable for normal FSH synthesis in vivo. Furthermore, the observation that deletion of proximal exons does not remove all SMAD3 function may facilitate interpretation of divergent phenotypes previously described in different Smad3 knockout mouse lines.—Fortin, J., Boehm, U., Weinstein, M. B., Graff, J. M., Bernard, D. J. Follicle-stimulating hormone synthesis and fertility are intact in mice lacking SMAD3 DNA binding activity and SMAD2 in gonadotrope cells. PMID:24308975

Control of follicle-stimulating hormone by estradiol and the inhibins: critical role of estradiol at the hypothalamus during the luteal-follicular transition.

PubMed

Welt, Corrine K; Pagan, Yanira L; Smith, Patricia C; Rado, Kimberly B; Hall, Janet E

2003-04-01

To test the hypothesis that estradiol, inhibin A, and inhibin B contribute differentially to FSH negative feedback in specific phases of the menstrual cycle, daily blood samples were obtained across a control cycle and after selective estrogen blockade with tamoxifen. To examine the site of estradiol-negative feedback in control and tamoxifen treatment cycles, early follicular phase GnRH (free alpha-subunit) pulse frequency was assessed in normal women, and FSH levels were examined in GnRH-deficient women in whom hypothalamic output was fixed with GnRH administration. FSH was higher in the early follicular phase in the presence of estrogen receptor blockade (15.7 +/- 3.1 vs. 13.2 +/- 1.9 IU/liter; P < 0.05) but was not increased in the late follicular phase. In the luteal phase, FSH was elevated (10.1 +/- 0.7 vs. 7.3 +/- 0.6 IU/liter; P < 0.01). In normal women, free alpha-subunit pulse frequency increased (7.3 +/- 0.4 vs. 4.8 +/- 0.4 pulses per 8 h; P < 0.003), but in GnRH-deficient women, there was no FSH increase (11.1 +/- 1.6 vs. 12.5 +/- 3.6 IU/liter) in the early follicular phase in the presence of estrogen blockade. In conclusion, estradiol exerts a greater role over inhibin in FSH-negative feedback regulation during the luteal phase and the luteal-follicular transition. In contrast, inhibin A and/or B plays a more critical role as the follicular phase progresses. In addition, these studies support a primary if not exclusive hypothalamic site of estrogen-negative feedback in the early follicular phase.

Serum LH and FSH Responses to Synthetic LH-RH in Normal Infants, Children and Patients With Turner's Syndrome

ERIC Educational Resources Information Center

Suwa, Seizo; And Others

1974-01-01

Effects of luteinizing hormone-releasing hormone (LH-RH) on LH and follicle-stimulating hormone (FSH) release were studied in 26 normal children and six patients (from 1-to 14-years-old) with Turner's syndrome. (Author)

Supplemented base medium containing Amburana cearensis associated with FSH improves in vitro development of isolated goat preantral follicles.

PubMed

Gouveia, B B; Macedo, T J S; Santos, J M S; Barberino, R S; Menezes, V G; Müller, M C; Almeida, J R G S; Figueiredo, J R; Matos, M H T

2016-09-15

The effects of Amburana cearensis ethanolic extract, with or without addition of a mix of supplements associated or not with FSH, on in vitro morphology and development of caprine secondary follicles were evaluated. In experiment 1, isolated follicles (250 μm in diameter) were cultured for 12 days in alpha-modified minimal essential medium (α-MEM) alone (control) or in medium composed of different concentrations of A. cearensis extract (Amb 0.1; 0.2, or 0.4 mg/mL). In experiment 2, culture media were α-MEM or Amb 0.2 mg/mL (both without supplements), or these same media supplemented with BSA, insulin, transferrin, selenium, glutamine, hypoxanthine, and ascorbic acid (referred as α-MEM(+) and Amb 0.2(+), respectively), or these last groups also supplemented with sequential FSH (100 ng/mL from Day 0 to Day 6; 500 ng/mL from Day 6 to Day 12), constituting groups α-MEM(+) + FSH and Amb 0.2(+) + FSH. At the end of culture in experiment 1, control medium (α-MEM) and Amb 0.2 mg/mL had higher percentages (P < 0.05) of morphologically normal follicles and percentage of fully grown oocytes, i.e., oocyte greater than 110 μm, compared to the other A. cearensis extract concentrations. In experiment 2, all supplemented media had higher percentages (P < 0.05) of normal follicles and antrum formation than nonsupplemented media. In addition, follicles cultured in Amb 0.2(+) + FSH showed an average increase in diameter higher (P < 0.05) than the other treatments. Oocytes cultured in both treatments supplemented with FSH showed greater glutathione and active mitochondria levels than nonsupplemented media but similar to the other treatments. In conclusion, A. cearensis extract (0.2 mg/mL) added by supplements and FSH improves follicular growth. Therefore, it can be an alternative culture medium for goat preantral follicle development. Copyright © 2016 Elsevier Inc. All rights reserved.

Commercial radioimmunoassay for beta subunit of human chorionic gonadotropin: falsely positive determinations due to elevated serum luteinizing hormone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fowler, J.E. Jr.; Platoff, G.E.; Kubrock, C.A.

1982-01-01

Among 17 men who had received seemingly curative treatment for unilateral non-seminomatous germ cell tumors for the testis and who had consistently normal serum human chorionic gonadotropin (HCG) levels at a reference laboratory, 7 (41%) had at least one falsely positive commercial serum HCG determination. To investigate the cause of these falsely positive determinations the authors measured the cross reactivity of luteinizing hormone (LH) and follicle stimulating hormone (FSH) standards in the commercial HCG assay, and studied the relationships between commercial HCG levels and serum LH levels, serum FSH levels and gonadal status in men with and without normal gonadalmore » function. The falsely positive HCG determinations appeared to be due to elevated serum LH levels and cross reactivity of LH in the commercial HCG assay because: 1) there was substantial cross reactivity of the LH standards in the commercial assay, 2) the serum LH was elevated in four of six men with solitary testes, 3) there was a striking correlation between elevated serum LH levels and falsely elevated commercial HCG levels in ten men with solitary or absent testes, and 4) there were no falsely positive HCG determinations in 13 normal men but there were falsely positive HCG determinations in seven of ten anorchid men.« less

High Serum FSH is Associated with Brown Oocyte Formation and a Lower Pregnacy Rate in Human IVF Parctice.

PubMed

Xu, Hongyi; Deng, Kai; Luo, Qingbing; Chen, Juan; Zhang, Xin; Wang, Xiaoyan; Diao, Honglu; Zhang, Changjun

2016-01-01

To investigate whether brown zona pellucida (ZP) of oocytes affects the outcome of fertilization, embryo quality and pregnancy rate in in vitro fertilization-embryo transfer (IVF-ET). Based on the ZP color of their oocytes, a total number of 703 patients dated from 2012 to 2014 were divided into a normal egg group (group A) and a brown oocyte group (group B), with 629 and 74 cases, respectively. Clinical characteristics, gonadotropin (Gn) days, Gn dosage, serum hormone levels on the day of human chorionic gonadotropin (HCG) injection, ZP thickness (ZPT) of the eggs, fertilization rate, rescue intracytoplasmic sperm injection (rICSI) rate, good-quality embryo rate and pregnancy rate were compared between the two groups. No significant differences were found in the duration and the causes of infertility, and their basal level of endocrine hormone before IVF-ET between normal egg group and brown egg group. The level of serum hormone including estradiol, progesterone and luteinizing hormone on the day of HCG injection were again similar. Moreover, there were no differences in number of mature oocytes, oocyte fertilization rates and rICSI rates after IVF between the two groups. However, we observed that the ZPT of brown oocytes (group B) was higher than that of normal oocytes (group A). Moreover, the Gn dosage and FSH levels on the day of HCG injection were significantly higher in group B than in group A and the good-quality embryo rate and pregnancy rate in group B were lower than those in group A. Compared with normal eggs, oocytes with a brown ZP were found to have a higher ZPT, lower embryo quality and lower pregnancy rate, which might be due to a high Gn dosage injection and high serum FSH levels during IVT-ET cycles. © 2016 The Author(s) Published by S. Karger AG, Basel.

Analyses of risk factors for polycystic ovary syndrome complicated with non-alcoholic fatty liver disease.

PubMed

Zhang, Jianhai; Hu, Jian; Zhang, Chunxia; Jiao, Yanni; Kong, Xiang; Wang, Wei

2018-05-01

The risk factors related to polycystic ovary syndrome (PCOS) patients complicated with non-alcoholic fatty liver disease (NAFLD) were investigated. A total of 188 PCOS patients treated in Shengli Oilfield Central Hospital (Dongying, China) from February 2014 to February 2015 were retrospectively analyzed as PCOS group, and PCOS group was further divided into NAFLD group and non-NAFLD (N-NAFLD) group according to the liver B ultrasound. In the same time-period, 65 healthy people were selected as normal control group. The differences of clinical, biochemical and metabolic indexes were compared. The levels of luteinizing hormone (LH), LH/follicle stimulating hormone (FSH), testosterone (T), free androgen index (FAI), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) index in PCOS group were higher than those in normal control group, but the sex hormone binding globulin (SHBG) level was lower than that in normal control group (P<0.05); there were no statistically significant differences in comparisons of age, body mass index (BMI), waist-hip ratio (WHR), FSH, dehydroepiandrosterone sulfate (DHEAs) and fasting blood glucose (FBG) between the two groups (P>0.05). The prevalence rate of NAFLD in PCOS group (44.68%) was significantly higher than that in control group (24.62%) (P<0.05). The proportion of NAFLD in PCOS patients in obesity group (63.51%) was significantly higher than that in non-obesity group (15.79%) (P<0.05). In PCOS group, NAFLD patients had more obvious metabolic abnormalities [high BMI, WHR, FBG, FINS, HOMA-IR index, total cholesterol (TC) and triglyceride (TG), and low high-density lipoprotein HDL and SHBG] and androgen excess compared with those in N-NAFLD patients (P<0.05). The levels of LH, LH/FSH, FINS and HOMA-IR index in PCOS group complicated with NAFLD were higher than those in control group complicated with NAFLD (P<0.05), but the differences in age, BMI, WHR, FSH and FBG levels were not statistically significant between the two groups (P>0.05). HOMA-IR index, BMI, WHR and TG were independent risk factors for PCOS complicated with NAFLD (P<0.05).

Hypogonadism in DM1 and its relationship to erectile dysfunction.

PubMed

Antonini, Giovanni; Clemenzi, Alessandro; Bucci, Elisabetta; De Marco, Emanuela; Morino, Stefania; Di Pasquale, Antonella; Latino, Pamela; Ruga, Gilda; Lenzi, Andrea; Vanacore, Nicola; Radicioni, Antonio F

2011-07-01

Myotonic dystrophy type 1 (DM1) is characterized by both a premature appearance of age-related phenotypes and multiple organ involvement, which affects skeletal and smooth muscle as well as the eye, heart, central nervous system, and endocrine system. Although erectile dysfunction (ED) is a frequent complaint in patients with DM1, it has not been investigated in great depth. Hypogonadism, which is reported to be one of the physical causes of ED in the general population, frequently occurs in DM1. We planned this case-control study to evaluate the relationship between hypogonadism, as defined by the sexual hormone profile (FSH, LH, testosterone (T) and prolactin) and ED, as assessed by means of an internationally validated self-administered questionnaire (IIEF). DM1 patients had significantly increased mean levels of both gonadotropins (FSH and LH) (p < 0.0001) and a reduced mean level of T (p < 0.0001) when compared to controls. Twelve patients were eugonadic (normal LH, T, and FSH), while 18 displayed hormonal evidence of hypogonadism, characterized by tubular failure (increased FSH) in all the subjects and associated with interstitial failure in 14 subjects: seven with primary hypogonadism (increased LH and reduced T) and seven with compensated hypogonadism (increased LH and normal T). Patients with hormonal evidence of interstitial failure had a larger CTG expansion (p = 0.008), longer disease duration (p = 0.013), higher grade of disease (p = 0.004) and lower erectile function score (p = 0.02) than eugonadic patients. Impotence occurred in 13/14 hypogonadic patients with interstitial failure and in 5/12 eugonadic patients (p = 0.017, OR = 18.2).

[Number of teeth and hormonal profile of postmenopausal women with osteoporosis, osteopenia and normal bone mineral density--a preliminary study].

PubMed

Stagraczyński, Maciej; Kulczyk, Tomasz; Leszczyński, Piotr; Męczekalski, Błażej

2015-10-01

Profound hypoestrogenism causes increased risk of osteoporosis and bone fracture in menopause. This period of women life is also characterized by decrease number of teeth and deterioration of oral cavity health. The aim of the study was to assess the number of teeth, hormonal profile (Follicle-stimualting hormone (FSH), estradiol (E2), testosterone (T) and dehydroepiandrosterone sulphate (DHEA-S) and the bone mineral density (BMD) of the lumbar part of the spine in postmenopausal women with osteoporosis, osteopenia and normal BMD. The next step of the study was to determine whether there was a correlation between vertebral mineral bone density, the hormonal profile and the number of teeth. A total number of 47 women was involved in the study. Based on the results of densitometry tests (DEXA) of vertebral column the subjects were divided into 3 groups: 10 with osteoporosis, 20 with osteopenia and 17 with normal BMD. All the subjects had undergone a hormonal assessment which included blood serum estimation for FSH, E2, DHEA-S and T levels. Also the total number of teeth present was recorded. Serum estradiol and testosterone levels in postmenopausal women were found to be positively correlated with the number of teeth present. A negative correlation was found between age and the number of maxillary teeth in postmenopausal women with osteopenia. There was no influence of serum FSH, estradiol, testosterone and DHEA-S levels on vertebral BMD loss in postmenopausal women. There was no correlation between teeth number and BMD of vertebral column. Serum levels of estradiol and testosterone in postmenopausal women positively correlate with teeth numbers. Age is the main risk factor for teeth loss in postmenopausal women. © 2015 MEDPRESS.

Dose-Effect Relationship of Alkylating Agents on Testicular Function in Male Survivors of Childhood Lymphoma.

PubMed

Servitzoglou, Marina; De Vathaire, Florent; Oberlin, Odile; Patte, Catherine; Thomas-Teinturier, Cécile

2015-01-01

The purpose of our study was to assess the gonadal function in male survivors of childhood lymphoma. We studied 171 male survivors of childhood lymphoma (83 with B-cell non-Hodgkin lymphoma [B-NHL], 32 with T-cell non-Hodgkin lymphoma [T-NHL], 50 with Hodgkin lymphoma [HL], and 6 with anaplastic large-cell lymphoma [ALCL]), measuring follicle-stimulating hormone [FSH] and luteinizing hormone [LH] levels at a median age of 21.1 (17-30.4) years after a median delay of 9.3 (2-22.4) years from treatment. FSH levels were above normal range (≥10 IU/L) in 42.1% and LH levels ≥8 IU/L in only 8.9% of survivors. In multivariate analysis, only the following chemotherapeutic agents were associated with higher FSH or LH levels: cyclophosphamide (P < .0001, .04), lomustine (CCNU; P = .002, 0.04), and procarbazine (P < .0001, .07). No significant correlation was found between FSH or LH levels and age or pubertal status at diagnosis. Mean FSH level was significantly lower in NHL survivors treated more recently: 6 ± 5.1 IU/L in B-NHL survivors treated since 1986 versus 12.3 ± 5.4 IU/L for those treated before 1981 (P = .0001), and 6.8 ± 9.6 IU/L in T-NHL survivors treated since 1989 versus 9.4 ± 5.7 IU/L for those treated before 1989 (P = .035). In HL, mean FSH level was 12.4 ± 9.9 IU/L following procarbazine containing chemotherapy versus 3.4 ± 1.9 IU/L in the absence of procarbazine and increased significantly with the number of MOPP/OPPA (mechlorethamine, Oncovin [vincristine], procarbazine, and prednisone/Oncovin, procarbazine, and prednisone, and Adriamycin [doxorubicin]) courses received, from 6.8 ± 5.7 IU/L for 1-2 MOPP/OPPA to 12.6 ± 7.5 for 3-4 MOPP/OPPA and 19.6 ± 13.3 for more than 4 MOPP/OPPA (P for trend = .006). Testicular toxicity of alkylating agents on childhood lymphoma survivors is dose dependent and not correlated to diagnosis, age, or pubertal status at diagnosis.

Transient dwarfism and hypogonadism in mice lacking Otx1 reveal prepubescent stage-specific control of pituitary levels of GH, FSH and LH.

PubMed

Acampora, D; Mazan, S; Tuorto, F; Avantaggiato, V; Tremblay, J J; Lazzaro, D; di Carlo, A; Mariano, A; Macchia, P E; Corte, G; Macchia, V; Drouin, J; Brûlet, P; Simeone, A

1998-04-01

Genetic and molecular approaches have enabled the identification of regulatory genes critically involved in determining cell types in the pituitary gland and/or in the hypothalamus. Here we report that Otx1, a homeobox-containing gene of the Otx gene family, is postnatally transcribed and translated in the pituitary gland. Cell culture experiments indicate that Otx1 may activate transcription of the growth hormone (GH), follicle-stimulating hormone (betaFSH), luteinizing hormone (betaLH) and alpha-glycoprotein subunit (alphaGSU) genes. Analysis of Otx1 null mice indicates that, at the prepubescent stage, they exhibit transient dwarfism and hypogonadism due to low levels of pituitary GH, FSH and LH hormones which, in turn, dramatically affect downstream molecular and organ targets. Nevertheless, Otx1-/- mice gradually recover from most of these abnormalities, showing normal levels of pituitary hormones with restored growth and gonadal function at 4 months of age. Expression patterns of related hypothalamic and pituitary cell type restricted genes, growth hormone releasing hormone (GRH), gonadotropin releasing hormone (GnRH) and their pituitary receptors (GRHR and GnRHR) suggest that, in Otx1-/- mice, hypothalamic and pituitary cells of the somatotropic and gonadotropic lineages appear unaltered and that the ability to synthesize GH, FSH and LH, rather than the number of cells producing these hormones, is affected. Our data indicate that Otx1 is a new pituitary transcription factor involved at the prepubescent stage in the control of GH, FSH and LH hormone levels and suggest that a complex regulatory mechanism might exist to control the physiological need for pituitary hormones at specific postnatal stages.

Night shift work and hormone levels in women.

PubMed

Davis, Scott; Mirick, Dana K; Chen, Chu; Stanczyk, Frank Z

2012-04-01

Night shift work may disrupt the normal nocturnal rise in melatonin, resulting in increased breast cancer risk, possibly through increased reproductive hormone levels. We investigated whether night shift work is associated with decreased levels of urinary 6-sulfatoxymelatonin, the primary metabolite of melatonin, and increased urinary reproductive hormone levels. Participants were 172 night shift and 151 day shift-working nurses, aged 20-49 years, with regular menstrual cycles. Urine samples were collected throughout work and sleep periods and assayed for 6-sulfatoxymelatonin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estrone conjugate (E1C). 6-Sulfatoxymelatonin levels were 62% lower and FSH and LH were 62% and 58% higher, respectively, in night shift-working women during daytime sleep than in day shift-working women during nighttime sleep (P ≤ 0.0001). Nighttime sleep on off-nights was associated with 42% lower 6-sulfatoxymelatonin levels among the night shift workers, relative to the day shift workers (P < 0.0001); no significant differences in LH or FSH were observed. 6-Sulfatoxymelatonin levels during night work were approximately 69% lower and FSH and LH were 35% and 38% higher, compared with day shift workers during nighttime sleep. No differences in E1C levels between night and day shift workers were observed. Within night shift workers, 6-sulfatoxymelatonin levels were lower and reproductive hormone levels were higher during daytime sleep and nighttime work, relative to nighttime sleep (P < 0.05). These results indicate that night shift workers have substantially reduced 6-sulfatoxymelatonin levels during night work and daytime sleep and that levels remain low even when a night shift worker sleeps at night. Shift work could be an important risk factor for many other cancers in addition to breast cancer. ©2012 AACR.

Anti-müllerian hormone and sertoli cell function in paediatric male hypogonadism.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2010-01-01

In the prepubertal male, Sertoli cells are the most active testicular cell population. Without stimulation tests, prepubertal hypogonadism can only be evidenced if Sertoli cell function is assessed. Anti-müllerian hormone (AMH) is a distinctive marker of the prepubertal Sertoli cell. Serum AMH is high from fetal life until puberty. In postnatal life, AMH testicular production is stimulated by FSH and potently inhibited by androgens. In anorchid patients, AMH is undetectable. In prepubertal males with fetal- or childhood-onset primary or central hypogonadism affecting the whole gonad, serum AMH is low. Conversely, when hypogonadism only affects Leydig cells (i.e., LH/human chorionic gonadotrophin receptor or steroidogenic enzyme defects), serum AMH is normal/high. AMH is also normal/high in patients with androgen insensitivity. In patients of pubertal age with central hypogonadism, AMH is low for Tanner stage - reflecting lack of FSH stimulus, - but high for age - reflecting lack of testosterone inhibitory effect. FSH treatment results in serum AMH rise, whereas human chorionic gonadotrophin treatment increases testosterone levels which inhibit AMH production. In conclusion, AMH determination is helpful in assessing gonadal function, without need for stimulation tests, and orientates the aetiological diagnosis of paediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action in the testis. Copyright 2010 S. Karger AG, Basel.

Cullen's sign and massive ovarian enlargement secondary to primary hypothyroidism in a patient with a normal FSH receptor

PubMed Central

Sultan, A; Velaga, M R; Fleet, M; Cheetham, T

2006-01-01

Ovarian hyperstimulation is a recognised complication of longstanding hypothyroidism. A 12 year old girl with atrophic thyroiditis who presented with abdominal pain and distension is reported. She was noted to have bruising in the vicinity of the umbilicus (Cullen's sign). She had pronounced ovarian enlargement on ultrasonography and it was hypothesised that this profound phenotype might reflect an abnormal FSH receptor. However sequencing of the FSH receptor was normal. The ovarian enlargement resolved with thyroxine replacement. Physicians and surgeons should consider longstanding hypothyroidism in patients presenting with Cullen's sign. PMID:16714722

Effects of long-term fasting on female hormone levels: Ramadan model.

PubMed

Cağlayan, E K; Göçmen, A Y; Delibas, N

2014-01-01

Ramadan fasting is a special model of hunger and particularly affects metabolic processes, including carbohydrate and lipid levels. Endocrine changes induced by Ramadan fasting are not well known. The aim of this article was to evaluate the changes in hormone levels in women before and after the special Muslim fasting period of Ramadan. This study was performed in 30 healthy women in Obstetrics and Gynecology department during the Ramadan month of2011. Patients during and after the first menstrual period had menstrual cycles fasting blood samples taken on the same days. Luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, and prolactin (PRL) levels were determined. Before and during fasting LH, FSH, E2, testosterone and PRL levels were not statistically different. Despite the limited available studies on these subjects in women, effect of Ramadan fasting on hormone levels were found to be within the normal limits.

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism

PubMed Central

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Learning points: Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty. Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH. Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function. PMID:28721217

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism.

PubMed

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier; Mercado, Moisés

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.

Circulating basal anti-Müllerian hormone levels as predictor of ovarian response in women undergoing ovarian stimulation for in vitro fertilization.

PubMed

Nardo, Luciano G; Gelbaya, Tarek A; Wilkinson, Hannah; Roberts, Stephen A; Yates, Allen; Pemberton, Phil; Laing, Ian

2009-11-01

To evaluate the clinical value of basal anti-Müllerian hormone (AMH) measurements compared with other available determinants, apart from chronologic age, in the prediction of ovarian response to gonadotrophin stimulation. Prospective cohort study. Tertiary referral center for reproductive medicine and an IVF unit. Women undergoing their first cycle of controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Basal levels of FSH and AMH as well as antral follicle count (AFC) were measured in 165 subjects. All patients were followed prospectively and their cycle outcomes recorded. Predictive value of FSH, AMH, and AFC for extremes of ovarian response to stimulation. Out of the 165 women, 134 were defined as normal responders, 15 as poor responders, and 16 as high responders. Subjects in the poor response group were significantly older then those in the other two groups. Anti-Müllerian hormone levels and AFC were markedly raised in the high responders and decreased in the poor responders. Compared with FSH and AFC, AMH performed better in the prediction of excessive response to ovarian stimulation-AMH area under receiver operating characteristic curve (ROC(AUC)) 0.81, FSH ROC(AUC) 0.66, AFC ROC(AUC) 0.69. For poor response, AMH (ROC(AUC) 0.88) was a significantly better predictor than FSH (ROC(AUC) 0.63) but not AFC (ROC(AUC) 0.81). AMH prediction of ovarian response was independent of age and PCOS. Anti-Müllerian hormone cutoffs of >3.75 ng/mL and <1.0 ng/mL would have modest sensitivity and specificity in predicting the extremes of response. Circulating AMH has the ability to predict excessive and poor response to stimulation with exogenous gonadotrophins. Overall, this biomarker is superior to basal FSH and AFC, and has the potential to be incorporated in to work-up protocols to predict patient's ovarian response to treatment and to individualize strategies aiming at reducing the cancellation rate and the iatrogenic complications of COH.

Plasma inhibin A in heifers: relationship with follicle dynamics, gonadotropins, and steroids during the estrous cycle and after treatment with bovine follicular fluid.

PubMed

Bleach, E C; Glencross, R G; Feist, S A; Groome, N P; Knight, P G

2001-03-01

The relationship between follicle growth and plasma inhibin A, FSH, LH, estradiol (E), and progesterone was investigated during the normal bovine estrous cycle and after treatment with steroid-free bovine follicular fluid (bFF) to arrest follicle development. In the first study, four heifers were monitored over three prostaglandin (PG)-synchronized cycles. Blood was collected every 2-8 h, and ovaries were examined daily by ultrasonography. Inhibin A was measured using a modified enzyme-linked immunosorbent assay that employed a new monoclonal antibody against the alpha subunit of bovine inhibin. Plasma inhibin A ( approximately 50 pg/ml before luteolysis) rose steadily during the induced follicular phase (P < 0.05) to a peak ( approximately 125 pg/ml) coincident with the preovulatory E/LH/FSH surge. After ovulation, inhibin A fell sharply (P < 0.05) to a nadir ( approximately 55 pg/ml) coincident with the secondary FSH rise. During the next 3 days, inhibin A increased to approximately 90 pg/ml in association with growth of the new dominant follicle (DF). Plasma E also rose twofold during this period, whereas FSH fell by approximately 50%. Inhibin A was negatively correlated with FSH (r = -0.37, P < 0.001) and positively correlated with E (r = 0.49, P < 0.0001). Observations on eight cycles (two cycles/heifer), in which growth of the ovulatory DF was monitored from emergence to ovulation, showed that the first-wave DF (DF1) ovulated in three cycles and the second-wave DF (DF2) in five cycles. After PG, plasma inhibin A and E increased similarly in both groups, with concomitant falls in FSH. In the former group, the restricted ability of DF1 to secrete both inhibin A and E was restored after luteolysis. Results indicate that dynamic changes in the secretion of both E and inhibin A from the DF contribute to the fall in FSH during the follicular phase and to the generation and termination of the secondary FSH surge, both of which play a key role in follicle selection. In the second study, bFF (two dose levels) was administered to heifers (n = 3-4) for 60 h starting from the time of DF1 emergence. Both doses suppressed FSH (P < 0.05) and blocked DF1 growth to the same extent (P < 0.01), although inhibin A levels were only marginally raised by the lower dose (not significant compared to controls). The high bFF dose raised (P < 0.001) inhibin A to supraphysiological levels ( approximately 1 ng/ml). A large "rebound" rise in FSH occurred within 1 day of stopping both treatments, even though the inhibin A level in the high-dose bFF group was still approximately threefold higher than that in controls. This indicates that desensitization of gonadotropes to inhibin negative feedback is a contributory factor, together with reduced ovarian output of E, in generation of the post-bFF rebound in FSH.

Serum FSH level below 10 mIU/mL at twelve years old is an index of spontaneous and cyclical menstruation in Turner syndrome.

PubMed

Aso, Keiko; Koto, Shinobu; Higuchi, Asako; Ariyasu, Daisuke; Izawa, Masako; Miyamoto Igaki, Junko; Hasegawa, Yukihiro

2010-01-01

The gonadal function of patients with Turner syndrome (TS) is variable. Individuals with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX are more likely to experience spontaneous menarche compared with other karyotypes. Prepubertal gonadotropins of TS patients with spontaneous menarche are reportedly normal or significantly lower than those of patients with induced menarche. The present study investigated an index of spontaneous and cyclical menstruation at 10-12 years old in TS. Subjects comprised 50 patients with TS, divided into three groups: Group A (n=7), with spontaneous menarche before 16 years old and regular menstruation for at least 1 year and 6 months; Group B (n=6), with irregular menstruation since menarche leading to secondary amenorrhea despite spontaneous menarche before 16 years old; and Group C (n=37), without spontaneous breast budding before 14 years old or without spontaneous menarche before 16 years old. Karyotype, LH and FSH concentrations at 10 and 12 years old were analyzed retrospectively. Spontaneous and cyclical menstruation was more frequently observed in TS with mosaicism characterized by 45,X/46,XX or 45,X/47,XXX than in TS with other karyotypes, as previously described. Spontaneous and cyclical menstruation in TS was observed when serum FSH level was <10 mIU/mL at 12 years old, suggesting this FSH level as an index of spontaneous and cyclical menstruation in TS.

Subclinical impairment of ovarian reserve in systemic lupus erythematosus patients with normal menstruation not using alkylating therapy.

PubMed

Ma, Wenhong; Zhan, Zhongping; Liang, Xiaoyan; Chen, Jianhui; Huang, Xingfang; Liao, Caiyun

2013-12-01

Disease activity is a major factor in menstrual disorders in systemic lupus erythematosus (SLE) patients not receiving alkylating therapy. However, the ovarian reserve of SLE women with normal menstruation is still unclear. Twenty-three SLE patients naïve to cytotoxic agents (SLE group) and nineteen SLE patients receiving current or previous cyclophosphamide (CTX) therapy (without other cytotoxic agents; SLE-CTX group) were enrolled. Twenty-one age-matched healthy women served as controls. All patients and controls had a regular menstrual cycle. Basal hormone levels, including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), and antral follicle count (AFC) were analyzed in the two study groups and compared with the control group. No significant differences were found between the SLE, SLE-CTX, and control groups in age, body mass index (BMI), and basal FSH and LH levels. The E2 (P=0.023) levels were high and the AMH (P=0.000) values and AFC (P=0.001) were significantly lower in the SLE and SLE-CTX groups compared to control. However, these values were similar between the SLE and SLE-CTX groups. SLE patients not receiving alkylating therapy who had normal menstruation and short illness duration still had an impaired ovarian reserve.

Luteal phase deficiency: abnormal gonadotropin and progesterone secretion patterns.

PubMed

Soules, M R; Clifton, D K; Cohen, N L; Bremner, W J; Steiner, R A

1989-10-01

Luteal phase deficiency (LPD) is a reproductive disorder associated with infertility and spontaneous abortion. This study was undertaken to determine whether LPD might be related to an abnormal pattern of gonadotropin secretion. We tested this hypothesis by evaluating the pattern of pulsatile LH secretion in both the follicular and luteal phases of the menstrual cycle in normal women (n = 21) and women with LPD (n = 20), which was diagnosed on the basis of two out of phase endometrial biopsies. In addition, we sought to determine whether changes in progesterone (P) pulse patterns could account for the decrease in average serum P levels in women with LPD. To this end, we examined the pulse patterns of P and compared these patterns between normal women and those with LPD. Frequent blood sampling was performed in both groups to determine their respective hormone secretion patterns. In the follicular phase, blood samples were obtained every 10 min for 12 h; in the luteal phase the samples were obtained every 10 min for 12 h; in the luteal LH, FSH, and P were assayed in each sample. Pulse detection was performed by an adaptive threshold method of pulse analysis. The LH pulse frequency was significantly higher in the women with LPD than in the normal women in the early follicular phase [P less than 0.05; LPD, 12.8 +/- 1.4 (+/- SE); normal, 8.2 +/- 0.7 pulses/12 h]. LH pulse frequency was similar in the early and late follicular phases in the women with LPD, whereas it was higher in the late follicular phase in normal women. Mean serum FSH levels were not different between groups in both the early and late follicular phases. In the luteal phase the P pulse amplitude and mean serum P level were significantly lower in the LPD group than in the normal women (P less than 0.01). We conclude that 1) a too rapid LH pulse pattern in the early follicular phase may lead to inadequate LH support of the corpus luteum and become manifest as LPD; 2) the mechanism for inadequate P secretion in LPD is decreased P pulse amplitude; 3) the finding of similar serum FSH levels in the two groups in both the early and late follicular phases did not support compromised folliculogenesis as an etiological factor for LPD.

Interactions between androgens, FSH, anti-Müllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary.

PubMed

Dewailly, Didier; Robin, Geoffroy; Peigne, Maëliss; Decanter, Christine; Pigny, Pascal; Catteau-Jonard, Sophie

2016-11-01

Androgens, FSH, anti-Müllerian hormone (AMH) and estradiol (E2) are essential in human ovarian folliculogenesis. However, the interactions between these four players is not fully understood. The purpose of this review is to highlight the chronological sequence of the appearance and function of androgens, FSH, AMH and E2 and to discuss controversies in the relationship between FSH and AMH. A better understanding of this interaction could supplement our current knowledge about the pathophysiology of the polycystic ovary syndrome (PCOS). A literature review was performed using the following search terms: androgens, FSH, FSH receptor, anti-Mullerian hormone, AMHRII, estradiol, follicle, ovary, PCOS, aromatase, granulosa cell, oocyte. The time period searched was 1980-2015 and the databases interrogated were PubMed and Web of Science. During the pre-antral ('gonadotropin-independent') follicle growth, FSH is already active and promotes follicle growth in synergy with theca cell-derived androgens. Conversely, AMH is inhibitory by counteracting FSH. We challenge the hypothesis that AMH is regulated by androgens and propose rather an indirect effect through an androgen-dependent amplification of FSH action on granulosa cells (GCs) from small growing follicles. This hypothesis implies that FSH stimulates AMH expression. During the antral ('gonadotropin-dependent') follicle growth, E2 production results from FSH-dependent activation of aromatase. Conversely, AMH is inhibitory but the decline of its expression, amplified by E2, allows full expression of aromatase, characteristic of the large antral follicles. We propose a theoretical scheme made up of two triangles that follow each other chronologically. In PCOS, pre-antral follicle growth is excessive (triangle 1) because of intrinsic androgen excess that renders GCs hypersensitive to FSH, with consequently excessive AMH expression. Antral follicle growth and differentiation are disturbed (triangle 2) because of the abnormally persisting inhibition of FSH effects by AMH that blocks aromatase. Beside anovulation, this scenario may also serve to explain the higher receptiveness to gonadotropin therapy and the increased risk of ovarian hyperstimulation syndrome (OHSS) in patients with PCOS. Within GCs, the balance between FSH and AMH effects is pivotal in the shift from androgen- to oestrogen-driven follicles. Our two triangles hypothesis, based on updated data from the literature, offers a pedagogic template for the understanding of folliculogenesis in the normal and polycystic ovary. It opens new avenues for the treatment of anovulation due to PCOS. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Potent therapeutic effects of shouwu jiangqi decoction on polycystic ovary syndrome with insulin resistance in rats.

PubMed

Wang, Li-hong; Wang, Xu; Yu, Xi-zhong; Xu, Wen-ting

2016-02-01

To investigate the effect of Shouwu Jiangqi Decoction (SJD) on polycystic ovary syndrome (PCOS) with insulin resistance (IR) in rats and to explore the underlining molecular mechanisms. A total of 51 female Sprague-Dawley rats were randomly divided into 6 groups: control group (n=7), model group (n=8), SJD high-dose group (n=9), SJD medium-dose group (n=9), SJD low-dose group (n=9) and DMBG group (n=9). Radioimmunoassay was used to measure serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone concentrations and qRT-PCR and western blot were used to examine the expression levels of mRNA and protein respectively of insulin receptor substrate 1 (IRS-1) and phosphatidylinositide 3-kinases (PI3K) p85α in different groups. FSH level significantly decreased in the model group compared with the normal control (P<0.01), and high-dose SJD and DMBG can significantly increase FSH level (P<0.01). LH level showed a mild increase without statistic significance in the model group compared with the control and different dosages of SJD had no significance effect on LH level, while DMBG can significantly decrease LH level (P<0.01). Testosterone level significantly increased in the model group compared with the control group (P<0.01), and high-dose SJD and DMBG can significantly decrease testosterone level (P<0.01). The expression of IRS-1 as well as PI3Kp85α were significantly decreased in the model group compared with the normal control group at both mRNA (P<0.001) and protein (P<0.01) level, and both high-dose SJD and DMBG can enhance IRS-1 and PI3K expression (P<0.05). SJD has potent therapeutic effects on PCOS with IR in rats. The therapeutic effects of SJD on IR and ovulatory dysfunction are probably achieved through correcting the defective insulin signaling transduction.

Stimulatory effect of clebopride on human prolactin secretion.

PubMed

Perez-Lopez, F R; Legido, A; Sisskin, M; Abos, M D

1980-11-01

Serum levels of prolactin (PRL), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in normally cycling women and normal men before and after oral admiministration of 1 mg of clebopride, a derivative of procainamide used in the treatment of gastrointestinal diseases. Clebopride produced a significant increase (P < 0.001) in serum PRL to a 6-fold peak as compared with basal levels. After 240 minutes the levels remained significantly higher (P < 0.05) than the mean basal level at -30 and 0 minutes. No significant effects of clebopride were noted upon the circulating levels of LH and FSH. The peak PRL response to clebopride was unaffected by pretreatment with 100 mg of nomifensine, although the secretory area from 120 to 210 minutes after clebopride was greater (P < 0.05) in the nomifensine-treated group than in the control experiment. When 5 mg of bromocriptine were given before clebopride, the PRL response was completely abolished as compared with the control experiment (P < 0.001). Our data provide new evidence that dopaminergic receptors of the adeylate cyclase system are involved in the regulation of PRL secretion, acting at the pituitary level rather than acting on the hypothalamus. The PRL-releasing activity of clebopride could be the explanation for the occasional menstrual disorders and galactorrhea registered in some cases of long-term treatment.

Follicle-stimulating hormone (FSH) activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization

PubMed Central

Piketty, Vincent; Kara, Elodie; Guillou, Florian; Reiter, Eric; Crepieux, Pascale

2006-01-01

Background The follicle-stimulating hormone receptor (FSH-R) is a seven transmembrane spanning receptor (7TMR) which plays a crucial role in male and female reproduction. Upon FSH stimulation, the FSH-R activates the extracellular signal-regulated kinases (ERK). However, the mechanisms whereby the agonist-stimulated FSH-R activates ERK are poorly understood. In order to activate ERK, some 7 TMRs require beta-arrestin-and dynamin-dependent internalization to occur, whereas some others do not. In the present study, we examined the ability of the FSH-activated FSH-R to induce ERK phosphorylation, in conditions where its beta-arrestin- and dynamin-mediated internalization was impaired. Methods Human embryonic kidney (HEK) 293 cells were transiently transfected with the rat FSH-R. Internalization of the FSH-R was manipulated by co-expression of either a beta-arrestin (319–418) dominant negative peptide, either an inactive dynamin K44A mutant or of wild-type beta-arrestin 1 or 2. The outcomes on the FSH-R internalization were assayed by measuring 125I-FSH binding at the cell surface when compared to internalized 125I-FSH binding. The resulting ERK phosphorylation level was visualized by Western blot analysis. Results In HEK 293 cells, FSH stimulated ERK phosphorylation in a dose-dependent manner. Co-transfection of the beta- arrestin (319–418) construct, or of the dynamin K44A mutant reduced FSH-R internalization in response to FSH, without affecting ERK phosphorylation. Likewise, overexpression of wild-type beta-arrestin 1 or 2 significantly increased the FSH-R internalization level in response to FSH, without altering FSH-induced ERK phosphorylation. Conclusion From these results, we conclude that the FSH-R does not require beta-arrestin- nor dynamin-mediated internalization to initiate ERK phosphorylation in response to FSH. PMID:16787538

Responses to constant infusion of LH-RH in girls with primary hypogonadism.

PubMed

Reiter, E O; Duckett, G E; Root, A W

1980-09-01

To further assess quantitative pituitary gonadotropin release in patients with primary hypogonadism, a 3-hour constant infusion of the synthetic gonadotropin-releasing hormone, LH-RH, was administered to 12 functionally agonadal girls (11 with Turner syndrome and 1 who had been overiectomized), aged 9.5 to 19.42 years. Gonadotropin and sex steroid responses were determined before and during the infusion and contrasted to those in normal pubertal females. in girls with skeletal age under 11 years, mean control LH increased (P < .001) from 2.2 +/- 0.3 (mean +/- SEM) mIU/ml to 21.3 +/- 7.3 during LH-RH infusion, while luteinizing hormone (LH) rose (P < .001) from 89.2 +/- 24.6 to 276.5 +/- 42.6 girls with skeletal age over 11 years. This age-related augmentation is an exaggeration of data in normal girls and occcurs despite minimal gonadal secretion of sex steroids. A similar age-related discrepancy was not seen in follicle-stimulating hormone (FSH) secretion evoked by LH-RH; all girls had FSH increments into the castrate range with a rise from mean control levels of 78.6 +/- 6.7 to 133.9 +/- 8.3. These data demonstrate an age-related increase in LH-RH-evoked LH secretion, but not of FSH, in children and adolescents with primary hypogonadism.

Effects of FSH addition to an enriched medium containing insulin and EGF after long-term culture on functionality of equine ovarian biopsy tissue.

PubMed

Aguiar, F L N; Gastal, G D A; Ishak, G M; Gastal, M O; Teixeira, D I A; Feugang, J M; Figueiredo, J R; Gastal, E L

2017-09-01

The effect of FSH supplementation on an enriched cultured medium containing insulin (10 ng/mL) and EGF (50 ng/mL) was investigated on in vitro culture of equine ovarian biopsy tissue. Ovarian tissue fragments were collected from mares (n = 10) and distributed in the following treatments: noncultured control, cultured control, and cultured + FSH. Both treated groups were cultured for 7 or 15 days. The end points evaluated were: follicular morphology, estradiol levels in the culture medium, fluorescence intensity for TUNEL, EGFR and Ki-67 detection, and gene expression of GDF-9, BMP-15, and Cyclin-D2 in the ovarian tissue. After seven days of culture, medium supplemented with FSH had a similar (P > 0.05) percentage of morphologically normal follicles compared to the noncultured control group. Estradiol levels increased (P < 0.05) from Day 7 to Day 15 of culture for both treated groups. No difference (P > 0.05) was observed for TUNEL and EGFR intensity between the noncultured control group and the treated groups after 15 days of culture. Ki-67 intensity did not differ (P > 0.05) between treated groups after 15 days of culture, but decreased (P < 0.05) when compared with the noncultured control group. Similar (P > 0.05) mRNA expression for GDF-9, BMP-15, and Cyclin-D2 was observed among all treatments after 15 days of culture. In conclusion, an enriched medium supplemented or not with FSH was able to maintain the functionality of equine ovarian biopsy tissue after a long-term in vitro culture. Copyright © 2017 Elsevier Inc. All rights reserved.

Sertoli cell markers in the diagnosis of paediatric male hypogonadism.

PubMed

Grinspon, Romina P; Loreti, Nazareth; Braslavsky, Débora; Bedecarrás, Patricia; Ambao, Verónica; Gottlieb, Silvia; Bergadá, Ignacio; Campo, Stella M; Rey, Rodolfo A

2012-01-01

During childhood, the pituitary-testicular axis is partially dormant: testosterone secretion decreases following a drop in luteinising hormone levels; follicle-stimulating hormone (FSH) levels also go down. Conversely, Sertoli cells are most active, as revealed by the circulating levels of anti-Müllerian hormone (AMH) and inhibin B. Therefore, hypogonadism can best be evidenced, without stimulation tests, if Sertoli cell function is assessed. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Inhibin B is high in the first years of life, then decreases partially while remaining clearly higher than in females, and increases again at puberty. Serum AMH and inhibin B are undetectable in anorchid patients. In primary or central hypogonadism affecting the whole gonad established in fetal life or childhood, all testicular markers are low. Conversely, when hypogonadism only affects Leydig cells, serum AMH and inhibin B are normal. In males of pubertal age with central hypogonadism, AMH and inhibin B are low. Treatment with FSH provokes an increase in serum levels of both Sertoli cell markers, whereas human chorionic gonadotrophin (hCG) administration increases testosterone levels. In conclusion, measurement of serum AMH and inhibin B is helpful in assessing testicular function, without need for stimulation tests, and orientates the aetiological diagnosis of paediatric male hypogonadism.

How to personalize ovarian stimulation in clinical practice.

PubMed

Sighinolfi, Giovanna; Grisendi, Valentina; La Marca, Antonio

2017-09-01

Controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles is the starting point from which couple's prognosis depends. Individualization in follicle-stimulating hormone (FSH) starting dose and protocol used is based on ovarian response prediction, which depends on ovarian reserve. Anti-Müllerian hormone levels and the antral follicle count are considered the most accurate and reliable markers of ovarian reserve. A literature search was performed for studies that addressed the ability of ovarian reserve markers to predict poor and high ovarian response in assisted reproductive technology cycles. According to the predicted response to ovarian stimulation (poor- normal- or high- response), it is possible to counsel couples before treatment about the prognosis, and also to individualize ovarian stimulation protocols, choosing among GnRH-agonists or antagonists for endogenous FSH suppression, and the FSH starting dose in order to decrease the risk of cycle cancellation and ovarian hyperstimulation syndrome. In this review we discuss how to choose the best COS therapy, based on ovarian reserve markers, in order to enhance chances in IVF.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth.

PubMed

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth.

A new way of setting rFSH deposit: a case of severe injection error in IVF/ICSI cycle ending with live birth

PubMed Central

Mayer, Richard Bernhard; Ebner, Thomas; Shebl, Omar; Tews, Gernot

2012-01-01

We present a case with a severe injection error: a 25- year old woman with secondary infertility caused by a male factor was enrolled in our IVF/ICSI-ET program. Stimulation was performed in a long- protocol and ovarian stimulation, using rFSH follitropin beta, starting on the third day of the menstrual cycle. The rFSH dose per day was 900 IU-0 IU-0 IU-0 IU. Due to normal ovarian response and follicle growth, stimulation was continued and there was no detriment in oocyte quality and no symptoms of OHSS. Following blastocyte transfer cesarean section was unpreventable at 37+5 weeks of gestation due to an impacted transverse lie. Different stimulation protocols are needed for appropriate treatment of various patients provided that the administration of treatment was done correctly. In the case of injection errors, continuing stimulation protocol seems to be achievable in certain cases considering hormone levels and the process of follicle growth. PMID:24592042

Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.

PubMed

Kavanagh, Kylie; Koudy Williams, J; Wagner, Janice D

2005-08-01

Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.

Dynamics of prolactin, gonadotropin, and of sex steroids in the blood serum of parturients during laser therapy

NASA Astrophysics Data System (ADS)

Kovalyov, M. I.

2001-04-01

An investigation was made of the effect (lambda) equals 0.63 micrometers diode laser radiation with the energy density of 0.6 to 0.8 J cm-2 on parturients affected by nipples' rhagades. In our experiments, we determined the content of prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and of progesterone (P) in the parturients' blood serum. It was found that laser radiation produced an insignificant effect on the prolactic (PRL) content in parturients with the normal lactation level. On the contrary, it produced a stimulating effect on the PRL level in parturients with hypogalactia. Possibly, laser radiation promoted the decrease in the FSH level in the parturients' blood serum. It was also found that this laser radiation produced an insignificant effect on the levels of LH, estradiol (E2), and of progesterone. Women subsequently affected by mastitis exhibited a significantly higher PRL level in their blood serum, as compared with women of the control group.

Dynamics of the h-LH and h-FSH response after the stimulation test with Gn-RH-LH/FSH in man.

PubMed

Klepsch, I; Grigorescu, A; Eşanu, C

1976-01-01

A study was carried out on a number of 17 subjects concerning the dynamics of LH and FSH response after stimulation with Gn-RH-LH/FSH. The results show a stimulation 10 minutes after quick i.v. injection of synthetic RH, with a peak at 20-30 minutes and a persistence of the response of up to 180 min. The variation of the response is proportional with the dose, the response to stimulation being higher for LH than for FSH. The response in the normal adult male is of 82-858% for LH and of 157-250% for FSH. In aged subjects there is an increased response capacity showing that the hypophysis still reacts at an advanced age, with variations depending on the individual characteristics. In Sheehan's syndrome the basal values of FSH and LH are low, with a slight response after stimulation with RH, suggesting the possibility of a partial regeneration of the hypophysis if any intact areas were left after the initial necrotic process.

Evaluating the role of the FSH receptor gene Thr307-Ala and Asn680-Ser polymorphisms in male infertility and their association with semen quality and reproductive hormones.

PubMed

Safarinejad, Mohammad Reza; Shafiei, Nayyer; Safarinejad, Saba

2011-07-01

To determine whether Thr(307)-Asn(680) and Ala(307)-Ser(680) polymorphisms of the follicle-stimulating hormone receptor (FSH-R) gene are associated with male infertility, semen quality, and reproductive hormones. The FSH-R polymorphisms at codons 680 and 307 were analysed by restriction-fragment-length polymorphism (RFLP) in 172 infertile men and in an equal number of age-matched healthy fertile men. Genotyping of the FSH-R gene was performed using the polymerase chain reaction RFLP technique. All of the participants underwent semen analysis, and reproductive hormones were also measured. Allelic frequencies were 29.7% serine (Ser) and 70.3% asparagine (Asn) for fertile men (the control group), and 33.1% Ser and 66.9% Asn for infertile men (P > 0.05). The FSH-R genotype at position 680 was 49.4% (Asn/Asn), 41.9% (Asn/Ser), and 8.7% (Ser/Ser) in the control group and 40.1% (Asn/Asn), 46.5% (Asn/Ser), and 13.4% (Ser/Ser) in infertile men, respectively (P > 0.05, chi-squared test). Allelic frequencies were 33.1% alanine (Ala) and 66.9% threonine (Thr) for the control group, and 37.8% Ala and 62.2% Thr for the infertile men. The frequencies of genotypes at position 307 were 45.5% Thr/Thr, 43% Thr/Ala, and 11.6% Ala/Ala for the control group and 36.1% Thr/Thr, 52.3% Thr/Ala, and 11.6% Ala/Ala for infertile men. No significant association between codon 680 and codon 307 genotypes and infertility was observed (P = 0.076 and P = 0.073, respectively). The odds ratio (OR) values indicated that individuals with the Thr/Thr + Asn/Ser combined genotypes had a > 50% decreased risk for developing infertility (OR = 0.44; 95% confidence interval [CI]: 0.22-0.77; P = 0.006). The patients with heterozygous Thr/Ala + Asn/Ser combined genotype were 2.65 times more susceptible to infertility than the control group (OR = 2.65; 95% CI: 1.74-3.82; P = 0.0053). The FSH-R codon 680 and codon 307 genotypes did not result in different serum FSH levels either in men with normal spermatogenesis (the control group) or in men with oligoasthenoteratozoospermia (infertile men). We did not observe any significant association of FSH-R genotype frequencies with any of the sperm characteristics analysed in either group. No significant correlation between serum FSH levels and semen characteristics, or fertility status and FSH-R gene polymorphisms was found. The combination of heterozygous Thr/Ala + Asn/Ser genotypes increases the risk for male infertility. © 2010 THE AUTHOR. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.

[Severe postmenopausal hyperandrogenism due to an ovarian lipoid cell tumor: a case report].

PubMed

Bernasconi, D; Del Monte, P; Marinaro, E; Marugo, A; Marugo, M

2004-03-01

The case of a 62-year-old woman with severe post-menopausal hirsutism is described. Her clinical history revealed regular menstrual periods until menopause at the age of 50, hysterectomy for fibromatosis at 58 years, non-insulin dependent diabetes mellitus, hypertension, obesity, severe hirsutism, which had developed in the previous 3 years, with a deeping of the voice. Examination showed android obesity, hypertension and severe hirsutism involving the face and the trunk. Endocrine evaluation pointed out regular adrenal function, serum total and free-testosterone in the adult male range, with normal androstenedione, DHEAS and 17OHP levels. Estradiol was slightly increased and LH and FSH were inappropriately low for her post-menopausal age. Computed tomography of the abdomen showed regular adrenal glands, and a radio-labeled cholesterol scan was negative. A further pelvic transvaginal ultrasonography revealed a small cystic formation near the right ovary and a slight increase in the size of the left ovary. The patient underwent bilateral ovariectomy. Histological examination showed a lipoid cell tumor within the left ovary. Immunohistochemical studies were positive for inhibin and cytokeratin. After surgery, serum testosterone fell to normal levels, gonadotropins increased to menopausal levels, confirming that the tumor was able to produce both LH, and FSH-inhibiting factors, and hirsutism greatly improved. Periodic hormonal tests remained normal and CT of the abdomen and pelvic ultrasonography did not show alterations at a 3 years follow-up.

Serum levels of inhibin A and inhibin B in women with normal and abnormal luteal function.

PubMed

Yamoto, M; Imai, M; Otani, H; Nakano, R

1997-05-01

To determine whether serum inhibin A and inhibin B concentrations are lower in patients with luteal dysfunction than in women with normal luteal function. Serum samples were collected from seven healthy women with regular menstrual cycles. Serum samples on days +5 to +9 after the LH surge were collected from patients with luteal dysfunction. The diagnosis of luteal dysfunction was based on a luteal phase duration less than 11 days and a single midluteal progesterone level below 10 ng/mL. Serum levels of inhibin A, inhibin B, progesterone, estradiol (E2), FSH, and LH were measured. The serum inhibin A levels were increased toward the late follicular phase. The levels reached a maximum during the midluteal phase, followed by a fall during the late luteal phase. The serum inhibin B levels were high during the follicular phases and the early luteal phase. The levels decreased during the midluteal and late luteal phases. Serum levels (mean +/- standard error of the mean) of inhibin A in patients with luteal dysfunction were significantly lower than those in women during the midluteal phase (26.2 +/- 2.9 compared to 41.9 +/- 2.8 pg/mL; P < .01) in addition to the expected decrease in serum progesterone levels (6.3 +/- 0.7 compared to 14.7 +/- 1.2 ng/mL; P < .01). Serum inhibin B levels did not differ significantly between normal women and those with luteal dysfunction. There also were no significant differences in the E2, FSH, and LH levels. Levels of inhibin A, but not of inhibin B, may reflect the human luteal function.

Effects of cetrorelix, a GnRH-receptor antagonist, on gonadal axis in women with functional hypothalamic amenorrhea.

PubMed

Berardelli, Rita; Gianotti, Laura; Karamouzis, Ioannis; Picu, Andreea; Giordano, Roberta; D'Angelo, Valentina; Zinnà, Domenico; Lanfranco, Fabio; Ghigo, Ezio; Arvat, Emanuela

2011-10-01

Gonadotropin Releasing Hormone (GnRH) antagonists (GnRHa) suppress gonadotropin and sex-steroid secretion. In normal women, acute GnRHa administration induces inhibitory effect on pituitary-gonadal axis, followed by Luteinizing Hormone (LH) rebound. Functional hypothalamic amenorrhea (HA) is characterised by impaired gonadotropin secretion and hypogonadism secondary to blunted GnRH pulsatility. We studied the effects of a GnRHa, cetrorelix (CTX 3.0 mg), in six women with HA (age 30.7 ± 3.2 years; BMI 21.5 ± 1.7 kg/m(2)) and six control subjects (CS, 28.2 ± 0.6 years; 22.6 ± 0.9 kg/m(2)) on LH, Follicle-Stimulating Hormone (FSH) and oestradiol levels over 4 h (08.00-12.00 am) before, +24 h and +96 h after CTX; LH, FSH, and oestradiol were also evaluated at +6, +8, +12, +48, +72 h after CTX. CS: CTX reduced (p < 0.05) LH, FSH, and oestradiol (nadir at +12 h, +24 h, and +24 h); LH rebounded at +96 h, FSH and oestradiol recovered at +48 h and +72 h. The 4-h evaluation showed LH and FSH reduction (p < 0.05) at +24 h, with LH rebound at +96 h. HA: CTX reduced (p < 0.05) LH, FSH, and oestradiol, (nadir at +24 h, +48 h, and +48 h, recovery at +48 h, +72 h, and +96 h). The 4-h evaluation showed gonadotropin reduction (p < 0.05) 24 h after CTX, without any rebound effect. One single CTX dose still modulates gonadotropin secretion in HA. Its 'paradoxical' stimulatory effect on gonadotropins needs to be verified after prolonged administration.

Subtotal obstruction of the male reproductive tract.

PubMed

Dohle, G R; van Roijen, J H; Pierik, F H; Vreeburg, J T M; Weber, R F A

2003-03-01

Bilateral obstruction of the male reproductive tract is suspected in men with azoospermia, normal testicular volume and normal FSH. A testicular biopsy is required to differentiate between an obstruction and a testicular insufficiency. Unilateral or subtotal bilateral obstructions and epididymal dysfunction may cause severe oligozoospermia in men with a normal spermatogenesis. However, information on spermatogenesis in oligozoospermic men is lacking, since testicular biopsy is not routinely performed. Men with a sperm concentration of <1 x 10(6) spermatozoa/ml were investigated for possible partial obstruction by performing a testicular biopsy under local anaesthesia. Spermatogenesis was determined by the Johnsen scoring method. A testicular biopsy was performed in 78 men with severe oligozoospermia. The medical history showed male accessory gland infection in 12.8%, previous hernia repair in 14.1% and a history of cryptorchidism in 12.8%. A normal or slightly disturbed spermatogenesis (Johnsen score >8) was present in 39/78 (50%) of the men. Hernia repair occurred more often in men with normal spermatogenesis. A varicocele was predominantly seen in men with a disturbed spermatogenesis. FSH was significantly lower ( P<0.0001) in men with normal spermatogenesis. Subtotal obstruction of the male reproductive tract is a frequent cause of severe oligozoospermia in men with a normal testicular volume and a normal FSH. In other cases, an epididymal dysfunction might explain the oligozoospermia in men with a normal testicular biopsy score.

Immunization with FSHβ fusion protein antigen prevents bone loss in a rat ovariectomy-induced osteoporosis model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Wenxin; Yan, Xingrong; Du, Huicong

Highlights: •A GST-FSH fusion protein was successfully expressed in E. coli. •Immunization with GST-FSH antigen can raise high-titer anti-FSH polyclonal sera. •Anti-FSH polyclonal sera can neutralize osteoclastogenic effect of FSH in vitro. •FSH immunization can prevent bone loss in a rat osteoporosis model. -- Abstract: Osteoporosis, a metabolic bone disease, threatens postmenopausal women globally. Hormone replacement therapy (HTR), especially estrogen replacement therapy (ERT), is used widely in the clinic because it has been generally accepted that postmenopausal osteoporosis is caused by estrogen deficiency. However, hypogonadal α and β estrogen receptor null mice were only mildly osteopenic, and mice with eithermore » receptor deleted had normal bone mass, indicating that estrogen may not be the only mediator that induces osteoporosis. Recently, follicle-stimulating hormone (FSH), the serum concentration of which increases from the very beginning of menopause, has been found to play a key role in postmenopausal osteoporosis by promoting osteoclastogenesis. In this article, we confirmed that exogenous FSH can enhance osteoclast differentiation in vitro and that this effect can be neutralized by either an anti-FSH monoclonal antibody or anti-FSH polyclonal sera raised by immunizing animals with a recombinant GST-FSHβ fusion protein antigen. Moreover, immunizing ovariectomized rats with the GST-FSHβ antigen does significantly prevent trabecular bone loss and thereby enhance the bone strength, indicating that a FSH-based vaccine may be a promising therapeutic strategy to slow down bone loss in postmenopausal women.« less

Early effects of cranial irradiation on hypothalamic-pituitary function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, K.S.; Tse, V.K.; Wang, C.

1987-03-01

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordantmore » changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.« less

New perspectives in the diagnosis of pediatric male hypogonadism: the importance of AMH as a Sertoli cell marker.

PubMed

Grinspon, Romina P; Rey, Rodolfo A

2011-11-01

Sertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHβ mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.

[Effect of Transcutaneuos Acupoint Electrostimulation on Serum Sex Hormone Levels and Expression of Ovarian Steroid Hormone Metabolic Enzymes in Polycystic Ovary Syndrome Rats].

PubMed

Zhou, Jian-yong; Zhang, Xiao-yue; Yu, Mei-ling; Lu, Sheng-feng; Chen, Xia

2016-02-01

To observe the effect of transcutaneuos acupoint electrostimulation(TAES) on ovarian serum sex hormone levels and ovarian follicle granular cell aromatase cytochrome P 450 (P 450 arom) protein and follicle theca cell cytochrome P 450 17 α-hydroxylase/c 17-20 lyase cytochrome P 450 (P 450 c 17 α) protein expression in polycystic ovary syndrome (PCOS)rats, so as to explore its mechanisms underlying improvement of PCOS. METHODS Forty SD rats were randomly divided into four groups: normal control, model, medication and TAES (10 rats/group). The PCOS model was established by giving (gavage) the animals with letrozole solution (1.0 mg/kg, once daily for 21 consecutive days). Rats of the medication group were treated with Clomiphene (1 mg/kg) once daily for 7 days, and those of the TAES group were treated with electrical stimulation (2 Hz, 3 mA) of "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) areas for 30 min, once daily for 7 consecutive days. The rats body weight and bilateral ovarian weight were detected, and the ovarian structure and follicular development degree were observed under light microscope after H. E. stain, and the serum testosterone (T), estradiol (E2), luteotrophic hormone (LH) and follicle-stimulating hormone (FSH) contents were detected using radioimmunoassay. The expression of ovarian P 450 arom (for production of estrogen)protein and P 450 c 17 α (for production of androgen) protein was detected by using immunohistochemical stain and Western blot, respectively. The body weight, bilateral ovary weight, serum T and LH contents, and ratio of LH/FSH, and ovarian P 450 c 17 α immunoactivity and protein expression levels in the model group were all significantly increased compared with the normal control group (P < 0.01), and the levels of serum E2 and ovarian P 450 arom immunoactivity and protein expression were significantly decreased after modeling (P < 0.01). Following the treatment, the increased body weight, ovary weight, serum T and LH contents, ratio of LH/FSH, and ovarian P 450 c 17 α immunoactivity and protein expression levels, and the decreased ovarian P 450 arom immunoactivity and protein expression levels were reversed in the TAES group (P < 0.01, P < 0.05) rather than in the medication group, except serum T and ratio of LH/FSH in the medication group. No significant differences were found between the medication and TAES groups in the serum T and ratio of LH/FSH (P > 0.05). In addition, the increased vesicular follicle number, the decreased corepus luteum number and the thickness of granular cell layer were markedly improved in the TAES group. TAES intervention can reduce both body weight and ovarian weight and regulate the levels of serum sex hormones and ovarian P 450 c 17 α and P 450 arom protein expression levels in PCOS rats, which may contribute to its effect in improving PCOS.

A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

PubMed

Elhadd, Tarik A; Ghosh, Sujoy; Teoh, Wei Leng; Trevethick, Katy Ann; Hanzely, Zoltan; Dunn, Laurence T; Malik, Iqbal A; Collier, Andrew

2009-08-01

Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, <3.0 IU/L). There was no evidence of an abnormal thyroid hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

Determination of porcine plasma follitropin levels during superovulation treatment in cows.

PubMed

Demoustier, M M; Beckers, J F; Van Der Zwalmen, P; Closset, J; Gillard, J L; Ectors, F

1988-08-01

Porcine follicle stimulating hormone (pFSH) and porcine luteinizing hormone (pLH), are widely used to induce superovulation in cows. An advantage of this treatment is that the LH:FSH ratio can be varied to optimize the growth of the ovarian follicles. However, due to the relatively short half-life of FSH, the superovulatory treatment requires numerous injections. A performant radioimmunoassay system (sensitivity=0.2 ng/ml plasma) was used to determine plasma pFSH levels in cows that were superovulated with 2 daily injections of 4 Armour Units (A.U.) of pFSH for 4 d. From plasma profiles, the half-life and the disappearance of pFSH were estimated at 5 h and at 10 to 12 h, respectively, confirming the necessity of using two daily injections.

rs4889 polymorphism in KISS1 gene, its effect on polycystic ovary syndrome development and anthropometric and hormonal parameters in Saudi women.

PubMed

Albalawi, Fadwa S; Daghestani, Maha H; Daghestani, Mazin H; Eldali, Abdelmoneim; Warsy, Arjumand S

2018-05-30

Kisspeptin is involved in female reproduction. This study was designed to i- estimate kisspeptin levels in women with polycystic ovary syndrome (PCOS), in comparison with controls, ii- study the correlations between kisspeptin and PCOS-related reproductive hormones, and iii- investigate the relation between KISS1 gene polymorphisms and hormone levels in women suffering from PCOS. The investigation was a clinically designed study on 28 women with PCOS, and 30 normal, healthy women with no signs of PCOS as controls. Blood samples were collected between day 3 and day 6 of the menstrual cycle in both groups at 8:00 a.m., and circulating levels of LH, FSH and kisspeptin were estimated. DNA was extracted from whole blood and all coding exons of KISS1 gene were sequenced. Women with PCOS had higher LH levels and BMI compared to controls. Plasma kisspeptin levels were positively correlated with LH levels. There was no statistically significant difference between the groups in terms of kisspeptin and FSH levels. The SNP rs4889 C/G, a non-synonymous SNP, was investigated in the PCOS group. The frequency of GG genotype was significantly higher in the PCOS compared to the controls. These patients were more obese, had higher kisspeptin and FSH levels. The results of the study show that the genetic variation of KISS1 gene may be a factor contributing to PCOS development. The association between the gene and the gene variation and PCOS need further validation in large-scaled and functional studies.

Cadmium, follicle-stimulating hormone, and effects on bone in women age 42-60 years, NHANES III

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallagher, Carolyn M., E-mail: 2crgallagher@optonline.net; Department of Preventive Medicine, Stony Brook University Medical Center, Stony Brook, New York; Moonga, Baljit S.

Background: Increased body burden of environmental cadmium has been associated with greater risk of decreased bone mineral density (BMD) and osteoporosis in middle-aged and older women, and an inverse relationship has been reported between follicle-stimulating hormone (FSH) and BMD in middle-aged women; however, the relationships between cadmium and FSH are uncertain, and the associations of each with bone loss have not been analyzed in a single population. Objectives: The objective of this study was to evaluate the associations between creatinine-adjusted urinary cadmium (UCd) and FSH levels, and the associations between UCd and FSH with BMD and osteoporosis, in postmenopausal andmore » perimenopausal women aged 42-60 years. Methods: Data were obtained from the Third National Health Examination and Nutrition Survey, 1988-1994 (NHANES III). Outcomes evaluated were serum FSH levels, femoral bone mineral density measured by dual energy X-ray absorptiometry, and osteoporosis indicated by femoral BMD cutoffs based on the international standard. Urinary cadmium levels were analyzed for association with these outcomes, and FSH levels analyzed for association with bone effects, using multiple regression. Subset analysis was conducted by a dichotomous measure of body mass index (BMI) to proxy higher and lower adipose-synthesized estrogen effects. Results: UCd was associated with increased serum FSH in perimenopausal women with high BMI (n=642; {beta}=0.45; p{<=}0.05; R{sup 2}=0.35) and low BMI (n=408; {beta}=0.61; p{<=}0.01; R{sup 2}=0.34). Among perimenopausal women with high BMI, BMD was inversely related to UCd ({beta}=-0.04; p{<=}0.05) and FSH ({beta}=-0.03; p{<=}0.05). In postmenopausal women with low BMI, an incremental increase in FSH was associated with 2.78 greater odds for osteoporosis (109 with and 706 without) (OR=2.78; 95% CI=1.43, 5.42; p{<=}0.01). Conclusion: Long-term cadmium exposure at environmental levels is associated with increased serum FSH, and both FSH and UCd are associated with bone loss, in US women aged 42-60 years.« less

Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grasso, P.; Reichert, L.E. Jr.

1990-08-01

We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+more » influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.« less

Effects of recombinant gonadotropin hormones on the expression of vitellogenin, gonadotropin subunits and gonadotropin receptors in cinnamon clownfish, Amphiprion melanopus.

PubMed

Kim, Na Na; Habibi, Hamid R; Lee, Jehee; Choi, Cheol Young

2012-08-01

Gonadotropins (GTHs) are the key regulators of reproduction in vertebrates. The present study investigated autoregulatory effects of gonadotropins, using recombinant FSH (rFSH) and LH (rLH) in cinnamon clownfish (Amphiprion melanopus). Experiments were carried out to investigate the actions of cinnamon clownfish rFSH and rLH on expression of GTH subunits, GTH receptors, and vitellogenin (Vtg) mRNA in vivo and in vitro. Plasma estradiol-17β (E(2)) level was also measured in immature fish following treatments with rFSH and rLH. The results demonstrate increasing levels of GTH subunits, GTH-receptors, Vtg mRNA levels, as well as plasma E(2) levels following injection with rFSH and rLH. The findings support the hypothesis that LH and FSH stimulate reproduction, in part, by autoregulatory mechanisms leading to upregulation of GTH receptors and GTH hormone production in cinnamon clownfish. The results provide a framework for better understanding of the mechanisms of GTH-mediated control of reproduction in cinnamon clownfish and other vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

Therapeutic effect of ozone and rutin on adriamycin-induced testicular toxicity in an experimental rat model.

PubMed

Salem, E A; Salem, N A; Hellstrom, W J

2017-02-01

To evaluate the cytoprotective effects of rutin, ozone and their combination on adriamycin (ADR)-induced testicular toxicity, 50 male albino rats were classified into five groups of ten animals each as follows: placebo group; ADR group; ADR + rutin group; ADR + ozone group and ADR + rutin + ozone group. Sperm functions, testosterone (T), luteinising hormone (LH), follicle stimulating hormone (FSH), testicular enzymes, oxidant/antioxidant status, C-reactive protein, monocyte chemoattractant proteins-1 and leukotriene B4 were determined. After ADR injection, a decline in sperm functions was observed. FSH and LH levels were increased, T level and testicular enzymes were decreased, significant enhancement in oxidative stress with subsequent depletion in antioxidants was detected and inflammatory markers were significantly elevated. Treatment with rutin and/or ozone, however, improved the aforementioned parameters. Ozone therapy alone almost completely reversed the toxic effects of ADR and restored all parameters to normal levels. © 2016 Blackwell Verlag GmbH.

Expression of FSH receptor in the hamster ovary during perinatal development

PubMed Central

Chakraborty, Prabuddha; Roy, Shyamal K.

2014-01-01

FSH plays an important role in ovarian follicular development, and it functions via the G-protein coupled FSH receptor. The objectives of the present study were to determine if full-length FSHR mRNA and corresponding protein were expressed in fetal through postnatal hamster ovaries to explain the FSH-induced primordial follicle formation, and if FSH or estrogen (E) would affect the expression. A full-length and two alternately spliced FSHR transcripts were expressed from E14 through P20. The level of the full-length FSHR mRNA increased markedly through P7 before stabilizing at a lower level with the formation and activation of primordial follicles. A predicted 87kDa FSHR protein band was detected in fetal through P4 ovaries, but additional bands appeared as ovary developed. FSHR immunosignal was present in undifferentiated somatic cells and oocytes in early postnatal ovaries, but was granulosa cells specific after follicles formed. Both eCG and E significantly up-regulated full-length FSHR mRNA levels. Therefore, FSHR is expressed in the hamster ovary from the fetal life to account for FSH-induced primordial follicle formation and cAMP production. Further, FSH or E regulates the receptor expression. PMID:25462586

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism.

PubMed

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-06-05

Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD.

Bone Mineral Density in Adolescent Girls with Hypogonadotropic and Hypergonadotropic Hypogonadism

PubMed Central

Özbek, Mehmet Nuri; Demirbilek, Hüseyin; Baran, Rıza Taner; Baran, Ahmet

2016-01-01

Objective: Deficiency of sex steroids has a negative impact on bone mineral content. In studies conducted on postmenopausal women and animal studies, elevated follicle-stimulating hormone (FSH) levels were found to be correlated with a decrease in bone mineralization and osteoporosis. The aim of the present study was to evaluate bone mineral density (BMD) in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism and also to investigate the correlation between FSH level and BMD. Methods: The study group included 33 adolescent girls with hypogonadism (14 with hypogonadotropic hypogonadism and 19 with hypergonadotropic hypogonadism). FSH, luteinizing hormone, estradiol levels, and BMD (using dual energy x-ray absorptiometry) were measured. Results: There were no statistically significant differences between the chronological age and bone age of the two patient groups, namely, with hypogonadotropic and hypergonadotropic hypogonadism. There was also no significant difference between BMD z-score values obtained from measurements from the spine and the femur neck of patients in the two groups (p-values were 0.841 and 0.281, respectively). In the hypergonadotropic group, a moderately negative correlation was detected between FSH level and BMD z-score measured from the femur neck (ρ=-0.69, p=0.001), whilst no correlation was observed between FSH levels and height adjusted BMD-z scores measured from the spine (ρ=0.17, p=0.493). FSH level was not found to be an independent variable affecting BMD z-score. Conclusion: BMD z-scores were detected to be similar in adolescent girls with hypogonadotropic and hypergonadotropic hypogonadism, and FSH levels were not found to have a clinically relevant impact on BMD. PMID:27087454

Central hypogonadism due to a giant, "silent" FSH-secreting, atypical pituitary adenoma: effects of adenoma dissection and short-term Leydig cell stimulation by luteinizing hormone (LH) and human chorionic gonadotropin (hCG).

PubMed

Santi, Daniele; Spaggiari, Giorgia; Casarini, Livio; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Granata, Antonio R M; Carani, Cesare; Simoni, Manuela

2017-06-01

We present a case report of an atypical giant pituitary adenoma secreting follicle-stimulating hormone (FSH). A 55-year-old patient presented for erectile dysfunction, loss of libido and fatigue. The biochemical evaluation showed very high FSH serum levels in the presence of central hypogonadism. Neither testicular enlargement nor increased sperm count was observed, thus a secretion of FSH with reduced biological activity was supposed. The histological examination after neuro-surgery showed an atypical pituitary adenoma with FSH-positive cells. Hypogonadism persisted and semen analyses impaired until azoospermia in conjunction with the reduction in FSH levels suggesting that, at least in part, this gonadotropin should be biologically active. Thus, we hypothesized a concomitant primary testicular insufficiency. The patient underwent short-term treatment trials with low doses of either recombinant luteinizing hormone (LH) or human chorionic gonadotropin (hCG) in three consecutive treatment schemes, showing an equal efficacy in stimulating testosterone (T) increase. This is the first case of atypical, giant FSH-secreting pituitary adenoma with high FSH serum levels without signs of testicular hyperstimulation, in presence of hypogonadism with plausible combined primary and secondary etiology. Hypophysectomized patients may represent a good model to assess both pharmacodynamics and effective dose of LH and hCG in the male.

Lowered reference limits for hCG improve follow-up of patients with hCG-producing tumors.

PubMed

Nome, Ragnhild V; Bjøro, Trine; Paus, Elisabeth; Bjerner, Johan; Fosså, Sophie D; Steen, Rita; Nustad, Kjell; Bolstad, Nils

2018-02-01

Human Chorionic Gonadotropin (hCG) is produced by germ cell tumors, but can also be elevated in benign conditions such as primary hypogonadism, where hCG is produced by the pituitary gland. In our experience, the reference limits for hCG (Elecsys hCG+β-assay, Roche Diagnostics), were unnecessarily high and did not reflect levels encountered in clinical practice. We wanted to establish new reference limits to increase the clinical utility of the hCG-assay. We analysed hCG in serum samples from a healthy adult population and in a cohort of testicular cancer survivors. The gonadotropins LH and FSH were measured in the cohort and in a selection of the reference population to assess gonadal function. We found low hCG levels for all men and women <45years (97.5 percentiles 0.1 and 0.2IU/L, respectively) from the healthy population (n=795) having normal FSH and LH. Due to assay limitations, we suggest a common reference limit of <0.3IU/L. For the age group ≥45, the 97.5 percentiles in the healthy population were 0.5IU/L for men and 6.0IU/L for women. In all subjects from both the reference population and the cohort (n=732), hCG levels exceeding the reference limit could be fully explained by reduced gonadal function indicated by elevated LH and FSH levels. The Elecsys hCG+β-assay should have lower reference limits than recommended by the manufacturer, with important implications for tumor follow-up. Elevated hCG is rare with intact gonadal function, both in a normal population and among survivors of testicular cancer, and should lead to further investigations when encountered in clinical practice. Copyright © 2017 Oslo University Hospital. Published by Elsevier Inc. All rights reserved.

Effects of gonadotropin-releasing hormone agonist/recombinant follicle-stimulating hormone versus gonadotropin-releasing hormone antagonist/recombinant follicle-stimulating hormone on follicular fluid levels of adhesion molecules during in vitro fertilization.

PubMed

Fornaro, Felice; Cobellis, Luigi; Mele, Daniela; Tassou, Argyrò; Badolati, Barbara; Sorrentino, Simona; De Lucia, Domenico; Colacurci, Nicola

2007-01-01

To compare the effects of GnRH-agonist/recombinant rFSH versus GnRH-antagonist/recombinant FSH stimulation on follicular fluid levels of soluble intercellular adhesion molecule (sICAM)-1 and vascular cell adhesion molecule-1 (sVCAM-1) during in vitro fertilization (IVF). Prospective, randomized study. University hospital. Seventy-three women underwent IVF. GnRH-agonist/rFSH or GnRH-antagonist/rFSH administration and collection of follicular fluid from 3 small (11-14 mm in diameter) and 3 large (18-21 mm in diameter) follicles on the day of oocyte retrieval. Follicular fluid levels of sICAM-1 and sVCAM-1 and intrafollicular estradiol and progesterone were also measured. Women who underwent GnRH-agonist/rFSH showed higher concentrations of sICAM-1 in both small and large follicles were compared with patients who received GnRH-antagonist/rFSH treatment; follicular fluid levels of sVCAM-1 were similar between the 2 stimulation protocols. Content of sICAM-1 in small and large follicles positively correlated with the number of follicles of > or =15 mm and the number of oocytes that were retrieved in both study groups. Concentrations of follicular fluid sVCAM-1 and progesterone were higher in large than in small follicles and were correlated positively to each other in both follicular classes. In IVF, GnRH-agonist/rFSH is associated with higher follicular fluid levels of sICAM-1 compared with GnRH-antagonist/rFSH regimen. Intrafollicular sICAM-1 content may predict ovarian response, and sVCAM-1 appears as an indicator of the degree of follicular luteinization.

mRNA-Selective Translation Induced by FSH in Primary Sertoli Cells

PubMed Central

Musnier, Astrid; León, Kelly; Morales, Julia; Reiter, Eric; Boulo, Thomas; Costache, Vlad; Vourc'h, Patrick; Heitzler, Domitille; Oulhen, Nathalie; Poupon, Anne; Boulben, Sandrine; Cormier, Patrick

2012-01-01

FSH is a key hormonal regulator of Sertoli cell secretory activity, required to optimize sperm production. To fulfil its biological function, FSH binds a G protein-coupled receptor, the FSH-R. The FSH-R-transduced signaling network ultimately leads to the transcription or down-regulation of numerous genes. In addition, recent evidence has suggested that FSH might also regulate protein translation. However, this point has never been demonstrated conclusively yet. Here we have addressed this issue in primary rat Sertoli cells endogenously expressing physiological levels of FSH-R. We observed that, within 90 min of stimulation, FSH not only enhanced overall protein synthesis in a mammalian target of rapamycin-dependent manner but also increased the recruitment of mRNA to polysomes. m7GTP pull-down experiments revealed the functional recruitment of mammalian target of rapamycin and p70 S6 kinase to the 5′cap, further supported by the enhanced phosphorylation of one of p70 S6 kinase targets, the eukaryotic initiation factor 4B. Importantly, the scaffolding eukaryotic initiation factor 4G was also recruited, whereas eukaryotic initiation factor 4E-binding protein, the eukaryotic initiation factor 4E generic inhibitor, appeared to play a minor role in translational regulations induced by FSH, in contrast to what is generally observed in response to anabolic factors. This particular regulation of the translational machinery by FSH stimulation might support mRNA-selective translation, as shown here by quantitative RT-PCR amplification of the c-fos and vascular endothelial growth factor mRNA but not of all FSH target mRNA, in polysomal fractions. These findings add a new level of complexity to FSH biological roles in its natural target cells, which has been underappreciated so far. PMID:22383463

Exposure to organophosphate pesticides and male hormone profile in floriculturist of the state of Morelos, Mexico.

PubMed

Blanco-Muñoz, Julia; Morales, Magally Mayanin; Lacasaña, Marina; Aguilar-Garduño, Clemente; Bassol, Susana; Cebrián, Mariano E

2010-07-01

Studies on experimental animals have found that organophosphate (OP) pesticides may act as endocrine disruptors; however, their effects on the human hormonal profile have not yet been adequately characterized. We evaluate the association between exposure to OP pesticides, measured through dialkyl phosphate (DAP) metabolites urinary levels, and the male hormone profile. A cross-sectional study was performed in 104 floriculturists of Morelos, Mexico. A structured questionnaire was applied to get information on sociodemographic characteristics, anthropometry, clinical history, alcohol and tobacco consumption, and work history. DAP metabolites [dimethylphosphate (DMP), dimethylthiophosphate, dimethyldithiophosphate, diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate] were determined using gas-liquid chromatography. Serum levels of FSH, LH, prolactin, testosterone, inhibin B and estradiol were determined using enzyme-linked immunosorbent assay. Multiple linear regression was used to study the association between DAP metabolite levels and male hormonal profile. Data were adjusted by p,p'-dichlorodiphenyldichloroethene serum levels and other potential confounders. There was a negative association between inhibin B and urinary levels of DMP, DEP, DETP and total DAP metabolites. DEP levels were negatively associated with serum FSH concentrations, but marginally and positively associated with those of testosterone. DETP was marginally associated with lower LH serum levels. There were no other significant associations among OP metabolites and serum hormone levels. Inhibin B and FSH vary according to levels of DAP metabolites in men occupationally exposed to OP pesticides. These results suggest that OP pesticides could act as endocrine disruptors in humans; however, most hormonal values fell within the wide normal range and associations were small. There is, therefore, a need for further investigation to elucidate their biological and clinical relevance.

Testicular growth and spermatogenesis: new goals for pubertal hormone replacement in boys with hypogonadotropic hypogonadism? -a multicentre prospective study of hCG/rFSH treatment outcomes during adolescence.

PubMed

Rohayem, Julia; Hauffa, Berthold P; Zacharin, Margaret; Kliesch, Sabine; Zitzmann, Michael

2017-01-01

Testosterone treatment for pubertal induction in boys with hypogonadotropic hypogonadism (HH) provides virilization, but does not induce testicular growth or fertility. Larger studies evaluating the outcomes of gonadotropin replacement during adolescence have not been reported to date; whether previous testosterone substitution affects testicular responses is unresolved. We aimed to assess the effects of human chorionic gonadotropin (hCG) and recombinant FSH (rFSH) in boys and adolescents with HH with respect to a) testicular growth, b) spermatogenesis, c) quality of life (QoL) and to identify factors influencing therapeutic success. A prospective case study was conducted in 26 paediatric endocrine centres PATIENTS/INTERVENTIONS: HCG and rFSH were administered until cessation of testicular growth and plateauing of spermatogenesis to (1) prepubertal HH boys with absent or early arrested puberty (group A) and to (2) HH adolescents who had previously received full testosterone replacement (group B). Bi-testicular volumes (BTVs), sperm concentrations and QoL. Sixty (34 A/26 B) HH patients aged 14-22 years were enrolled. BTVs rose from 5 ± 5 to 34 ± 3 ml in group A vs 5 ± 3 to 32 ± 3 ml in group B, with normal final BTVs (≥24 ml) attained in 74%/70% after 25/23 months in A/B, respectively. Sperm in the ejaculate were found in 21/23(91%)/18/19(95%), with plateauing concentrations after 31/30 months of hCG and 25/25 months of combined treatment in A/B. Sperm concentrations were normal (≥15 mill/ml) in 61%/32%, with mean concentrations of 40 ± 73 vs 19 ± 38 mill/ml in A/B (n.s.). Outcomes were better in patients without bilateral cryptorchidism, with non-congenital HH causes, higher baseline BTVs, and higher baseline inhibin B and AMH levels. QoL increased in both groups. HCG/rFSH replacement during adolescence successfully induces testicular growth and spermatogenesis, irrespective of previous testosterone replacement, and enhances QoL. © 2016 John Wiley & Sons Ltd.

Regulatory influence of germ cells on sertoli cell function in the pre-pubertal rat after acute irradiation of the testis.

PubMed

Guitton, N; Touzalin, A M; Sharpe, R M; Cheng, C Y; Pinon-Lataillade, G; Méritte, H; Chenal, C; Jégou, B

2000-12-01

While germ cell regulation of Sertoli cells has been extensively explored in adult rats in vivo, in contrast, very little is known about germ cell influence on Sertoli cell function at the time when spermatogenesis begins and develops. In the present study various Sertoli cell parameters (number, testicular androgen binding protein (ABP) and testin, serum inhibin-B and, indirectly, follicle-stimulating hormone (FSH)) were investigated after the exposure of 19-day-old rats to a low dose of 3 Grays of gamma-rays. Differentiated spermatogonia were the primary testicular targets of the gamma-rays, which resulted in progressive maturation depletion, sequentially and reversibly affecting all germ cell classes. Testicular weight declined to a nadir when pachytene spermatocytes and spermatids were depleted from the seminiferous epithelium and complete or near complete recovery of spermatogenesis and testicular weight was observed at the end of the experiment. Blood levels of FSH and ABP were normal during the first 11 days after irradiation, when spermatogonia and early spermatocytes were depleted. While the number of Sertoli cells was not significantly affected by the irradiation, from days 11-66 after gamma-irradiation, ABP production declined and FSH levels increased when pachytene spermatocytes and spermatids were depleted and the recovery of these parameters was only observed when spermatogenesis was fully restored. Comparison of the pattern of change in serum levels of inhibin-B and testicular levels of testin and of germ cell numbers strongly suggest a relationship between the disappearance of spermatocytes and spermatids from the seminiferous epithelium and the decrease in levels of inhibin-B and increase in levels of testin from 7 to 36 days post-irradiation. Levels of testin and inhibin-B were restored before spermatogenesis had totally returned to normal. In conclusion, this in vivo study shows that pre-pubertal Sertoli cell function is under the complex control of various germ cell classes. This control presents clear differences when compared with that previously observed in adult animals and depends on the Sertoli cell parameter of interest, as well as on the germ cell type.

Polycystic ovarian disease.

PubMed

Raj, S G; Talbert, L M

1984-01-01

Polycystic ovarian disease (PCOD) was first described as a single disease by Stein and Leventhal in 1935, but now has been separated into several distinct entities, comprising a symptom complex. The most frequent presenting symptoms associated with PCOD are obesity, hirsutism, amenorrhea or anovulation, dysfunctional uterine bleeding, irregular menses, and infertility. The common finding of hirsutism in PCOD patients is a reflection of the hyperandrogenism resulting from elevation of all the androgens, including testosterone, androstenediol, dehydroepiandrostrone sulfate (DHEA-S), and androstenedione. Some patients with all the clinical features of PCOD can be shown, through appropriate testing, to have an attenuated form of classic congenital adrenal hyperplasia (CAH). Serum follicle stimulating hormone (FSH) levels are usually low or in the normal range, and serum luteinizing hormone (LH) levels are usually elevated in patients with PCOD, resulting in an altered LH/FSH ratio. Treatment for PCOD must be based on the needs and desires of the individual patient, and on the pathophysiology of the patient's particular abnormalities. When pregnancy is desired, ovulation induction with clomiphene is indicated. Clomiphene is a weak estrogen that induces a transient rise in serum LH and FSH, followed by a gonadotropic pattern similar to normal cycles. A 72% ovulation rate and a 41.8% conception rate have been reported after treatment with clomiphene. In patients who do not respond to clomiphene, or clomiphene with added human chorionic gonadotropin (hCG), human menopausal gonadotropin (hMG) can be used to induce ovulation, but the patient should be closely monitored for multiple ovulation, multiple pregnancy, or hyperstimulation syndrome. For patients not interested in conception, regular menstrual cyclicity can be restored and hyperandrogenism reduced with oral contraceptives (OCs).

Follicle-stimulating hormone levels in male workers exposed to urban chemical, physical, and psychosocial stressors.

PubMed

Tomei, G; Tomao, E; Ciarrocca, M; Rosati, M V; Caciari, T; Gamberale, D; Palermo, P; De Sio, S; Tria, M; Panfili, A; Tomei, F

2009-07-01

The aim of this study is to evaluate whether occupational exposure to urban stressors could cause alterations in the follicle-stimulating hormone (FSH) levels in traffic policemen compared to a control group. After excluding the subjects with main confounding factors, traffic policemen and male controls were matched by age, working life, body mass index (BMI), drinking habit, cigarette smoking history, and daily consumption of Italian coffee, 166 traffic policemen and 166 controls were included into the study. FSH levels were significantly higher in traffic policemen compared to male controls (P < 0.05). The distribution of FSH values in traffic policemen and controls was significant (P < 0.05). Our results suggest that occupational exposure to low doses of chemical and psychosocial stressors may alter plasma levels of FSH in traffic policemen more than in the control group. If the results obtained are confirmed by further research, the plasma levels of FSH may be used as early biological markers, valuable for the group, used in occupational set even before the appearance of disorders of male fertility.

Sexual dimorphism in postnatal gonadotrophin levels in infancy reflects diverse maturation of the ovarian and testicular hormone synthesis.

PubMed

Kuiri-Hänninen, Tanja; Dunkel, Leo; Sankilampi, Ulla

2018-04-18

The postnatal gonadotrophin surge is sexually dimorphic: FSH levels predominate in girls and LH levels in boys. However, in preterm (PT) girls, both gonadotrophin levels are higher than in PT boys. To evaluate how gonadal maturation contributes to the sex differences in FSH and LH. Monthly follow-up of 58 full-term (FT, 29 boys) and 67 PT (33 boys) infants from 1 week (D7) to 6 months of age (M1-M6). Analyses were also carried out according to postmenstrual (PM) age in PT infants. Urinary LH, FSH, oestradiol (E2), testosterone (T) and serum inhibin B (InhB) levels. High gonadotrophin levels in PT girls abruptly decreased (P < .001) by M2, corresponding to a PM age of 38-42 weeks, and LH levels fell below the levels found in boys. This decrease was parallel to a steep increase in E2 levels (P < .001), and, from M4 to M6, LH and E2 correlated positively in PT girls (P < .01). T levels in PT boys increased earlier than E2 levels in PT girls. In addition, InhB levels were high in PT boys already at D7, in contrast to low InhB in PT girls. InhB and FSH correlated negatively in the whole group (P < .001). Ovarian hormone synthesis is immature and incapable of responding to gonadotrophin stimulus before 38-42 PM weeks in PT girls, which may explain their highly elevated FSH and LH levels. The higher InhB levels in boys compared to girls may explain sexual dimorphism in FSH levels. © 2018 John Wiley & Sons Ltd.

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43

PubMed Central

Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

2016-01-01

Aim: Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Methods: Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg−1·d−1, po) or testosterone replacement (0.5 mg·kg−1·d−1, sc) for 5 days, and STZ-injected rats were treated with argirein (40–120 mg·kg−1·d−1, po) or aminoguanidine (100 mg·kg−1·d−1, po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). Results: ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3–3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Conclusion: Two types of hypogonadism of male rats exhibit increased expression of ETA and depressed expression of Cx43 in testes, despite different patterns of serum FSH and LH. Argirein alleviates the two types of male hypogonadism via normalizing ETA and Cx43 in testes. PMID:26775665

Argirein alleviates stress-induced and diabetic hypogonadism in rats via normalizing testis endothelin receptor A and connexin 43.

PubMed

Xu, Ming; Hu, Chen; Khan, Hussein-hamed; Shi, Fang-hong; Cong, Xiao-dong; Li, Qing; Dai, Yin; Dai, De-zai

2016-02-01

Argirein (rhein-arginine) is a derivative of rhein isolated from Chinese rhubarb (Rheum Officinale Baill.) that exhibits antioxidant and anti-inflammatory activities. In the present study we investigated the effects of argirein on stress-induced (hypergonadotrophic) and diabetic (hypogonadotrophic) hypogonadism in male rats. Stress-induced and diabetic hypogonadism was induced in male rats via injection of isoproterenol (ISO) or streptozotocin (STZ). ISO-injected rats were treated with argirein (30 mg·kg(-1)·d(-1), po) or testosterone replacement (0.5 mg·kg(-1)·d(-1), sc) for 5 days, and STZ-injected rats were treated with argirein (40-120 mg·kg(-1)·d(-1), po) or aminoguanidine (100 mg·kg(-1)·d(-1), po) for 4 weeks. After the rats were euthanized, blood samples and testes were collected. Serum hormone levels were measured, and the expression of endothelin receptor A (ETA), connexin 43 (Cx43) and other proteins in testes was detected. For in vitro experiments, testis homogenate was prepared from normal male rats, and incubated with ISO (1 μmol/L) or high glucose (27 mmol/L). ISO injection induced hyper-gonadotrophic hypogonadism characterized by low testosterone and high FSH and LH levels in the serum, whereas STZ injection induced hypogonadotrophic hypogonadism as evidenced by low testosterone and low FSH and LH levels in the serum. In the testes of ISO- and STZ-injected rats, the expression of ETA, MMP-9, NADPH oxidase and pPKCε was significantly increased, and the expression of Cx43 was decreased. Administration of argirein attenuated both the abnormal serum hormone levels and the testis changes in ISO- and STZ-injected rats, and aminoguanidine produced similar actions in STZ-injected rats; testosterone replacement reversed the abnormal serum hormone levels, but did not affect the testis changes in ISO-injected rats. Argirein (0.3-3 μmol/L) exerted similar effects in testis homogenate incubated with ISO or high glucose in vitro. Two types of hypogonadism of male rats exhibit increased expression of ETA and depressed expression of Cx43 in testes, despite different patterns of serum FSH and LH. Argirein alleviates the two types of male hypogonadism via normalizing ETA and Cx43 in testes.

Hypothalamic-pituitary-ovarian axis during infancy, early and late prepuberty in an aromatase-deficient girl who is a compound heterocygote for two new point mutations of the CYP19 gene.

PubMed

Belgorosky, Alicia; Pepe, Carolina; Marino, Roxana; Guercio, Gabriela; Saraco, Nora; Vaiani, Elisa; Rivarola, Marco A

2003-11-01

A loss of function mutation of the CYP19 aromatase gene leads to excess circulating androgens in the fetus and in the mother, resulting in ambiguous genitalia in the female fetus. Later on, lack of aromatase is responsible for sexual infantilism, primary amenorrhea, tall stature, and multicystic ovaries, even in preadolescent girls. Up to now, 11 CYP19 aromatase point mutations and 10 well-documented cases have been reported. In the present case, we are reporting the clinical and hormonal follow-up, from birth to 7 yr of age, of an affected girl with ambiguous genitalia. Gene analysis showed that she was a compound heterozygote for two new CYP19 aromatase point mutations. In the father's allele, there was a consensus 5' splice donor sequence mutation, GAA-AAA at cDNA position bp 655 in exon 5, which probably results in a cryptic donor site. In the mother's allele, there was a base A deletion in exon 9 (Delta A GLU 412X), causing a frame shift mutation, and a stop codon after 98 bp (33 codons) downstream, altering the critical heme-binding region. Basal serum LH and FSH levels were high at 8 d of age (42.9 and 51.3 U/liter), 26 d of age (76.2 and 119 U/liter), and 60 d of age (58.7 and 150 U/liter, respectively). Both gonadotropins dropped dramatically between the second and fifth months of age (to 1.79 and 14.9 U/liter) but remained higher than in normal control girls (0.64 and 8.5 U/liter, respectively). Serum testosterone (T) and androstenedione (Delta(4)A) levels were high during the first month, but Delta(4)A was normal at 2 months of age. However, at 5 months of age, along with significant decrements of serum LH and FSH levels and increments in serum Delta(4)A and T levels, a large ovarian cyst was removed from each gonad. Relatively high levels of T [27.3 ng/ml (94.6 nmol/liter); control, 34.9 ng/ml (121 nmol/liter)], but not of estradiol [1.8 ng/ml (6.6 nmol/liter); control 62.9 ng/ml (231 nmol/liter)], and a high T/estradiol ratio [15.2; control < 1] were found in the follicular fluid. Serum Delta(4)A and T levels remained normal from 1-5 yr of age, but they were high at the last visit (late prepuberty). A GnRH test was performed at 3.9, 6, and 7.1 yr of age. At 3.9 yr, a low prepubertal serum LH peak (2.12 U/liter) was found, but at the older ages, higher serum LH peaks (8.25 and 22.5 U/liter, respectively) were observed. Growth pattern and body mass index were normal, but after the age of 5.2 yr, delays in bone age greater than 2 yr were observed. We concluded that: 1) these two new CYP19 aromatase gene mutations are responsible for the phenotype of aromatase deficiency; 2) in girls, aromatase deficiency results in a decrease of the negative feedback of both serum LH and FSH, which can be detected as early as the second week after birth and persists up to the sixth month of life, and of FSH during the rest of prepuberty; and 3) because large ovarian cysts developed when serum LH and FSH dropped, aromatization of androgens might be required to prevent formation of cystic ovaries.

Intact follicular maturation and defective luteal function in mice deficient for cyclin- dependent kinase-4.

PubMed

Moons, David S; Jirawatnotai, Siwanon; Tsutsui, Tateki; Franks, Roberta; Parlow, A F; Hales, Dale B; Gibori, Geula; Fazleabas, Asgerally T; Kiyokawa, Hiroaki

2002-02-01

Cell cycle progression of granulosa cells is critical for ovarian function, especially follicular maturation. During follicular maturation, FSH induces cyclin D2, which promotes G1 progression by activating cyclin-dependent kinase-4 (Cdk4). Because cyclin D2-deficient mice exhibit a block in follicular growth, cyclin D2/Cdk4 has been hypothesized to be required for FSH-dependent proliferation of granulosa cells. Here we investigate ovarian function in Cdk4-knockout mice we recently generated. Cdk4(-/-) females were sterile, but the morphology of their ovaries appeared normal before sexual maturation. The number of preovulatory follicles and the ovulation efficiency were modestly reduced in gonadotropin-treated Cdk4(-/-) mice. However, unlike cyclin D2-deficient mice, Cdk4(-/-) mice showed no obvious defect in FSH-induced proliferation of granulosa cells. Cdk4(-/-) ovaries displayed normal preovulatory expression of aromatase, PR, and cyclooxygenase-2. Postovulatory progesterone secretion was markedly impaired in Cdk4(-/-) mice, although granulosa cells initiated luteinization with induction of p450 side-chain cleavage cytochrome and p27(Kip1). Progesterone treatment rescued implantation and restored fertility in Cdk4(-/-) mice. Serum PRL levels after mating were significantly reduced in Cdk4(-/-) mice, suggesting the involvement of perturbed PRL regulation in luteal failure. Thus, Cdk4 is critical for luteal function, and some redundant protein(s) can compensate for the absence of Cdk4 in proliferation of granulosa cells.

Evaluation of different ranges of LH:FSH ratios in polycystic ovarian syndrome (PCOS) - Clinical based case control study.

PubMed

Malini, N A; Roy George, K

2018-05-01

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder among reproductive aged women, leading to infertility. One of the common clinical manifestations in PCOS is that there is a difference in the range of LH production in different case of PCOS and accordingly variability in LH:FSH ratio was observed. The aim of the present study was to evaluate different ranges of LH:FSH ratios in PCOS. In this cross sectional study, a consecutive series of 745 women (aged 28.11 ± 0.2) who were subjected to infertility treatment at specialist infertility clinics in central Travancore region were considered. About 50 healthy females (aged 27.58 ± 0.4) with regular menstrual cycles were regarded as control. The data were collected from hospital records using subject's written informed consent. PCOS patients were observed to have different ranges of LH:FSH ratios from < 1 range to 4.6-5.5 and subjects were classified into 7 PCO subgroups on the basis of their LH:FSH ratios. In whole PCO group, body weight, LH, FSH, LH:FSH ratio, insulin, HbA1c, estradiol, testosterone and TSH were significantly (P < .05) increased whereas progesterone and SHBG levels were significantly (P < .05) decreased in comparison to control. In various PCO subgroups as LH levels and LH:FSH ratios were increased, levels of insulin, testosterone and AMH were increased and SHBG levels were decreased accordingly. This finding suggested a dependence of insulin, LH and testosterone in initiating the hormonal imbalances in PCOS. Copyright © 2018 Elsevier Inc. All rights reserved.

Chronic glue sniffing with transient central hypothyroidism and hypergonadotropism.

PubMed

Chen, Hua-Fen; Chen, Shwe-Winn; Chen, Peter; Su, Mei-Chin; See, Ting-Ting; Lee, Hsin-Yu

2003-12-01

Neuropsychiatric, gastrointestinal and muscular disorders associated with glue sniffing have been widely reported, but endocrinologic abnormalities of glue exposure are rarely mentioned in the literature. We report a 26-year old male patient, a chronic glue sniffer, who presented with weakness of both lower limbs. On physical examination, he had reduced muscle strength of his 4 limbs, especially in his lower limbs. Laboratory examination revealed hypokalemia with hyperchloremic metabolic acidosis. His thyroid function showed low TSH, T4, T3, free T4 and reverse T3 level. Other pituitary functions were normal apart from high FSH and LH level. TSH response to TRH stimulation was normal, but there was impaired T3 response to TRH. MRI of pituitary showed no significant changes. He continued glue sniffing after discharge. He repeatedly came to our hospital for recurrent hypokalemic paralysis. His serum T4 and free T4 level were low when he had certain amount of glue sniffing and it returned to normal after he stopped sniffing or sniffed less amount of glue. His serum T3 concentrations were normal most of the times thereafter. His FSH and LH level were persistently elevated, even after he did not sniff glue for 2 weeks. Low free T4, TSH and reverse T3 level associated with glue sniffing in our patient were compatible with central hypothyroidism. Toluene, a neurotoxic organic solvent, is present in glues. Being highly lipophilic, it can easily enter and is retained within the lipid-rich nervous system after being inhaled. Like other organic solvents, toluene has been shown to affect dopaminergic and adrenergic turnover within various parts of the brain. The effects on these neurotransmitters could lead to abnormal secretion of pituitary hormones resulting in transient central hypothyroidism and abnormal gonadotropin levels. Long-term harmful effect of central hypothyroidism and chronic influence of abnormal gonadotropins to reproduction function needs further observation.

Serum androgen and gonadotropin levels decline after progestogen-induced withdrawal bleeding in oligomenorrheic women with or without polycystic ovaries.

PubMed

Anttila, L; Koskinen, P; Kaihola, H L; Erkkola, R; Irjala, K; Ruutiainen, K

1992-10-01

To examine the effect of short-term progestogen treatment on androgen, gonadotropin, and sex hormone-binding globulin (SHBG) levels in oligomenorrheic women. Comparative study of changes in hormonal parameters in patients with or without ultrasonographically diagnosed polycystic ovarian disease (PCOD). Open patient clinic of reproductive endocrinology at University Central Hospital of Turku, Finland. Seventy-five oligomenorrheic women with (n = 51) or without (n = 24) PCOD. Serum concentrations of testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and SHBG. The levels of T, A, LH, and the LH:FSH ratios decreased significantly after oral treatment with medroxyprogesterone acetate (10 mg/d for 10 days) in non-PCOD women and in women with PCOD decreasing the frequencies of pathological laboratory findings, in particular elevated levels of LH:FSH ratio and A in PCOD women and of LH:FSH ratio in non-PCOD women. The levels of T, A, and LH as well as the LH:FSH ratio were significantly higher in women with PCOD. Obesity was associated with high free androgen indices, low LH:FSH ratios, and low concentrations of LH, A, and SHBG. The serum samples for hormonal analyses used as an aid in diagnosing PCOD should be obtained without pretreatment with progestogen because it masks the biochemical findings of PCOD.

Male patients with partial androgen insensitivity syndrome: a longitudinal follow-up of growth, reproductive hormones and the development of gynaecomastia.

PubMed

Hellmann, Philip; Christiansen, Peter; Johannsen, Trine Holm; Main, Katharina M; Duno, Morten; Juul, Anders

2012-05-01

To describe the natural history of phenotype, growth and gonadal function in patients with partial androgen insensitivity syndrome. Tertiary paediatric endocrine centre. Retrospective evaluation of 14 male patients with partial androgen insensitivity syndrome (PAIS) with verified androgen receptor (AR) mutations. The authors recorded phenotypic characteristics at birth and external masculinisation score (EMS), registered longitudinal growth, circulating levels of testosterone, estradiol, luteinising hormone (LH), follicle-stimulating hormone (FSH), inhibin-B and sex hormone binding globulin (SHBG), in addition to phenotype at postpubertal follow up. The EMS ranged from 5 to 12 in PAIS at birth. Six patients were born with hypospadias and all patients developed gynaecomastia in puberty. Eight of the patients received testosterone treatment. At follow-up penile size was impaired irrespective of EMS at birth, but responded to pubertal androgen therapy in some of the patients. Serum levels of testosterone, estradiol, SHBG and LH, but not FSH and inhibin B, were markedly elevated in puberty. Final height was 181.3 cm (165.7-190.5 cm) corresponding to an SD score of 0.7 (-2.1 to +2.1 SD, n=10). Gynaecomastia and impaired phallic growth are frequently observed in adults with PAIS, but may be ameliorated by androgen therapy. The authors suggest that male patients presenting with gynaecomastia in puberty, and elevated circulating levels of testosterone, estradiol and LH in puberty, but normal FSH, should be suspected of having PAIS and undergo genetic testing for AR mutations.

Ovarian size and response to laparoscopic ovarian electro-cauterization in polycystic ovarian disease.

PubMed

Alborzi, S; Khodaee, R; Parsanejad, M E

2001-09-01

To evaluate endocrine and ovulatory changes in polycystic ovarian disease (PCOD) in relation to patients' ovarian size. Three hundred and seventy-one women with clomiphene citrate-resistant PCOD underwent laparoscopic ovarian cauterization [type I or typical with ovarian volume >8 cm(3) or cross-sectional area >10 cm(2) (n=211), type II with normal size ovary (n=160)]. Serum levels of LH, FSH, DHEAS, PRL, and T before and 10 days after ovarian cautery, spontaneous and induced ovulation and pregnancy rates were compared. Both groups responded to therapy in a similar manner, with a marked decrease in LH, FSH, DHEAS and T levels, with ovulation rates in type I 90.99%, type II 88.75% and pregnancy rates, 73.45% and 71.25%, respectively, with no statistical differences. Hormonal changes, ovulation and pregnancy rates were similar in the two types of PCOD, therefore it can be concluded that ovarian size is not a prognostic factor for response of PCOD patients to laparoscopic ovarian electro-cauterization.

Relationships between the transcriptome and physiological indicators of reproduction in female rainbow trout over an annual cycle.

PubMed

Hook, Sharon E; Nagler, James J; Cavileer, Tim; Verducci, Joseph; Liu, Yushi; Hayton, William; Schultz, Irvin R

2011-02-01

Normal transcriptomic patterns along the brain-pituitary-gonad-liver (BPGL) axis should be better characterized if endocrine-disrupting compound-induced changes in gene expression are to be understood. Female rainbow trout were studied over a complete year-long reproductive cycle. Tissue samples from pituitary, ovary, and liver were collected for microarray analysis using the 16K Genomic Research on Atlantic Salmon Project (GRASP) microarray and for quantitative polymerase chain reaction measures of estrogen receptor (ER) isoform messenger RNA (mRNA) levels. Plasma was collected to determine levels of circulating estradiol-17β (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). As an a priori hypothesis, changes in gene expression were correlated to either circulating levels of E2, FSH, and LH, or ER mRNAs quantified by quantitative polymerase chain reaction. In the liver, most transcriptomic patterns correlated to levels of either E2, LH, or ERs. Fewer ovarian transcripts could be correlated to levels of E2, ERα, or FSH. No significant associations were obvious in the pituitary. As a post hoc hypothesis, changes in transcript abundance were compared with microarray features with known roles in gonadal maturation. Many altered transcripts in the ovary correlated to transcript levels of estradiol 17-beta-dehydrogenase 8 or 17 B HSD12, or to glycoprotein alpha chain 1 or 2. In the pituitary, genes involved with the growth axis (e.g., growth hormone, insulin-related growth factor binding protein) correlated with the most transcripts. These results suggest that transcriptional networks along the BPGL axis may be regulated by factors other than circulating steroid hormones. © 2010 SETAC.

Chorionic morphine, naltrexone and pentoxifylline effect on hypophyso-gonadal hormones of male rats.

PubMed

Moradi, M; Mahmoodi, M; Raoofi, A; Ghanbari, A

2015-01-01

Knowledge about harmful effects of morphine on hormone secretion seems to be necessary. The aim of the present study was to evaluate the effect of pentoxifylline on side effects derived by morphine on hypophyso-gonadal hormones of male rats. 32 male rats were divided into the 4 groups of OSS: control (received 40 g Sucrose/l drinking water and intraperitoneal injection of 1 l/kg normal saline), OMS: morphine group (received 0.4 mg/l + 40 g Sucrose/l in drinking water and intraperitoneal injection of 1 l/kg normal saline), NMS: morphine+naltrexane group (received 0.4 mg/l + 40 g Sucrose/l in drinking water and IP injection dose of 10 mg/kg/ml/day Naltrexane) and PMS: morphine + pentoxifylline group (received 0.4 mg/dl + 40 g Sucrose/l in drinking water and IP injection dose of 12 mg/kg/ml/day Pentoxifylline) for 56 days, respectively. Serum levels of testosterone, LH, FSH hormones were measured. Pentoxifylline increased serum levels of testosterone, LH, FSH hormones compared to control, morphine and morphine-naltrexane groups. Pentoxifylline has a significant efficacy for increasing serum levels of sexual hormones. Considering that Pentoxifylline is safe and cheap, with easy application, we suggest for the usage of this drug for improving semen parameter's quality before performing ART for the treatment of morphine addicts (Fig. 1, Ref. 31).

[Dwarfism due to familial panhypopituitarism].

PubMed

Cos Welsh, J; Espinosa de los Monteros, A; de la Luz Ajuria, M; Morillo Almao, E

1977-01-01

Three sisters of 27 7/12, 13 8/12 and 9 1/12 years of age, respectively, with proportionate dwarfism, high pitched voice and lack of sexual development are described. All the patients had very low serum levels of immunoreactive growth hormone (GH), as well as of LH and FSH. Hypoglycemia induced by insulin and arginine infusion failed to increase GH levels, and the administration of the hypothalamic LH-FSH releasing hormone (LH-RH) did not elicit any response in the secretion of gonadotropins. The oldest sister developed hypothyroidism in recent years, since the I131 thyroid uptake was normal ten years before; her serum TSH was low and did not change with TRH stimulation. In addition, a low pituitary ACTH reserve was demonstrated by the hypoglycemia and metirapone tests. Case 2 showed partial pituitary TSH and ACTH reserve, whereas the youngest child only had low TSH pituitary reserve. These patients had all the clinical and laboratory characteristics of familial panhypopituitarism, with normal sella turcica. Genetic transmission in this cases is consistent with the autosomal recessive form, which is the most frequent type of inheritance of this entity. Consanguinity can not be ruled out. The results of the hypothalamic-pituitary functional tests apparently suggest that the primary defect could be located at the pituitary level. It is also possible that the pathological process may have a progressive evolution.

Lack of biochemical hypogonadism in elderly Arab males with low bone mineral density disease.

PubMed

Al Attia, Haider M; Jaysundaram, Krishnasamy; Saraj, Fouad

2010-01-01

The aim of the study is to study the relationship between androgen levels and bone mineral density (BMD) in elderly Arab males. Forty-five elderly Arab males underwent Dual X-ray absorptiometry for measurement of BMD. The outcomes were defined as per WHO description. Assays for testosterone (T), gonadotropins (LH and FSH) and estradiol (E2), in the serum were carried out. The ratio of T/LH was used as a surrogate for the cFT assay. We excluded patients receiving hormonal ablation for prostatic neoplasm and patients with chronic liver or renal disease and patients receiving corticosteroids. Twelve were osteoporotic (26.5%); 22 osteopenic (49%); and 11(24.5%) had normal outcome. Osteoporotic patients were significantly older (78.17 +/- 7.59 years) than the osteopenic (70.14 +/- 5.92, P

Photonic homeostatics

NASA Astrophysics Data System (ADS)

Liu, Timon C.; Li, Fan-Hui

2010-11-01

Photonic homeostatics is a discipline to study the establishment, maintenance, decay, upgrading and representation of function-specific homoestasis (FSH) by using photonics. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stress may increase sirtuin 1 (SIRT1) activities above FSH-specific SIRT1 activity to induce a function far from its FSH. On the one hand, low level laser irradiation or monochromatic light (LLL) can not modulate a function in its FSH or a stress in its stress-specific homeostasis (StSH), but modulate a function far from its FSH or a stress far from its StSH. On the other hand, the biophotons from a biosystem with its function in its FSH should be less than the one from the biosystem with its function far from its FSH. The non-resonant interaction of low intensity laser irradiation or monochromatic light (LIL) and a kind of membrane protein can be amplified by all the membrane proteins if the function is far from its FSH. This amplification might hold for biophoton emission of the membrane protein so that the photonic spectroscopy can be used to represent the function far from its FSH, which is called photonomics.

[Effects of electroacupuncture with branch-foundation acupoint combination on the pituitary-target gland axis in aging rats with yang deficiency].

PubMed

Hao, Qing; Wu, Song; Liu, Jian-min; Wang, Hua

2014-10-01

To observe the effects of electroacupuncture (EA) with branch-foundation acupoint combination on the indices regarding pituitary-target gland axis in aging rats with yang deficiency, so as to explore its regulating mechanism on aging rats with yang deficiency. Forty healthy Sprague-Dawley female rats were randomly divided into a normal control group, a model group, an EA group and an EA control group, 10 rats in each group. Except the normal control group, the rats in the rest 3 groups were all treated with subcutaneous injection of D-galactose for 40 d, followed by intramuscular injection of hydrocortisone for 7 d to establish aging model with yang deficiency. After the successful establishment of model, the EA group was treated with EA at "Guanyuan" (CV 4), "Housanli" (ST 36) and "Baihui "(GV 20) while the EA control group was treated with EA at "Zhongji" (CV 3) "Yinlingquan" (SP 9) and "Yintang" (GV 29); the rats in the normal control group and model group were immobilized and fixed during the same time period. The treatments were given 6 times per week totally for 4 weeks. With radiation immunity analysis method, the 8 biological indices of pituitary-target gland axis, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine-4 (T4), adrenocorticotropic hormone (ACTH), corticosterone (CORT), estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were detected to observe the changes of their content. Compared with the normal control group, the serum level of TSH, T3, T4 and E2 were reduced in the model group (P<0.05, P< 0.01) while those of ACTH, CORT, FSH and LH were increased (P<0.05, P<0.01). Compared with the model group, the serum level of TSH, T3, T4 and E2 were increased in the EA group (P<0.05, P<0.01) while those of ACTH, CORT, FSH and LH were significantly reduced (P<0.05, P<0.01). Compared with the EA control group, the content of TSH was increased in the EA group without statistical significance (P>0.05), that of T3, T4 and E2 was increased (all P<0.05) and that of ACTH, CORT, FSH and LH was significantly reduced (all P<0.05). The electroacupuncture with branch-foundation acupoint combination has benign regulating effects on the key hormones of pituitary-target gland axis, which could effectively improve the dysfunction of pituitary-target gland axis that is caused by aging with yang deficiency; the efficacy of electroacupuncture with branch-foundation acupoint combination is superior to that of adjacent control acupoint combination.

Factors affecting the outcome of "endometrial scratch" in women with recurrent implantation failure.

PubMed

Coughlan, Carol; Yuan, Xi; Demirol, Aygul; Ledger, William; Li, Tin Chiu

2014-01-01

To examine factors affecting the outcome of the endometrial scratch in women with recurrent implantation failure. A total of 57 eligible patients with a history of recurrent implantation failure underwent an endometrial biopsy in the luteal phase of the menstrual cycle in the month immediately preceding the embryo transfer cycle. The comparative group consisted of a retrospective cohort of 66 women with recurrent implantation failure but without endometrial biopsy. There were no significant differences between the intervention and control groups in terms of age, follicle-stimulating hormone (FSH), free androgen index, anti-Müllerian hormone, body mass index, the number of embryos transferred, and the number of embryo transfer cycles. The clinical pregnancy rate in the intervention group (53%) was significantly (p < 0.001) higher than that of the control group (15%). The only predictive factor was FSH. Women with FSH < or =10 IU/L had a pregnancy rate of 57.8%, significantly (p < 0.05) higher than that (20%) of women with FSH >10 IU/L. Women with a normal FSH are more likely to derive benefit from endometrial scratch.

Correlation of normal-range FMR1 repeat length or genotypes and reproductive parameters.

PubMed

Maslow, Bat-Sheva L; Davis, Stephanie; Engmann, Lawrence; Nulsen, John C; Benadiva, Claudio A

2016-09-01

This study aims to ascertain whether the length of normal-ranged CGG repeats on the FMR1 gene correlates with abnormal reproductive parameters. We performed a retrospective, cross-sectional study of all FMR1 carrier screening performed as part of routine care at a large university-based fertility center from January 2011 to March 2014. Correlations were performed between normal-range FMR1 length and baseline serum anti-Müllerian hormone (AMH), cycle day 3 follicle stimulating hormone (FSH), ovarian volumes (OV), antral follicle counts (AFC), and incidence of diminished ovarian reserve (DOR), while controlling for the effect of age. Six hundred three FMR1 screening results were collected. One subject was found to be a pre-mutation carrier and was excluded from the study. Baseline serum AMH, cycle day 3 FSH, OV, and AFC data were collected for the 602 subjects with normal-ranged CGG repeats. No significant difference in median age was noted amongst any of the FMR1 repeat genotypes. No significant correlation or association was found between any allele length or genotype, with any of the reproductive parameters or with incidence of DOR at any age (p > 0.05). However, subjects who were less than 35 years old with low/low genotype were significantly more likely to have below average AMH levels compared to those with normal/normal genotype (RR 3.82; 95 % CI 1.38-10.56). This large study did not demonstrate any substantial association between normal-range FMR1 repeat lengths and reproductive parameters.

BAC mediated transgenic Large White boars with FSHα/β genes from Chinese Erhualian pigs.

PubMed

Xu, Pan; Li, Qiuyan; Jiang, Kai; Yang, Qiang; Bi, Mingjun; Jiang, Chao; Wang, Xiaopeng; Wang, Chengbin; Li, Longyun; Qiao, Chuanmin; Gong, Huanfa; Xing, Yuyun; Ren, Jun

2016-10-01

Follicle-stimulating hormone (FSH) is a critical hormone regulating reproduction in mammals. Transgenic mice show that overexpression of FSH can improve female fecundity. Using a bacterial artificial chromosome (BAC) system and somatic cell nuclear transfer, we herein generated 67 Large White transgenic (TG) boars harboring FSHα/β genes from Chinese Erhualian pigs, the most prolific breed in the world. We selected two F0 TG boars for further breeding and conducted molecular characterization and biosafety assessment for F1 boars. We showed that 8-9 copies of exogenous FSHα and 5-6 copies of exogenous FSHβ were integrated into the genome of transgenic pigs. The inheritance of exogenous genes conforms to the Mendel's law of segregation. TG boars had higher levels of serum FSH, FSHα mRNA in multiple tissues, FSHβ protein in pituitary and more germ cells per seminiferous tubule compared with their wild-type half sibs without any reproductive defects. Analysis of growth curve, hematological and biochemical parameters and histopathology illustrated that TG boars grew healthily and normally. By applying 16S rRNA gene sequencing, we demonstrated that exogenous genes had no impact on the bacterial community structures of pig guts. Moreover, foreign gene drift did not occur as verified by horizontal gene transfer. Our findings indicate that overexpression of FSH could improve spermatogenesis ability of boars. This work provides insight into the effect of FSHα/β genes on male reproductive performance on pigs by a BAC-mediated transgenic approach.

Antimullerian hormone and obesity: insights in oral contraceptive users

PubMed Central

Steiner, Anne Z.; Stanczyk, Frank Z.; Patel, Stan; Edelman, Alison

2009-01-01

Background The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women. Study design Ovulatory women, ages 18–35 years, of normal (< 25 kg/m2; n = 10) and obese (> 30 kg/m2; n = 10) body mass index (BMI) received a low-dose OC (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for two cycles. Serum samples obtained at several time points during active pill use and hormone-free intervals were analyzed for AMH, FSH, LH, estradiol and inhibin B. Results AMH levels did not differ by OC cycle day in either BMI group. On average, AMH levels were 34% lower in the obese group (2.9±2.1 versus 4.4±1.8ng/ml, p<0.05). Modeling to determine differences in AMH throughout the cycle based on obesity status demonstrated significiantly lower levels (p<0.05), whereras serum AMH, FSH, LH, estradiol and inhibin B levels revealed no correlations when all time points were included. Conclusions In reproductive-aged women, serum AMH levels do not appear to fluctuate during OC use but AMH levels are significantly lower in obese women. Lower levels do not appear to be due to differences in gonadotropin levels or ovarian activity. PMID:20159182

Effects of exemestane and tamoxifen on hormone levels within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German substudy.

PubMed

Hadji, P; Kauka, A; Bauer, T; Tams, J; Hasenburg, A; Kieback, D G

2012-10-01

The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)-intact were measured at screening and after 3, 6 and 12 months of treatment. Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact.

Pituitary imaging findings in male patients with hypogonadotrophic hypogonadism.

PubMed

Hirsch, Dania; Benbassat, Carlos; Toledano, Yoel; S'chigol, Irena; Tsvetov, Gloria; Shraga-Slutzky, Ilana; Eizenberg, Yoav; Shimon, Ilan

2015-08-01

Data on pituitary imaging in adult male patients presenting with hypogonadotrophic hypogonadism (HH) and no known pituitary disease are scarce. To assess the usefulness of pituitary imaging in the evaluation of men presenting with HH after excluding known pituitary disorders and hyperprolactinemia. A historical prospective cohort of males with HH. Men who presented for endocrine evaluation from 2011 to 2014 with testosterone levels <10.4 nmol/L (300 ng/mL), normal LH and FSH levels and no known pituitary disease. Seventy-five men were included in the analysis. Their mean age and BMI were 53.4 ± 14.8 years and 30.7 ± 5.2 kg/m2, respectively. Mean total testosterone, LH, and FSH were 6.2 ± 1.7 nmol/L, 3.4 ± 2 and 4.7 ± 3.1 mIU/L, respectively. Prolactin level within the normal range was obtained in all men (mean 161 ± 61, range 41-347 mIU/L). Sixty-two men had pituitary MRI and 13 performed CT. In 61 (81.3%) men pituitary imaging was normal. Microadenoma was found in 8 (10.7%), empty sella and thickened pituitary stalk in one patient (1.3%) each. In other four patients (5.3%) a small or mildly asymmetric pituitary gland was noted. No correlation was found between testosterone level and the presence of pituitary anomalies. This study suggests that the use of routine hypothalamic-pituitary imaging in the evaluation of IHH, in the absence of clinical characteristics of other hormonal loss or sellar compression symptoms, will not increase the diagnostic yield of sellar structural abnormalities over that reported in the general population.

Comparing Serum Follicle-Stimulating Hormone (FSH) Level with Vaginal PH in Women with Menopausal Symptoms.

PubMed

Vahidroodsari, Fatemeh; Ayati, Seddigheh; Yousefi, Zohreh; Saeed, Shohreh

2010-01-01

Despite the important implication for women's health and reproduction, very few studies have focused on vaginal PH for menopausal diagnosis. Recent studies have suggested vaginal PH as a simple, noninvasive and inexpensive method for this purpose. The aim of this study is to compare serum FSH level with vaginal PH in menopause. This is a cross-sectional, descriptive study, conducted on 103 women (aged 31-95 yrs) with menopausal symptoms who were referred to the Menopausal Clinic at Ghaem Hospital during 2006. Vaginal pH was measured using pH meter strips and serum FSH levels were measured using immunoassay methods. The data was analyzed using SPSS software (version 11.5) and results were evaluated statistically by the Chi-square and Kappa tests. p≤0.05 was considered statistically significant. According to this study, in the absence of vaginal infection, the average vaginal pH in these 103 menopausal women was 5.33±0.53. If the menopausal hallmark was considered as vaginal pH>4.5, and serum FSH as ≥20 mIU/ml, then the sensitivity of vaginal pH for menopausal diagnosis was 97%. The mean of FSH levels in this population was 80.79 mIU/ml. Vaginal pH is a simple, accurate, and cost effective tool that can be suggested as a suitable alternative to serum FSH measurement for the diagnosis of menopause.

Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

PubMed

Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

2017-10-01

Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P < 0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P < 0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax > 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

Relationship between Lipids Levels of Serum and Seminal Plasma and Semen Parameters in 631 Chinese Subfertile Men

PubMed Central

Yao, Qi; Fan, Kai; Wang, Guo-Hong; Feng, Rui-Xiang; Liang, Yuan-Jiao; Chen, Li; Ge, Yi-Feng; Yao, Bing

2016-01-01

Objective This prospective study was designed to investigate the relationship between lipids levels in both serum and seminal plasma and semen parameters. Methods 631 subfertile men were enrolled. Their obesity-associated markers were measured, and semen parameters were analyzed. Also, seminal plasma and serum TC, TG, HDL and LDL and serum FFA, FSH, LH, total testosterone (TT), estradiol (E2) and SHBG levels were detected. Results Seminal plasma and serum TG, TC and LDL levels were positively related to age. Serum TC, TG and LDL were positively related to obesity-associated markers (P < 0.001), while only seminal plasma TG was positively related to them (P < 0.05). For lipids levels in serum and seminal plasma, only TG level had slightly positive correlation between them (r = 0.081, P = 0.042). There was no significant correlation between serum lipids levels and semen parameters. However, seminal plasma TG, TC, LDL and HDL levels were negatively related to one or several semen parameters, including semen volume (SV), sperm concentration (SC), total sperm count (TSC), sperm motility, progressive motility (PR) and total normal-progressively motile sperm counts (TNPMS). Moreover, seminal plasma TG, TC, LDL and HDL levels in patients with oligospermatism, asthenospermia and teratozoospermia were higher than those with normal sperm concentration, motility or morphology. After adjusting age and serum LH, FSH, TT, E2 and SHBG levels, linear regression analysis showed that SV was still significantly correlated with seminal plasma LDL (P = 0.012), both of SC and TSC with seminal plasma HDL (P = 0.028 and 0.002), and both of PR and sperm motility with seminal plasma TC (P = 0.012 and 0.051). Conclusion The abnormal metabolism of lipids in male reproductive system may contribute to male factor infertility. PMID:26726884

Early effects of equine FSH (eFSH) treatment on hormonal and reproductive parameters in mares intended to carry their own pregnancy.

PubMed

Raz, Tal; Gray, Allister; Hunter, Barbara; Card, Claire

2009-10-01

Superovulatory treatment may potentially increase the embryo recovery rate and the per-cycle pregnancy rate in normal or subfertile mares that are managed properly. However, some studies suggest a possible negative effect of superovulatory treatment on ovarian follicular maturation and embryo viability. Objectives of the present study were to investigate the early effects of eFSH treatment in reproductively normal mares in terms of: folliculogenesis, pregnancy rate, early embryonic development, reproductive tract parameters (tone and edema), and serum estradiol-17beta and progesterone concentrations. Reproductively sound mares (n=26) were evaluated daily by transrectal palpation and ultrasonography. Five days after spontaneous ovulation, mares were randomly assigned to one of two treatment groups. In the eFSH group, mares (n=16 estrous cycles) were administered eFSH twice daily; beginning when a follicle > or =20mm was detected, and continuing until at least one follicle reached a diameter of > or =35 mm. PGF2alpha was administered 2 days following initiation of eFSH therapy, and hCG was administered approximately 36h after cessation of eFSH therapy. In the control group, mares (n=26 estrous cycles) were administered PGF2alpha 7 days after spontaneous ovulation, and hCG when a follicle > or =35 mm was detected. All mares were bred with fresh semen, monitored for ovulation (Day 0), and evaluated for pregnancy on Days 11-16. Serum estradiol-17beta and progesterone concentrations were analyzed using radioimmunoassay on the Day of hCG administration, and Days 8, 11 and 16. Mares treated with eFSH had more follicles > or =30 mm at the time of hCG administration (2.6+/-0.4 compared with 1.1+/-0.1; P<0.01), and more ovulations (2.3+/-0.5 compared with 1.1+/-0.3; P<0.01). However, pregnancy rates were not significantly different between groups (50%; 8/16 compared with 62%; 16/26). Mean overall daily growth rate of embryonic vesicles from Day 11 to 16 was not statistically different between the two groups (3.3+/-0.3 compared with 3.7+/-0.1 mm/day) (P=0.2); however, was more variable (P<0.01) in the eFSH group (95%CI: 2.6-3.8mm/day) than in the control group (95%CI: 3.5-3.9 mm/day). Administration of eFSH modified the reproductive tract variables and serum concentrations of progesterone and estradiol-17beta on the days that oocyte maturation, fertilization, and early embryonic development are expected to occur. These alterations may be related to the greater incidence of non-ovulatory follicles (25% compared with 0%), fewer embryos per ovulation rate (0.3+/-0.1 compared with 0.6+/-0.1), and the lesser than expected pregnancy rates in the eFSH-treated mares.

Weight loss increases follicle stimulating hormone in overweight postmenopausal women [corrected].

PubMed

Kim, Catherine; Randolph, John F; Golden, Sherita H; Labrie, Fernand; Kong, Shengchun; Nan, Bin; Barrett-Connor, Elizabeth

2015-01-01

To examine the impact of a weight loss intervention upon follicle stimulating hormone (FSH) levels in postmenopause. Participants were postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n = 382) in the Diabetes Prevention Program. Women were randomized to intensive lifestyle change (ILS) with the goals of weight reduction of at least 7% of initial weight and 150 min per week of moderate-intensity exercise, metformin 850 mg twice a day, or placebo administered twice a day. Randomization to ILS led to small increases in FSH between baseline and 1-year follow-up vs. placebo (2.3 IU/l vs. -0.81 IU/l, P < 0.01). Increases in FSH were correlated with decreases in weight (r = -0.165, P < 0.01) and estradiol (E2) (r = -0.464, P < 0.0001) after adjustment for age, race/ethnicity, and randomization arm. Changes in FSH were still significantly associated with changes in weight even after adjustment for E2 levels. Metformin users had reductions in weight but non-significant changes in FSH and E2 levels vs. placebo. Weight loss leads to small increases in FSH among overweight, postmenopausal women, potentially through pathways mediated by endogenous estrogen as well as other pathways. © 2014 The Obesity Society.

FSH supplementation to culture medium is beneficial for activation and survival of preantral follicles enclosed in equine ovarian tissue.

PubMed

Aguiar, F L N; Lunardi, F O; Lima, L F; Rocha, R M P; Bruno, J B; Magalhães-Padilha, D M; Cibin, F W S; Nunes-Pinheiro, D C S; Gastal, M O; Rodrigues, A P R; Apgar, G A; Gastal, E L; Figueiredo, J R

2016-04-01

This study investigated the effect of adding different concentrations of bovine recombinant follicle-stimulating hormone on the IVC of equine preantral follicles enclosed in ovarian tissue fragments. Randomized ovarian fragments were fixed immediately (fresh noncultured control) or cultured for 1 or 7 days in α-MEM(+) supplemented with 0, 10, 50, and 100 ng/mL FSH and subsequently analyzed by classical histology. Culture media collected on Day 1 or Day 7 and were analyzed for steroids (estradiol and progesterone) and reactive oxygen species (ROS). After Day 1 and Day 7 of culture, 50-ng/mL FSH treatment had a greater (P < 0.05) percentage of morphologically normal follicles when compared to the other groups, except the 10-ng/mL FSH treatment at Day 1 of culture. The percentage of developing follicles (transition, primary, and secondary), and follicular and oocyte diameters were higher (P < 0.05) in the 50-ng/mL FSH treatment compared to the other groups after Day 7 of culture. Furthermore, estradiol secretion and ROS production were maintained (P > 0.05) throughout the culture in the 50-ng/mL FSH treatment. In conclusion, the addition of 50 ng/mL of FSH promoted activation of primordial follicles to developing follicles, improved survival of preantral follicles, and maintained estradiol and ROS production of equine ovarian tissue after 7 days of culture. Copyright © 2016 Elsevier Inc. All rights reserved.

FOLLITROPIN RECEPTORS CONTAIN CRYPTIC LIGAND BINDING SITES1

PubMed Central

Lin, Win; Bernard, Michael P.; Cao, Donghui; Myers, Rebecca V.; Kerrigan, John E.; Moyle, William R.

2007-01-01

Human choriogonadotropin (hCG) and follitropin (hFSH) have been shown to contact different regions of the extracellular domains of G-protein coupled lutropin (LHR) and follitropin (FSHR) receptors. We report here that hCG and hFSH analogs interact with an FSHR/LHR chimera having only two unique LHR residues similar to the manners in which they dock with LHR and FSHR, respectively. This shows that although the FSHR does not normally bind hCG, it contains a cryptic lutropin binding site that has the potential to recognize hCG in a manner similar to the LHR. The presence of this cryptic site may explain why equine lutropins bind many mammalian FSHR and why mutations in the transmembrane domain distant from the extracellular domain enable the FSHR to bind hCG. The leucine-rich repeat domain (LRD) of the FSHR also appears to contain a cryptic FSH binding site that is obscured by other parts of the extracellular domain. This will explain why contacts seen in crystals of hFSH complexed with an LRD fragment of the human FSHR are hard to reconcile with the abilities of FSH analogs to interact with membrane G-protein coupled FSHR. We speculate that cryptic lutropin binding sites in the FSHR, which are also likely to be present in thyrotropin receptors (TSHR), permit the physiological regulation of ligand binding specificity. Cryptic FSH binding sites in the LRD may enable alternate spliced forms of the FSHR to interact with FSH. PMID:17059863

Effects of exosome-like vesicles on cumulus expansion in pigs in vitro.

PubMed

Matsuno, Yuta; Onuma, Asuka; Fujioka, Yoshie A; Yasuhara, Kazuma; Fujii, Wataru; Naito, Kunihiko; Sugiura, Koji

2017-02-16

Cell-secreted vesicles, such as exosomes, have recently been recognized as mediators of cell communication. A recent study in cattle showed the involvement of exosome-like vesicles in the control of cumulus expansion, a prerequisite process for normal ovulation; however, whether this is the case in other mammalian species is not known. Therefore, this study aimed to examine the presence of exosome-like vesicles in ovarian follicles and their effects on cumulus expansion in vitro in pigs. The presence of exosome-like vesicles in porcine follicular fluid (pFF) was confirmed by transmission electron microscopic observation, the detection of marker proteins, and RNA profiles specific to exosomes. Fluorescently labeled exosome-like vesicles isolated from pFF were incorporated into both cumulus and mural granulosa cells in vitro. Exosome-like vesicles were not capable of inducing cumulus expansion to a degree comparable to that induced by follicle-stimulating hormone (FSH). Moreover, exosome-like vesicles had no significant effects on the expression levels of transcripts required for the normal expansion process (HAS2, TNFAIP6, and PTGS2). Interestingly, FSH-induced expression of HAS2 and TNFAIP6 mRNA, but not of PTGS2 mRNA, was significantly increased by the presence of exosome-like vesicles; however, the degree of FSH-induced expansion was not affected. In addition, porcine exosome-like vesicles had no significant effects on the expansion of mouse cumulus-oocyte complexes. Collectively, the present results suggest that exosome-like vesicles are present in pFF, but they are not efficient in inducing cumulus expansion in pigs.

Effects of exosome-like vesicles on cumulus expansion in pigs in vitro

PubMed Central

MATSUNO, Yuta; ONUMA, Asuka; FUJIOKA, Yoshie A; YASUHARA, Kazuma; FUJII, Wataru; NAITO, Kunihiko; SUGIURA, Koji

2017-01-01

Cell-secreted vesicles, such as exosomes, have recently been recognized as mediators of cell communication. A recent study in cattle showed the involvement of exosome-like vesicles in the control of cumulus expansion, a prerequisite process for normal ovulation; however, whether this is the case in other mammalian species is not known. Therefore, this study aimed to examine the presence of exosome-like vesicles in ovarian follicles and their effects on cumulus expansion in vitro in pigs. The presence of exosome-like vesicles in porcine follicular fluid (pFF) was confirmed by transmission electron microscopic observation, the detection of marker proteins, and RNA profiles specific to exosomes. Fluorescently labeled exosome-like vesicles isolated from pFF were incorporated into both cumulus and mural granulosa cells in vitro. Exosome-like vesicles were not capable of inducing cumulus expansion to a degree comparable to that induced by follicle-stimulating hormone (FSH). Moreover, exosome-like vesicles had no significant effects on the expression levels of transcripts required for the normal expansion process (HAS2, TNFAIP6, and PTGS2). Interestingly, FSH-induced expression of HAS2 and TNFAIP6 mRNA, but not of PTGS2 mRNA, was significantly increased by the presence of exosome-like vesicles; however, the degree of FSH-induced expansion was not affected. In addition, porcine exosome-like vesicles had no significant effects on the expansion of mouse cumulus-oocyte complexes. Collectively, the present results suggest that exosome-like vesicles are present in pFF, but they are not efficient in inducing cumulus expansion in pigs. PMID:28163264

Quantitative Biology of Exercise-Induced Signal Transduction Pathways.

PubMed

Liu, Timon Cheng-Yi; Liu, Gang; Hu, Shao-Juan; Zhu, Ling; Yang, Xiang-Bo; Zhang, Quan-Guang

2017-01-01

Exercise is essential in regulating energy metabolism. Exercise activates cellular, molecular, and biochemical pathways with regulatory roles in training response adaptation. Among them, endurance/strength training of an individual has been shown to activate its respective signal transduction pathways in skeletal muscle. This was further studied from the viewpoint of quantitative difference (QD). For the mean values, [Formula: see text], of two sets of data, their QD is defined as [Formula: see text] ([Formula: see text]). The function-specific homeostasis (FSH) of a function of a biosystem is a negative-feedback response of the biosystem to maintain the function-specific conditions inside the biosystem so that the function is perfectly performed. A function in/far from its FSH is called a normal/dysfunctional function. A cellular normal function can resist the activation of other signal transduction pathways so that there are normal function-specific signal transduction pathways which full activation maintains the normal function. An acute endurance/strength training may be dysfunctional, but its regular training may be normal. The normal endurance/strength training of an individual may resist the activation of other signal transduction pathways in skeletal muscle so that there may be normal endurance/strength training-specific signal transduction pathways (NEPs/NSPs) in skeletal muscle. The endurance/strength training may activate NSPs/NEPs, but the QD from the control is smaller than 0.80. The simultaneous activation of both NSPs and NEPs may enhance their respective activation, and the QD from the control is larger than 0.80. The low level laser irradiation pretreatment of rats may promote the activation of NSPs in endurance training skeletal muscle. There may be NEPs/NSPs in skeletal muscle trained by normal endurance/strength training.

[Gigantism with low serum level of growth hormone: a case report].

PubMed

Ran, X; Zhang, L; Xiong, P; Zhao, T; Tong, N; Li, X

2001-12-01

Gigantism with low or normal basal concentrations of growth hormone (GH) is a rare condition, possibly due to abnormal GH secretory patterns, enhanced tissue sensitivity to GH, or the existence of an unidentified growth promoting factor. Here we report an 11 year-old female case of gigantism with a normal pituitary gland. Her height was 181 cm, body weight 77 kg, and bone age 11.1 years. Her basal serum GH levels were lower than 1 ng/ml. The levels of T3, T4, FT3, FT4, TSH, E2, LH, FSH, PRL, PTC and ACTH were normal. Serum GH response to insulin-induced hypoglycemia or arginine stimulation tests was blunted. In this case, non-pulsatile GH secretion and enhanced tissue sensitivity to GH may induce hypersecretion of IGF-1 and the existence of an unidentified growth promoting factor or biologically active anti-GH receptor antibodies may cause clinical gigantism.

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary.

PubMed

Geber, Selmo; Brandão, Augusto H F; Sampaio, Marcos

2012-06-15

Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student's t-test and Pearson's correlation test. We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG.

PubMed

Celik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Cetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student's t-test) and the total dose of gonadotropin received (p=0.392, Student's t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation.

Comparison of ovulation induction and pregnacy outcomes in IVF patients with normal ovarian reserve who underwent long protocol with recombinant-FSH and highly purified-hMG

PubMed Central

Çelik, Cem; Sofuoğlu, Kenan; Selçuk, Selçuk; Asoğlu, Mehmet Reşit; Abalı, Remzi; Çetingöz, Elçin; Baykal, Bahar; Uludoğan, Mehmet

2011-01-01

Objective Gonadotropins used in controlled ovarian stimulation have been increasing in number. Beside the recombinant preparations such as rec-FSH, rec-LH and h-hMG human-derived preparations have entered the market. We decided to compare the effects of rec-FSH and HP-hMG with GnRHa on embryo quality and pregnancy outcome in women undergoing an IVF cycle. Material and Methods In this study, data of 87 patients who had applied to our center from 2007 to 2008 and who had met all inclusion criteria, were analyzed. The patients underwent controlled ovarian hyperstimulation with HP-hMG, rec-FSH following down-regulation with a GnRHa in a long protocol, selected according to determined criteria and acquired embryo via IVF transfer. Results Of the 87 patients, 44 were stimulated with rec-FSH and 43 with HP-hMG. Distribution of infertility causes was similar between the groups. Duration of gonadotropin administration (p=0.677, Student’s t-test) and the total dose of gonadotropin received (p=0.392, Student’s t-test) were similar between the two groups. The fertilization rate of the rec-FSH group was significantly higher than the HP-hMG group (p=0.001, Mann-Whitney U test). No significant differences were observed between the study groups in biochemical, clinical and ongoing pregnancy parameters. Conclusion The higher oocyte yield with rec-FSH does not result in higher quality embryos. LH activity in combination with FSH activity positively affected the oocyte and embryo maturation. Therefore, when we consider the clinical and ongoing pregnancy rates there is no inferiority of HP-hMG in controlled ovarian stimulation. PMID:24591951

The effect of lead intoxication on endocrine functions.

PubMed

Doumouchtsis, K K; Doumouchtsis, S K; Doumouchtsis, E K; Perrea, D N

2009-02-01

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

Obesity, serum steroid levels, and pulsatile gonadotropin secretion in polycystic ovarian disease.

PubMed

Laatikainen, T; Tulenheimo, A; Andersson, B; Kärkkäinen, J

1983-04-01

Serum binding capacity of sex-hormone binding globulin (SHBG-BC), steroid concentrations, and secretion patterns of LH and FSH were compared between groups of seven nonobese and seven obese patients with polycystic ovarian disease (PCOD). Obese patients with PCOD differed from those with normal weight in having very low SHBG-BC and elevated serum levels of free and albumin bound testosterone. Compared to healthy women in the follicular phase, both nonobese and obese patients with PCOD showed equally elevated serum levels of androstenedione, estrone, and albumin-bound and free estradiol. Pattern of gonadotropin secretion was studied from blood samples taken at 15 min intervals for 6 h. In 6 patients of both groups low pulses of FSH were found coincidently with pulses of LH. Serum level of LH showed a clear pulsatile pattern in all patients with PCOD, varying from 4.5 to 7.5 pulses per 6 h. The mean pulse rate in the groups of nonobese and obese patients with PCOD was similar, 5.9 pulses per 6 h. In the obese patients the mean LH levels were, however, less elevated and the pulse amplitudes were smaller than those in the nonobese patients. We suggest that this difference is due to high levels of biologically active testosterone in obese patients with PCOD.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myllymaeki, S.A.; Karjalainen, M.; Haavisto, T.E.

Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg)more » subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening.« less

Follicle-stimulating hormone levels in female workers exposed to urban pollutants.

PubMed

Ciarrocca, Manuela; Caciari, Tiziana; Ponticiello, Barnaba Giuseppina; Gioffrè, Pier Agostino; Tomei, Gianfranco; Sancini, Angela; Schifano, Maria Pia; Palermo, Paola; Nardone, Nadia; Scimitto, Lara; Fiaschetti, Maria; Tomei, Francesco

2011-12-01

The aim of this study was to evaluate if there were alterations in FSH plasma levels in female outdoor workers (traffic policewomen and drivers) exposed to chemical urban stressors vs. control group. After excluding subjects with main confounding factors, traffic policewomen, drivers and indoor workers were matched by age, working life, socioeconomic status, marital status, menstrual cycle day, age of menarche, habitual consumption of Italian coffee and soy. A total of 129 female subjects were included in the study: some 63 workers studied during proliferative phase and 66 during secretory phase of menstrual cycle. Proliferative phase of menstrual cycle: FSH mean values were significantly higher in traffic policewomen compared to controls (p < 0.05). Results suggest that in outdoor workers exposed to urban chemical stressors there are alterations in FSH levels; therefore FSH may be used as an early biological marker, valuable for the group, used in occupational set.

The Increased Expression of Connexin and VEGF in Mouse Ovarian Tissue Vitrification by Follicle Stimulating Hormone

PubMed Central

Yang, Yanzhou; Chen, Jie; Wu, Hao; Pei, Xiuying; Chang, Qing; Ma, Wenzhi; Ma, Huiming; Hei, Changchun; Zheng, Xiaomin; Cai, Yufang; Zhao, Chengjun; Yu, Jia; Wang, Yanrong

2015-01-01

Ovarian follicular damages were caused by cryoinjury during the process of ovarian vitrification and ischemia/reperfusion during the process of ovarian transplantation. And appropriate FSH plays an important role in antiapoptosis during ovarian follicle development. Therefore, in this study, 0.3 IU/mL FSH was administered into medium during mouse ovarian cryopreservation by vitrification to ascertain the function of FSH on ovarian vitrification and avascular transplantation. The results suggested that the expressions of Cx37, Cx43, apoptotic molecular caspase-3, and angiogenesis molecular VEGF were confirmed using immunohistochemistry, western blotting, and real-time PCR, and the results suggested that the treatment with FSH remarkably increased the number of morphologically normal follicles in vitrified/warmed ovaries by upregulating the expression of Cx37, Cx43, VEGF, and VEGF receptor 2, but downregulating the expression of caspase-3. In addition, the vitrified/warmed ovaries were transplanted, and the related fertility was analyzed, and the results suggested that the fertility, neoangiogenesis, and follicle reserve were remarkably increased in the FSH administrated group. Taken together, administration of 0.3 IU/mL FSH during ovarian cryopreservation by vitrification can maintain ovarian survival during ovarian vitrification and increases the blood supply with avascular transplantation via upregulation of Cx43, Cx37, and VEGF/VEGFR2, as well as through its antiapoptotic effects. PMID:26539488

Serum chemerin level in women with PCOS and its relation with the risk of spontaneous abortion.

PubMed

Yang, Xuezhou; Quan, Xiaozhen; Lan, Yanli; Wei, Qipeng; Ye, Jinhai; Yin, Xiaofang; Ji, Zhisong; Xing, Hui; Yang, Ying

2018-04-16

Insulin resistance (IR) was recognized as a risk factor for the occurrence of abortion in patients with polycystic ovary syndrome (PCOS). Chemerin was an adipokine which could induce IR and associated with reproductive process closely. However, few studies have inquired the relativity between chemerin and the occurrence of abortion in patients with PCOS. The aim of this study was to evaluate the relationship between serum chemerin and the occurrence of abortion in women with PCOS. We recruited 198 women with PCOS to participate in our study. On the third day of menstrual cycle or a random day in women with amenorrhea, we obtained their venous blood and measured the fasting insulin, fasting plasma glucose, total cholesterol, high density lipoprotein cholesterol, triglyceride, chemerin, and hormones including FSH, E2, P, PRL, LH, and T. Additionally, BMI, HOMA-IR and LH/FSH of each subject were calculated. Finally, 58 of them were included in the study, in which 30 of them had normal pregnancy and the other 28 had an early miscarriage. We compared the biochemical characteristics between the normal pregnancy group and abortion group by independent-samples t test. In our study, those with a normal pregnancy had a lower level of BMI, FINs, HOMA-IR, and chemerin compared to abortion patients (p < .05). After adjusted for BMI, only chemerin was associated with the occurrence of abortion in PCOS patients (p < .05). Serum chemerin level is associated with the occurrence of abortion in patients with PCOS. Thus, serum chemerin may serve as a biomarker to identify pregnant women with PCOS who are at particular risk for later abortion, and who may benefit from prevention strategies.

Seasonally and experimentally induced changes in testicular function of the Australian bush rat (Rattus fuscipes).

PubMed

Irby, D C; Kerr, J B; Risbridger, G P; de Kretser, D M

1984-03-01

Serum concentrations of LH, FSH and testosterone were measured monthly throughout the year in male bush rats. Testicular size and ultrastructure, LH/hCG, FSH and oestradiol receptors and the response of the pituitary to LHRH were also recorded. LH and FSH rose in parallel with an increase in testicular size after the winter solstice with peak gonadotrophin levels in the spring (September). The subsequent fall in LH and FSH levels was associated with a rise in serum testosterone which reached peak levels during summer (December and January). In February serum testosterone levels and testicular size declined in parallel, while the pituitary response to an LHRH injection was maximal during late summer. The number of LH/hCG, FSH and oestradiol receptors per testis were all greatly reduced in the regressed testes when compared to active testes. In a controlled environment of decreased lighting (shortened photoperiod), temperature and food quality, the testes of sexually active adult males regressed at any time of the year, the resultant testicular morphology and endocrine status being identical to that of wild rats in the non-breeding season. Full testicular regression was achieved only when the photoperiod, temperature and food quality were changed: experiments in which only one or two of these factors were altered failed to produce complete sexual regression.

The effect of estradiol on granulosa cell responses to FSH in women with polycystic ovary syndrome.

PubMed

Homer, Michael V; Rosencrantz, Marcus A; Shayya, Rana F; Chang, R Jeffrey

2017-02-10

The influence of estradiol (E 2 ) on granulosa cell (GC) function has not been tested clinically in women with polycystic ovary syndrome (PCOS). The objective of this study is to determine if E 2 influences GC responses to FSH in women with PCOS. This is a two phase, single cohort study conducted over a 2-year period at a single academic center. Nine women with PCOS according to NIH criteria. In Phase 1, FSH stimulation of GC responses as measured by E 2 and Inhibin B (Inh B) were assessed before and at 5 and 6 weeks after GnRH agonist administration. In Phase 2, the same protocol was employed with the addition of an aromatase inhibitor (letrozole, LET) administered daily beginning at week 4 for 2 weeks. In Phase 1, recovery of FSH, E 2 and Inh B from ovarian suppression occurred at 5 and 6 weeks after GnRH agonist injection and preceded resumption of LH and androgen secretion. In Phase 2, hormone recovery after GnRH agonist was characterized by elevated FSH and suppressed E 2 levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E 2 and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E 2 and Inh B fold changes after FSH were significantly reduced at weeks 5 (p < 0.04) and 6 (p < 0.01), respectively. In anovulatory women with PCOS, chronic, unopposed E 2 secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH. NCT02389088.

High FSH decreases the developmental potential of mouse oocytes and resulting fertilized embryos, but does not influence offspring physiology and behavior in vitro or in vivo.

PubMed

Li, Min; Zhao, Yue; Zhao, Cui H; Yan, Jie; Yan, Ying L; Rong, Li; Liu, Ping; Feng, Huai-Liang; Yu, Yang; Qiao, Jie

2013-05-01

Do different concentrations of FSH in the assisted reproductive technology (ART) procedure in vitro or in vivo affect the developmental competence of oocytes, the embryos and the offspring conceived from these embryos? Improper FSH treatment (200 IU/l in vitro, 10 IU/ml in vivo and 200 IU/ml in vivo) impairs the development competence of oocyte and embryo, but does not influence offspring physiology and behavior. Exogenous FSH has been widely used in the field of ART. However, the effects of different concentrations of FSH on the developmental competence of oocytes, embryos and the offspring conceived from these embryos, are still unknown. In a prospective study, a total of 45 mice at 8-10 weeks of age were primed in vivo with different dosages of FSH (9 mice in the 10 IU/ml, 10 mice in the 50 IU/ml, 10 mice in the 100 IU/ml and 16 mice in the 200 IU/ml groups). Fresh MII oocytes were retrieved from ovaries: this was designated as in vivo group. Thirty six mice at 8-10 weeks of age were sacrificed by cervical dislocation to obtain ovaries without FSH treatment (9 mice in the 0 IU/l, 9 mice in the 50 IU/l, 8 mice in the 100 IU/l and 10 mice in the 200 IU/l groups), and then the immature oocytes were collected from these ovaries and cultured in vitro matured medium supplemented with 0, 50, 100 and 200 IU/l FSH: this was designated as in vitro group. Spindle assembly of matured MII oocytes was stained via an immunofluorescence method and the oocytes ratio of normal spindle was analyzed. The developmental competence of the resulting fertilized embryos in the pre- and post-implantation stages was examined in in vitro and in vivo groups. Furthermore, physiological index, including reproductive potential and body weight, of the offspring was investigated by mating experiments and behavior index, including learning, memory, probing and intelligence, was tested by Morris water maze in in vitro and in vivo groups. In the in vitro groups, the oocyte maturation competence, normal spindle assembly, blastocyst formation and implantation, as well as viable pup production were all impaired in the group treated with 200 IU/l FSH (P < 0.05). No differences were observed among the other three groups (P > 0.05). In the in vivo groups, 10 IU/ml FSH but not 200 IU/ml treatment influenced blastocyst formation and viable pup production (P < 0.05), although the high proportion of spindle assembly abnormality was only observed in the 200 IU/ml FSH treatment group (P < 0.05). Furthermore, there were no significant differences in terms of physiological index (reproductive potential and body weight) and behavior index (learning, memory, probing and intelligence) in offspring from in vitro and in vivo groups (P > 0.05). The mouse model was used in this study. The results of the mouse follicle growth and oocyte development in responding to different concentrations of FSH are not 100% transferable to human, because of the physiological differences between mouse and human. The findings indicated that FSH application in the field of ART is safe to the resulted offspring, but it should be more carefully used for each women in ART cycles because the inappropriate FSH concentration would decrease the oocyte developmental competence. This work was partially supported by the Ministry of Science and Technology of China Grants (973 program; 2011CB944504), the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (30825038), the National Natural Science Funds for Young Scholar (31000661) and by the Joint Research Fund for Overseas, Hong Kong and Marco Scholars (31128013/C120205). None of the authors has any conflicts of interest.

Effects of estradiol and FSH on leptin levels in women with suppressed pituitary

PubMed Central

2012-01-01

Background Female fertility depends on adequate nutrition and energy reserves, suggesting a correlation between the metabolic reserve and reproductive capacity. Leptin regulates body weight and energy homeostasis. The aim of this study was to investigate whether estradiol or FSH alone has a direct effect on the production of leptin. Methods A total of 64 patients submitted to controlled ovarian hyperstimulation with recombinant FSH for assisted reproduction and 20 patients using estradiol valerate for endometrial preparation for oocyte donation treatment were included in the study. All patients used GnRH analogues before starting treatment to achieve pituitary suppression. Blood samples for hormonal measurements were collected before starting and after completing the respective treatments. Data were analyzed statistically by the chi-square test, Student’s t-test and Pearson’s correlation test. Results We observed an elevation of serum leptin levels secondary to the increase in estradiol, in the absence of influence of any other ovarian or pituitary hormone. The rising rate of leptin levels was higher in women treated with recombinant FSH, which also had higher levels of estradiol, than in those treated with estradiol valerate. Conclusions This study demonstrates a correlation between serum levels of estradiol and leptin, suggesting that estradiol is an important regulator of leptin production and that its effects can be amplified by its association with FSH. PMID:22703959

Free androgen index and Irisin in polycystic ovary syndrome.

PubMed

Li, H; Xu, X; Wang, X; Liao, X; Li, L; Yang, G; Gao, L

2016-05-01

PCOS is associated with hyperandrogenism and insulin resistance (IR). Recent studies have shown that circulating Irisin levels increase in PCOS women. However, no report has demonstrated a relationship between Irisin and hyperandrogenism in PCOS women. The purpose of the study was to compare interrelationship between Irisin or androgen excess with IR in PCOS and normal subjects. 166 PCOS and 103 control women were prospectively studied. Euglycemic- hyperinsulinemic clamps were preformed to assess their insulin sensitivity, which was expressed as M value. Circulating Irisin was determined by ELISA kit. Circulating androgens were measured using ultrasensitive assays. PCOS women with high FAI had significantly higher BMI, FAT%, TC, DHEA-S and HOMA-IR, and significantly lower levels of M values and SHBG than PCOS women with low FAI or the controls. Pearson correlations showed that in the entire population, FAI correlated positively with BMI, WHR, FAT%, blood pressure, TG, DHEA-S, LH/FSH, AUCinsulin, HOMA-IR and Irisin, and negatively with M values. In multiple stepwise regression analysis, only FAT%, DHEA-S and LH/FSH were independent related factors with FAI. The elevated Irisin levels in PCOS women were associated with androgen excess. Circulating Irisin is a primary predictor of hyperandrogenism, MetS and IR in PCOS women.

Human cord blood mononuclear cell transplantation for the treatment of premature ovarian failure in nude mice

PubMed Central

Dang, Jianhong; Jin, Zhijun; Liu, Xiaojun; Hu, Dian; Wang, Zhifeng

2015-01-01

Objective: This study explored the potential of human cord blood mononuclear cell (HCMNC) transplantation as a treatment for premature ovarian failure (POF) in a nude mouse model. Methods: Female nude mice were randomly divided into three groups; a normal control group (n = 35), a POF group (POF plus vehicle, n = 35) and a POF plus cell transplantation group (HCMNCs were implanted into the ovaries, n = 35). HCMNCs were isolated by Ficoll density gradient centrifugation and labeled with BrdU. Four weeks after transplantation, the nude mice were sacrificed to determine serum levels of E2, FSH and LH as indicators of ovarian function, and the ovaries were examined both histologically and immunochemically. Results: The transplanted HCMNCs survived in the transplantation group and were detected by BrdU. In the transplantation group, serum levels of E2 significantly increased while serum levels of FSH and LH significantly decreased compared to the POF control group. Additionally, the transplantation group had a recovery in follicle number. Conclusion: HCMNCs can be successfully transplanted into the ovaries of nude mice and can improve ovarian function in POF. PMID:26064319

Hypothalamic amenorrhea with normal body weight: ACTH, allopregnanolone and cortisol responses to corticotropin-releasing hormone test.

PubMed

Meczekalski, B; Tonetti, A; Monteleone, P; Bernardi, F; Luisi, S; Stomati, M; Luisi, M; Petraglia, F; Genazzani, A R

2000-03-01

Hypothalamic amenorrhea (HA) is a functional disorder caused by disturbances in gonadotropin-releasing hormone (GnRH) pulsatility. The mechanism by which stress alters GnRH release is not well known. Recently, the role of corticotropin-releasing hormone (CRH) and neurosteroids in the pathophysiology of HA has been considered. The aim of the present study was to explore further the role of the hypothalamic-pituitary-adrenal axis in HA. We included 8 patients (aged 23.16+/-1.72 years) suffering from hypothalamic stress-related amenorrhea with normal body weight and 8 age-matched healthy controls in the follicular phase of the menstrual cycle. We measured basal serum levels of FSH, LH, and estradiol and evaluated ACTH, allopregnanolone and cortisol responses to CRH test in both HA patients and healthy women. Serum basal levels of FSH, LH, and estradiol as well as basal levels of allopregnanolone were significantly lower in HA patients than in controls (P<0.001) while basal ACTH and cortisol levels were significantly higher in amenorrheic patients with respect to controls (P<0.001). The response (area under the curve) of ACTH, allopregnanolone and cortisol to CRH was significantly lower in amenorrheic women compared with controls (P<0.001, P<0.05, P<0.05 respectively). In conclusion, women with HA, despite the high ACTH and cortisol levels and, therefore, hypothalamus-pituitary-adrenal axis hyperactivity, are characterized by low allopregnanolone basal levels, deriving from an impairment of both adrenal and ovarian synthesis. The blunted ACTH, allopregnanolone and cortisol responses to CRH indicate that, in hypothalamic amenorrhea, there is a reduced sensitivity and expression of CRH receptor. These results open new perspectives on the role of neurosteroids in the pathogenesis of hypothalamic amenorrhea.

Reproductive hormones of ICSI-conceived young adult men: the first results.

PubMed

Belva, Florence; Roelants, Mathieu; De Schepper, Jean; Van Steirteghem, André; Tournaye, Herman; Bonduelle, Maryse

2017-02-01

Are reproductive hormone levels (FSH, LH, inhibin B and testosterone) in male offspring conceived by ICSI because of male infertility comparable with those from peers born after spontaneous conception? In this cohort of 54 young men conceived by ICSI because of male-factor infertility, mean and median reproductive hormone levels were found to be comparable with results from spontaneously conceived peers, but ICSI-conceived men were more likely to have low inhibin B (<10th percentile) and high FSH (>90th percentile) levels. Since the worldwide oldest ICSI offspring have recently reached young adulthood, their reproductive health can now be investigated. This typically involves semen analysis and a hormonal profiling including the measurement of FSH, LH, inhibin B and testosterone. Circulating levels of FSH and inhibin B are generally known as markers of the exocrine function of the testis, i.e. spermatogenesis, while LH and testosterone reflect its endocrine function. We have previously observed a normal pubertal development and comparable levels of inhibin B and testosterone among pubertal ICSI boys when compared to spontaneously conceived peers. However, at present, information on the gonadal function of ICSI offspring in adulthood is still lacking. This study, conducted between March 2013 and April 2016 at the UZ Brussel, is part of a larger follow-up project focusing on reproductive and metabolic health of young adults between 18 and 22 years and conceived after ICSI because of male infertility. The ICSI men are part of a longitudinally followed cohort while the spontaneously conceived controls were recruited cross-sectionally. Results of a single fasting blood sample from 54 young adult ICSI men were compared to that of 57 spontaneously conceived peers. Reproductive hormone analysis involved FSH, LH, testosterone and inhibin B measurement. Furthermore, the association between their reproductive hormones and their sperm parameters was examined. Data were analyzed by multiple linear and logistic regression adjusted for covariates. ICSI men had comparable mean levels of FSH, LH, testosterone and inhibin B in comparison to spontaneously conceived counterparts, even after adjustment for confounders, such as age, BMI and season. Young ICSI-conceived men were more likely to have inhibin B levels below the 10th percentile (<125.2 ng/l; Adjusted Odds Ratio (AOR) 4.0; 95% CI: 0.9-18.4; P = 0.07) compared with spontaneously conceived peers and were more likely to have FSH levels above the 90th percentile (>5.5 IU/L; AOR 3.3; 95% CI: 0.9-11.9; P = 0.06) compared with spontaneously conceived peers, but neither difference reached statistical significance. FSH, LH and inhibin B, but not testosterone, levels were significantly associated with sperm concentration and total sperm count. The main limitation is the small study population. Furthermore, the results of this study should be interpreted according to the background of the participants: all subjects in our study group were conceived by ICSI because of severe male infertility and hence the results cannot be generalized to all ICSI offspring because the indications for performing ICSI have since been widened. These first results in a small group of ICSI men show reassuring reproductive hormonal levels. However, larger studies are required to confirm our results. Since inhibin B and FSH are consistently correlated with semen characteristics, we would suggest that the reproductive status of young adults conceived by ICSI is explored with a hormonal assessment given its easier acceptance compared to semen sampling. This study was supported by Methusalem grants and by grants from Wetenschappelijk Fonds Willy Gepts, all issued by the Vrije Universiteit Brussel (VUB). A grant from the Belgian Society for Pediatric Endocrinology and Diabetology was received for this project. All co-authors, except M.B. and H.T., declare no conflict of interest. M.B. has received consultancy fees from MSD, Serono Symposia and Merck. The Universitair Ziekenhuis Brussel (UZ Brussel) and the Centre for Medical Genetics have received several educational grants from IBSA, Ferring, Organon, Shering-Plough, Merck for establishing the database for follow-up research and organizing the data collection. The institution of HT receives research grants from the 'Research Fund of Flanders' (FWO), an unconditional grant from Ferring for research on testicular stem cells and research grants from Ferring, Merck, MSD, Roche, Besins, Goodlife and Cook for several research projects in female infertility. H.T. has received consultancy fees from Finox, Abbott and ObsEva for research projects in female infertility. N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Amount of bone loss in relation to time around the final menstrual period and follicle-stimulating hormone staging of the transmenopause.

PubMed

Sowers, MaryFran R; Zheng, Huiyong; Jannausch, Mary L; McConnell, Daniel; Nan, Bin; Harlow, Sioban; Randolph, John F

2010-05-01

The objective of the study was to describe bone loss rates across the transmenopause related to FSH staging and the final menstrual period (FMP). This was a population-based cohort of 629 women (baseline age 24-44 yr) with annual data points over 15 yr. Measures were bone mineral density (BMD), FSH to define four FSH stages, and menstrual bleeding cessation to define the FMP. Bone loss rates were reported by obesity status. Annualized rates of lumbar spine bone loss began in FSH stage 3, which occurs approximately 2 yr prior to the FMP (1.67%/yr); bone loss continued into FSH stage 4 (1.21%/yr). Mean spine BMD in FSH stage 4 was 6.4% less than spine BMD value in FSH stage 1. Annualized rates of femoral neck (FN) bone loss began in FSH stage 3 (0.55%/yr) and continued into FSH stage 4 (0.72%/yr). The FN difference between mean values in FSH stage 1 and FSH stage 4 was 5%. Annualized rates of spine bone loss in the 2 yr prior to the FMP were 1.7%/yr, 3.3%/yr in the 2 yr after the FMP, and 1.1%/yr in the 2- to 7-yr period after the FMP. Nonobese women had lower BMD levels and greater bone loss rates. Spine and FN bone loss accelerates in FSH stage 3. Bone loss also began to accelerate 2 yr before the FMP with the greatest loss occurring in the 2 yr after the FMP. Bone loss rates in both spine and FN BMD were greater in nonobese women than obese women.

[Revelation of a polymicrocystic ovary syndrome after one month's treatment by pulsatile GnRH in a patient presenting with functional hypothalamic amenorrhea].

PubMed

Reyss, A C; Merlen, E; Demerle, C; Dewailly, D

2003-12-01

Polycystic ovary syndrome (PCOS) and hypothalamic amenorrhea (HA) are the most frequent causes of endocrine infertility, but their association is an uncommon occurrence. We report the case of a 28-year old woman suffering from infertility and amenorrhea. Her weight was normal (BMI = 19) and she had no hirsutism. She self-reported food restriction and a 10 kg weight loss 5 years ago, concomitant with the onset of amenorrhea. At the initial evaluation, the patient was considered as having HA due to food restriction. At ultrasonography, ovaries were small and multifollicular (right and left area: 2.2 and 2.5 cm(2), respectively; number of cysts 2-9 mm in diameter: 15 and 12, respectively), and no stromal hypertrophy was noted. She has been treated for 1 month by intravenous pulsatile GnRH administration. Although the doses were increased from 5 to 15 microg/pulse every 90 min, no E2 response and no follicular development were observed. Hormonal re-evaluation revealed normal levels of serum LH, FSH and androgens, and a normal LH/FSH ratio. However, a typical aspect of PCO was found at ultrasound (right and left area: 6.5 and 5.5 cm(2), respectively, and more than 15 small cysts arranged peripherally around an increased central stroma in each ovary). The treatment has been then switched to hMG, using the low dose step-up regimen and starting with 75 U/day. In the absence of response after 2 weeks, the dose was increased to 112.5 U/day and a multifollicular reaction occurred, leading to cancellation. In conclusion, we hypothesize that this patient had a "hidden" PCOS when she was hypogonadotrophic and that it developed very rapidly after restitution of a normal gonadotropin level under exogenous GnRH. This occurred despite a low insulin level, showing that hyperinsulinism is not a prerequisite for the development of PCOS in every case.

Number of blastocysts biopsied as a predictive indicator to obtain at least one normal/balanced embryo following preimplantation genetic diagnosis with single nucleotide polymorphism microarray in translocation cases.

PubMed

Wang, Yi-Zi; Ding, Chen-Hui; Wang, Jing; Zeng, Yan-Hong; Zhou, Wen; Li, Rong; Zhou, Can-Quan; Deng, Ming-Fen; Xu, Yan-Wen

2017-01-01

The aim of this study is to investigate the minimum number of blastocysts for biopsy to increase the likelihood of obtaining at least one normal/balanced embryo in preimplantation genetic diagnosis (PGD) for translocation carriers. This blinded retrospective study included 55 PGD cycles for Robertsonian translocation (RT) and 181 cycles for reciprocal translocation (rcp) to indicate when only one of the couples carried a translocation. Single-nucleotide polymorphism microarray after trophectoderm biopsy was performed. Reliable results were obtained for 355/379 (93.7 %) biopsied blastocysts in RT group and 986/1053 (93.6 %) in rcp group. Mean numbers of biopsied embryos per patient, normal/balanced embryos per patient, and mean normal/balanced embryo rate per patient were 7.4, 3.1, and 40.7 % in RT group and 8.0, 2.1, and 27.3 %, respectively, in rcp group. In a regression model, three factors significantly affected the number of genetically transferrable embryos: number of biopsied embryos (P = 0.001), basal FSH level (P = 0.040), and maternal age (P = 0.027). ROC analysis with a cutoff of 1.5 was calculated for the number of biopsied embryos required to obtain at least one normal/balanced embryo for RT carriers. For rcp carriers, the cutoff was 3.5. The clinical pregnancy rate per embryo transfer was 44.2 and 42.6 % in RT and rcp groups (P = 0.836). The minimum numbers of blastocysts to obtain at least one normal/balanced embryo for RT and rcp were 2 and 4 under the conditions of female age < 37 years with a basal FSH level < 11.4 IU/L.

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

PubMed

Iglesias, P; Prado, F; Muñoz, A; Guerrero, M T; Macías, M C; Ridruejo, E; Tajada, P; García-Arévalo, C; Díez, J J

2015-04-01

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, p<0.001). At this point, more than half of the patients (n=27, 62.8%) showed normal serum T concentrations. Both gonadotropins, FSH (p<0.001), and LH (p=0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1%) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7±33.9 ng/dl) than those who persisted with hypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, p<0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95%, 1.010-1.050; p<0.001). In conclusion, about 63% of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Mutations and polymorphisms in FSH receptor: functional implications in human reproduction.

PubMed

Desai, Swapna S; Roy, Binita Sur; Mahale, Smita D

2013-12-01

FSH brings about its physiological actions by activating a specific receptor located on target cells. Normal functioning of the FSH receptor (FSHR) is crucial for follicular development and estradiol production in females and for the regulation of Sertoli cell function and spermatogenesis in males. In the last two decades, the number of inactivating and activating mutations, single nucleotide polymorphisms, and spliced variants of FSHR gene has been identified in selected infertile cases. Information on genotype-phenotype correlation and in vitro functional characterization of the mutants has helped in understanding the possible genetic cause for female infertility in affected individuals. The information is also being used to dissect various extracellular and intracellular events involved in hormone-receptor interaction by studying the differences in the properties of the mutant receptor when compared with WT receptor. Studies on polymorphisms in the FSHR gene have shown variability in clinical outcome among women treated with FSH. These observations are being explored to develop molecular markers to predict the optimum dose of FSH required for controlled ovarian hyperstimulation. Pharmacogenetics is an emerging field in this area that aims at designing individual treatment protocols for reproductive abnormalities based on FSHR gene polymorphisms. The present review discusses the current knowledge of various genetic alterations in FSHR and their impact on receptor function in the female reproductive system.

High levels of testosterone inhibit ovarian follicle development by repressing the FSH signaling pathway.

PubMed

Liu, Tao; Cui, Yu-qian; Zhao, Han; Liu, Hong-bin; Zhao, Shi-dou; Gao, Yuan; Mu, Xiao-li; Gao, Fei; Chen, Zi-jiang

2015-10-01

The effect of high concentrations of testosterone on ovarian follicle development was investigated. Primary follicles and granulosa cells were cultured in vitro in media supplemented with a testosterone concentration gradient. The combined effects of testosterone and follicle-stimulating hormone (FSH) on follicular growth and granulosa cell gonadotropin receptor mRNA expression were also investigated. Follicle growth in the presence of high testosterone concentrations was promoted at early stages (days 1-7), but inhibited at later stage (days 7-14) of in vitro culture. Interestingly, testosterone-induced follicle development arrest was rescued by treatment with high concentrations of FSH (400 mIU/mL). In addition, in cultured granulosa cells, high testosterone concentrations induced cell proliferation, and increased the mRNA expression level of FSH receptor (FSHR), and luteinized hormone/choriogonadotropin receptor. It was concluded that high concentrations of testosterone inhibited follicle development, most likely through regulation of the FSH signaling pathway, although independently from FSHR downregulation. These findings are an important step in further understanding the pathogenesis of polycystic ovary syndrome.

Efficacy of a single intramuscular injection of porcine FSH in hyaluronan prior to ovum pick-up in Holstein cattle.

PubMed

Vieira, L M; Rodrigues, C A; Castro Netto, A; Guerreiro, B M; Silveira, C R A; Freitas, B G; Bragança, L G M; Marques, K N G; Sá Filho, M F; Bó, G A; Mapletoft, R J; Baruselli, P S

2016-03-15

Plasma FSH profiles, in vitro embryo production (IVP) after ovum pickup (OPU), and establishment of pregnancy with IVP embryos were compared in untreated Holstein oocyte donors and those superstimulated with multiple injections or a single intramuscular (IM) injection of porcine FSH (pFSH) in hyaluronan (HA). Plasma FSH profiles were determined in 23 heifers randomly allocated to one of four groups. Controls received no treatment, whereas the F200 group received 200 mg of pFSH in four doses, 12 hours apart. The F200HA and F300HA groups received 200- or 300-mg pFSH in 5 mL or 7.5 mL, respectively of a 0.5% HA solution by a single IM injection. Plasma FSH levels were determined before the first pFSH treatment and every 6 hours over 96 hours. All data were analyzed by orthogonal contrasts. Circulating FSH area under curve (AUC) in pFSH-treated animals was greater than that in the control group (P = 0.02). Although the AUC did not differ among FSH-treated groups (P = 0.56), the total period with elevated plasma FSH was greater in the F200 group than in the HA groups (P < 0.0001). However, the F300HA group had a greater AUC than the F200HA group (P = 0.006), with a similar total period with elevated plasma FSH (P = 0.17). The IVP was performed in 90 nonlactating Holstein cows randomly allocated to one of the four treatment groups as in the first experiment. A greater proportion of medium-sized (6-10 mm) follicles was observed in cows receiving pFSH, regardless of the treatment group (P < 0.0001). Also, numbers of follicles (P = 0.01), cumulus-oocyte complexes (COCs) retrieved (P = 0.01) and matured (P = 0.02), cleavage rates (P = 0.002), and blastocysts produced per OPU session (P = 0.06) were greater in cows receiving pFSH, regardless of the treatment group. Cows in the F200HA group had a greater recovery rate (P = 0.009), number of COCs cultured (P = 0.04), and blastocysts produced per OPU session (P = 0.06) than cows in the F300HA group. Similar pregnancy rates were observed 50 to 60 days after transferring IVP embryos from donors in the different treatment groups (P > 0.05). In conclusion, a single IM injection of pFSH combined in 0.5% HA resulted in similar plasma FSH profiles as twice-daily pFSH treatments. Treatment of nonlactating donors with pFSH, with or without HA, resulted in increased IVP over untreated controls. A single dose of 200 mg of pFSH in 0.5% HA resulted in greater IVP than 300-mg pFSH in HA. Finally, pregnancy rates with IVP embryos were similar, regardless donor treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of eCG and FSH on ovarian response, recovery rate and number and quality of oocytes obtained by ovum pick-up in Holstein cows.

PubMed

Sendag, Sait; Cetin, Yunus; Alan, Muhammet; Hadeler, Klaus-Gerd; Niemann, Heiner

2008-06-01

The goal of the present study was to compare the ovarian response, oocyte yields per animal, and the morphological quality of oocytes collected by ultrasound guided follicular aspiration from Holstein cows treated either with FSH or eCG. Twenty four normal cyclic, German Holstein cows were randomly divided into two groups. Fourteen cows received 3000 IU eCG on day-4 prior to ovum pick-up (OPU) (day 0), 2 days later (day-2), 625 microg cloprostenol was administered. On day-1 GnRH was administered i.m. and 24h later OPU (day 0) was performed. In ten cows a total dose of 500 IU follicle stimulating hormone (Pluset) was administered intramuscularly in a constant dosage for 4 days with intervals of 12h, starting on day-5. Luteolysis was induced by application of 625 microg cloprostenol on day-2. On day-1 (24h after the last FSH treatment) GnRH was administered i.m. and 24h later OPU (day 0) was performed. Ovarian follicles were visualized on the ultrasound monitor, counted and recorded. All visible antral follicles were punctured. Recovered oocytes were graded morphologically based on the cumulus investment. Average follicle number in ovaries was higher in FSH group than eCG group (p<0.05). Oocyte yields per animal did not differ between FSH and eCG groups. The proportion of grade A oocytes was higher in the FSH group in the than eCG group (p<0.05). Likewise, rate of grade C oocytes in FSH group were lower than eCG group (p<0.05). In conclusion, these results suggest that ovarian response, follicle number in ovaries and oocyte quality are affected by the type of gonadotropin and FSH is better alternative than eCG for OPU treatment.

CRTC2 and Nedd4 ligase involvement in FSH and TGFβ1 upregulation of connexin43 gap junction.

PubMed

Fang, Wei-Ling; Lai, Si-Yi; Lai, Wei-An; Lee, Ming-Ting; Liao, Ching-Fong; Ke, Ferng-Chun; Hwang, Jiuan-Jiuan

2015-12-01

The major mission of the ovarian follicle is the timely production of the mature fertilizable oocyte, and this is achieved by gonadotropin-regulated, gap junction-mediated cell-cell communication between the oocyte and surrounding nurturing granulosa cells. We have demonstrated that FSH and transforming growth factor beta 1 (TGFβ1) stimulate Gja1 gene-encoded connexin43 (Cx43) gap junction formation/function in rat ovarian granulosa cells is important for their induction of steroidogenesis; additionally, cAMP-protein kinase A (PKA)- and calcium-calcineurin-sensitive cAMP response element-binding (CREB) coactivator CRTC2 plays a crucial role during steroidogenesis. This study was to explore the potential molecular mechanism whereby FSH and TGFβ1 regulate Cx43 synthesis and degradation, particularly the involvement of CRTC2 and ubiquitin ligase Nedd4. Primary culture of granulosa cells from ovarian antral follicles of gonadotropin-primed immature rats was used. At 48 h post-treatment, FSH plus TGFβ1 increased Cx43 level and gap junction function in a PKA- and calcineurin-dependent manner, and TGFβ1 acting through its type I receptor modulated FSH action. Chromatin-immunoprecipitation analysis reveals FSH induced an early-phase (45 min) and FSH+TGFβ1 further elicited a late-phase (24 h) increase in CRTC2, CREB and CBP binding to the Gja1 promoter. Additionally, FSH+TGFβ1 increased the half-life of hyper-phosphorylated Cx43 (Cx43-P2). Also, the proteasome inhibitor MG132 prevented the brefeldin A (blocker of protein transport through Golgi)-reduced Cx43-P2 level and membrane Cx43 gap junction plaque. This is associated with FSH+TGFβ1-attenuated Cx43 interaction with Nedd4 and Cx43 ubiquitination. In all, this study uncovers that FSH and TGFβ1 upregulation of Cx43 gap junctions in ovarian granulosa cells critically involves enhancing CRTC2/CREB/CBP-mediated Cx43 expression and attenuating ubiquitin ligase Nedd4-mediated proteosomal degradation of Cx43 protein. © 2015 Society for Endocrinology.

Assessing The Impact Of Cancer Therapies On Ovarian Reserve

PubMed Central

Gracia, Clarisa R.; Sammel, Mary D.; Freeman, Ellen; Prewitt, Maureen; Carlson, Claire; Ray, Anushree; Vance, Ashley; Ginsberg, Jill P.

2013-01-01

Objective To determine whether measures of ovarian reserve differ between females exposed to cancer therapies in a dose-dependent manner as compared to healthy controls of similar age and late-reproductive age. Design Cross-sectional analysis of data from a prospective cohort study Setting University Medical Center Patients 71 cancer survivors age 15-39; 67 healthy, similarly aged unexposed subjects; 69 regularly menstruating women of late-reproductive age (40-52 years). Interventions: None Main Outcome measures Early follicular phase hormones (FSH, Estradiol, Inhibin B, AMH) and ovarian ultrasound measurements (ovarian volume and Antral Follicle Counts) were compared using multivariable linear regression. Results In adjusted models, FSH, AMH and AFC differed between exposed vs. unexposed (FSH 11.12mIU/ml vs. 7.25mIU/ml, p=0.001; AMH 0.81ng/ml vs. 2.85ng/ml, p<0.001; AFC: 14.55 vs. 27.20, p<0.001. In participants with an FSH<10, survivors had lower levels of AMH and AFC compared to controls. Alkylating agent dose score was associated with increased levels of FSH (p= 0.016) and decreased levels of AMH (p=0.003). Exposure to pelvic radiation was associated with impairment in FSH, AMH, AFC and ovarian volume. AMH was similar in women previously exposed to high-dose cancer therapy and 40-42 year old controls. Conclusions Measures of ovarian reserve are impaired in a dose-dependent manner among cancer survivors compared to unexposed females of similar age. Reproductive hormone levels in menstruating survivors exposed to high-dose therapy are similar to late-reproductive women. The predictive value of measures for pregnancy and menopause must be studied. PMID:22137491

Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.

PubMed

Pogrmic-Majkic, Kristina; Samardzija, Dragana; Fa, Svetlana; Hrubik, Jelena; Glisic, Branka; Kaisarevic, Sonja; Andric, Nebojsa

2014-11-01

Premature luteinization is a possible cause of infertility in women. It is currently unknown whether environmental chemicals can induce changes associated with premature luteinization. Using rat granulosa cells (GC) in vitro, we demonstrated that exposure to atrazine (ATR), a widely used herbicide, causes GC phenotype that resembles that of human premature luteinization. At the end of the 48-h stimulation with FSH, ATR-exposed GC showed (1) higher levels of progesterone, (2) overexpression of luteal markers (Star and Cyp11a1), and (3) an increase in progesterone:estradiol ratio above 1. Mechanistic experiments were conducted to understand the signaling events engaged by ATR that lead to this phenotype. Western blot analysis revealed prolonged phosphorylation of protein kinase B (AKT) and cAMP response element-binding protein (CREB) in ATR- and FSH-exposed GC. An increased level of ERK1/2-dependent transcriptional factor CCATT/enhancer-binding protein beta (CEBPB) was observed after 4 h of ATR exposure. Inhibitors of PI3K (wortmannin) and MEK (U0126) prevented ATR-induced rise in progesterone level and expression of luteal markers in FSH-stimulated GC. Atrazine intensified AKT and CEBPB signaling and caused Star overexpression in forskolin-stimulated GC but not in epidermal growth factor (EGF)-stimulated GC. In the presence of rolipram, a specific inhibitor of phosphodiesterase 4 (PDE4), ATR was not able to further elevate AKT phosphorylation, CEBPB protein level, and Star mRNA in FSH-stimulated GC, suggesting that ATR inhibits PDE4. Overall, this study showed that ATR acts as a FSH sensitizer leading to enhanced cAMP, AKT, and CEBPB signaling and progesterone biosynthesis, which promotes premature luteinization phenotype in GC. © 2014 by the Society for the Study of Reproduction, Inc.

Anti-mullerian hormon level and polycystic ovarian syndrome diagnosis.

PubMed

Zadehmodarres, Shahrzad; Heidar, Zahra; Razzaghi, Zahra; Ebrahimi, Leili; Soltanzadeh, Kaveh; Abed, Farhang

2015-04-01

Polycystic ovarian syndrome (PCOS) is a common endocrinopathy that accompanied with long term complications. The early diagnosis of this syndrome can prevent it. The aim was to determine the role of anti-mullerian hormon (AMH) in PCOS diagnosis and to find cut off level of it. In this cross sectional study, 117 women between 20-40 years old were participated in two groups: 60 PCOS women (based on Rotterdam criteria consensus) as the case group and 57 normal ovulatory women as the control group. In day 2-4 of cycle, transvaginal sonography was performed and serum hormonal level of AMH, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), testosterone, fasting blood sugar (FBS), thyroid stimulating hormone (TSH), and prolactin (PRL) were measured in all of participants. For all of them score of hirsutism (base on Freeman-Galloway scoring) was determined. There were statistically significant in irregular pattern of menstruation, AMH and FSH level, and presence of hirsutism between two groups. But regarding mean of age, body mass index, plasma level of PRL, TSH, LH, Testosterone, FBS, and E2 differences were not significant. Construction by ROC curve present 3.15 ng/ml as AMH cut off with 70.37% sensitivity and 77.36% specificity in order to PCOS diagnosis. AMH with cut off level of 3.15 ng/ml with sensitivity 70.37% and specificity 77.36% could use for early diagnosis of PCOS patients.

A comparison of the efficacy of two doses of letrozole alone or with continuous recombinant follicle-stimulating hormone for ovulation induction in anovulatory women.

PubMed

Wang, Hai-Yan; Zheng, Peng-Sheng

2015-01-01

To determine the efficacy of letrozole alone or with recombinant follicle-stimulating hormone (rFSH) for ovarian induction in anovulatory women. A total of 322 patients undergoing intrauterine insemination (IUI) were included in this retrospective study. Letrozole (2.5 or 5.0 mg) was administered from days 5 to 9 of menses, alone or followed with rFSH started on day 9 until the day of human chorionic gonadotropin administration. A single IUI was performed 24 h after ovulation. The number of follicles, endometrial thickness and serum estradiol levels were significantly higher in the letrozole + rFSH groups than in the letrozole-alone groups (p < 0.05), but no significant difference was found between the two doses of letrozole, whether alone or with rFSH. Women treated with 5.0 mg/day of letrozole + rFSH required a total dose of rFSH similar to women treated with 2.5 mg/day of letrozole + rFSH (230.77 ± 118.29 vs. 258.55 ± 130.13 IU, respectively; p = 0.205). There was no significant difference in pregnancy rates between the two doses of letrozole, whether alone or with rFSH. Treatment with letrozole + rFSH was more efficacious than letrozole alone for pregnancy in the IUI program; however, the effect of 5.0 mg/day of letrozole versus 2.5 mg/day of letrozole on ovulation was equivalent, regardless of whether rFSH was used. © 2014 S. Karger AG, Basel.

Ovulation induction with pulsatile gonadotropin-releasing hormone (GnRH) or gonadotropins in a case of hypothalamic amenorrhea and diabetes insipidus.

PubMed

Georgopoulos, N A; Markou, K B; Pappas, A P; Protonatariou, A; Vagenakis, G A; Sykiotis, G P; Dimopoulos, P A; Tzingounis, V A

2001-12-01

Hypothalamic amenorrhea is a treatable cause of infertility. Our patient was presented with secondary amenorrhea and diabetes insipidus. Cortisol and prolactin responded normally to a combined insulin tolerance test (ITT) and thyrotropin-releasing hormone (TRH) challenge, while thyroid-stimulating hormone (TSH) response to TRH was diminished, and no response of growth hormone to ITT was detected. Both luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels increased following gonadotropin-releasing hormone (GnRH) challenge. No response of LH to clomiphene citrate challenge was detected. Magnetic resonance imaging findings demonstrated a midline mass occupying the inferior hypothalamus, with posterior lobe not visible and thickened pituitary stalk. Ovulation induction was carried out first with combined human menopausal gonadotropins (hMG/LH/FSH) (150 IU/day) and afterwards with pulsatile GnRH (150 ng/kg/pulse). Ovulation was achieved with both pulsatile GnRH and combine gonadotropin therapy. Slightly better results were achieved with the pulsatile GnRH treatment.

Clinical and metabolic characteristics of Turkish adolescents with polycystic ovary syndrome.

PubMed

Ates, Seda; Aydın, Serdar; Ozcan, Pinar; Soyman, Zeynep; Gokmen Karasu, Ayse Filiz; Sevket, Osman

2018-02-01

The aim of this study was to investigate the clinical, endocrine, metabolic features and prevalence of metabolic syndrome (MBS) in Turkish adolescents with polycystic ovary syndrome (PCOS) and the differences in metabolic parameters between adolescent PCOS with or without the presence of polycystic ovaries (PCO) on ultrasound. Subjects (n = 77) were classified into two groups: oligomenorrhea (O) and clinical and/or biochemical hyperandrogenism (HA) (n = 38), without PCO and O + HA with PCO (n = 39). The control group consisted of 33 age-matched adolescents. Adolescents with PCOS had a significantly higher body mass index (BMI), waist circumference and levels of LH, LH/FSH ratio, triglyceride, insulin, HOMA-IR, free androgen index and lower levels of SHBG and FSH. After adjustment for BMI, LH, LH: FSH ratio remained significantly higher. Adolescents with PCOS had a higher prevalence of MBS. No significant differences in lipid profiles, insulin levels and insulin sensitivity in both the PCOS groups were seen. HDL-C levels were lower in the O + HA + PCO group compared to the controls. BMI may be the major contributing factor in the development of metabolic abnormalities in adolescents with PCOS. Impact statement Many studies have investigated the effect of PCOS on metabolic and cardiovascular risks. It is thought that PCOS increases metabolic and cardiovascular risks. Increase in metabolic and cardiovascular risks associated with PCOS may be handled with early diagnosis and early intervention of PCOS in adolescents, although the diagnosis of PCOS in adolescents could be hard because of the features of PCOS overlapping normal pubertal physiological events. However, early identification of adolescent girls with PCOS may provide opportunities for prevention of well-known health risks associated with this syndrome and reduction of long-term health consequences of PCOS by reducing androgen levels and improving metabolic profile. Our results also support that BMI may be the major contributing factor in the development of metabolic abnormalities in adolescents with PCOS.

What is the optimum maximal gonadotropin dosage used in microdose flare-up cycles in poor responders?

PubMed

Berkkanoglu, Murat; Ozgur, Kemal

2010-07-01

To find out the optimum maximal dosage of recombinant follicle stimulating hormone (rFSH) in microdose gonadotropin-releasing hormone analog (GnRH-a) flare cycles in poor responders. Prospective randomized study. Private infertility clinic. A total of 119 women were taken into the study. The study group underwent a microdose protocol with a GnRH-agonist followed by rFSH administration. On the third day of GnRH-a administration, 119 patients were randomized in three groups to receive daily fixed doses of 300 IU of rFSH (group A, n = 38), or 450 IU of rFSH (group B, n = 39), or 600 IU of rFSH (group C, n = 42). Peak E(2) levels, days of stimulation with rFSH, total rFSH dosage, total number of oocytes retrieved, M2 oocytes retrieved, total number of embryos, number of embryos transferred, number of Grade-1 embryos transferred, clinical pregnancy rate (positive fetal cardiac activity), and cancellation rates of stimulation and embryo transfer. Clinical pregnancy rates were 13.1%, 15.3%, and 16.1% for group A, group B, and group C, respectively. There were no significant differences in the age, peak serum E(2) concentration, days of stimulation with rFSH, total number of M2 oocytes retrieved, number of embryos transferred, clinical pregnancy rates, and cancellation rates of stimulation and embryo transfer between the three groups except for total rFSH dosage. There is no need to use doses above 300 IU of rFSH to increase the pregnancy rate in microdose cycles. In addition, because the duration of stimulation does not differ between the groups, the usage of 300 IU rFSH in microdose cycles results in less total amount of rFSH consumed in a cycle compared with higher dosages, and this would obviously cost less money to the patients. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats.

PubMed

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women.

Follicle-Stimulating Hormone Regulates igfbp Gene Expression Directly or via Downstream Effectors to Modulate Igf3 Effects on Zebrafish Spermatogenesis

PubMed Central

Safian, Diego; van der Kant, Henk J. G.; Crespo, Diego; Bogerd, Jan; Schulz, Rüdiger W.

2017-01-01

Previous work showed that pharmacological inactivation of Igf-binding proteins (Igfbps), modulators of Igf activity, resulted in an excessive differentiation of type A undifferentiated (Aund) spermatogonia in zebrafish testis in tissue culture when Fsh was present in the incubation medium. Using this testis tissue culture system, we studied here the regulation of igfbp transcript levels by Fsh and two of its downstream effectors, Igf3 and 11-ketotestosterone (11-KT). We also explored how Fsh-modulated igfbp expression affected spermatogonial proliferation by adding or removing the Igfbp inhibitor NBI-31772 at different times. Fsh (100 ng/mL) decreased the transcript levels of igfbp1a, -3, and -6a after 1 or 3 days, while increasing igfbp2a and -5b expression, but only after 5 days of incubation. Igf3 down-regulated the same igfbp transcripts as Fsh but with a delay of at least 4 days. 11-KT increased the transcripts (igfbp2a and 5b) that were elevated by Fsh and decreased those of igfbp6a, as did Fsh, while 11-KT did not change igfbp1a or -3 transcript levels. To evaluate Igfbps effects on spermatogenesis, we quantified under different conditions the mitotic indices and relative section areas occupied by the different spermatogonial generations (type Aund, type A differentiating (Adiff), or type B (B) spermatogonia). Igf3 (100 ng/mL) increased the area occupied by Adiff and B while decreasing the one for Aund. Interestingly, a concentration of Igf3 that was inactive by itself (25 ng/mL) became active in the presence of the Igfbp inhibitor NBI-31772 and mimicked the effect of 100 ng/mL Igf3 on spermatogonia. Studies exploiting the different dynamics of igfbp expression in response to Fsh and adding or removing NBI-31772 at different times showed that the quick downregulation of three igfbp as well as the delayed upregulated of two igfbps all support Igf3 bioactivity, namely the stimulation of spermatogonial differentiation. We conclude that Fsh modulates, directly or via androgens and Igf3, igfbp gene expression, supporting Igf3 bioactivity either by decreasing igfbp1a, -3, -6a or by increasing igfbp2a and -5b gene expression. PMID:29209278

Serum immunoreactive inhibin levels in polycystic ovarian disease (PCOD) and hypogonadotropic amenorrhea.

PubMed

Mizunuma, H; Andoh, K; Obara, M; Yamaguchi, M; Kamijo, T; Hasegawa, Y; Ibuki, Y

1994-08-01

To evaluate the physiological significance of inhibin in various types of amenorrhea, serum immunoreactive (IR)-inhibin levels were measured and compared with those in normal cycling women. Amenorrheic women were as follows: (1) 23 women with PCOD, 11 women with hypogonadotropic amenorrhea (HA, n = 23) and 11 women with regular menstrual cycles. Women with HA were further divided into 2 groups according to the presence or absence of withdrawal bleeding (WDB) after progesterone administration. HA with WDB was categorized as HA1, while HA without as HA 2. Serum IR-inhibin levels in women with PCOD were significantly higher than those in HA 2 and normal women at days 2 to 5 from the onset of menstruation and significantly lower than those in normal women in the mid-luteal phase. A significant positive correlation was obtained between IR-inhibin and FSH in HA 2 (r = 0.681) and HA 1 (r = 0.658), but no significant correlation between these two hormones in PCOD and normal women. These results indicated that basal IR-inhibin levels vary with types of amenorrhea. High IR-inhibin levels in PCOD patients suggest that inhibin plays a part in the discordant gonadotropin secretion in these patients.

Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer.

PubMed

Stricker, Reto; Eberhart, Raphael; Chevailler, Marie-Christine; Quinn, Frank A; Bischof, Paul; Stricker, René

2006-01-01

During a normal menstrual cycle, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone can vary widely between cycles for the same woman, as well as between different woman. Reliable reference values based on the local population are important for correct interpretation of laboratory results. The purpose of our study was to determine detailed reference values for these hormones throughout the menstrual cycle using the Abbott ARCHITECT system. From 20 volunteers (age 20-36 years) with normal cycles and no use of oral contraceptives, samples were taken every day during their cycle. Volunteers received three vaginal ultrasound examinations (days 10 and 13, and 1 or 2 days after ovulation) to measure follicular and corpus luteum development. Hormone levels were measured using the corresponding ARCHITECT assay and were synchronized to the LH peak. Median, and 5th and 95th percentile values were determined for each day of the cycle, as well as for early follicular (days -15 to -6), late follicular (days -5 to -1), LH peak (day 0), early luteal (+1 to +4), mid-luteal (days +5 to +9), and late luteal (days +10 to +14) phases of the cycle. Based on our data, we were able to establish detailed reference values for LH, FSH, estradiol, and progesterone, which should aid in the interpretation of results for these reproductive hormones in a variety of circumstances.

Submaximal doses of ghrelin do not inhibit gonadotrophin levels but stimulate prolactin secretion in postmenopausal women.

PubMed

Messini, Christina I; Malandri, Maria; Anifandis, George; Dafopoulos, Konstantinos; Georgoulias, Panagiotis; Sveronis, Georgios; Garas, Antonios; Daponte, Alexandros; Messinis, Ioannis E

2017-07-01

An inhibitory effect of ghrelin on gonadotrophin secretion has been reported in normally menstruating women possibly modulated by endogenous oestrogen. The aim of this study was to examine the effect of ghrelin on gonadotrophin and prolactin (PRL) secretion in oestrogen-deprived postmenopausal women. Prospective intervention study. Ten healthy postmenopausal volunteer women were studied during two 15-days periods of oestrogen treatment (A and B) a month apart. Four experiments (Exp) were performed in total, two on day 1 (Exp 1A and Exp 1B) and two on day 15 (Exp 15A and Exp 15B) of the two periods. The women received in Exp 1A and in Exp 15A two iv injections of ghrelin (0.15 μg/kg at time 0 minute and 0.30 μg/kg at time 90 minutes) and in Exp1B and in Exp 15B normal saline (2 mL), respectively. Blood samples were taken at -15, 0, 30, 60, 90, 120, 150 and 180 minutes. After oestrogen treatment, late follicular phase serum oestradiol levels were attained on day 15 of periods A and B. Ghrelin administration did not affect serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), whereas it increased significantly those of growth hormone (GH) and PRL. In Exp 15A, serum PRL increment in response to ghrelin (area under the curve, net increment) was significantly greater than in Exp 1A (P<.05). This study demonstrates for the first time that in oestrogen-deprived postmenopausal women, ghrelin administration affects neither FSH nor LH levels but stimulates PRL secretion, that is amplified by exogenous oestrogen administration. © 2017 John Wiley & Sons Ltd.

Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders.

PubMed

Ecemis, Tolga; Tasci, Yasemin; Caglar, Gamze Sinem

2016-01-01

To investigate the effect of co-administration of letrozole in an ovarian stimulation protocol using recombinant FSH and GnRH antagonists for ICSI in normo/high responders. Computerized data of 320 antagonist ICSI/ET cycles with or without letrozole were retrospectively analyzed. In 105 cases, letrozole (5 mg/day) was started at the second day of the cycle continued for 5 days. At the second day of letrozole, gonadotropins were added. The remaining 215 cases were stimulated with recombinant FSH only. In all cases on day 6, GnRH antagonist was started. Ovarian stimulation protocols with or without letrozole were compared for cycle outcome parameters. In cycles with letrozole, significantly lower gonadotropin consumption and lower peak estradiol levels were found. In cycles with letrozole, mean number of metaphase II and fertilized oocytes retrieved were significantly higher compared to cycles without letrozole. The pregnancy and clinical pregnancy rates were similar. Should the number of oocytes retrieved being higher in letrozole group might indicate that letrozole might contribute to successful ovarian stimulation with a lower dosage of gonadotropins. Despite the lower peak estradiol levels, pregnancy rates being similar to other group also support the idea that letrozole can contribute to normal potential of implantation.

Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

PubMed

Bakas, Panagiotis; Boutas, Ioannis; Creatsa, Maria; Vlahos, Nicos; Gregoriou, Odysseas; Creatsas, George; Hassiakos, Dimitrios

2015-10-01

To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins. A total of 195 patients underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH) (50-150 IU/d). All patients were submitted upto three cycles of IUI. Primary outcome was the ability of AMH levels to predict clinical pregnancy at first attempt and the cumulative clinical pregnancy probability of upto three IUI cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity and basic estradiol levels with each other and the outcome of IUI. The area under the receiver operating characteristic (ROC) curve in predicting clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy rate at first attempt and with cumulative clinical pregnancy rate, but negatively correlated with patient's age and FSH levels. Patient's FSH, LH levels were negatively correlated with cumulative clinical pregnancy rate. AMH levels seem to have a positive correlation and patient's age and LH levels had a negative correlation with the outcome of IUI and COS with gonadotropins. AMH concentration was significantly higher and LH was significantly lower in patients with a clinical pregnancy after three cycles of IUI treatment compared with those who did not achieve pregnancy.

Alterations in gonadotropin secretion and ovarian function in prepubertal gilts by elevated environmental temperature.

PubMed

Flowers, B; Day, B N

1990-03-01

The effect of chronic exposure to elevated environmental temperature on gonadotropin secretion and ovarian function was studied in prepubertal gilts. Gilts were maintained under control (15.6 degrees C) or elevated temperature (33.3 degrees C) conditions from 150 to 180 days of age. Endocrine and ovarian responses to bilateral (BLO), unilateral (ULO), and sham ovariectomy were evaluated between 175 and 180 days of age. During the 96-h sampling period after BLO, plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were suppressed in heat-stressed females. Similarly, elevated temperatures abolished the transient rise in FSH and subsequent follicular growth normally associated with ULO. In contrast, environmental treatment had no effect on the secretion of FSH and LH after sham ovariectomy, yet the number of small follicles was lower in gilts exposed to elevated temperatures than in females maintained under control conditions. These results indicate that a chronic exposure to elevated environmental temperature during pubertal development diminished the ability of the hypothalamo-hypophyseal axis to secrete FSH and LH, which had physiological consequences on follicular growth. When provided an appropriate stimulus (ULO), an acute period of FSH secretion and subsequent development of follicles failed to occur in females exposed to elevated temperatures. Consequently, we propose that delayed puberty in gilts during periods of elevated environmental temperatures is due, in part, to a diminished capacity for gonadotropin secretion.

On the synergistic action of androgen and FSH on progestin secretion of cultured rat granulosa cells. Cellular and mitochondrial cholesterol metabolism.

PubMed

Nimrod, A

1981-01-01

The effect of FSH and androgen on the conversion of cholesterol into progesterone by cultured rat granulosa cells (GC) was studied in intact cells or mitochondrial preparations. Culture of GC for immature hypophysectomized diethylstilbestrol-treated rats for 48 h in the presence of ovine FSH (5 microgram/ml) alone, or FSH + testosterone (Te; 0.5 microgram/ml) caused a slight increase in the activity of the mitochondrial marker enzyme succinic dehydrogenase, while Te had no effect. Culture with the hormones for 48 h had no significant effect on the levels of free and esterified cellular cholesterol. GC monolayers after 48 h with or without FSH and Te converted [3H]cholesterol into 4 major metabolites, 3 of which were secreted into the medium and, in thin-layer chromatographic behavior, resembled pregnenolone, progesterone and 20 alpha-dihydroprogesterone. The total amount of the 3 C-21 steroids was higher (p less than 0.01) in FSH- or Te-treated than in control cells, and combined treatment had a synergistic effect. The uptake of labeled cholesterol (4--10%) was significantly higher (p less than 0.01) in cells pretreated with FSH or Te, whereas a combined FSH and Te treatment had an additive effect. Mitochondria isolated from GC monolayers took up cholesterol in a temperature-dependent fashion, but this uptake was not affected by hormonal pretreatment. In the presence of cyanoketone, the mitochondrial fractions activity converted cholesterol into pregnenolone. This activity was enhanced by FSH or Te (p less than 0.01), and further enhancement was observed with FSH + Te; the combined effect appeared to be more than additive (p = 0.05). The results suggest that both FSH and Te enhance the activity of cholesterol side-chain cleavage, but do not affect the transport of cholesterol into the mitochondria. A possible hormonal effect on a pre-mitochondrial step is discussed.

Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana

Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA.more » Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine prevents hCG-induced expression of the ovulatory genes. • ERK1/2 activation is required for atrazine action in granulosa cells. • Atrazine does not interfere with FSH-stimulated ERK1/2 phosphorylation.« less

Targeting of follicle stimulating hormone peptide-conjugated dendrimers to ovarian cancer cells

NASA Astrophysics Data System (ADS)

Modi, Dimple A.; Sunoqrot, Suhair; Bugno, Jason; Lantvit, Daniel D.; Hong, Seungpyo; Burdette, Joanna E.

2014-02-01

Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles.Ovarian cancer is the most lethal gynecological malignancy. Current treatment modalities include a combination of surgery and chemotherapy, which often lead to loss of fertility in premenopausal women and a myriad of systemic side effects. To address these issues, we have designed poly(amidoamine) (PAMAM) dendrimers to selectively target the follicle stimulating hormone receptor (FSHR), which is overexpressed by tumorigenic ovarian cancer cells but not by immature primordial follicles and other non-tumorigenic cells. Fluorescein-labeled generation 5 (G5) PAMAM dendrimers were conjugated with the binding peptide domain of FSH (FSH33) that has a high affinity to FSHR. The targeted dendrimers exhibited high receptor selectivity to FSHR-expressing OVCAR-3 cells, resulting in significant uptake and downregulation of an anti-apoptotic protein survivin, while showing minimal interactions with SKOV-3 cells that do not express FSHR. The selectivity of the FSH33-targeted dendrimers was further validated in 3D organ cultures of normal mouse ovaries. Immunostaining of the conjugates revealed their selective binding and uptake by ovarian surface epithelium (OSE) cells that express FSHR, while sparing the immature primordial follicles. In addition, an in vivo study monitoring tissue accumulation following a single intraperitoneal (i.p.) injection of the conjugates showed significantly higher accumulation of FSH33-targeted dendrimers in the ovary and oviduct compared to the non-targeted conjugates. These proof-of-concept findings highlight the potential of these FSH33-targeted dendrimers to serve as a delivery platform for anti-ovarian cancer drugs, while reducing their systemic side effects by preventing nonspecific uptake by the primordial follicles. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr05042d

Hot flushes and reproductive hormone levels during the menopausal transition.

PubMed

Dhanoya, Tanveer; Sievert, Lynnette Leidy; Muttukrishna, Shanthi; Begum, Khurshida; Sharmeen, Taniya; Kasim, Adetayo; Chowdhury, Osul; Bentley, Gillian R

2016-07-01

Evidence suggests that hot flushes are associated with fluctuating levels of oestradiol (E2) during menopause, as well as changes in the levels of follicle-stimulating hormone (FSH) and inhibin B. The relationship between hot flushes and anti-Müllerian hormone (AMH) is unknown. To examine specific hormone levels and ethnic differences in relation to hot flushes. Data were drawn from 108 women aged 40-59 years. There were three groups of participants: European women in London, UK; Bangladeshi women in Sylhet, Bangladesh; and Bangladeshi women who had migrated to London as adults. Symptom information was collected via questionnaires. Serum blood samples were collected to detect inhibin B, AMH, FSH, and E2. AMH and FSH were significantly associated with the experience of hot flushes in the past 2 weeks. Inhibin B and E2 were not associated with hot flushes. Body mass index (BMI), ethnicity, and education level were associated with both the occurrence and the frequency hot flushes. Menopausal status was also associated with the frequency of hot flushes. Relationships between AMH, FSH and symptoms are indicative of women's progress through the menopausal transition. The influence of BMI and education suggest that lifestyle changes may contribute to the management of symptoms. This merits further research. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

C-reactive protein and lipoprotein-a as markers of coronary heart disease in polycystic ovary syndrome.

PubMed

Güdücü, Nilgün; Işçi, Herman; Yiğiter, Alin Başgül; Dünder, Ilkkan

2012-01-01

The aim of this study was to investigate the risk factors of coronary heart disease, CRP and Lipoprotein-a in polycystic ovary syndrome patients. Prospectively collected data of polycystic ovary syndrome patients (n=62) and control group (n=40) were compared. PCOS patients had higher HOMA-IR, CRP, DHEAS, free testosterone, FAI, LH and prolactin levels when compared to the control group. Lipoprotein-a levels did not differ between the groups. The obese PCOS group had statistically significantly higher fasting blood glucose, total cholesterol, triglyceride, free testosterone, insulin, CRP and HOMA-IR and statistically significantly lower HDL and SHBG when compared to normal weight PCOS persons. Fasting blood glucose, total cholesterol, LDL, SHBG, CRP, Lipoprotein-a, FSH, LH, TSH, DHEAS and prolactin levels did not differ between the normal weight and obese control groups. CRP levels increase in polycystic ovary syndrome patients and can be used as a marker of coronary heart disease. Future studies can be directed at treatments to decrease CRP levels, including antiinflammatory treatments.

Effect of ethanolic extract of Lepidium meyenii Walp on serum hormone levels in ovariectomized rats

PubMed Central

Zhang, Yongzhong; Yu, Longjiang; Jin, Wenwen; Ao, Mingzhang

2014-01-01

Objective: To evaluate the effect of long-term ethanol extract of Lepidium meyenii (Maca) on serum hormone levels in ovariectomized (OVX) rats and compare them with the effect of diethylstilbestrol. Materials and Methods: Fifty female Sprague-Dawley rats were ovariectomized or sham operated. Both sham and OVX control groups (n = 10, respectively) received the vehicle. The remaining OVX rats were oral administrated with ethanol extract of Maca (0.096, or 0.24g/kg; n = 10, respectively) and diethylstilbestrol (0.05 mg/kg; n = 10). The treatment continued for 28 weeks. At week 12 and week 28, the blood of rats was collected and serum hormone levels, including estradiol (E2), testosterone (T) and follicle-stimulating hormone (FSH) were measured by radioimmunoassay. Results: At week 12, the levels of serum E2 were slightly higher in Maca groups than that in OVX group; T levels were significantly decreased; and FSH levels were advanced slightly in Maca groups than that in sham group. After 28 weeks administration, serum E2 levels in Maca-treated animals did not differ significantly from sham control, the low dose of Maca increased serum E2 levels, and Maca prevented increase in serum FSH levels compared with OVX group. Conclusions: Long-term Maca supply modulates endocrine hormone balance in OVX rats, especially it decreases enhanced FSH levels. It is proposed that Maca may become a potential choice for postmenopausal women. PMID:25097281

Effect of caricapryl-99 seed alkaloid extract on the serum levels of sex hormones and pituitary gonadotrophins in male albino rats.

PubMed

Udoh, P B; Udoh, F V; Umoren, E B; James, U W; Okeke, C P; Agwu, B

2009-06-01

Activity of alkaloid extract of caricapryl-99 seeds [Carica papaya Linn seeds] on the serum levels of steroid hormones was studied in adult male albino rats. Three tolerated doses obtained from the graph of percentage toxicity [10, 50 and 150 mg/kg] were separately administered orally, daily for three days to three groups of male rats [n=5] while group four of 5 rats received the vehicle [corn oil] as control. The results showed that 10 mg/kg/d caused increase serum levels of FSH and estrogen but decrease in the serum levels of LH and testosterone compared to control; 50 mg/kg/d elevated the serum levels of FSH, estrogen but inhibited testosterone; while 150 mg/kg/d pretreatments caused a significant decrease [p<0.01] in the serum levels of FSH, LH and testosterone. The results suggest that caricapryl-99 treatment inhibited the serum level of the androgen, testosterone which might result in a male infertility.

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

PubMed

Ou-Yang, Li-Xue; Yang, Fan

2017-07-01

To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

FSH (Follicle-Stimulating Hormone) Test

MedlinePlus

... Time and International Normalized Ratio (PT/INR) PSEN1 Quantitative Immunoglobulins Red Blood Cell (RBC) Antibody Identification Red ... National Institutes of Health Office of Rare Diseases Research. Klinefelter Syndrome. Available online at http://rarediseases.info. ...

Altered ovarian function affects skeletal homeostasis independent of the action of follicle-stimulating hormone.

PubMed

Gao, Jianjun; Tiwari-Pandey, Rashmi; Samadfam, Rana; Yang, Yinzhi; Miao, Dengshun; Karaplis, Andrew C; Sairam, M Ram; Goltzman, David

2007-06-01

Osteoporosis is a leading public health problem. Although a major cause in women is thought to be a decline in estrogen, it has recently been proposed that FSH or follitropin is required for osteoporotic bone loss. We examined the FSH receptor null mouse (FORKO mouse) to determine whether altered ovarian function could induce bone loss independent of FSH action. By 3 months of age, FORKO mice developed age-dependent declines in bone mineral density and trabecular bone volume of the lumbar spine and femur, which could be partly reversed by ovarian transplantation. Bilateral ovariectomy reduced elevated circulating testosterone levels in FORKO mice and decreased bone mass to levels indistinguishable from those in ovariectomized wild-type controls. Androgen receptor blockade and especially aromatase inhibition each produced bone volume reductions in the FORKO mouse. The results indicate that ovarian secretory products, notably estrogen, and peripheral conversion of ovarian androgen to estrogen can alter bone homeostasis independent of any bone resorptive action of FSH.

Effects of environmental lead pollution on blood lead and sex hormone levels among occupationally exposed group in an E-waste dismantling area.

PubMed

Yang, Yan; Lu, Xiao Song; Li, Ding Long; Yu, Yun Jiang

2013-06-01

To study the effects of environmental multi-media lead pollution on blood lead and sex hormone levels among lead exposed males engaged in E-waste dismantling, and the correlation between confounding factors and sex hormone levels. An E-waste dismantling area in Taizhou of Zhejiang Province was selected as the research site. One hundred and fifty two samples were collected from the groundwater, soil, rice, corn, chicken, and pork in the dismantling area. The effects of the multi-media lead pollution on the male blood lead and sex hormone levels of FSH, LH, and T, as well as the correlation with confounding factors, were studied. The blood lead concentrations in the males aged under 31, from 31 to 45 and from 46 to 60 were 98.55, 100.23, and 101.45 μg/L, respectively. Of all the environmental media lead exposures, the groundwater, rice and soil were main contributing factors to the lead accumulation in humans. FSH and LH levels increased with the age while the T levels decreased with the age instead. There was a significant correlation between the FSH and LH levels and wearing masks. There was correlation between the FSH, LH, and T levels, and the mean values of lead concentrations in environmental media, and the sex hormone levels were correlated with the confounding factor of wearing masks. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Testicular growth and development in puberty.

PubMed

Koskenniemi, Jaakko J; Virtanen, Helena E; Toppari, Jorma

2017-06-01

To describe pubertal testicular growth in humans, changes in testicular cell populations that result in testicular growth, and the role of testosterone and gonadotrophins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in testicular growth. When human data were not available, studies in nonhuman primates and/or rodents were used as surrogates. Testicular growth in puberty follows a sigmoidal growth curve, with a large variation in timing of testicular growth and adult testicular volume. Testicular growth early in puberty is due to increase in Sertoli cell number and length of seminiferous tubules, whereas the largest and fastest growth results from the increase in the diameter of the seminiferous tubules first due to spermatogonial proliferation and then due to the expansion of meiotic and haploid germ cells. FSH stimulates Sertoli cell and spermatogonial proliferation, whereas LH/testosterone is mandatory to complete spermatogenesis. However, FSH and LH/testosterone work in synergy and are both needed for normal spermatogenesis. Testicular growth during puberty is rapid, and mostly due to germ cell expansion and growth in seminiferous tubule diameter triggered by androgens. Pre-treatment with FSH before the induction of puberty may improve the treatment of hypogonadotropic hypogonadism, but remains to be proven.

Assessment of protective and anti-oxidant properties of Tribulus terrestris fruits against testicular toxicity in rats.

PubMed

Shalaby, Mostafa Abbas; Hammouda, Ashraf Abd El-Khalik

2014-01-01

This study was carried out to assess the protective and anti-oxidant activities of the methanolic extract of Tribulus terrestris fruits (METT) against sodium valproate (SVP)-induced testicular toxicity in rats. Fifty mature male rats were randomly divided into five equal groups (n = 10). Group 1 was used normal (negative) control, and the other four groups were intoxicated with SVP (500 mg/kg(-1), orally) during the last week of the experiment. Group 2 was kept intoxicated (positive) control, and Groups 3, 4 and 5 were orally pre-treated with METT in daily doses 2.5, 5.0, and 10.0 mg/kg(-1) for 60 days, respectively. Weights of sexual organs, serum testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, semen picture, testicular anti-oxidant capacity and histopathology of testes were the parameters used in this study. Oral pre-treatment with METT significantly increased weights of testes and seminal vesicles; serum testosterone, FSH and LH levels and sperm motility, count and viability in SVP-intoxicated rats. METT enhanced the activity of testicular anti-oxidant enzymes and partially alleviated degenerative changes induced by SVP in testes. The pre-treatment with METT has protective and anti-oxidant effects in SVP-intoxicated rats. Mechanisms of this protective effect against testicular toxicity may be due to the increased release of testosterone, FSH and LH and the enhanced tissue anti-oxidant capacity. These results affirm the traditional use of T. terrestris fruits as an aphrodisiac for treating male sexual impotency and erectile dysfunction in patients. The study recommends that T. terrestris fruits may be beneficial for male patients suffering from infertility.

Assessment of protective and anti-oxidant properties of Tribulus terrestris fruits against testicular toxicity in rats

PubMed Central

Shalaby, Mostafa Abbas; Hammouda, Ashraf Abd El-Khalik

2014-01-01

Aims: This study was carried out to assess the protective and anti-oxidant activities of the methanolic extract of Tribulus terrestris fruits (METT) against sodium valproate (SVP)-induced testicular toxicity in rats. Materials and Methods: Fifty mature male rats were randomly divided into five equal groups (n = 10). Group 1 was used normal (negative) control, and the other four groups were intoxicated with SVP (500 mg/kg–1, orally) during the last week of the experiment. Group 2 was kept intoxicated (positive) control, and Groups 3, 4 and 5 were orally pre-treated with METT in daily doses 2.5, 5.0, and 10.0 mg/kg–1 for 60 days, respectively. Weights of sexual organs, serum testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels, semen picture, testicular anti-oxidant capacity and histopathology of testes were the parameters used in this study. Results: Oral pre-treatment with METT significantly increased weights of testes and seminal vesicles; serum testosterone, FSH and LH levels and sperm motility, count and viability in SVP-intoxicated rats. METT enhanced the activity of testicular anti-oxidant enzymes and partially alleviated degenerative changes induced by SVP in testes. Conclusion: The pre-treatment with METT has protective and anti-oxidant effects in SVP-intoxicated rats. Mechanisms of this protective effect against testicular toxicity may be due to the increased release of testosterone, FSH and LH and the enhanced tissue anti-oxidant capacity. These results affirm the traditional use of T. terrestris fruits as an aphrodisiac for treating male sexual impotency and erectile dysfunction in patients. The study recommends that T. terrestris fruits may be beneficial for male patients suffering from infertility. PMID:26401358

Combined pituitary hormone deficiency in german shepherd dogs with dwarfism.

PubMed

Kooistra, H S; Voorhout, G; Mol, J A; Rijnberk, A

2000-10-01

In German shepherd dogs pituitary dwarfism is known as an autosomal recessive inherited abnormality. To investigate whether the function of cells other than the somatotropes may also be impaired in this disease, the secretory capacity of the pituitary anterior lobe (AL) cells was studied by a combined pituitary AL stimulation test with four releasing hormones (4RH test) in four male and four female German shepherd dwarfs. In addition, the morphology of the pituitary was investigated by computed tomography. The physical features of the eight German shepherd dwarfs were primarily characterized by growth retardation and stagnant development of the hair coat. The results of the 4RH test confirmed the presence of hyposomatotropism. The basal plasma TSH and prolactin concentrations were also low and did not change upon stimulation. Basal plasma concentrations of LH were relatively low and responded only slightly to suprapituitary stimulation. With respect to the plasma FSH levels there was a clear gender difference. In the males plasma FSH concentrations remained below the detection limit throughout the 4RH test, whereas in the females the basal plasma FSH levels were slightly lower and there was only a small increase following suprapituitary stimulation, compared with the values in age-matched controls. In contrast, basal and stimulated plasma ACTH concentrations did not differ between the dwarfs and the controls. Computed tomography of the pituitary fossa revealed a normal sized pituitary with cysts in five dogs, an enlarged pituitary with cysts in two dogs, and a small pituitary gland without cysts in the remaining dog. The results of this study demonstrate that German shepherd dwarfs have a combined deficiency of GH, TSH, and prolactin together with impaired release of gonadotropins, whereas ACTH secretion is preserved. The combined pituitary hormone deficiency is associated with cyst formation and pituitary hypoplasia.

Disruption of Zebrafish Follicle-Stimulating Hormone Receptor (fshr) But Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males.

PubMed

Zhang, Zhiwei; Lau, Shuk-Wa; Zhang, Lingling; Ge, Wei

2015-10-01

Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH-β genes (fshb and lhb) using transcription activator-like effector nuclease (TALEN) technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the primary growth-previtellogenic transition, which is the marker for puberty onset in females. Interestingly, after blockade at the primary growth stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of the lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of the fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.

Clinical application of a nomogram based on age, serum FSH and AMH to select the FSH starting dose in IVF/ICSI cycles: a retrospective two-centres study.

PubMed

Papaleo, Enrico; Zaffagnini, Stefano; Munaretto, Maria; Vanni, Valeria Stella; Rebonato, Giorgia; Grisendi, Valentina; Di Paola, Rossana; La Marca, Antonio

2016-12-01

To externally validate a nomogram based on ovarian reserve markers as a tool to optimize the FSH starting dose in IVF/ICSI cycles. A two-centres retrospective study including 398 infertile women undergoing their first IVF/ICSI cycle (June 2013-June 2014). IVF data were retrieved from two independent IVF centres in Italy (San Raffaele Hospital, Centre 1; Verona Hospital, Centre 2). A central lab for the routine measurement of AMH and FSH was used for both centres. All women were treated based on physical and hormonal characteristics according to locally adopted protocols. The nomogram was then retrospectively applied to the patients comparing the calculated starting dose to the one actually given. In Centre 1, 64/131 women (48.8%) had an ovarian response below the target. While 45 of these patients were treated with a maximal FSH starting dose (≥225 IU), n=19/131 (14.5%) were treated with a submaximal dose. The vast majority of them (n=17/19) would have received a higher FSH starting dose by using the nomogram. Seventeen patients (n=17/131) had hyper response and about half of them would have been treated with a reduced FSH starting dose according to the nomogram. In Centre 2, 142/267 patients (53.2%) had an ovarian response below the target. While 136 of these were treated with a maximal FSH starting dose (≥225 IU), n=6/267 were treated with a submaximal dose. The majority of them (n=5/6) would have received a higher FSH starting dose. Thirty-two (n=32/267) patients had hyper response and more than half of them would have been treated with a reduced FSH dose. In both Centres, applying the nomogram would have resulted in more appropriate FSH starting doses compared to the the ones actually given based on clinicians choices. The use of an objective algorithm based on patient's age, serum FSH and AMH levels may thus be an effective advice on the selection of the tailored FSH starting dose. Hence, the use of this easily available nomogram could increase the proportion of patients achieving the optimal ovarian response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gynaecomastia complicating the treatment of myeloma.

PubMed Central

Large, D. M.; Jones, J. M.; Shalet, S. M.; Scarffe, J. H.; Gibbs, A. C.

1983-01-01

The hormonal mechanisms involved in the development of gynaecomastia accompanying the treatment of multiple myeloma in adult men have been investigated by studying levels of circulating testosterone (T), oestrone (EI), oestradiol (E2), sex-hormone binding globulin (SHBG), prolactin (PRL) and the gonadotrophins LH and FSH, before, during and after development of gynaecomastia in 4 men. These have been compared with 5 closely matched men who did not develop gynaecomastia during similar treatment for myeloma. Levels of circulating T fell, and levels of E1 and E2 rose during treatment periods in all subjects, and the changes were statistically significant in subjects developing gynaecomastia, which resolved as levels of sex steroid returned towards normal following cessation of treatment. We conclude that treatment of adult men for myeloma results in testicular dysfunction with a reduction in circulating T and a rise in circulating oestrogens. These changes are most marked in subjects developing gynaecomastia in whom the normal breast tissue is stimulated by a subtle, transient oestrogen:androgen imbalance in favour of oestrogens. PMID:6409138

Sexually dimorphic expression of gonadotropin subunits in the pituitary of protogynous honeycomb grouper (Epinephelus merra): evidence that follicle-stimulating hormone (FSH) induces gonadal sex change.

PubMed

Kobayashi, Yasuhisa; Alam, Mohammad Ashraful; Horiguchi, Ryo; Shimizu, Akio; Nakamura, Masaru

2010-06-01

Recent studies have suggested that the hypothalamic-pituitary-gonadal axis is involved in gonadal sex change in sex-changing teleosts. However, its underlying mechanism remains largely unknown. In this study, we focused on the distinct roles of two gonadotropins (GTHs), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), in the protogynous hermaphrodite teleost, honeycomb grouper (Epinephelus merra). First, we investigated the expression pattern of mRNAs for GTH subunits (cga, fshb, and lhb) in the pituitaries from fish at the different sexual phases. Real-time RT-PCR analyses showed that fhsb mRNA levels in the female pituitary were low. However, fshb transcripts increased dramatically in association with testis development. In contrast, levels of cga and lhb mRNAs did not significantly vary during sex change. In addition, immunohistochemical observations of Fshb- and Lhb-producing cells in the pituitary, through the use of specific antibodies for detections of teleost GTH subunits, were consistent with sexually dimorphic expression of Fshb. In order to identify the role of GTH in gonad of honeycomb grouper, we treated females with bovine FSH (50 or 500 ng/fish) or LH (500 ng/fish) in vivo. After 3 wk, FSH treatments induced female-to-male sex change and up-regulated endogenous androgen levels and fshb transcripts, whereas LH treatment had no effect on sex change. These results suggest that FSH may trigger the female-to-male sex change in honeycomb grouper.

Endocrine antecedents of polycystic ovary syndrome (PCOS) in fetal and infant prenatally androgenized female rhesus monkeys

PubMed Central

Abbott, David H; Barnett, Deborah K; Levine, Jon E; Padmanabhan, Vasantha; Dumesic, Daniel A; Jacoris, Steve; Tarantal, Alice F

2008-01-01

Experimentally induced fetal androgen excess induces polycystic ovary syndrome (PCOS)-like traits in adult female rhesus monkeys. Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily subcutaneous injections of 15 mg testosterone propionate (TP) and six received injections of oil vehicle (controls) from 40 through 80 days of gestation (term 165 [range: ±10] days), and all fetuses were delivered by Cesarean-section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH. TP injections elevated serum testosterone and androstenedione levels in the dams and prenatally androgenized (PA) fetuses. After cessation of TP injections, testosterone levels mostly normalized, while serum androstenedione levels in PA infants were elevated. TP injections did not increase estrogen levels in the dams, PA fetuses and infants, yet conjugated estrogen levels were elevated in the TP-injected dams. Serum levels of LH and FSH were elevated in late gestation PA fetuses, and LH levels were elevated in PA infants. These studies suggest that experimentally-induced fetal androgen excess increases gonadotropin secretion in PA female fetuses and infants, and elevates endogenous androgen levels in PA infants. Thus, in this nonhuman primate model, differential programming of the fetal hypothalamo-pituitary unit with concomitant hyperandrogenism provides evidence to suggest developmental origins of LH and androgen excess in adulthood. PMID:18385445

[Low-dose desmopressin (DDAVP) and blood levels of FSH, LH and testosterone in men].

PubMed

García-Pascual, I J; Rozán Flores, M A

1996-03-01

The effect of desmopressin (DDAVP) administration (2.5 micrograms/12 hours) on serum concentrations of FSH, LH and testosterone was studied in six men. No significant changes were observed in serum concentrations of FSH and LH after 9 days with DDAVP therapy. Nevertheless, serum concentrations of testosterone after 12 hours of DDAVP administration were significantly higher than basal concentrations. Three hours after the administration of DDAVP, serum testosterone concentrations decreased significantly. The conclusion reached was that low doses of desmopressin do not change serum concentrations of FSH and LH, but serum concentration of testosterone is decreased within three hours after the administration, although an increase is observed 12 hours later possibly due to a "rebound effect". Desmopressin would therefore directly act upon human testicle.

Constitution and behavior of follicular structures in the human anterior pituitary gland.

PubMed Central

Ciocca, D. R.; Puy, L. A.; Stati, A. O.

1984-01-01

The follicular structures present in the human pituitary gland were studied, at the light-microscopic level, using histochemical and immunocytochemical techniques. The antisera applied in the peroxidase-antiperoxidase procedure were anti-hFSH beta, anti-hLH beta, anti-hPRL, anti-hGH, anti-hTSH beta, anti-hLPH beta, anti-pACTH, and anti-hACTH. In the 10 normal pituitaries examined, follicles were always found in the three areas of the adenohypophysis. The wall of the pars distalis follicles showed the seven immunoreactive cell types studied, while follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells were the only ones present in the wall of the pars tuberalis follicles. Most of the cell types studied were also present in the wall of the intermediate area follicles, but these follicles had characteristics not found in the other two areas. They were very large, with frequent interconnections forming a three-dimensional network of anastomotic cavities, and the colloid had different histochemical affinity. None of the hormones studied could be detected by immunocytochemistry within the follicular colloid. Three of the ten pituitary adenomas examined showed numerous follicular structures. Some of the follicles in the adenomatous pituitaries were similar to those found in the normal adenohypophysis, but there were also follicles filled with only traces of colloid and numerous blood cells in the cavity, and follicles filled with neoformed connective tissue. In one of these cases, FSH/LH immunoreactive adenoma cells were seen in the wall of the follicles. The results obtained suggest that the finding of pituitary adenomas with follicular structures is not uncommon and that the follicles originate from the tumor cells. In addition, the follicles seem to have several functional stages, explaining the finding of different types of follicular formation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 PMID:6326578

Shortened estrous cycle length, increased FSH levels, FSH variance, oocyte spindle aberrations, and early declining fertility in aging senescence-accelerated mouse prone-8 (SAMP8) mice: concomitant characteristics of human midlife female reproductive aging.

PubMed

Bernstein, Lori R; Mackenzie, Amelia C L; Kraemer, Duane C; Morley, John E; Farr, Susan; Chaffin, Charles L; Merchenthaler, István

2014-06-01

Women experience a series of specific transitions in their reproductive function with age. Shortening of the menstrual cycle begins in the mid to late 30s and is regarded as the first sign of reproductive aging. Other early changes include elevation and increased variance of serum FSH levels, increased incidences of oocyte spindle aberrations and aneuploidy, and declining fertility. The goal of this study was to investigate whether the mouse strain senescence-accelerated mouse-prone-8 (SAMP8) is a suitable model for the study of these midlife reproductive aging characteristics. Midlife SAMP8 mice aged 6.5-7.85 months (midlife SAMP8) exhibited shortened estrous cycles compared with SAMP8 mice aged 2-3 months (young SAMP8, P = .0040). Midlife SAMP8 mice had high FSH levels compared with young SAMP8 mice, and mice with a single day of high FSH exhibited statistically elevated FSH throughout the cycle, ranging from 1.8- to 3.6-fold elevation on the days of proestrus, estrus, metestrus, and diestrus (P < .05). Midlife SAMP8 mice displayed more variance in FSH than young SAMP8 mice (P = .01). Midlife SAMP8 ovulated fewer oocytes (P = .0155). SAMP8 oocytes stained with fluorescently labeled antitubulin antibodies and scored in fluorescence microscopy exhibited increased incidence of meiotic spindle aberrations with age, from 2/126 (1.59%) in young SAMP8 to 38/139 (27.3%) in midlife SAMP8 (17.2-fold increase, P < .0001). Finally, SAMP8 exhibited declining fertility from 8.9 pups/litter in young SAMP8 to 3.5 pups/litter in midlife SAMP8 mice (P < .0001). The age at which these changes occur is younger than for most mouse strains, and their simultaneous occurrence within a single strain has not been described previously. We propose that SAMP8 mice are a model of midlife human female reproductive aging.

A clinical trial of injectable testosterone undecanoate as a potential male contraceptive in normal Chinese men.

PubMed

Zhang, G Y; Gu, Y Q; Wang, X H; Cui, Y G; Bremner, W J

1999-10-01

This is a pilot dose-finding study of spermatogenic suppression using testosterone undecanoate (TU) injections alone in normal Chinese men. Thirty-two healthy men were recruited. Volunteers underwent pretreatment evaluation, then a treatment period in which group I (n = 13) received 500 mg TU, group II (n = 12) received 1000 mg TU, and group III (n = 7) received placebo, respectively, at monthly intervals during the treatment period (or until azoospermia was achieved). Thereafter, they underwent a recovery period until all parameters returned to pretreatment levels. Eleven of 12 volunteers in the 500-mg TU group, and all volunteers in the 1000-mg TU group became azoospermic. Faster suppression of spermatogenesis was achieved in the 1000-mg TU group. Serum testosterone increased significantly in the higher dose group at weeks 8 and 12, but remained within the normal range. Mean serum LH and FSH were profoundly suppressed by both doses to undetectable levels at week 16. TU injections did not cause a significant change in high density lipoprotein cholesterol levels. No serious side-effects were found. We conclude that both dosages of TU can effectively, safely, and reversibly suppress spermatogenesis in normal Chinese men.

[A case of multiple sclerosis with hypothalamic amenorrhea].

PubMed

Miyamoto, T; Miyamoto, M; Yokota, N; Kubo, J; Hirata, K

2000-03-01

We present a 31-year-old woman of multiple sclerosis. At age 28, she was admitted with complaints of echolalia and a gradual onset of weakness affecting the right upper and bilateral lower limbs. Brain MRI showed high intensity areas in the bilateral frontal gyri, lobuli paracentralis, and left anterior thalamus. Although she had been in remission for 3 years, she developed dysesthesia of left upper and lower limbs. Cervical T2 weighted MRI showed a new high signal intensity lesion in the spinal cord from the C2 to C3 level. The combination of the cerebral, thalamic and spinal cord lesions with remission and excerbations allowed the diagnosis of clinically MS to be made. She suffered amenorrhea from the onset of her illness. Serum prolactin was within the normal range. The LH and FSH basal secretions were decreased and there were low delayed secretions of LH and FSH after intravenous injection of 100 micrograms LHRH. We consider that her amenorrhea was caused by the hypothalamic lesion, supported by MR findings of dilatation of the third ventricle.

Probable gamma-aminobutyric acid involvement in bisphenol A effect at the hypothalamic level in adult male rats.

PubMed

Cardoso, Nancy; Pandolfi, Matías; Lavalle, Justina; Carbone, Silvia; Ponzo, Osvaldo; Scacchi, Pablo; Reynoso, Roxana

2011-12-01

The aim of the present study was to investigate the effects of bisphenol A (BPA) on the neuroendocrine mechanism of control of the reproductive axis in adult male rats exposed to it during pre- and early postnatal periods. Wistar mated rats were treated with either 0.1% ethanol or BPA in their drinking water until their offspring were weaned at the age of 21 days. The estimated average dose of exposure to dams was approximately 2.5 mg/kg body weight per day of BPA. After 21 days, the pups were separated from the mother and sacrificed on 70 day of life. Gn-RH and gamma-aminobutyric acid (GABA) release from hypothalamic fragments was measured. LH, FSH, and testosterone concentrations were determined, and histological and morphometrical studies of testis were performed. Gn-RH release decreased significantly, while GABA serum levels were markedly increased by treatment. LH serum levels showed no changes, and FSH and testosterone levels decreased significantly. Histological studies showed abnormalities in the tubular organization of the germinal epithelium. The cytoarchitecture of germinal cells was apparently normal, and a reduction of the nuclear area of Leydig cells but not their number was observed. Taken all together, these results provide evidence of the effect caused by BPA on the adult male reproductive axis when exposed during pre- and postnatal period. Moreover, our findings suggest a probable GABA involvement in its effect at the hypothalamic level.

Differential regulation of luteinizing hormone and follicle-stimulating hormone expression during ovarian development and under sexual steroid feedback in the European eel.

PubMed

Schmitz, Monika; Aroua, Salima; Vidal, Bernadette; Le Belle, Nadine; Elie, Pierre; Dufour, Sylvie

2005-01-01

Pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are, in teleosts as in mammals, under the control of hypothalamic factors and steroid feedbacks. In teleosts, feedback regulations largely vary depending on species and physiological stage. In the present study the regulation of FSH and LH expression was investigated in the European eel, a fish of biological and phylogenetical interest as a representative of an early group of teleosts. The eel FSHbeta subunit was cloned, sequenced and together with earlier isolated eel LHbeta and glycoprotein hormone alpha (GPalpha) subunits used to study the differential regulation of LH and FSH. In situ hybridization indicated that FSHbeta and LHbeta are expressed by separate cells of the proximal pars distalis of the adenohypophysis, differently from the situation in mammals. The profiles of LHbeta and FSHbeta subunit expression were compared during experimental ovarian maturation, using dot-blot assays. Expression levels for LHbeta and GPalpha increased throughout ovarian development with a positive correlation between these two subunits. Conversely, FSHbeta mRNA levels decreased. To understand the role of sex steroids in these opposite variations, immature eels were treated with estradiol (E2)and testosterone (T), both steroids being produced in eel ovaries during gonadal development. E2 treatment induced increases in both LHbeta and GPalpha mRNA levels, without any significant effect on FSHbeta. In contrast, T treatment induced a decrease in FSHbeta mRNA levels, without any significant effect on the other subunits. These data demonstrate that steroids exert a differential feedback on eel gonadotropin expression, with an E2-specific positive feedback on LH and a T-specific negative feedback on FSH, leading to an opposite regulation of LH and FSH during ovarian development. Copyright 2005 S. Karger AG, Basel

The Pregnancy in Polycystic Ovary Syndrome Study II: Baseline Characteristics and Effects of Obesity from a Multi-Center Randomized Clinical Trial

PubMed Central

Legro, Richard S.; Brzyski, Robert G.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Alvero, Ruben; Casson, Peter; Christman, Gregory M.; Huang, Hao; Yan, Qingshang; Haisenleder, Daniel J.; Barnhart, Kurt T.; Bates, G. Wright; Usadi, Rebecca; Lucidi, Richard; Baker, Valerie; Trussell, J.C.; Krawetz, Stephen A.; Snyder, Peter; Ohl, Dana; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2014-01-01

Objective To summarize baseline characteristics from a large multi-center infertility clinical trial. Design Cross-sectional baseline data from a double-blind randomized trial of 2 treatment regimens (letrozole vs. clomiphene). Setting Academic Health Centers throughout the U.S. Interventions None Main Outcome Measure(s) Historical, biometric, biochemical and questionnaire parameters. Participants 750 women with PCOS and their male partners took part in the study. Results Females averaged ~30 years old and were obese (BMI 35) with ~20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). . Most of the females had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH:FSH ratio (~2), and AMH levels (8.0 ng/mL). Additionally, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH:FSH levels, AMH levels and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Males were obese (BMI 30) and had normal mean semen parameters. Conclusions The treatment groups were well-matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators. PMID:24156957

Impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in premenopausal HIV infected females at NAUTH, Nnewi, Nigeria

PubMed Central

Emelumadu, Obiageli Fidelia; Igwegbe, Anthony Osita; Monago, Ifeoma Nwamaka; Ilika, Amobi Linus

2017-01-01

Background This was a prospective study designed to evaluate the impact of thyroid function abnormalities on reproductive hormones during menstrual cycle in HIV infected females at Nnamdi Azikiwe University Teaching Hospital Nnewi, South-East Nigeria. Methods The study randomly recruited 35 Symptomatic HIV infected females and 35 Symptomatic HIV infected females on antiretroviral therapy (HAART) for not less than six weeks from an HIV clinic and 40 apparently heathy control females among the hospital staff of NAUTH Nnewi. They were all premenopausal females with regular menstrual cycle and aged between 15–45 years. Blood samples were collected at follicular and luteal phases of their menstrual cycle for assay of Thyroid indices (FT3, FT4 and TSH) and Reproductive indices (FSH, LH, Estrogen, Progesterone, Prolactin and Testosterone) using ELISA method. Results The result showed significantly higher FSH and LH but significantly lower progesterone (prog) and estrogen (E2) in the test females compared to control females at both phases of menstrual cycle (P<0.05). There was significantly lower FT3 but significantly higher TSH value in Symptomatic HIV females (P<0.05). FSH, LH and TSH values were significantly lowered while prog and FT3 were significantly higher in Symptomatic HIV on ART compared to Symptomatic HIV females (P<0.05). FT3, FT4, Prog and E2 were inversely correlated while FSH and LH were positively correlated with duration of HIV infection in HIV females (P<0.05 respectively). There was a direct correlation between CD4+ count and FT3 while inverse correlation was found between CD4+ count and TSH levels (P<0.05). Discussion The present study demonstrated hypothyroidism with a significant degree of primary hypogonadism in Symptomatic HIV infected females at both follicular and luteal phases of menstrual cycle which tends to normalize on treatments. PMID:28723963

Evaluation of irregular menses in perimenarcheal girls: a pilot study.

PubMed

Browner-Elhanan, Karen J; Epstein, Jonathan; Alderman, Elizabeth M

2003-12-01

Acyclic vaginal bleeding in girls within three years of menarche is most commonly attributed to an immature hypothalamic-pituitary-ovarian axis. Assuming this diagnosis may preclude the practitioner from performing more definitive studies and thereby diagnosing other, treatable causes of menstrual irregularities. A retrospective chart review of 178 girls presenting to an inner-city hospital-based adolescent clinic within three years of menarche was performed. Personal and family medical and menarcheal history was assessed, and findings on physical and laboratory examination performed were evaluated. Of the 178 girls still perimenarcheal at presentation, 47 were the focus of this study. Of these, 39 had no significant findings on physical examination, while 3 had signs of functional ovarian hyperandrogenism (FOH) including obesity, hirsutism, and moderate acne with corresponding LH/FSH ratios>3, although pelvic ultrasound examination revealed normal ovaries. Four of the 39 patients with normal physical exams had LH/FSH testing done, and 1 of the 4 had an abnormal LH/FSH ratio, indicating possible FOH. Two of the 47 patients were pregnant. Other laboratory abnormalities included microcytic, hypochromic anemia in patients, and an elevated Erythrocyte Sedimentation Rate in a patient later diagnosed with a rheumatologic disorder. Those perimenarcheal girls presenting with irregular menses and findings including obesity, acne, or pallor, were likely to have treatable causes of menstrual irregularities. In one of the four girls with a normal physical examination, hormonal testing indicated possible FOH, thus suggesting that hormonal evaluation of perimenarcheal girls with menstrual irregularities may be justified, as it may reveal previously unsuspected pathology.

[Hormonal and metabolic effects of drinking mineral water and phytoaeronisation in experimental prostatitis].

PubMed

Polushina, N D; Agaev, A A; Shchelkunov, A V; Eseneev, S M

2004-01-01

Prostatitis modelled in 53 Wistar male rats (300-350 body mass) 7 days after its induction was treated with mineral water "Essentuki N 17" (MW) which was taken in a dose 1.5-2 ml per 100 g body mass for 23-24 days. In addition, some animals received phytoaeroionisation (PAI) with solution of essential oils of mint, sage and lavender. Prostatitis is associated with disorders in prostatic tissue, levels of sex hormones (testosterone, prolactin, FSH, LH), a rise in total cholesterol, glucose. Watering of animals with MW and PAI raised blood insulin, hydrocortisone and testosterone, normalized blood glucose and cholesterol. There was a correlation between blood levels of hydrocortisone and testosterone.

[The lh-rh-test in men with fertility disorders (author's transl)].

PubMed

Krause, W; Höbel, W

1976-11-01

89 mal patients with fertility disorders underwent a test with 50 mug synthetic LH-RH. The basal levels of FSH and LH are elevated in patients with azoospermia, with testicular atrophy, varicocele and Klinefelters syndrome. They increase with age. After stimulation with LH-RH the highest relative peaks (maximal value divided by control value) of LH are seen younger patients, in those with varicocele, and oligozoospermia. The FSH-values do not differ significantly between these groups. Low relative peaks of LH are seen in older patients. In Klinefelter's syndrome the relative peaks of FSH and LH are significantly lowered.

Serum bioactive and immunoreactive luteinizing hormone and follicle-stimulating hormone levels in women with cycle abnormalities, with or without polycystic ovarian disease.

PubMed

Fauser, B C; Pache, T D; Lamberts, S W; Hop, W C; de Jong, F H; Dahl, K D

1991-10-01

Serum steroid, gonadotropin, and alpha-subunit levels were assessed in 35 women with cycle abnormalities [11 with and 24 without polycystic ovarian disease (PCOD) according to strict clinical and biochemical criteria] and 8 regularly cycling women in the early (cycle day 3 or 4) and mid (cycle day 7 or 8) follicular phase. LH and FSH levels were estimated using two immunological techniques [RIA and immunoradiometric assay (IRMA)] and in vitro bioassays (BIO), using mouse Leydig cells and rat granulosa cells, respectively. In PCOD patients mean alpha-subunit, free androgen index [FAI; testosterone x 100/sex hormone-binding globulin (SHBG)], androstenedione, estrone, and estradiol (E2) were significantly elevated compared to levels in the early follicular phase of control cycles and non-PCOD patients. In addition, in PCOD patients mean IRMA-LH and RIA-LH levels were distinctly increased (2.8- to 3.6 fold, respectively; both comparisons, P less than 0.001) compared to control values, but in the same order of magnitude (1.3- to 1.4-fold increments) as that in non-PCOD patients. However, the median BIO-LH level in PCOD patients was 5.9-fold higher than that in non-PCOD patients and 4.0-fold higher than the BIO-LH in the early follicular phase of control women. Consequently, the median BIO/IRMA-LH ratio was 4.8-fold higher in PCOD patients compared to non-PCOD patients. In women with cycle abnormalities, individual BIO/IRMA-LH ratios correlated with BIO-LH (rs = 0.48), FAI (rs = 0.39), free estrogens (E2/SHBG ratios; rs = 0 0.47), and dehydroepiandrosterone sulfate (rs = 0.60) concentrations. Mean IRMA-, RIA-, and BIO-FSH levels and BIO/IRMA-FSH ratios were not significantly different when various groups were compared. Although RIA- and IRMA-LH levels showed good correlation (rs = 0.88), RIA-LH levels were consistently higher, resulting in distinctly higher RIA-LH/FSH ratios (mean, 4.5) compared to IRMA-LH/FSH ratios (median, 1.8) in PCOD patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Glycosylation Effects on FSH-FSHR Interaction Dynamics: A Case Study of Different FSH Glycoforms by Molecular Dynamics Simulations

PubMed Central

Meher, Biswa Ranjan; Dixit, Anshuman; Bousfield, George R.; Lushington, Gerald H.

2015-01-01

The gonadotropin known as follicle-stimulating hormone (FSH) plays a key role in regulating reproductive processes. Physiologically active FSH is a glycoprotein that can accommodate glycans on up to four asparagine residues, including two sites in the FSHα subunit that are critical for biochemical function, plus two sites in the β subunit, whose differential glycosylation states appear to correspond to physiologically distinct functions. Some degree of FSHβ hypo-glycosylation seems to confer advantages toward reproductive fertility of child-bearing females. In order to identify possible mechanistic underpinnings for this physiological difference we have pursued computationally intensive molecular dynamics simulations on complexes between the high affinity site of the gonadal FSH receptor (FSHR) and several FSH glycoforms including fully-glycosylated (FSH24), hypo-glycosylated (e.g., FSH15), and completely deglycosylated FSH (dgFSH). These simulations suggest that deviations in FSH/FSHR binding profile as a function of glycosylation state are modest when FSH is adorned with only small glycans, such as single N-acetylglucosamine residues. However, substantial qualitative differences emerge between FSH15 and FSH24 when FSH is decorated with a much larger, tetra-antennary glycan. Specifically, the FSHR complex with hypo-glycosylated FSH15 is observed to undergo a significant conformational shift after 5–10 ns of simulation, indicating that FSH15 has greater conformational flexibility than FSH24 which may explain the more favorable FSH15 kinetic profile. FSH15 also exhibits a stronger binding free energy, due in large part to formation of closer and more persistent salt-bridges with FSHR. PMID:26402790

Comparison of the effects of laparoscopic bipolar electrocoagulation and intracorporeal suture application to ovarian reserve in benign ovarian cysts.

PubMed

Özgönen, Hakan; Erdemoglu, Evrim; Günyeli, Ilker; Güney, Mehmet; Mungan, Tamer

2013-04-01

Aim of the present study is to determine the effects of bipolar electrocoagulation and intracorporeal suture on the ovarian reserve after ovarian cystectomy. Sixty patients aged 18-42 years old and with a persistent adnexal mass were recruited to the study. Patients were randomized into suture hemostasis group or bipolar hemostasis group. Laparoscopic ovarian cystectomy was performed to all patients. Hemostasis was obtained by bipolar coagulation in 30 patients and by intracorporeal sutures in 30 patients. Serum levels of FSH, LH, estradiol, inhibin B and ultrasonographic measurements (antral follicle count and ovarian volume) were analyzed and recorded at day 3 of menstrual cycle, 1 and 3 months after the surgery. Basal FSH level measurement at the postoperative third month was significantly increased to 6.96 ± 1.86 mIU/ml (p < 0.05) in the bipolar electrocoagulation group. However, the decreased ovarian volume and antral follicle count was restored at the postoperative third month in the bipolar electrocoagulation group. Preoperative and postoperative FSH, LH, estradiol and inhibin B levels and ultrasonographic measurements were similar in the intracorporeal suture group. The unwanted effect of bipolar electrocoagulation on ovarian reserve is probably transient and causes minimal damage to ovary. FSH levels may be slightly elevated. Gentle use of bipolar electrocoagulation or intracorporeal are not found to effect ovarian reserve.

Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

PubMed

Ding, Yu; Li, Juan; Yu, Yongguo; Yang, Peirong; Li, Huaiyuan; Shen, Yongnian; Huang, Xiaodong; Liu, Shijian

2018-03-28

This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

FSH-FSHR3-stem cells in ovary surface epithelium: basis for adult ovarian biology, failure, aging, and cancer.

PubMed

Bhartiya, Deepa; Singh, Jarnail

2015-01-01

Despite extensive research, genetic basis of premature ovarian failure (POF) and ovarian cancer still remains elusive. It is indeed paradoxical that scientists searched for mutations in FSH receptor (FSHR) expressed on granulosa cells, whereas more than 90% of cancers arise in ovary surface epithelium (OSE). Two distinct populations of stem cells including very small embryonic-like stem cells (VSELs) and ovarian stem cells (OSCs) exist in OSE, are responsible for neo-oogenesis and primordial follicle assembly in adult life, and are modulated by FSH via its alternatively spliced receptor variant FSHR3 (growth factor type 1 receptor acting via calcium signaling and the ERK/MAPK pathway). Any defect in FSH-FSHR3-stem cell interaction in OSE may affect folliculogenesis and thus result in POF. Ovarian aging is associated with a compromised microenvironment that does not support stem cell differentiation into oocytes and further folliculogenesis. FSH exerts a mitogenic effect on OSE and elevated FSH levels associated with advanced age may provide a continuous trigger for stem cells to proliferate resulting in cancer, thus supporting gonadotropin theory for ovarian cancer. Present review is an attempt to put adult ovarian biology, POF, aging, and cancer in the perspective of FSH-FSHR3-stem cell network that functions in OSE. This hypothesis is further supported by the recent understanding that: i) cancer is a stem cell disease and OSE is the niche for ovarian cancer stem cells; ii) ovarian OCT4-positive stem cells are regulated by FSH; and iii) OCT4 along with LIN28 and BMP4 are highly expressed in ovarian cancers. © 2015 Society for Reproduction and Fertility.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Hui; Lin, Lu; Haq, Ihtesham Ul

The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdownmore » of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. - Highlights: • FSH inhibits the activation of NF-κB in porcine primary granulosa cells. • Inhibition of NF-κB by FSH promotes autophagy via JNK signaling in granulosa cells. • Increased autophagy contributes to progesterone production in granulosa cells. • This is the first report against beclin1 regulation in porcine granulosa cells.« less

Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation.

PubMed

Chowdhury, Indrajit; Thomas, Kelwyn; Zeleznik, Anthony; Thompson, Winston E

2016-05-01

Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E2 and P4 synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs. © 2016 The authors.

High frequency of discordance between antimüllerian hormone and follicle-stimulating hormone levels in serum from estradiol-confirmed days 2 to 4 of the menstrual cycle from 5,354 women in U.S. fertility centers.

PubMed

Leader, Benjamin; Hegde, Aparna; Baca, Quentin; Stone, Kimberly; Lannon, Benjamin; Seifer, David B; Broekmans, Frank; Baker, Valerie L

2012-10-01

To determine the frequency of clinical discordance between antimüllerian hormone (AMH, ng/mL) and follicle-stimulating hormone (FSH, IU/L) by use of cut points defined by response to controlled ovarian stimulation in the same serum samples drawn on estradiol-confirmed, menstrual cycle days 2 to 4. Retrospective analysis. Fertility centers in 30 U.S. states and a single reference laboratory with uniform testing protocols. 5,354 women, 20 to 45 years of age. None. Frequency of discordance between serum AMH and FSH values. Of the 5,354 women tested, 1 in 5 had discordant AMH and FSH values defined as AMH <0.8 (concerning) with FSH <10 (reassuring) or AMH ≥ 0.8 (reassuring) with FSH ≥ 10 (concerning). Of the women with reassuring FSH values (n = 4,469), the concerning AMH values were found in 1 in 5 women in a highly age-dependent fashion, ranging from 1 in 11 women under 35 years of age to 1 in 3 women above 40 years of age. On the other hand, of the women with reassuring AMH values (n = 3,742), 1 in 18 had concerning FSH values, a frequency that did not vary in a statistically significant fashion by age. Clinical discordance in serum AMH and FSH values was frequent and age dependent using common clinical cut points, a large patient population, one reference laboratory, and uniform testing methodology. This conclusion is generalizable to women undergoing fertility evaluation, although AMH testing has not been standardized among laboratories, and the cut points presented are specific to the laboratory in this study. Copyright © 2012. Published by Elsevier Inc.

The influence of organophosphate and carbamate on sperm chromatin and reproductive hormones among pesticide sprayers.

PubMed

Jamal, Farrukh; Haque, Quazi S; Singh, Sangram; Rastogi, S K

2016-08-01

This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes. © The Author(s) 2015.

3',5'-cyclic adenosine monophosphate response element binding protein up-regulated cytochrome P450 lanosterol 14alpha-demethylase expression involved in follicle-stimulating hormone-induced mouse oocyte maturation.

PubMed

Ning, Gang; Ouyang, Hong; Wang, Songbo; Chen, Xiufen; Xu, Baoshan; Yang, Jiange; Zhang, Hua; Zhang, Meijia; Xia, Guoliang

2008-07-01

Cytochrome P450 lanosterol 14alpha-demethylase (CYP51) is a key enzyme in sterols and steroids biosynthesis that can induce meiotic resumption in mouse oocytes. The present study investigated the expression mechanism and function of CYP51 during FSH-induced mouse cumulus oocyte complexes (COCs) meiotic resumption. FSH increased cAMP-dependent protein kinase (PKA) RIIbeta level and induced cAMP response element-binding protein (CREB) phosphorylation and CYP51 expression in cumulus cells before oocyte meiotic resumption. Moreover, CYP51 and epidermal growth factor (EGF)-like factor [amphiregulin (AR)] expression were blocked by (2)-naphthol-AS-Ephosphate (KG-501) (a drug interrupting the formation of CREB functional complex). KG-501 and RS21607 (a specific inhibitor of CYP51 activity) inhibited oocyte meiotic resumption, which can be partially rescued by progesterone. These two inhibitors also inhibited FSH-induced MAPK phosphorylation. EGF could rescue the suppression by KG-501 but not RS21607. Furthermore, type II PKA analog pairs, N(6)-monobutyryl-cAMP plus 8-bromo-cAMP, increased PKA RIIbeta level and mimicked the action of FSH, including CREB phosphorylation, AR and CYP51 expression, MAPK activation, and oocyte maturation. All these data suggest that CYP51 plays a critical role in FSH-induced meiotic resumption of mouse oocytes. CYP51 and AR gene expression in cumulus cells are triggered by FSH via a type II PKA/CREB-dependent signal pathway. Our study also implicates that CYP51 activity in cumulus cells participates in EGF receptor signaling-regulated oocyte meiotic resumption.

Testosterone concentrations in female athletes and ballet dancers with menstrual disorders.

PubMed

Łagowska, Karolina; Kapczuk, Karina

2016-01-01

Menstrual disorders are common among female athletes and ballet dancers. Endocrine changes, such as high testosterone (HT) levels and high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratios, may suggest functional ovarian hyperandrogenism which may induce such dysfunction. The aim of this study was therefore to evaluate endocrine status in female athletes and ballet dancers with menstrual disorders. Their nutritional status and dietary habits were analysed in relation to the testosterone levels. In a cross-sectional approach, 31 female athletes (18.1 ± 2.6 years) and 21 ballerinas (17.1 ± 0.9) with menstrual disorders participated in the study. The levels of serum LH, FSH, progesterone (P), estradiol (E2), prolactin (PRL), thyroid-stimulating hormone, testosterone (T) and sex hormone-binding globulinwere measured to assess hormonal status. In addition, the free androgen index (FAI) was calculated. Nutritional status, total daily energy expenditure and nutritional habits were evaluated. Girls were assigned to one of the following groups: low testosterone (LT) level, normal testosterone level or HT level. There were significant differences between ballerinas and other female athletes in terms of testosterone levels, FAI, age at the beginning of training, length of training period and age at menarche. The PRL level was lowest in the LT group while the FAI index was highest in the HT group. Daily energy and carbohydrate intakes were significantly lower in the HT group. T levels in the study subjects were found to be associated with nutritional factors, energy availability, age at the beginning of training and frequency of training. This is the first report of HT levels being associated with the status of a female ballet dancer, the age of menarche and the length of the training history. Further research is necessary to confirm the results in a larger study group.

Observations on the use of purified follicle-stimulating hormone in the treatment of luteal phase defects.

PubMed

Di Carlo, C; Affinito, P; Farace, M J; Gargiulo, A R; Zullo, F; Nappi, C

1995-06-01

We treated 18 infertile patients affected by histologically confirmed luteal phase deficiency with 75 IU of purified follicle-stimulating hormone (FSH) daily during the first 5 days of the cycle. Patients who were not pregnant after the first cycle of treatment underwent a second cycle. In the second cycle the daily doses of purified FSH were doubled if luteal phase deficiency had persisted during the first cycle. During the two cycles before treatment and during treatment, patients underwent an endometrial biopsy 1-3 days before the expected onset of menses. An assessment of progesterone serum concentrations was also performed on days 8, 6 and 4 before the expected onset of menses. Treatment was administered in a total of 33 cycles resulting in 30 ovulatory cycles. Six pregnancies were achieved. Among non-conception ovulatory cycles, 13 presented delayed endometrial dating and 11 normal endometrium. The mean +/- SD of the sum of the three progesterone determinations was 14.7 +/- 1.4 ng/ml in pretreatment cycles, 14.6 +/- 1.6 ng/ml in cycles with normalization of endometrial dating, 14.8 +/- 1.7 ng/ml in cycles with persistence of luteal phase deficiency and 30.4 +/- 3.0 ng/ml in conception cycles (P < 0.05 versus other groups). We conclude that purified FSH, if effective in the treatment of luteal phase deficiency, does not act through an increase in progesterone concentrations.

Effects of hormones on cognition in schizophrenic male patients--preliminary results.

PubMed

Bratek, Agnieszka; Koźmin-Burzyńska, Agnieszka; Krysta, Krzysztof; Cierpka-Wiszniewska, Katarzyna; Krupka-Matuszczyk, Irena

2015-09-01

Schizophrenia is a prevalent neurodevelopmental disorder of an unknown etiology and a variable phenotypic expression. In the recent years, the impact of hormones on the course of schizophrenia has been investigated. This study is aimed at assessing the level of correlating serum levels of hormones in schizophrenic male patients with their cognitive functioning measured with neuropsychological tests. In the index group there were 15 medicated male schizophrenic patients. In the control group there were 15 age and education matched healthy men. All subjects underwent analysis of serum hormones level (TSH, testosterone, estradiol, FSH, LH, progesterone and prolactin) and a battery of tests (Trail Making Test A and B, Stroop Test, Verbal and Semantic Fluency Test). The mean serum levels of the following hormones were higher in the index group than in the control group: TSH (1.76 mIU/L vs 1.58 mIU/L; p=0.66), progesterone (0.85 ng/ml vs 0.69 ng/ml; p=0.22) and prolactin (558.71 uIU/ml vs 181 uIU/ml; p=0.025). The mean levels of estradiol (24.36 pg/ml vs 25.40 ng/ml; p=0.64), FSH (3.17 mIU/ml vs 5.72 mIU/ml; p=0.019), LH (3.85 mIU/ml vs 5.77 mIU/ml; p=0.056) and testosterone (2.90 ng/ml vs 5.38 ng/ml; p=0.003) were higher in the control group. In the index group there were significant negative correlations between FSH and semantic fluency (ρ=-0.678606), progesterone and: TMT B (ρ=-0.586763), Stroop 1 (ρ=-0.701880) and Stroop 2 (ρ=-0.601074) and prolactin and TMT A (ρ=-0.579607). The preliminary results of our study show that serum levels of FSH and testosterone are significantly lower, whereas the level of prolactin is markedly higher, in schizophrenic male patients than in healthy men. There is an inverse correlation between serum levels of progesterone, FSH and prolactin and the results of certain cognitive functioning tests in schizophrenic men.

Follicle-stimulating hormone (FSH) unmasks specific high affinity FSH-binding sites in cell-free membrane preparations of porcine granulosa cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ford, K.A.; LaBarbera, A.R.

1988-11-01

The purpose of these studies was to determine whether changes in FSH receptors correlated with FSH-induced attenuation of FSH-responsive adenylyl cyclase in immature porcine granulosa cells. Cells were incubated with FSH (1-1000 ng/ml) for up to 24 h, treated with acidified medium (pH 3.5) to remove FSH bound to cells, and incubated with (125I)iodo-porcine FSH to quantify FSH-binding sites. FSH increased binding of FSH in a time-, temperature-, and FSH concentration-dependent manner. FSH (200 ng/ml) increased binding approximately 4-fold within 16 h. Analysis of equilibrium saturation binding data indicated that the increase in binding sites reflected a 2.3-fold increase inmore » receptor number and a 5.4-fold increase in apparent affinity. The increase in binding did not appear to be due to 1) a decrease in receptor turnover, since the basal rate of turnover appeared to be very slow; 2) an increase in receptor synthesis, since agents that inhibit protein synthesis and glycosylation did not block the increase in binding; or 3) an increase in intracellular receptors, since agents that inhibit cytoskeletal components had no effect. Agents that increase intracellular cAMP did not affect FSH binding. The increase in binding appeared to result from unmasking of cryptic FSH-binding sites, since FSH increased binding in cell-free membrane preparations to the same extent as in cells. Unmasking of cryptic sites was hormone specific, and the sites bound FSH specifically. Unmasking of sites was reversible in a time- and temperature-dependent manner after removal of bound FSH. The similarity between the FSH dose-response relationships for unmasking of FSH-binding sites and attenuation of FSH-responsive cAMP production suggests that the two processes are functionally linked.« less

Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy.

PubMed

DeWire, Mariko; Green, Daniel M; Sklar, Charles A; Merchant, Thomas E; Wallace, Dana; Lin, Tong; Vern-Gross, Tamara; Kun, Larry E; Krasin, Matthew J; Boyett, James M; Wright, Karen D; Wetmore, Cynthia; Broniscer, Alberto; Gajjar, Amar

2015-02-01

Female survivors of central nervous system (CNS) tumors are at an increased risk for gonadal damage and variations in the timing of puberty following radiotherapy and alkylating agent-based chemotherapy. Clinical and laboratory data were obtained from 30 evaluable female patients with newly diagnosed embryonal CNS tumors treated on a prospective protocol (SJMB 96) at St. Jude Children's Research Hospital (SJCRH). Pubertal development was evaluated by Tanner staging. Primary ovarian insufficiency (POI) was determined by Tanner staging and FSH level. Females with Tanner stage I-II and FSH > 15 mIU/ml, or Tanner stage III-V, FSH > 25 mIU/ml and FSH greater than LH were defined to have ovarian insufficiency. Recovery of ovarian function was defined as normalization of FSH without therapeutic intervention. Median length of follow-up post completion of therapy was 7.2 years (4.0-10.8 years). The cumulative incidence of pubertal onset was 75.6% by the age of 13. Precocious puberty was observed in 11.1% and delayed puberty in 11.8%. The cumulative incidence of POI was 82.8%, though recovery was observed in 38.5%. Treatment for primary CNS embryonal tumors may cause variations in the timing of pubertal development, impacting physical and psychosocial development. Female survivors are at risk for POI, a subset of whom will recover function over time. Further refinement of therapies is needed in order to reduce late ovarian insufficiency. Pediatr Blood Cancer 2015;62:329-334. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Comparison between testosterone enanthate-induced azoospermia and oligozoospermia in a male contraceptive study. I: Plasma luteinizing hormone, follicle stimulating hormone, testosterone, estradiol, and inhibin concentrations.

PubMed

Wallace, E M; Gow, S M; Wu, F C

1993-07-01

Sex-steroid based male contraceptive regimes induce azoospermia in only 40-70% of Caucasian men. The reason(s) why the remainder maintains a low level of spermatogenesis (oligozoospermia) despite gonadotrophin suppression is unclear. In order to improve our understanding of this phenomenon, we examined the changes in sperm density and plasma LH, FSH, testosterone (T), oestradiol (E2), and inhibin (IN) in 28 normal men who received 200 mg testosterone enanthate (TE) im weekly during a male contraceptive efficacy trial. Gonadotrophins were measured by an ultrasensitive time-resolved immunofluorometric assay (DELFIA) with a sensitivity of 0.04 U/L, to determine the adequacy of suppression. Seventeen of the 28 men achieved azoospermia; the other 11 remained oligozoospermic (sperm density 3.3-4.7 x 10(6)/mL) after 6 months of TE exposure. Azoospermic subjects displayed a more rapid decline in sperm density, a significant difference being apparent by 5 weeks after starting TE. During TE treatment, both LH and FSH were consistently suppressed to below the limits of detection, whereas there was a 2.5-fold rise in T and E2 with a similar decrease in IN. There were no consistent differences in any of these hormone concentrations between the azoospermic and oligozoospermic groups. Recovery of sperm density to baseline levels or above 20 x 10(6)/mL was significantly slower in the azoospermic group. During the recovery phase, the azoospermic men exhibited significantly higher LH and FSH levels compared to baseline and to the oligozoospermic subjects even though no differences in circulating T, E2, or IN were observed. We conclude that incomplete gonadotrophin suppression or differences in sex steroid or inhibin levels are unlikely to be responsible for the maintenance of minor degrees of spermatogenesis in some men during TE administration. The rebound rise in gonadotrophins in azoospermic but not oligozoospermic responders during recovery may reflect a more profound degree of spermatogenic suppression in the former group.

[Genetic aspects of premature ovarian failure].

PubMed

Warenik-Szymankiewicz, Alina; Słopień, Radosław

2005-01-01

Among the causes of premature ovarian failure (POF) two groups of factors are reported: factors which lead to decrease of follicular number and factors which stimulate follicular atresia. In the first group genetic factors are the most important whereas in the second: enzymatic autoimmunological, iatrogenic, toxins and infections are reported. In 1986 familiar POF on the background of long arm of chromosome X deletion was reported. Other chromosomes which are important for normal ovarian function are: chromosome 21 (AIRE gene), chromosome 11 (gene of beta FSH, ATM gene), chromosome 3 (gene responsible for BEPS syndrome) and chromosome 2 (genes of FSH and LH receptors). In this review the role of these genes and results of several epidemiological studies are reported.

Age-Specific Normal Reference Range for Serum Anti-Müllerian Hormone in Healthy Chinese Han Women: A nationwide Population-Based Study.

PubMed

Du, Xiaofang; Ding, Ting; Zhang, Hanwang; Zhang, Cuilian; Ma, Wenmin; Zhong, Ying; Qu, Wenyu; Zheng, Jie; Liu, Yi; Li, Zhiying; Huang, Kecheng; Deng, Song; Ma, Lanfang; Yang, Jun; Jiang, Jingjing; Yang, Shuhong; Huang, Jia; Wu, Meng; Fang, Li; Lu, Yunping; Luo, Aiyue; Wang, Shixuan

2016-08-01

The increasing use of anti-Müllerian hormone (AMH) in clinic has raised concerns regarding the reliable reference range for this test. However, the reference range for AMH in normal Chinese female population has not been established. Furthermore, relationship between AMH and other clinical markers such as body mass index (BMI) and antral follicle counts (AFCs) and other sex-related hormones have not been examined in normal population-based women. We aimed to determine the age-specific reference range for serum AMH in healthy Chinese women throughout reproductive age to menopause and to estimate relationship between AMH and other clinical markers in healthy women. In this multicenter and nationwide study, advertisements were used to recruit 2055 women, aged 20 to 55 years, from 6 different regions in China; 1590 (77.37%) women met the inclusion criteria for the reference range population. We measured the baseline serum AMH levels using new Beckman Coulter Gen II assay. Serum concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), progesterone (PRG), and AFCs were also determined in the follicular phase. The AMH-Age nomogram and AMH levels of different age-groups and the relationship between AMH and other clinical markers. Serum AMH concentrations declined progressively with age. A quadratic model defined as log (AMH) = (-1.970 + 0.296 × Age - 0.006 × Age(2)) fitted best the decline of AMH with age. The median AMH levels were 6.23, 5.65, 4.55, 3.74, 2.78, and 1.09 ng/mL for the 20 ≤ age < 25, 25 ≤ age < 30, 30 ≤ age < 33, 33 ≤ age < 37, 37 ≤ age < 40, and 40 ≤ age < 55 groups, respectively. The 5th to 95th percentiles of the AMH levels, as the reference range, were 2.06 to 12.66, 1.77 to 13.83, 1.48 to 11.45, 0.87 to 9.76, 0.56 to 9.49, and 0.08 to 5.70 ng/mL for each age-group. The AMH levels were positively correlated with AFCs and T, LH, PRL and PRG levels and negatively correlated with BMI and FSH levels and were not significantly correlated with E2 levels. The relationship between AMH and other variables remain unchanged except for PRL, which was not significantly correlated with AMH levels after controlling for both age and BMI. This study determined the normal reference ranges for serum AMH levels in a large population-based sample of healthy Chinese women. © The Author(s) 2016.

The BET protein FSH functionally interacts with ASH1 to orchestrate global gene activity in Drosophila

PubMed Central

2013-01-01

Background The question of how cells re-establish gene expression states after cell division is still poorly understood. Genetic and molecular analyses have indicated that Trithorax group (TrxG) proteins are critical for the long-term maintenance of active gene expression states in many organisms. A generally accepted model suggests that TrxG proteins contribute to maintenance of transcription by protecting genes from inappropriate Polycomb group (PcG)-mediated silencing, instead of directly promoting transcription. Results and discussion Here we report a physical and functional interaction in Drosophila between two members of the TrxG, the histone methyltransferase ASH1 and the bromodomain and extraterminal family protein FSH. We investigated this interface at the genome level, uncovering a widespread co-localization of both proteins at promoters and PcG-bound intergenic elements. Our integrative analysis of chromatin maps and gene expression profiles revealed that the observed ASH1-FSH binding pattern at promoters is a hallmark of active genes. Inhibition of FSH-binding to chromatin resulted in global down-regulation of transcription. In addition, we found that genes displaying marks of robust PcG-mediated repression also have ASH1 and FSH bound to their promoters. Conclusions Our data strongly favor a global coactivator function of ASH1 and FSH during transcription, as opposed to the notion that TrxG proteins impede inappropriate PcG-mediated silencing, but are dispensable elsewhere. Instead, our results suggest that PcG repression needs to overcome the transcription-promoting function of ASH1 and FSH in order to silence genes. PMID:23442797

The cost-effectiveness of IVF in the UK: a comparison of three gonadotrophin treatments.

PubMed

Sykes, D; Out, H J; Palmer, S J; van Loon, J

2001-12-01

The objective of this study was to evaluate the cost-effectiveness of women undergoing IVF treatment with recombinant FSH (rFSH) in comparison with highly purified urinary FSH (uFSH-HP) and human menopausal gonadotrophins (HMG). A decision-analytic model was used to estimate cost-effectiveness ratios for 'the average cost per ongoing pregnancy' and 'incremental cost per additional pregnancy' for women entering into IVF treatment for a maximum of three cycles. The model was constructed based on a previously published large prospective randomized clinical trial comparing rFSH and uFSH-HP. Where necessary, these data were augmented with a combination of expert opinion, evidence from the literature and observational data relating to the management and cost of IVF treatment in the UK. The cost of rFSH, uFSH-HP and HMG were obtained from National Health Service list prices in the UK. The model predicted a cumulative pregnancy rate after three cycles of 57.1% for rFSH and 44.4% for both uFSH-HP and HMG. The cost of IVF treatment was 5135 pounds sterling for rFSH, 4806 pounds sterling for uFSH-HP and 4202 pounds sterling for HMG. When assessed in association with outcomes, the average cost per ongoing pregnancy was more favourable with rFSH (8992 pounds sterling) than with either uFSH-HP (10 834 pounds sterling) or HMG (9472 pounds sterling). The incremental cost per additional pregnancy was 2583 pounds sterling using rFSH instead of uFSH-HP and 7321 pounds sterling using rFSH instead of HMG. These results were robust to changes in the baseline assumptions of the model. rFSH is a cost-effective treatment strategy in ovulation induction prior to IVF.

Observational Study to Assess the Therapeutic Value of Four Ovarian Hyperstimulation Protocols in IVF After Pituitary Suppression with GnRH Antagonists in Normally Responding Women.

PubMed

Ana, Monzó; Vicente, Montañana; María, Rubio José; Trinidad, García-Gimeno; Alberto, Romeu

2011-02-22

To compare the clinical results of four different protocols of COH for IVF-ICSI in normovulatory women, using in all cases pituitary suppression with GnRH antagonists. A single center, open label, parallel-controlled, prospective, post-authorization study under the approved conditions for use where 305 normal responders women who were candidates to COH were assigned to r-FSH +hp-hMG (n = 51, Group I), hp-hMG (n = 61, Group II), fixed-dose r-FSH (n = 118, Group III), and r-FSH with potential dose adjustment (n = 75, Group IV) to subsequently undergo IVF-ICSI. During stimulation, Group IV needed significantly more days of stimulation as compared to Group II [8.09 ± 1.25 vs. 7.62 ± 1.17; P < 0.05], but was the group in which more oocytes were recovered [Group I: 9.43 ± 4.99 vs. Group II: 8.96 ± 4.82 vs. Group III: 8.78 ± 3.72 vs. Group IV: 11.62 ± 5.80; P < 0.05]. No significant differences were seen between the groups in terms of clinical and ongoing pregnancy, but among patients in whom two embryos with similar quality parameters (ASEBIR) were transferred, the group treated with hp-hMG alone achieved a significantly greater clinical pregnancy rate as compared to all other groups [Group I: 31.6%, Group II: 56.4%, Group III: 28.7%, Group IV: 32.7%; P < 0.05]. Although randomized clinical trials should be conducted to achieve a more reliable conclusion, these observations support the concept that stimulation with hp-hMG could be beneficial in normal responders women undergoing pituitary suppression with GnRH antagonists.

[A case of early onset cerebellar ataxia with hearing loss, mental disturbance and primary hypogonadism].

PubMed

Ikezoe, K; Yamada, A; Takeuchi, H; Miki, H; Katanaka, J

1992-09-01

A 14-year-old girl, whose birth and developmental history were normal till the age of 7, was admitted to our hospital because of slowly progressive difficulties in walking, speaking and hearing. She also complained of absence of menstruation. She showed poor school records since the age of 7. On neurological examination, she showed limb and truncal ataxia. There was no nystagmus but slurred speech was found. Muscular power was good and her sensory system was normal. Tendon reflexes were equally present, and plantar reflexes were flexor. Bilateral moderate nerve deafness was also present. Mental deficiency was diagnosed on an intelligence test. Brain CT and MRI showed cerebellar atrophy. Gynecological examination revealed scanty pubic hair and small uterus. Karyotype was 46XX. Endocrinological studies demonstrated high level of FSH, low level of E2, and the normal response to pituitary stimulation with LHRH, indicating the existence of primary hypogonadism. Although the etiology of this multisystem disorder is unknown, it is possible that both nervous and endocrine disorders were genetically determined.

The combined effect of age and basal follicle-stimulating hormone on the cost of a live birth at assisted reproductive technology.

PubMed

Henne, Melinda B; Stegmann, Barbara J; Neithardt, Adrienne B; Catherino, William H; Armstrong, Alicia Y; Kao, Tzu-Cheg; Segars, James H

2008-01-01

To predict the cost of a delivery following assisted reproductive technologies (ART). Cost analysis based on retrospective chart analysis. University-based ART program. Women aged >or=26 and

Wide excision of soft tissues adjacent to the ovary and fallopian tube does not impair the ovarian reserve in women undergoing prophylactic bilateral salpingectomy: results from a randomized, controlled trial.

PubMed

Venturella, Roberta; Morelli, Michele; Lico, Daniela; Di Cello, Annalisa; Rocca, Morena; Sacchinelli, Angela; Mocciaro, Rita; D'Alessandro, Pietro; Maiorana, Antonio; Gizzo, Salvatore; Zullo, Fulvio

2015-11-01

To study the effects of the wide excision of soft tissues adjacent to the ovary and fallopian tube on ovarian function and surgical outcomes in women undergoing laparoscopic bilateral prophylactic salpingectomy. Randomized, controlled trial. Teaching hospital. One hundred eighty-six women undergoing laparoscopic surgery for uterine myoma (n = 143) or tubal surgical sterilization (n = 43). Patients were randomly divided into two groups. In group A (n = 91), standard salpingectomy was performed. In group B (n = 95), the mesosalpinx was removed within the tubes. Prior to and 3 months after surgery, antimüllerian hormone (AMH), FSH, three-dimensional antral follicle count (AFC), vascular index (VI), flow index (FI), vascular-flow index (VFI), and OvAge were recorded for each patient. Ovarian reserve modification (Δ) before and after surgery was assessed as the primary outcome. Operative time, variation of the hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were assessed as secondary outcomes. No significant difference was observed between groups for ΔAMH, ΔFSH, ΔAFC, ΔVI, ΔFI, ΔVFI, and ΔOvAge. Moreover, the groups were similar for operative time, ΔHb, postoperative hospital stay, postoperative return to normal activity, and complication rate. Even when the surgical excision includes the removal of the mesosalpinx, salpingectomy does not damage the ovarian reserve. Moreover, wide salpingectomy with excision of the mesosalpinx did not alter blood loss, hospitalization stay, or return to normal activities. NCT02086370. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Alterations in Hormone Levels After Adjuvant Chemoradiation in Male Rectal Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Frederick H.; Perera, Francisco; Fisher, Barbara

Purpose: To evaluate follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels after postoperative chemoradiation in men with rectal cancer. Methods and Materials: Forty-three men with rectal cancer had baseline and postchemoradiation FSH, LH, and testosterone measured. Adjuvant chemoradiation consisted of two 5-day cycles of bolus 5-fluorouracil (5-FU) every 4 weeks at a dose of 500 mg/m{sup 2}/d followed by concurrent chemoradiation followed by two additional 5-day cycles of 5-FU at a dose of 450 mg/m{sup 2}/d. Continuous-infusion 5-FU at 225 mg/m{sup 2}/d was given during radiation. Pelvic radiation consisted of a three- or four-field technique with a median dosemore » of 54.0 Gy in 30 fractions. Results: Median follow-up was 6.1 years. Mean baseline FSH levels increased from 5.3 to a peak of 23.9 IU/L (p < 0.001) 13-24 months after chemoradiation. Mean baseline LH levels increased from 4.3 to a peak of 8.5 IU/L (p < 0.001) within 6 months after chemoradiation. Mean testosterone levels decreased from 15.4 nmol/L at baseline to 8.0 nmol/L more than 4 years after chemoradiation. Mean testosterone to mean LH ratio decreased from 4.4 at baseline to 1.1 after 48 months posttreatment, suggesting a continued decrease in Leydig cell function with time. Testicular dose was measured in 5 patients. Median dose was 4 Gy (range, 1.5-8.9 Gy). Conclusions: Chemoradiation in men with rectal cancer causes persistent increases in FSH and LH levels and decreases in testosterone levels.« less

A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency

PubMed Central

Hubayter, Ziad R; Popat, Vaishali; Vanderhoof, Vien H; Ndubizu, Obioma; Johnson, Diane; Mao, Edie; Calis, Karim A; Troendle, James F.; Nelson, Lawrence M.

2010-01-01

Objective To assess ovarian follicle function in women with 46,XX spontaneous primary ovarian insufficiency Design Case-control with nested prospective cohort Setting Clinical Research Center, National Institutes of Health Patients Women with primary ovarian insufficiency without estrogen replacement for two weeks (N=97) and regularly menstruating control women (N=42) Interventions Single injection of 300 IU hrFSH Main outcome measures Change in serum estradiol at 24 hours Results Antral follicles ≥ 3 mm were detected in 73% (69/95) of patients; both serum estradiol and progesterone levels correlated significantly with maximum follicle diameter in these women. Patients with a maximum follicle diameter ≥ 8 mm had significantly higher serum estradiol and progesterone levels and significantly lower FSH and LH levels as compared to patients without such follicles. In controls estradiol levels increased significantly after FSH administration but in patients this was not the case despite the presence of an antral follicle ≥ 8 mm. Conclusion Most women with 46,XX spontaneous primary ovarian insufficiency have antral follicles detectable by ultrasound, suggesting that down-regulation of FSH receptors is not the predominant mechanism of follicle dysfunction. Evidence of progesterone secretion by antral follicles ≥ 8 mm in these patients is consistent with prior histologic evidence that follicle luteinization is the predominant mechanism of follicle dysfunction in this condition. Prospective controlled investigation designed to improve ovulatory function and fertility in these women is indicated. PMID:19939372

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

PubMed

Lensen, Sarah F; Wilkinson, Jack; Leijdekkers, Jori A; La Marca, Antonio; Mol, Ben Willem J; Marjoribanks, Jane; Torrance, Helen; Broekmans, Frank J

2018-02-01

During a cycle of in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. Generally, the dose of FSH is associated with the number of eggs retrieved. A normal response to stimulation is often considered desirable, for example the retrieval of 5 to 15 oocytes. Both poor and hyper-response are associated with increased chance of cycle cancellation. Hyper-response is also associated with increased risk of ovarian hyperstimulation syndrome (OHSS). Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response such as age. More recently, clinicians have begun using ovarian reserve tests (ORTs) to predict ovarian response based on the measurement of various biomarkers, including basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose based on these markers improves clinical outcomes. To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, LILACS, DARE, ISI Web of Knowledge, ClinicalTrials.gov, and the World Health Organisation International Trials Registry Platform search portal from inception to 27th July 2017. We checked the reference lists of relevant reviews and included studies. We included trials that compared different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal or high responders based on AMH, AFC, and/or bFSH) and trials that compared an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. Secondary outcomes included clinical pregnancy, moderate or severe OHSS, multiple pregnancy, oocyte yield, cycle cancellations, and total dose and duration of FSH administration. We included 20 trials (N = 6088); however, we treated those trials with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence quality ranged from very low to moderate. The main limitations were imprecision and risk of bias associated with lack of blinding.Direct dose comparisons in women according to predicted responseAll evidence was low or very low quality.Due to differences in dose comparisons, caution is warranted in interpreting the findings of five small trials assessing predicted low responders. The effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy.Similarly, in predicted normal responders (nine studies, three comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units: OR 0.88, 95% CI 0.57 to 1.36; N = 522; 2 studies; I 2 = 0%) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the outcome of OHSS to enable any inferences.In predicted high responders, lower doses may or may not have an impact on rates of live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; N = 521; 1 study), OHSS, and clinical pregnancy. However, lower doses probably reduce the likelihood of moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; N = 521; 1 study).ORT-algorithm studiesFour trials compared an ORT-based algorithm to a non-ORT control group. Rates of live birth/ongoing pregnancy and clinical pregnancy did not appear to differ by more than a few percentage points (respectively: OR 1.04, 95% CI 0.88 to 1.23; N = 2823, 4 studies; I 2 = 34%; OR 0.96, 95% CI 0.82 to 1.13, 4 studies, I 2 =0%, moderate-quality evidence). However, ORT algorithms probably reduce the likelihood of moderate or severe OHSS (Peto OR 0.58, 95% CI 0.34 to 1.00; N = 2823; 4 studies; I 2 = 0%, low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.54, 95% CI 0.14 to 1.99; N = 1494; 3 studies; I 2 = 0%, low quality evidence). Our findings suggest that if the chance of live birth with a standard dose is 26%, the chance with ORT-based dosing would be between 24% and 30%. If the chance of moderate or severe OHSS with a standard dose is 2.5%, the chance with ORT-based dosing would be between 0.8% and 2.5%. These results should be treated cautiously due to heterogeneity in the study designs. We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT), influenced rates of live birth/ongoing pregnancy but we could not rule out differences, due to sample size limitations. In predicted high responders, lower doses of FSH seemed to reduce the overall incidence of moderate and severe OHSS. Moderate-quality evidence suggests that ORT-based individualisation produces similar live birth/ongoing pregnancy rates to a policy of giving all women 150 IU. However, in all cases the confidence intervals are consistent with an increase or decrease in the rate of around five percentage points with ORT-based dosing (e.g. from 25% to 20% or 30%). Although small, a difference of this magnitude could be important to many women. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU, probably by facilitating dose reductions in women with a predicted high response. However, the size of the effect is unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates, and many of the included studies had a serious risk of bias.Current evidence does not provide a clear justification for adjusting the standard dose of 150 IU in the case of poor or normal responders, especially as increased dose is generally associated with greater total FSH dose and therefore greater cost. However, a decreased dose in predicted high responders may reduce OHSS.

Influence of three lighting regimes during ten weeks growth phase on laying performance, plasma levels- and tissue specific gene expression- of reproductive hormones in Pengxian yellow pullets.

PubMed

Han, Shunshun; Wang, Yan; Liu, Lingyan; Li, Diyan; Liu, Zihao; Shen, Xiaoxu; Xu, Hengyong; Zhao, Xiaoling; Zhu, Qing; Yin, Huadong

2017-01-01

The study was conducted to optimize lighting schedule for pre-pubertal (12 to 22 weeks) Chinese native breed Pengxian yellow pullet. A total of 414 healthy pullets (10 weeks), with similar body weight were randomly distributed into three groups (n = 138) and housed in individual cages for up to 12 weeks of age in light controlled rooms and provided normal lighting schedule (10L:14D). At 12 to 18 weeks of age, pullets were housed in three rooms, having varying lighting schedule viz. G1 (8L: 16D), G2 (10L:14D), or G3 (12L:12D). From 19th week onwards lighting schedule was gradually increased every week in incremental manner till all groups started receiving 16L:8D lighting schedule. The age at first egg, weight of first egg laid, percent peak hen day egg production, concentration of plasma luteinizing and follicle-stimulating hormones and expression of genes regulating synthesis or/and secretion of hypothalamic gonadotropin-releasing hormone-I (GnRH-I), and pituitary LH-β and FSH-β were studied during experimental period (12 to 43 weeks of age) of this study. The result indicated that pullets of long day length (G3) group had higher plasma levels of FSH and LH and also better mRNA expression that regulates synthesis or/and secretion of GnRH-I, FSH-β, and LH-β before egg laying. The age at first egg (151.3 days) in pullets of G3 group receiving longer lighting hours (12L:12D) was 8.8 days less (P<0.05) compared to pullets of G1 group, while it was 6.9 days less (P>0.05) compared to G2. However, significantly higher (P<0.05) plasma levels of LH and FSH in pullets of G1 as compared to pullets belonging to G3 group corresponded with the higher (P<0.05) cumulative egg production during the experimental period, while these attributes in G2 group didn't differ from either G1 or G3 groups. Pullets of G1 group had significantly higher levels (P<0.05) of GnRH-I, FSH-β, and LH-β mRNA abundances at 43 weeks of age than other two groups and this corresponded with the percent (hen day) peak egg production (75.38%) in pullets in this G1 group that was attained at 32 weeks of age, while the peak production of 71.24% was attained at 30 weeks of age in G3 group. There was no effect of lighting schedule on body weight of pullets, recorded during experimental period, at all occasions; belonging to three groups (G1,G2 and G3) and receiving varying hours of photo-stimulation (P>0.05). It was inferred that the optimum lighting schedule for Chinese native breed Pengxian yellow pullets during 10 weeks of pre-pubertal growth period is short hours of photo-stimulation (i.e 8L:16D).

Influence of three lighting regimes during ten weeks growth phase on laying performance, plasma levels- and tissue specific gene expression- of reproductive hormones in Pengxian yellow pullets

PubMed Central

Li, Diyan; Liu, Zihao; Shen, Xiaoxu; Xu, Hengyong; Zhao, Xiaoling; Zhu, Qing

2017-01-01

The study was conducted to optimize lighting schedule for pre-pubertal (12 to 22 weeks) Chinese native breed Pengxian yellow pullet. A total of 414 healthy pullets (10 weeks), with similar body weight were randomly distributed into three groups (n = 138) and housed in individual cages for up to 12 weeks of age in light controlled rooms and provided normal lighting schedule (10L:14D). At 12 to 18 weeks of age, pullets were housed in three rooms, having varying lighting schedule viz. G1 (8L: 16D), G2 (10L:14D), or G3 (12L:12D). From 19th week onwards lighting schedule was gradually increased every week in incremental manner till all groups started receiving 16L:8D lighting schedule. The age at first egg, weight of first egg laid, percent peak hen day egg production, concentration of plasma luteinizing and follicle-stimulating hormones and expression of genes regulating synthesis or/and secretion of hypothalamic gonadotropin-releasing hormone-I (GnRH-I), and pituitary LH-β and FSH-β were studied during experimental period (12 to 43 weeks of age) of this study. The result indicated that pullets of long day length (G3) group had higher plasma levels of FSH and LH and also better mRNA expression that regulates synthesis or/and secretion of GnRH-I, FSH-β, and LH-β before egg laying. The age at first egg (151.3 days) in pullets of G3 group receiving longer lighting hours (12L:12D) was 8.8 days less (P<0.05) compared to pullets of G1 group, while it was 6.9 days less (P>0.05) compared to G2. However, significantly higher (P<0.05) plasma levels of LH and FSH in pullets of G1 as compared to pullets belonging to G3 group corresponded with the higher (P<0.05) cumulative egg production during the experimental period, while these attributes in G2 group didn’t differ from either G1 or G3 groups. Pullets of G1 group had significantly higher levels (P<0.05) of GnRH-I, FSH-β, and LH-β mRNA abundances at 43 weeks of age than other two groups and this corresponded with the percent (hen day) peak egg production (75.38%) in pullets in this G1 group that was attained at 32 weeks of age, while the peak production of 71.24% was attained at 30 weeks of age in G3 group. There was no effect of lighting schedule on body weight of pullets, recorded during experimental period, at all occasions; belonging to three groups (G1,G2 and G3) and receiving varying hours of photo-stimulation (P>0.05). It was inferred that the optimum lighting schedule for Chinese native breed Pengxian yellow pullets during 10 weeks of pre-pubertal growth period is short hours of photo-stimulation (i.e 8L:16D). PMID:28493941

True and sham acupuncture produced similar frequency of ovulation and improved LH to FSH ratios in women with polycystic ovary syndrome.

PubMed

Pastore, Lisa M; Williams, Christopher D; Jenkins, Jeffrey; Patrie, James T

2011-10-01

Acupuncture may represent a nonpharmaceutical treatment for women with polycystic ovary syndrome (PCOS), based on four studies. The objective of the study was to determine whether true, as compared with sham, acupuncture normalizes pituitary gonadotropin hormones and increases ovulatory frequency in women with PCOS. This was a randomized, double-blind, sham-controlled clinical trial (5 month protocol). The study was conducted in central Virginia. Eighty-four reproductive-aged women completed the intervention. Eligibility required a PCOS diagnosis and no hormonal intervention 60 d before enrollment. Intervention included 12 sessions of true or sham acupuncture (Park sham device) for 8 wk. Serum LH and FSH at baseline, after intervention, and 3 months later were measured. Ovulation was measured with weekly urine or blood samples. Both arms demonstrated a similar mean ovulation rate over the 5 months (0.37/month among n = 40 true acupuncture and 0.40/month among n = 44 sham participants, P = 0.6), similar LH to FSH ratio improvement (-0.5 and -0.8 true and sham, respectively, P < 0.04 after intervention vs. baseline) and a similar decline in LH over the 5-month protocol (P < 0.05). Neither arm experienced a change in FSH. There were seven pregnancies (no difference by intervention, P = 0.7). Lower fasting insulin and free testosterone were highly correlated with a higher ovulation rate within the true acupuncture group only (P = 0.03), controlling for prestudy menstrual frequency and body mass index. We were unable to discern a difference between the true and sham acupuncture protocols for these women with PCOS, and both groups had a similar improvement in their LH/FSH ratio.

Effects of human chorionic gonadotropin combined with clomiphene on Serum E2, FSH, LH and PRL levels in patients with polycystic ovarian syndrome.

PubMed

Yonggang, Huang; Xiaosheng, Lu; Zhaoxia, Huang; Yilu, Chen; Jiqiang, Lv; Huina, Zhang

2017-02-01

Effects of human chorionic gonadotropin combined with clomiphene on serum E 2 , FSH, LH and PRL levels in patients with polycystic ovarian syndrome were analyzed. 90 patients with polycystic ovarian syndrome treated from January 2015 to March 2016 were randomly and evenly divided into control group and observation group. Patients in the control group were only treated with clomiphene. On the basis of the treatment in control group, human chorionic gonadotropin was added in the treatment of observation group. The changes of E 2 , FSH, LH, PRL levels were compared between two groups before and after the treatment. Clinical curative effects of patients in the two groups was evaluated. Adverse reactions during treatment in two groups were observed and recorded. The incidence of adverse reactions was calculated. Serum E 2 , FSH, LH and PRL levels in the two groups decreased significantly after treatment compared with that before treatment. The difference is statistical significant ( P  < 0.05). After the treatment, E 2 , FSH, LH and PRL levels in the observation group were lower than that in the control group and the difference is statistical significant ( P  < 0.05). Total effective rate was 64.44% in the control group and 93.33% in the observation group. There were statistically significant difference in clinical curative effects in the two groups ( P  < 0.05). Different degrees of adverse reactions were found in both groups during treatment, such as nausea, vomiting, anorexia, liver dysfunction. There were 2 cases of nausea, 2 cases of vomiting, 3 cases of anorexia and 1 case of liver dysfunction from the 45 patients in control group. The total incidence of adverse reactions was 17.78% (8/45). There were 1 case of nausea, 1 case of vomiting, 1 case of anorexia and no liver dysfunction from the 45 patients in observation group. The total incidence of adverse reactions was 6.67% (3/45). The total incidence of adverse reactions in the observation group was significantly higher than that in the control group and the difference was not statistically significant ( P  > 0.05). Combined use of human chorionic gonadotropin can significantly reduce serum E 2 , FSH, LH and PRL levels, improve clinical curative effects and reduce the incidence of adverse reactions. Human chorionic gonadotropin has high application value on the treatment of polycystic ovary syndrome.

Interferon-γ acts as a regulator in the trade-off between phagocytosis and production performance in dwarf chickens.

PubMed

Yuan, Yitong; Liu, Shunqi; Zhao, Yue; Lian, Ling; Lian, Zhengxing

2018-01-01

Interferon-γ (IFN-γ) is critical for innate and adaptive immunity against viral and bacterial infections. IFN-γ reportedly affects the phagocytic ability of monocytes and macrophages as well as regulates pituitary function in humans and mice. The present study analyzed the impact of IFN-γ on monocyte and macrophage phagocytosis, production performance, and pituitary function in vivo and in vitro (in dwarf chickens). IFN-γ was injected into dwarf chickens through a vein, and then, the laying rate, average egg weight, and levels of follicle-stimulating hormone (FSH) and IFN-γ were measured in treatment and control groups. For the in vitro experiment, the pituitary tissues were supplemented with IFN-γ, and the mRNA expression levels of follicle-stimulating hormone beta subunit ( FSH-β ), interferon gamma receptor 1 ( IFNGR 1), and interferon gamma receptor 2 ( IFNGR 2) in the pituitary were assessed. Monocyte and macrophage phagocytosis product (PP) was decreased by IFN-γ treatment in a dose-dependent manner in vitro. In the in vivo experiment, the level of IFN-γ in the treatment group was higher than that in the control group at 7 d ( P  < 0.05), 14 d ( P  < 0.01), and 21 d ( P  < 0.01) post-injection. Compared with the control group, monocyte and macrophage PP was lower in the treatment group after injection ( P  < 0.01). The laying rate was higher in the treatment group than in the control group at 2 and 3 wk post-injection ( P  < 0.05). There was a significant difference between the treatment and control groups in the levels of FSH at 1, 3, 7, and 14 d post-injection ( P  < 0.01). In the in vitro experiment, increased mRNA expression levels of FSH-β , IFNGR 1, and IFNGR 2 were observed in the treatment group after stimulation with 100 U/mL IFN-γ for 24 h compared to those in the control group ( P  < 0.05). IFN-γ inhibited the phagocytosis of monocytes and macrophages; up-regulated the mRNA expression levels of the FSH-β , IFNGR 1, and IFNGR 2; enhanced the secretion of FSH; and improved the laying rate. IFN-γ might be an important regulator in the trade-off between the immune effect and production performance in dwarf chickens.

Persistent organic pollutants as predictors of increased FSH:LH ratio in naturally cycling, reproductive age women.

PubMed

Gallo, Mia V; Ravenscroft, Julia; Carpenter, David O; Schell, Lawrence M; Akwesasne Task Force On The Environment

2018-07-01

Although several recent studies suggest endocrine disrupting compounds, such as polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p', DDE), and hexachlorobenzene (HCB), target different organs and systems in the body, their impact on female reproductive function in humans is not well characterized. We seek to determine the relationship between several known endocrine disrupting compounds and a marker of ovarian responsivity, the FSH:LH ratio (higher ratio indicates less ovarian responsivity). For this analysis, 169 naturally cycling women between 21 and 38 years of age completed interviews and had their blood drawn on day 3 of their menstrual cycle for analyses of toxicants, gonadal sex hormones (E 2 and P 4 ), and gonadotropins (FSH and LH). PCB congeners were classified into five groups based on their environmental persistence, distribution in human tissue, and toxicological action, reflecting the structure, mechanism, and known biological activity of individual PCB congeners. For every unit (ppb) increase in the level of the estrogenic PCB group, there was a 5-fold greater risk of a FSH:LH ratio ≥ 2, controlling for individual differences in age, percent body fat, cycle day 3 estradiol levels, parity, alcohol use and cigarette smoking in the past year (exp[ß] = 5; p = ≤0.01). PCB congeners identified as estrogenic were analyzed individually, and, of the 19 potentially estrogenic congeners, five were significantly, and positively related to an increased FSH:LH ratio. Four of these congeners are non-persistent, easily volatilize in the environment, and are easily metabolized, and hence, are indicative of very recent or current exposure. p,p'-DDE and HCB were not associated with FSH:LH ratio. We find a clinical indicator of ovarian responsivity, FSH:LH ratio, is associated with a specific group of estrogenic PCBs. These congeners may become airborne when they volatilize from dredged PCB-contaminated soil or from indoor PCB-containing window caulk and sealants in older buildings leading to inhalation exposure. PCB exposure, particularly to non-persistent, estrogenic congeners, may pose an unrecognized threat to female fecundity within the general population. Copyright © 2018 Elsevier Inc. All rights reserved.

Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia.

PubMed

Juniarto, A Zulfa; van der Zwan, Yvonne G; Santosa, Ardy; Ariani, Mahayu Dewi; Eggers, Stefanie; Hersmus, Remko; Themmen, Axel P N; Bruggenwirth, Hennie T; Wolffenbuttel, Katja P; Sinclair, Andrew; White, Stefan J; Looijenga, Leendert H J; de Jong, Frank H; Faradz, Sultana M H; Drop, Stenvert L S

2016-08-01

The objective of this study was to determine the aetiological spectrum of disorders of sex development (DSD) in a large cohort of underprivileged and undiagnosed patients from Indonesia. A total of 286 patients with atypical external and/or internal genitalia were evaluated using clinical, hormonal, molecular genetic and histological parameters. The age (years) at presentation was 0-0·5 in 41 (14·3%), >0·5-12 in 181 (63·3%) and >12 in 64 cases (22·4%). 46,XY DSD was most common (68·2%, n = 195), 46,XX DSD was found in 23·4% (n = 67) and sex chromosomal DSD in 8·4% (n = 24). In 61·2% of 46,XX DSD patients, 17·9% of 46,XY DSD patients and all sex chromosome DSD patients (29·4% in total), a final diagnosis was reached based on genetic or histological gonadal tissue evaluation. 17-hydroxyprogesterone and androstenedione levels were the most distinctive parameters in 46,XX DSD patients. In 46,XY DSD, diagnostic groups were identified based on the external masculinization score: androgen action disorder (AAD), unknown male undermasculinization (UMU), and gonadal dysgenesis (GD). LH, FSH and testosterone levels were most informative especially in the older age group. HCG tests were of no additional value as no patients with androgen synthesis disorders were found. Hormonal profiles of patients with sex chromosome DSD and a Y-chromosome sequence containing karyotype showed high levels of LH and FSH, and low levels of AMH, inhibin B and testosterone compared with the normal male range. Gene mutations were found in all patients with CAH, but in only 24·5% and 1·8% of patients with AAD and UMU. In 32% of 46,XY GD patients, copy number variants of different genes were found. A stepwise diagnostic approach led to a molecularly or histologically proven final diagnosis in 29·4% of the patients. The most informative parameters were serum levels of 17-hydroxyprogesterone and androstenedione in 46,XX DSD patients, and serum LH, FSH and testosterone levels in 46,XY DSD patients. © 2016 John Wiley & Sons Ltd.

Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists.

PubMed

Yanofsky, Stephen D; Shen, Emily S; Holden, Frank; Whitehorn, Erik; Aguilar, Barbara; Tate, Emily; Holmes, Christopher P; Scheuerman, Randall; MacLean, Derek; Wu, May M; Frail, Donald E; López, Francisco J; Winneker, Richard; Arey, Brian J; Barrett, Ronald W

2006-05-12

The pituitary glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone (FSH), act through their cognate receptors to initiate a series of coordinated physiological events that results in germ cell maturation. Given the importance of FSH in regulating folliculogenesis and fertility, the development of FSH mimetics has been sought to treat infertility. Currently, purified and recombinant human FSH are the only FSH receptor (FSH-R) agonists available for infertility treatment. By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC50's = 20 microm) of the human FSH-R. Subsequent analog library screening and parallel synthesis optimization resulted in the identification of a potent agonist (EC50 = 2 nm) with full efficacy compared with FSH that was FSH-R-selective and -dependent. The compound mediated progesterone production in Y1 cells transfected with the human FSH-R (EC50 = 980 nm) and estradiol production from primary rat ovarian granulosa cells (EC50 = 10.5 nm). This and related compounds did not compete with FSH for binding to the FSH-R. Use of human FSH/thyroid-stimulating hormone (TSH) receptor chimeras suggested a novel mechanism for receptor activation through a binding site independent of the natural hormone binding site. This study is the first report of a high affinity small molecule agonist that activates a glycoprotein hormone receptor through an allosteric mechanism. The small molecule FSH receptor agonists described here could lead to an oral alternative to the current parenteral FSH treatments used clinically to induce ovarian stimulation for both in vivo and in vitro fertilization therapy.

Hormonal therapy (hCG and rhFSH) for infertile men with adult-onset idiopathic hypogonadotropic hypogonadism.

PubMed

Kobori, Yoshitomo; Suzuki, Keisuke; Iwahata, Toshiyuki; Shin, Takeshi; Sato, Ryo; Nishio, Kojiro; Yagi, Hiroshi; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

2015-04-01

Adult-onset idiopathic male hypogonadotropic hypogonadism (IMHH) is a very rare but treatable disease. This study was conducted to examine the efficacy and safety of a combination of human chorionic gonadotropin (hCG) and recombinant human follicle-stimulating hormone (rhFSH) for inducing spermatogenesis in men with adult-onset IMHH. Seven men (34-45 years of age) with azoospermia and/or sexual dysfunction, with a low serum testosterone concentration, and apulsatile secretion of luteinizing hormone, were referred to our hospital for infertility. All had normal secondary sexual characteristics. Thorough endocrinologic examination and magnetic resonance imaging revealed no identifiable cause of hypogonadotropic hypogonadism. Adult-onset IMHH was diagnosed in all cases and treatment was started with 150 IU rhFSH and 5,000 IU hCG, both administered two times per week. Spermatogenesis was restored in five of the seven patients. During treatment one patient achieved spontaneous pregnancy with his wife, and spermatozoa recovered from the other four patients were frozen for future use in intracytoplasmic sperm injection.

Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

PubMed

Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

2016-11-01

To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Spontaneous recovery from isolated post-traumatic central hypogonadism in a woman.

PubMed

Ruggeri, Rosaria M; Smedile, Giovanni; Granata, Francesca; Longo, Marcello; Cannaíò, Salvatore; Sarlis, Nicholas J; Trimarchi, Francesco; Benvenga, Salvatore

2010-01-01

Hypopituitarism is a recognized complication of Traumatic Brain Injury (TBI). Resolution of established anterior pituitary hormones deficiency is rare. A woman was initially presented at the age of 22 years with amenorrhoea. Two years earlier she had been involved in a car accident with consequent TBI. At our evaluation, serum oestradiol (E2) was low (3 pmol/l), Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) were borderline low [1.7 and 2.5 mIU/l, normal range (NR) for 20-35 yr old women being 1.4-13 and 2.5-13, respectively] with poor response to Gonadotropin Releasing Hormone (GnRH) (ΔLH = 2.4 and, ΔFSH = 4.0 mIU/l), while serum Prolactin (PRL) was elevated (951 mIU/l; NR: 102-496). No other pituitary hormone deficiencies were observed. Magnetic resonance imaging (MRI) showed a partially empty sella and very thin stalk. Ten years later a new endocrine evaluation was performed. On day 4 of her menstrual cycle, serum values of PRL (196 mIU/l), FSH (4.7 mIU/l), LH (4.8 mIU/l) and E2 (103 pmol/l) were within normal limits for women aged 20-35. Six months after this evaluation (that is, 12 years after trauma), the patient became pregnant and delivered a healthy baby. Our case shows that spontaneous resolution of post-head trauma anterior hypopituitarism occur even many years after head injury. Medicolegal implications are self-evident.

Effectiveness of Acupuncture for Primary Ovarian Insufficiency: A Systematic Review and Meta-Analysis.

PubMed

Jo, Junyoung; Lee, Yoon Jae; Lee, Hyangsook

2015-01-01

Objective. This systematic review aimed to assess current evidence from randomized controlled trials (RCTs) on the effects of acupuncture for patients with primary ovarian insufficiency (POI). Methods. We searched twelve databases to identify relevant studies published before July 2014. The outcomes were serum follicle-stimulating hormone (FSH) levels and resumption of menstruation. Two reviewers independently assessed the risk of bias using the Cochrane's tool, extracted the results, and evaluated the overall level of the evidence using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Results. Eight RCTs were selected. Acupuncture significantly lowered serum FSH levels and more women receiving acupuncture reported resumption of menses. However, the results should be interpreted with caution due to a small number of participants, high risk of bias for blinding, and likely publication bias. The level of evidence for FSH level and resumption of menses were assessed as "low" using GRADE. Conclusion. The current evidence on acupuncture for POI is insufficient to draw a firm conclusion due to scarcity of studies with a low risk of bias and likely publication bias. Further rigorously designed and conducted studies are needed to confirm the effectiveness and safety of acupuncture in patients with POI.

Heterophilic antibody interference affecting multiple hormone assays: Is it due to rheumatoid factor?

PubMed

Mongolu, Shiva; Armston, Annie E; Mozley, Erin; Nasruddin, Azraai

2016-01-01

Assay interference with heterophilic antibodies has been well described in literature. Rheumatoid factor is known to cause similar interference leading to falsely elevated hormone levels when measured by immunometric methods like enzyme-linked immunosorbent assay (ELISA) or multiplex immunoasays (MIA). We report a case of a 60-year-old male patient with a history of rheumatoid arthritis referred to our endocrine clinic for investigation of hypogonadism and was found to have high serum levels of LH, FSH, SHBG, Prolactin, HCG and TSH. We suspected assay interference and further tests were performed. We used Heteroblock tubes and PEG precipitation to eliminate the interference and the hormone levels post treatment were in the normal range. We believe the interference was caused by high serum levels of rheumatoid factor. Although he was treated with thyroxine for 3 years, we believe he may have been treated inappropriately as his Free T4 level was always normal despite high TSH due to assay interference. Our case illustrates the phenomenon of heterophilic antibody interference likely due to high levels of rheumatoid factor. It is essential for clinicians and endocrinologists in particular to be aware of this possibility when making treatment decisions in these groups of patients.

Prader-Willi syndrome with elevated follicle stimulating hormone levels and diabetes mellitus.

PubMed

Nagai, T; Mimura, N; Tomizawa, T; Monden, T; Mori, M

1998-12-01

A 21 -year-old man with Prader-Willi syndrome (PWS) was hospitalized due to hyperglycemia. After diet therapy and transient insulin administration, his blood glucose levels improved. Based on the fact that his urinary C-peptide levels increased, the diabetes mellitus may have been due to insulin resistance with obesity. In addition, his testes had become atrophied. Testosterone levels remained low even after human chorionic gonadotropin (HCG) administration. Luteinizing hormone (LH) levels were also low after LH releasing hormone (LHRH) administration. The LH response increased slightly after daily LHRH administration, indicating hypothalamic hypogonadism. Follicle stimulating hormone (FSH) levels were, however, high and increased after LHRH administration. The selective FSH elevation may have been due to the accompanying idiopathic oligospermia.

Synthetic peptides corresponding to human follicle-stimulating hormone (hFSH)-beta-(1-15) and hFSH-beta-(51-65) induce uptake of 45Ca++ by liposomes: evidence for calcium-conducting transmembrane channel formation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grasso, P.; Santa-Coloma, T.A.; Reichert, L.E. Jr.

1991-06-01

We have previously described FSH receptor-mediated influx of 45Ca++ in cultured Sertoli cells from immature rats and receptor-enriched proteoliposomes via activation of voltage-sensitive and voltage-independent calcium channels. We have further shown that this effect of FSH does not require cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding protein or activation of adenylate cyclase. In the present study, we have identified regions of human FSH-beta-subunit which appear to be involved in mediating calcium influx. We screened 11 overlapping peptide amides representing the entire primary structure of hFSH-beta-subunit for their effects on 45Ca++ flux in FSH receptor-enriched proteoliposomes. hFSH-beta-(1-15) and hFSH-beta-(51-65) inducedmore » uptake of 45Ca++ in a concentration-related manner. This effect of hFSH-beta-(1-15) and hFSH-beta-(51-65) was also observed in liposomes lacking incorporated FSH receptor. Reducing membrane fluidity by incubating liposomes (containing no receptor) with hFSH-beta-(1-15) or hFSH-beta-(51-65) at temperatures lower than the transition temperatures of their constituent phospholipids resulted in no significant (P greater than 0.05) difference in 45Ca++ uptake. The effectiveness of the calcium ionophore A23187, however, was abolished. Ruthenium red, a voltage-independent calcium channel antagonist, was able to completely block uptake of 45Ca++ induced by hFSH-beta-(1-15) and hFSH-beta-(51-65) whereas nifedipine, a calcium channel blocker specific for L-type voltage-sensitive calcium channels, was without effect. These results suggest that in addition to its effect on voltage-sensitive calcium channel activity, interaction of FSH with its receptor may induce formation of transmembrane aqueous channels which also facilitate influx of extracellular calcium.« less

Long-acting follicle-stimulating hormone analogs containing N-linked glycosylation exhibited increased bioactivity compared with o-linked analogs in female rats.

PubMed

Weenen, C; Peña, J E; Pollak, S V; Klein, J; Lobel, L; Trousdale, R K; Palmer, S; Lustbader, E G; Ogden, R T; Lustbader, J W

2004-10-01

The effects of altering the number and type of additional carbohydrate moieties on the pharmacokinetic and pharmacodynamic properties of FSH were examined in this report. A series of single-chain follitropins, containing variable numbers of additional N- (or O-) linked carbohydrates, were designed and expressed in Chinese hamster ovary cells. Proper folding, efficient receptor binding, and signal transduction were confirmed by in vitro assays. Pharmacokinetic and pharmacodynamic parameters were evaluated in immature female Sprague Dawley rats. Increasing the number of glycosylation sites with either N- (or O-) linked moieties extended the elimination half-life as much as 2-fold compared with recombinant human FSH (rhFSH). However, there was a maximum elimination half-life such that further glycosylation provided no additional lengthening of the half-life. Conversely, biopotency, as assessed by inhibin A levels 74 h post injection, and follicle production were significantly higher for the N-linked analogs. Rats stimulated with the longest acting analogs (either N- or O-linked) showed significantly higher ovarian weights than rats receiving a single injection of rhFSH. The analog containing four additional N-linked sites (rhFSH-N4) had the greatest number of large, preovulatory follicles. Although the half-life of rhFSH-N4 displayed no further enhancement beyond the other longest acting analogs, this analog exhibited significantly increased biopotency in rats. This work provides the basis for the generation of a series of reagents potentially useful for therapeutic applications.

Clinical efficacy and cost-effectiveness of HP-human FSH (Fostimon®) versus rFSH (Gonal-F®) in IVF-ICSI cycles: a meta-analysis.

PubMed

Gerli, Sandro; Bini, Vittorio; Favilli, Alessandro; Di Renzo, Gian Carlo

2013-06-01

Clinical efficacy of human-derived follicle-stimulating hormone (FSH) versus recombinant FSH (rFSH) in IVF-ICSI cycles has long been compared, but no clear evidence of the superiority of a preparation over the other has been found. Human gonadotropins have been often grouped together, but a different glycosylation may be present in each preparation, therefore influencing the specific bioactivity. To exclude confounding factors, a meta-analysis and a cost-effectiveness analysis were designed to compare effectiveness and cost-effectiveness of a specific highly purified human FSH (HP-hFSH) (Fostimon®) versus rFSH (Gonal-F®) in IVF/ICSI cycles. Research methodology filters were applied in MEDLINE, Current Contents and Web of Science from 1980 to February 2012. Eight randomized trials met selection criteria. The meta-analysis showed no significant differences between rFSH and HP-hFSH treatment in live-birth rate (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.63-1.11), clinical pregnancy rate (OR 0.85, 95% CI 0.68-1.07), number of oocytes retrieved, number of mature oocytes and days of stimulation. The cost-effectiveness ratio was € 7174 in the rFSH group and € 2056 in the HP-hFSH group. HP-hFSH is as effective as rFSH in ovarian stimulation for IVF-ICSI cycles, but the human preparation is more cost-effective.

Biological markers of fertility (inhibin-B) in HIV-infected men: influence of HIV infection and antiretroviral therapy.

PubMed

Moreno-Pérez, O; Boix, V; Merino, E; Picó, A; Reus, S; Alfayate, R; Giner, L; Mirete, R; Sánchez-Payá, J; Portilla, J

2016-06-01

Inhibin B (IB) levels and the IB: follicle-stimulating hormone (FSH) ratio (IFR), biomarkers of global Sertoli cell function, show a strong relationship with male fertility. The aim of the study was to examine the prevalence of impaired fertility potential in HIV-infected men and the influence of antiretroviral therapy (ART) on fertility biomarkers. A cross-sectional study with sequential sampling was carried out. A total of 169 clinically stable patients in a cohort of HIV-infected men undergoing regular ambulatory assessment in a tertiary hospital were included. The mean [± standard deviation (SD)] age of the patients was 42.6 ± 8.1 years, all were clinically stable, 61.5% had disease classified as Centers for Disease Control and Prevention (CDC) stage A, and were na?ve to ART or had not had any changes to ART for 6 months (91.1%). Morning baseline IB and FSH concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) and an electrochemiluminescent immunoassay (ECLIA), respectively. A multivariate logistic regression model was used to identify factors associated with impaired fertility, defined as IB < 119 pg/mL or IFR < 23.5. The mean (± SD) IB level was 250 ± 103 pg/mL, the median [interquartile range (IQR)] FSH concentration was 5.1 (3.3-7.8) UI/L and the median (IQR) IFR was 46.1 (26.3-83.7). The prevalence of impaired fertility was 21.9% [95% confidence interval (CI) 16.3-20.7%]. Negative correlations of body mass index and waist: hip ratio with FSH and IB levels were observed (P < 0.01), while a sedentary lifestyle and previous nevirapine exposure were associated with a decreased risk of IB levels ≤ 25th percentile in multivariate analysis. Only older age, as a risk factor, and sedentary lifestyle, with a protective effect, were independently associated with impaired fertility in multivariate analysis. Global testicular Sertoli cell function and fertility potential, assessed indirectly through serum IB levels and IB: FSH ratio, appear to be well maintained in HIV-infected men and not damaged by ART. © 2015 British HIV Association.

Insulin-like peptide 3 (INSL3) in men with congenital hypogonadotropic hypogonadism/Kallmann syndrome and effects of different modalities of hormonal treatment: a single-center study of 281 patients.

PubMed

Trabado, Séverine; Maione, Luigi; Bry-Gauillard, Hélène; Affres, Hélène; Salenave, Sylvie; Sarfati, Julie; Bouvattier, Claire; Delemer, Brigitte; Chanson, Philippe; Le Bouc, Yves; Brailly-Tabard, Sylvie; Young, Jacques

2014-02-01

Insulin-like factor 3 (INSL3) is a testicular hormone secreted during fetal life, the neonatal period, and after puberty. To measure INSL3 levels in a large series of men with congenital hypogonadotropic hypogonadism (CHH)/ Kallmann syndrome (KS), in order to assess its diagnostic value and to investigate its regulation. We studied 281 CHH/KS patients (91 untreated, 96 receiving T, and 94 receiving combined gonadotropin therapy [human chorionic gonadotropin, hCG, and FSH]) and 72 age-matched healthy men. Serum INSL3 was immunoassayed with a validated RIA. Mean (±SD) INSL3 levels (pg/mL) were 659 ± 279 in controls and lower (60 ± 43; P < .001) in untreated CHH/KS patients, with no overlap between the two groups, when the threshold of 250 pg/mL was used. Basal INSL3 levels were lower in both untreated CHH/KS men with cryptorchidism than in those with intrascrotal testes and in patients with testicular volumes below 4 mL. Significant positive correlations between INSL3 and both serum total T and LH levels were observed in untreated CHH/KS. Mean INSL3 levels remained low in T-treated CHH/KS patients and were significantly higher in men receiving combined hCG-FSH therapy (P < .001), but the increase was lower cryptorchid patients. FSH-hCG combination therapy or hCG monotherapy, contrary to T and FSH monotherapies, significantly increased INSL3 levels in CHH/KS. INSL3 is as sensitive a marker as T for the evaluation of altered Leydig cell function in CHH/KS patients. INSL3 levels correlate with LH levels in CHH/KS men showing, together with the rise in INSL3 levels during hCG therapy, that INSL3 secretion seems not constitutively secreted during adulthood but is dependence on pituitary LH.

Subcutaneous injection of kisspeptin-54 acutely stimulates gonadotropin secretion in women with hypothalamic amenorrhea, but chronic administration causes tachyphylaxis.

PubMed

Jayasena, Channa N; Nijher, Gurjinder M K; Chaudhri, Owais B; Murphy, Kevin G; Ranger, Amita; Lim, Adrian; Patel, Daksha; Mehta, Amrish; Todd, Catriona; Ramachandran, Radha; Salem, Victoria; Stamp, Gordon W; Donaldson, Mandy; Ghatei, Mohammad A; Bloom, Stephen R; Dhillo, Waljit S

2009-11-01

Kisspeptin is a critical regulator of normal reproductive function. A single injection of kisspeptin in healthy human volunteers potently stimulates gonadotropin release. However, the effects of kisspeptin on gonadotropin release in women with hypothalamic amenorrhea (HA) and the effects of repeated administration of kisspeptin to humans are unknown. The aim of this study was to determine the effects of acute and chronic kisspeptin administration on gonadotropin release in women with HA. We performed a prospective, randomized, double-blinded, parallel design study. Women with HA received twice-daily sc injections of kisspeptin (6.4 nmol/kg) or 0.9% saline (n = 5 per group) for 2 wk. Changes in serum gonadotropin and estradiol levels, LH pulsatility, and ultrasound measurements of reproductive activity were assessed. On the first injection day, potent increases in serum LH and FSH were observed after sc kisspeptin injection in women with HA (mean maximal increment from baseline within 4 h after injection: LH, 24.0 +/- 3.5 IU/liter; FSH, 9.1 +/- 2.5 IU/liter). These responses were significantly reduced on the 14th injection day (mean maximal increment from baseline within 4 h postinjection: LH, 2.5 +/- 2.2 IU/liter, P < 0.05; FSH, 0.5 +/- 0.5 IU/liter, P < 0.05). Subjects remained responsive to GnRH after kisspeptin treatment. No significant changes in LH pulsatility or ultrasound measurements of reproductive activity were observed. Acute administration of kisspeptin to women with infertility due to HA potently stimulates gonadotropin release, but chronic administration of kisspeptin results in desensitization to its effects on gonadotropin release. These data have important implications for the development of kisspeptin as a novel therapy for reproductive disorders in humans.

Neonatal handling and reproductive function in female rats.

PubMed

Gomes, C M; Raineki, C; Ramos de Paula, P; Severino, G S; Helena, C V V; Anselmo-Franci, J A; Franci, C R; Sanvitto, G L; Lucion, A B

2005-02-01

Neonatal handling induces anovulatory estrous cycles and decreases sexual receptivity in female rats. The synchronous secretion of hormones from the gonads (estradiol (E2) and progesterone (P)), pituitary (luteinizing (LH) and follicle-stimulating (FSH) hormones) and hypothalamus (LH-releasing hormone (LHRH)) are essential for the reproductive functions in female rats. The present study aimed to describe the plasma levels of E2 and P throughout the estrous cycle and LH, FSH and prolactin (PRL) in the afternoon of the proestrus, and the LHRH content in the medial preoptic area (MPOA), median eminence (ME) and medial septal area (MSA) in the proestrus, in the neonatal handled rats. Wistar pup rats were handled for 1 min during the first 10 days after delivery (neonatal handled group) or left undisturbed (nonhandled group). When they reached adulthood, blood samples were collected through a jugular cannula and the MPOA, ME and MSA were microdissected. Plasma levels of the hormones and the content of LHRH were determined by RIA. The number of oocytes counted in the morning of the estrus day in the handled rats was significantly lower than in the nonhandled ones. Neonatal handling reduces E2 levels only on the proestrus day while P levels decreased in metestrus and estrus. Handled females also showed reduced plasma levels of LH, FSH and PRL in the afternoon of the proestrus. The LHRH content in the MPOA was significantly higher than in the nonhandled group. The reduced secretion of E2, LH, FSH and LHRH on the proestrus day may explain the anovulatory estrous cycle in neonatal handled rats. The reduced secretion of PRL in the proestrus may be related to the decreased sexual receptiveness in handled females. In conclusion, early-life environmental stimulation can induce long-lasting effects on the hypothalamus-pituitary-gonad axis.

Investigative clinical study on prostate cancer part VI: Follicle-stimulating hormone and the pituitary-testicular-prostate axis at the time of initial diagnosis and subsequent cluster selection of the patient population.

PubMed

Porcaro, Antonio B; Migliorini, Filippo; Petrozziello, Aldo; Sava, Teodoro; Romano, Mario; Caruso, Beatrice; Cocco, Claudio; Ghimenton, Claudio; Zecchinini Antoniolli, Stefano; Lacola, Vincenzo; Rubilotta, Emanuele; Monaco, Carmelo; Comunale, Luigi

2012-01-01

To evaluate the physiopathology of follicle-stimulating hormone (FSH) along the pituitary-testicular-prostate axis at the time of initial diagnosis of prostate cancer in relation to the available clinical variables and to the subsequent cluster selection of the patient population. The study included 98 patients who were diagnosed with prostate cancer. Age, percentages of positive cores (P+) at transrectal ultrasound scan biopsy, biopsy Gleason score (bGS), luteinizing hormone (LH), FSH, total testosterone, free testosterone (FT) and prostate-specific antigen (PSA) were the continuous clinical variables. All patients had not previously received hormonal manipulations. FSH correlation and multiple linear analyses were computed in the population. The FSH/PSA ratio was computed and then ranked for clustering the population as groups A (0.13≤FSH/PSA≤0.57), B (0.57

[Specifics of hormonal and energy balance in patients with hyperplasia and endometrial neoplasia with metabolic syndrome in the background].

PubMed

Chernyshova, A L; Kolomiets, L A; Bochkarëva, N V; Kondakova, I V

2013-01-01

We conducted a comparative investigation of the hormonal status (LH, FSH, estradiol, progesterone, testosterone, prolactin, SHBG), energy status (leptin, ghrelin, insulin), and carbohydrate and lipid metabolism in patients with endometrial hyperplasia and neoplasia (168 patients) with or without metabolic syndrome in the background. Patients with metabolic syndrome had a high frequency of elevated estrogen (72%), testosterone (65%), insulin (81%), leptin (68%). There was a marked increase in the basal level of luteinizing hormone, prolactin, index, LH/FSH, but decrease in FSH and progesterone. There were significant changes in carbohydrate and lipid metabolism. The possible mechanisms for the contribution of the investigated factors to the development of the pathological processes in the endometrium are presented.

Laser homeostatics on delayed onset muscle soreness

NASA Astrophysics Data System (ADS)

Liu, T. C. Y.; Fu, D. R.; Liu, X. G.; Tian, Z. X.

2011-01-01

Delayed onset muscle soreness (DOMS) and its photobiomodulation were reviewed from the viewpoint of function-specific homeostasis (FSH) in this paper. FSH is a negative-feedback response of a biosystem to maintain the function-specific fluctuations inside the biosystem so that the function is perfectly performed. A stressor may destroy a FSH. A stress is a response of a biosystem to a stressor and may also be in stress-specific homeostasis (StSH). A low level light (LLL) is so defined that it has no effects on a function in its FSH or a stress in its StSH, but it modulate a function far from its FSH or a stress far from its StSH. For DOMS recovery, protein metabolism in the Z-line streaming muscular cell is the essential process, but the inflammation, pain and soreness are non-essential processes. For many DOMS phenomena, protein metabolism in the Z-line streaming muscular cell is in protein metabolism-specific homeostasis (PmSH) so that there are no effects of LLL although the inflammation can be inhibited and the pain can be relieved. An athlete or animal in the dysfunctional conditions such as blood flow restriction and exercise exhaustion is far from PmSH and the protein metabolism can be improved with LLL.

High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS).

PubMed

Ganie, Mohd Ashraf; Hassan, Saqib; Nisar, Sobia; Shamas, Nasir; Rashid, Aafia; Ahmed, Ishfaq; Douhat, Syed; Mudassar, Syed; Jan, Vicar M; Rashid, Fouzia

2014-11-01

C-reactive protein (CRP) is a risk marker for type 2 diabetes mellitus and cardiovascular diseases. In polycystic ovary syndrome (PCOS), limited data are available on high-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of PCOS especially in Indian women. The objective was to determine serum hs-CRP concentration in adolescent women with and without PCOS and to assess possible correlations of serum hs-CRP levels with components of PCOS in Indian women. One hundred and sixty women with PCOS and sixty non-PCOS women having normal menstrual cycles were included. Clinical assessment included anthropometry, Ferriman-Gallwey (FG) score and blood pressure (BP) measurement. Laboratory evaluation included estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, hs-CRP, lipid profile, and insulin, and glucose after 2-h oral glucose tolerance test. Homeostasis Model Assessment Insulin resistance index (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) and glucose intolerance was calculated. FG score, LH, FSH, total Testosterone, HOMA-IR and QUICKI were significantly different among women with or without PCOS (p < 0.01). Although hs-CRP levels showed a higher trend in women having PCOS, there was no significant difference between the groups (p > 0.05). A significant and positive correlation was found between hs-CRP and body mass index (BMI) (r = 0.308, p < 0.01) among PCOS group. The results in Indian adolescent women suggest that hs-CRP levels may not per se be associated with PCOS, rather can be related to fat mass in this subset of subjects.

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice1

PubMed Central

Kauffman, Alexander S.; Thackray, Varykina G.; Ryan, Genevieve E.; Tolson, Kristen P.; Glidewell-Kenney, Christine A.; Semaan, Sheila J.; Poling, Matthew C.; Iwata, Nahoko; Breen, Kellie M.; Duleba, Antoni J.; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J.; Mellon, Pamela L.

2015-01-01

Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition. PMID:26203175

Women with oligo-/amenorrhoea and polycystic ovaries have identical responses to GnRH stimulation regardless of their androgen status: comparison of the Rotterdam and Androgen Excess Society diagnostic criteria.

PubMed

Lewandowski, Krzysztof C; Cajdler-Luba, Agata; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

2011-01-01

As increased frequency of gonadotrophin-releasing hormone (GnRH) pulses is characteristic for polycystic ovary syndrome (PCOS), we assessed gonadotrophin response to GnRH in women with PCOS with normal and raised androgens and in regularly menstruating controls. The study involved 155 subjects: PCOS, n=121, age (mean±SD) 24.8±5.4 yrs, BMI 24.5±6.0 kg/m2, all with oligo-/amenorrhoea and PCO morphology, and 34 controls. Gonadotrophins were measured in early follicular phase after GnRH stimulation (0, 30 and 60 minutes). Fifty four (41.9%) women with PCOS had androgens (testosterone, androstendione, dihydroepiandrosterone sulphate) within the reference range, and would fulfil the "Rotterdam", but not the Androgen Excess Society PCOS criteria. Baseline and stimulated LH concentrations were higher in PCOS (9.09±5.56 vs 4.83±1.71 IU/l, 35.48±31.4 vs 16.30±6.68 IU/l, 33.86±31.8 vs 13.45±5.2 IU/l, at 0, 30 and 60 min post GnRH, respectively, p<0.0001). An LH/FSH ratio in PCOS increased further after GnRH stimulation. ROC analysis revealed that LH30min/FSH30min >2.11 or LH60min/FSH60min >1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for diagnosis of PCOS. Both baseline and GnRH-stimulated LH and FSH concentrations were similar in women with PCOS and raised androgens and with androgens within the reference range (p=0.71 and p=0.20 for LH and FSH, respectively). Regardless of their androgen status, women with PCO morphology and oligo-/amenorrhoea have higher baseline and GnRH-stimulated LH concentrations and higher GnRH-stimulated LH/FSH ratio than controls, suggestive of similar underlying mechanism accounting for menstrual irregularities. These observations support validity of PCOS diagnostic criteria based on the Rotterdam consensus.

Reproductive hormones in menstrual blood.

PubMed

Zhou, J P; Fraser, I S; Caterson, I; Grivas, A; McCarron, G; Norman, T; Tan, K

1989-08-01

Menstrual and peripheral blood samples were collected from 19 regularly cycling women on days 1-3 of the menstrual cycle. Menstrual samples were collected with a soft silicone rubber menstrual cup. Hematocrit, PRL, LH, FSH, estradiol (E2), and progesterone (P4) were measured in all samples. Validation studies were carried out for RIAs of PRL, LH, and FSH in menstrual plasma. The menstrual plasma PRL level was significantly higher than its peripheral blood level on day 1 (63.3 +/- 14.7 and 12.1 +/- 2.9 micrograms/L, respectively; t = 3.331; P less than 0.01), and menstrual PRL was significantly higher on day 1 than on day 2 (t = 3.340; P less than 0.01). There was a strong negative correlation between log menstrual PRL concentration and time of onset of menstruation (r = -0.596; P less than 0.01). Menstrual plasma FSH levels were significantly lower than peripheral levels on each of days 1-3 (day 1:t = 4.787; P less than 0.001), and there was a significant positive correlation between menstrual and peripheral levels (r = 0.607; P less than 0.01). By contrast, menstrual plasma LH was significantly higher than the peripheral level on days 1 and 2 (day 1:t = 3.105; day 2:t = 3.180; P less than 0.01), with no correlation between menstrual and peripheral levels. Menstrual E2 was slightly lower than and significantly positively correlated with peripheral E2 (r = 0.646; P less than 0.01). Menstrual P4 was lower than but showed no correlation with peripheral levels. As expected, the menstrual blood hematocrit was less than 0.20 and highly significantly lower than that of peripheral venous blood. These results suggest that PRL is released in substantial amounts from secretory endometrium into the menstrual flow during the first day of menstrual breakdown. LH may also be released in small amounts from menstrual endometrium, while menstrual FSH, E2, and P4 probably arise entirely from the peripheral circulation.

Effects of gonadectomy and hormonal replacement on rat hearts.

PubMed

Scheuer, J; Malhotra, A; Schaible, T F; Capasso, J

1987-07-01

To evaluate the effects of sex hormones on heart function and biochemistry, gonadectomy (GX) was performed in postpubertal male (M) and female (F) rats and compared with sham-operated controls (SH). The groups were MSH; MGX; MGX replaced with testosterone 3 mg/day s.c. (MGX + T), FSH, and FGX replaced with estrogen 2 mg/day (FGX + E), progesterone 0.4 mg/day (FGX + P), estrogen and progesterone (FGX + EP), or testosterone 2 mg/day (FGX + T). Body weight was decreased in MGX and was decreased further in MGX + T. Heart weight was decreased in both MGX and MGX + T. Body weights were increased in FGX and FTX + P and were increased further in FGX + T but were normal in FGX + E and FGX + EP. Heart weights were unchanged in F groups except in FGX + T, where it was increased. Cardiac performance in perfused hearts, as measured by stroke work, ejection fraction, fractional shortening and mean velocity of circumferential fiber shortening, was decreased in MGX but was slightly increased in MGX + T. Papillary muscle studies showed increases in time to peak tension and one-half relaxation in MGX, but these were decreased in MGX + T. Isotonic shortening studies showed decreased velocity of shortening in MGX and increased velocity in MGX + T. Heart function was significantly decreased in FGX and FGX + P compared with FSH but was similar to FSH in FGX + E and FGX + EP. FGX + T had greater stroke work and ejection fraction than FSH and FGX.(ABSTRACT TRUNCATED AT 250 WORDS)

Possible Involvement of Photoperiodic Regulation in Reproductive Endocrine System of Female Olive Flounder Paralichthys olivaceus.

PubMed

Kim, Hyun Chul; Lee, Chi Hoon; Hur, Sung Pyu; Kim, Byeong Hoon; Park, Jun Young; Lee, Young Don

2015-03-01

This study investigated possible involvement of photoperiodic regulation in reproductive endocrine system of female olive flounder. To investigate the influence on brain-pituitary axis in endocrine system by regulating photoperiod, compared expression level of Kisspeptin and sbGnRH mRNA in brain and FSH-β, LH-β and GH mRNA in pituitary before and after spawning. Photoperiod was treated natural photoperiod and long photoperiod (15L:9D) conditions from Aug. 2013 to Jun. 2014. Continuous long photoperiod treatment from Aug. (post-spawning phase) was inhibited gonadal development of female olive flounder. In natural photoperiod group, the Kiss2 expression level a significant declined in Mar. (spawning period). And also, FSH-β, LH-β and GH mRNA expression levels were increasing at this period. However, in long photoperiod group, hypothalamic Kiss2, FSH-β, LH-β and GH mRNA expression levels did not show any significant fluctuation. These results suggest that expression of hypothalamic Kiss2, GtH and GH in the pituitary would change in response to photoperiod and their possible involvement of photoperiodic regulation in reproductive endocrine system of the BPG axis.

Anorchia

MedlinePlus

... stimulating hormone ( FSH ) and luteinizing hormone ( LH ) levels Surgery to look for male reproductive tissue Testosterone levels (low) Ultrasound or MRI to look for testes in the abdomen XY karyotype

Hormonal Changes After Laparoscopic Ovarian Diathermy in Patients with Polycystic Ovarian Syndrome.

PubMed

Elnaggar, Elsayed A; Elwan, Youssef Abo; Ibrahim, Safaa A; Abdalla, Mena M

2016-10-01

To assess the changes in hormonal profile (serum FSH, LH, prolactin and total testosterone) following laparoscopic ovarian drilling (LOD) in patients with polycystic ovarian syndrome. Fifty patients with PCOS have been included in this study. Serum prolactin, total testosterone, follicular-stimulating hormone (FSH) and luteinizing hormone (LH) levels have been used as biochemical markers, before and after procedures. Laparoscopic ovarian drilling was successfully employed without any surgical complications and on an average follow-up time of 24 weeks after the procedure. During the follow-up serum values for prolactin, total testosterone and LH have decreased significantly and FSH levels remained unchanged after the procedure. The LOD in patients with PCOS may avoid or reduce the risk of OHSS and the multiple pregnancy rate induced by gonadotropin therapy. The high pregnancy rate and the economic aspect of the procedure offer an attractive management for patients with PCOS. However, LOD can be considered as second-line treatment after clomiphene citrate treatment failure and/or resistance.

Development and Application of a Sensitive, Second Antibody Format Enzymeimmunoassay (EIA) for Estimation of Plasma FSH in Mithun (Bos frontalis).

PubMed

Mondal, Mohan; Baruah, Kishore Kumar; Prakash, B S

2016-01-01

Mithun (Bos frontalis) is a semi-wild rare ruminant species. A simple sensitive enzymeimmunoassay suitable for assaying FSH in the blood plasma of mithun is not available which thereby limits our ability to understand this species reproductive processes. Therefore, the aim of this article was to develop a simple and sensitive enzymeimmunoassay (EIA) for estimation of FSH in mithun plasma and apply the assay to understand the estrous cycle and superovulatory process in this species. To accomplish this goal, biotinylated FSH was bridged between streptavidin-peroxidase and immobilized antiserum in a competitive assay. Forty microlitre mithun plasma was used directly in the EIA. The FSH standards were prepared in hormone free plasma and ranged from 5-1280 pg/well/40 μL. The sensitivity of EIA was 5 pg/well FSH, which corresponds to 0.125 ng/mL plasma and the 50% relative binding sensitivity was 90 pg/well/40 μL. Although the shape of the standard curve was not influenced by different plasma volumes viz. 40 and 80 μL, a slight drop in the OD450 was observed with the increasing volume of plasma. Parallelism tests conducted between the endogenous mithun FSH and bovine FSH standards showed good homology between them. Plasma FSH estimated using the developed EIA and commercially available FSH EIA kit in the same samples were correlated (r = 0.98) and showed linearity. Both the Intra- and inter-assay CV were below 6%. Recovery of known concentrations of added FSH showed linearity (r = 0.99). The developed EIA was further validated biologically by estimating FSH in cyclic cows for the entire estrous cycle, in mithun heifers administered with GnRH analogues and in mithun cows during superovulatory treatment with FSH. In conclusion, the EIA developed for FSH determination in mithun blood plasma is simple and highly sensitive for estimation of mithun FSH in all physiological conditions.

Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized Mouse Model

PubMed Central

Tessaro, Irene; Modina, Silvia; Lodde, Valentina; Sivelli, Giulia; Franciosi, Federica; Terzaghi, Laura; Luchini, Patrizia; Rumio, Cristiano; Luciano, Alberto Maria

2017-01-01

Background: Polycystic-ovary syndrome (PCOS) is a reproductive illness characterized by hyperandrogenism and anovulation. Using hyperandrogenized mice, it was demonstrated that the oral administration of incremental dose of follicle stimulating hormone (FSH) attenuated some of PCOS characteristics. This work aimed to study the effect of ultra-low doses of combined FSH and progesterone orally administered on PCOS murine model. Moreover, the effect of sequential kinetic activation of administered hormones was tested. Methods: Thirty-two female mice were used as animal model (four groups of eight animals each). Mice were hyperandrogenized by injection of dehyidroepiandrosterone diluted in sesame oil. Control group received only oil. Simultaneously, each animal daily received per os an activated or a not-activated combination of FSH (0.44 pg) plus progesterone (0.44 pg) or saline solution as control. Serum testosterone, estradiol, progesterone and luteinizing hormone were analyzed as endocrine markers and a morphological study of antral follicle was conducted. Data were analyzed by one-way ANOVA, followed by multiple comparison test. The p<0.05 was considered significant. Results: Dehyidroepiandrosterone treatment increased both estradiol and progesterone serum levels, besides testosterone, while reduced luteinizing hormone (p<0.05); histological examination revealed an increase of cystic follicles (p<0.05). Irrespective of activation, the combined FSH and progesterone treatments restored estradiol level (p>0.05 vs. control group) and reduced cystic signs in the follicles (p<0.05 vs. dehyidroepiandrosterone treatment). Conclusion: This study indicate that ultra-low doses of FSH and progesterone orally administrated can reduce the sternness of PCOS in the mouse model and open a route for the study of innovative approaches for PCOS treatment. PMID:29062793

Genetic and clinical predictors of ovarian response in assisted reproductive technology

NASA Astrophysics Data System (ADS)

Wiweko, B.; Damayanti, I.; Suryandari, D.; Natadisastra, M.; Pratama, G.; Sumapraja, K.; Meutia, K.; Iffanolia, P.; Harzief, A. K.; Hestiantoro, A.

2017-08-01

Several factors are known to influence ovarian response to rFSH stimulation such as age, antral follicle count (AFC), and basal FSH level, Mutation of allele Ser680Asn in FSHR gene was responsible to ovarian resistance toward exogenous FSH. The aim of this study is to develop a prediction model of ovarian response to COS in IVF. This study was a prospective cohort study. One hundred and thirteen women undergoing their first cycle of IVF in Yasmin IVF Clinic Jakarta were recruited to this study. Clinical datas included were age, BMI, and AFC. Basal FSH and E2 as well as serum AMH was measured from peripheral blood taken at second day of cycle. Bsr-1 enzyme is used to identify the polymorphism in exon 10 position 680 with RFLP technique. Three genotype polymorphism, Asn/Asn (255 bp ribbon), Asn/Ser (97 bp and 158 bp), and Ser/Ser (97 bp, 158 bp, and 255 bp). AFC has the highest predictor for ovarian response with AUC 0.922 (CI 95% 0.833-1.000). AMH also showed high predicting value (AUC 0.843 CI 95% 0.663-1.000). The multivariate analysis revealed combination of AFC, AMH, age, and basal FSH is a good model for ovarian response prediction (AUC=0.97). No significant relation between Asn/Asn, Asn/Ser, or Ser/Ser genotype FSHR polymorphism with ovarian response (p = 0.866) and total dose of rRSH (p = 0.08). This study showed that model combination of AFC, AMH, patient’s age and basal FSH are very good to predict number of mature oocytes.

Clinical value of serum anti-mullerian hormone and inhibin B in prediction of ovarian response in patients with polycystic ovary syndrome.

PubMed

Zhang, Fan; Liu, Xiao-Ling; Rong, Nan; Huang, Xiao-Wen

2017-02-01

The present study aimed to investigate the clinical value of serum anti-mullerian hormone (AMH) and inhibin B (INHB) in predicting the ovarian response of patients with polycystic ovary syndrome (PCOS). A total of 120 PCOS patients were enrolled and divided into three groups in terms of the ovarian response: a low-response group (n=36), a normal-response group (n=44), and a high-response group (n=40). The serum AMH and INHB levels were measured by enzyme-linked immunosorbent assay (ELISA). The follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels were determined by chemiluminescence microparticle immunoassay. The correlation of the serum AMH and INHB levels with other indicators was analyzed. A receiver operating characteristic (ROC) curve was established to analyze the prediction of ovarian response by AMH and INHB. The results showed that there were significant differences in age, body mass index (BMI), FSH, total gonadotropin-releasing hormone (GnRH), LH, E2, and antral follicle counts (AFCs) between the groups (P<0.05). The serum AMH and INHB levels were increased significantly with the ovarian response of PCOS patients increasing (P<0.05). The serum AMH and INHB levels were negatively correlated with the age, BMI, FSH level, Gn, and E2 levels (P<0.05). They were positively correlated with the LH levels and AFCs (P<0.05). ROC curve analysis of serum AMH and INHB in prediction of a low ovarian response showed that the area under the ROC curve (AUC) value of the serum AMH level was 0.817, with a cut-off value of 1.29 ng/mL. The sensitivity and specificity were 71.2% and 79.6%, respectively. The AUC value of serum INHB was 0.674, with a cut-off value of 38.65 ng/mL, and the sensitivity and specificity were 50.7% and 74.5%, respectively. ROC curve analysis showed when the serum AMH and INHB levels were used to predict a high ovarian response, the AUC value of the serum AMH level was 0.742, with a cut-off value of 2.84 ng/mL, and the sensitivity and specificity were 72.7% and 65.9%, respectively; the AUC value of the serum INHB level was 0.551 with a cut-off of 45.76 ng/mL, and the sensitivity and specificity were 76.3% and 40.2%, respectively. It was suggested the serum AMH and INHB levels have high clinical value in predicting the ovarian response of PCOS patients.

Effects and interactions of tachykinins and dynorphin on FSH and LH secretion in developing and adult rats.

PubMed

Ruiz-Pino, F; Garcia-Galiano, D; Manfredi-Lozano, M; Leon, S; Sánchez-Garrido, M A; Roa, J; Pinilla, L; Navarro, V M; Tena-Sempere, M

2015-02-01

Kisspeptin/neurokinin B/dynorphin (KNDy) neurons, which coexpress kisspeptins (Kps), neurokinin B (NKB), and dynorphin (Dyn), regulate gonadotropin secretion. The KNDy model proposes that NKB (a stimulator, through NK3R) and Dyn (an inhibitor, through κ-opioid receptor) shape Kp secretion onto GnRH neurons. However, some aspects of this paradigm remain ill defined. Here we aimed to characterize the following: 1) the effects of NKB signaling on FSH secretion and 2) the role of Dyn in gonadotropin secretion after NK3R activation; 3) additionally, we explored the roles of other tachykinin receptors, NK1R and NK2R, on gonadotropin release. Thus, the effects of the NK3R agonist, senktide, on FSH release were explored across postnatal development in male and female rats; gonadotropin responses to agonists of NK1R substance P and NK2R [neurokinin A (NKA)] were also monitored. Moreover, the effects of senktide on gonadotropin secretion were assessed after antagonizing Dyn actions by nor-binaltorphimine didydrochloride. Before puberty, rats of both sexes showed increased FSH secretion to senktide (and Kp-10). Conversely, adult female rats were irresponsive to senktide in terms of FSH, despite proven LH responses, whereas the adult males did not display FSH or LH responses to senktide, even at high doses. In turn, substance P and NKA stimulated gonadotropin secretion in prepubertal rats, whereas in adults modest gonadotropin responses to NKA were detected. By pretreatment with a Dyn antagonist, adult males became responsive to senktide in terms of LH secretion and displayed elevated basal LH and FSH levels; nor-binaltorphimine didydrochloride treatment uncovered FSH responses to senktide in adult females. Furthermore, the expression of Pdyn and Opkr1 (encoding Dyn and κ-opioid receptor, respectively) in the mediobasal hypothalamus was greater in males than in females at prepubertal ages. Overall, our data contribute to refining our understanding on how the elements of the KNDy node and related factors (ie, other tachykinins) differentially participate in the control of gonadotropins at different stages of rat postnatal maturation.

Distinct functions of neuromedin u and neuromedin s in orange-spotted grouper.

PubMed

Li, Shuisheng; Xiao, Ling; Liu, Qiongyu; Zheng, Binbin; Chen, Huapu; Liu, Xiaochun; Zhang, Yong; Lin, Haoran

2015-10-01

Neuromedin U (NMU) and neuromedin S (NMS) play inhibitory roles in the regulation of food intake and energy homeostasis in mammals. However, their functions are not clearly established in teleost fish. In the present study, nmu and nms homologs were identified in several fish species. Subsequently, their cDNA sequences were cloned from the orange-spotted grouper (Epinephelus coioides). Sequence analysis showed that the orange-spotted grouper Nmu proprotein contains a 21-amino acid mature Nmu peptide (Nmu-21). The Nms proprotein lost the typical mature Nms peptide, but it retains a putative 34-amino acid peptide (Nmsrp). In situ hybridization revealed that nmu- and nms-expressing cells are mainly localized in the hypothalamic regions associated with appetite regulation. Food deprivation decreased the hypothalamic nmu mRNA levels but induced an increase of nms mRNA levels. Periprandial expression analysis showed that hypothalamic expression of nmu increased significantly at 3 h post-feeding, while nms expression was elevated at the normal feeding time. I.p. injection of synthetic Nmu-21 peptide suppressed the hypothalamic neuropeptide y (npy) expression, while Nmsrp administration significantly increased the expression of npy and orexin in orange-spotted grouper. Furthermore, the mRNA levels of LH beta subunit (lhβ) and gh in the pituitary were significantly down-regulated after Nmu-21 peptide administration, while Nmsrp was able to significantly stimulate the expression of FSH beta subunit (fshβ), prolactin (prl), and somatolaction (sl). Our results indicate that nmu and nms possess distinct neuroendocrine functions and pituitary functions in the orange spotted grouper. © 2015 Society for Endocrinology.

Effects of Exercise Intervention on Preventing Letrozole-Exposed Rats From Polycystic Ovary Syndrome.

PubMed

Cao, Si-Fan; Hu, Wen-Long; Wu, Min-Min; Jiang, Li-Yan

2017-03-01

Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with a metabolic syndrome. To investigate whether exercise intervention promotes PCOS prevention, a rat model was used. Polycystic ovary syndrome was induced by letrozole administration, and animals presented with obesity, sex hormone disorder, no ovulation, large cystic follicles, and increasing fasting insulin (FINS) and leptin levels. The intervention was set at 3 different intensities of swimming exercise: low (0.5 h/d), moderate (1 h/d), and high (2 h/d), and compared with a PCOS model group (letrozole administration without exercise intervention) and a control group. The exercise intervention in the low-intensity group did not produce changes in obesity, testosterone, progesterone (P), and follicle-stimulating hormone (FSH) levels. Moderate-intensity exercise reduced body weight, retained ovulation, and P levels were increased but remained lower than those in the control group. The FSH levels were significantly higher, and FINS and leptin levels were lower than in the model group ( P < 0.05) but not in the control group. The high-intensity group demonstrated the greatest effect of PCOS prevention. Testosterone, luteinizing hormone, FINS, and leptin levels were significantly lower in the high-intensity group, and FSH and P levels were higher compared with the model group. These results suggest that high-intensity exercise intervention can effectively prevent PCOS development.

Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

PubMed Central

Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

2016-01-01

Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes.

PubMed

Nasrolahi, Ozra; Khaneshi, Fereshteh; Rahmani, Fatemeh; Razi, Mazdak

2013-12-01

The global prevalence of diabetes mellitus is on rise. Diabetes-induced oxidative stress has been known to affect liver, pancreas, kidney and reproductive organs pathologically. Honey is a natural product of bee with antioxidant properties. Current study aimed to analyze the protective effects of Metformin (MF) alone and MF+ natural honey co-administration on diabetes-induced histological derangements in testis of rats. Thirty six, mature male Wistar rats were randomly divided into six groups including; control, honey-dosed non-diabetic, diabetes-induced (65 mg/kg, single dose), honey-administrated diabetic (1.0 g/kg/day), Metformin-received diabetic (100 mg/kg/day), Metformin and honey-co-treated diabetic which were followed 40 days. The animals were anesthetized by diethyl ether and the blood samples were collected. The serum levels of testosterone, Insulin, LH and FSH analyzed using antibody enzyme immunoassay method. The testicular tissues were dissected out and underwent to histological analyses. The biochemical analyses revealed that the diabetes resulted in significantly reduced testosterone (p<0.01), LH and FSH (P<0.01, 0.001) levels in serum. Light microscopic analyses showed remarkable (p<0.01) reduction in seminiferous tubules diameter (STD), spermiogenesis index (SPI) and thickness of the epithelium in the diabetic group versus control and co-treated groups. Simultaneous administration of the honey with MF could fairly up-regulate testosterone, LH and FSH levels. The animals in metformin and honey-treated group exhibited with improved tubules atrophy, elevated spermiogenesis index and germinal epithelium thickness. Our data indicated that co-administration of Metformin and honey could inhibit the diabetes-induced damages in testicular tissue. Moreover, the simultaneous administration of metformin and honey up-regulated the diabetes-reduced insulin, LH, FSH and testosterone levels. This article extracted from M.Sc. thesis. (Ozra Nasrolahi).

Pituitary-gonadal hormones during prolonged residency in Antarctica.

PubMed

Sawhney, R C; Malhotra, A S; Prasad, R; Pal, K; Kumar, R; Bajaj, A C

1998-08-01

Plasma luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL) and testosterone levels were measured in nine eugonadal men in New Delhi and during the 1st week of different months of their stay at Dakshin Gangotri in Antarctica. During their 12-month stay in Antarctica, they were exposed to a severely cold climate, long polar nights and polar days, high wind velocity, increased amounts of solar and ultraviolet radiation and geomagnetism, as well as physical and social isolation. Plasma testosterone tended to increase in March, but a significant increase (P < 0.05) was not seen until April. The mean testosterone levels in May, June, September and November were also significantly higher than the March or New Delhi values. The absolute values of LH, FSH and PRL did not show any month-to-month changes in Antarctica. However, when the hormone levels were expressed as a percentage of the individual annual Antarctic mean, significant differences as a percentage of the individual annual Antarctic mean, significant differences were observed. The testosterone peak in April, May and June was associated with an increase in LH. The nadirs of testosterone, LH, FSH and PRL were seen in either July or August. FSH showed the highest values in March, whereas the highest PRL values were seen in November. These observations suggest the presence of circannual variations in gonadotropin, PRL and LH in Antarctica which are independent of polar days and polar nights. It appears that factors other than the duration of daylight might be involved in regulating these changes. The significance of maintenance of testosterone levels in the supra-physiological range in Antarctica remains unknown but may be important in acclimatization/habituation to the extreme polar cold by increasing basal metabolic rate, protein synthesis and erythropoiesis.

Influence of continuous illumination on estrous cycle of rats: time course of changes in levels of gonadotropins and ovarian steroids until occurrence of persistent estrus.

PubMed

Takeo, Y

1984-08-01

Plasma concentrations of LH, FSH, 17 beta-estradiol, estrone and progesterone were determined chronologically by radioimmunoassays in two groups of adult female rats exposed to continuous illumination (LL). Group 1 rats showing vaginal estrous cycles were sacrificed at 3- to 6-hour intervals during late proestrus through early estrus of the first 5 cycles after exposure to LL. Group 2 animals which displayed persistent vaginal estrus in an early period of exposure to LL were killed on the 2nd, 3rd, 4th, 5th and 7th days of vaginal estrus. In Group 1 rats, surges of the hormones, except estrone, took place in all the 5 cycles. The occurrence of peak hormone levels in each cycle was invariably delayed after transfer of animals to LL. According to regression analyses, the lengths of secretion cycles of LH, FSH, 17 beta-estradiol and progesterone in rats under LL were 100.89, 100.46, 101.14 and 101.06 h, respectively. Elevation of 17 beta-estradiol levels was observed prior to the LH surge, and peaks of progesterone and FSH occurred following it. However, the secretion patterns of these hormones appear to be disrupted with length of exposure to LL. In group 2 rats, the mean concentration of LH during persistent estrus was approximately similar to that on the morning of the days of proestrus of the 4-day cycles of rats placed under an alternating 12-hour light-dark regimen (LD), whereas the mean FSH concentration was continuously low. While the concentrations of 17 beta-estradiol and estrone in persistent-estrous rats were elevated, progesterone levels remained low.(ABSTRACT TRUNCATED AT 250 WORDS)

[In vitro fertilization in France: economic aspects and influence of the gonadotropin choice (urinary vs. recombinant) on cost].

PubMed

de Mouzon, J; Allavena, E; Schmitt, C; Frappé, M

2004-06-01

The objective of the study was to make an economic evaluation of in vitro fertilization and to determine the impact of some factors on its cost, particularly the choice between recombinant follicle stimulating hormone (r-FSH) and urinary FSH (u-FSH) for ovarian stimulation. Costs were calculated in a Public Health view, by studying two phases: the stimulation cycle (including down-regulation) and the pregnancy (including the neonatal period). The calculation has included the side effects and the frozen embryos transfers. Economic data came from various sources: the French nomenclature on medical treatments (NGAP), the French drugs dictionary (Vidal) and the French Information system medical plan (PMSI). FSH costs were computed according to the currently marketed products, i.e., Fostimon (Laboratoires Genévrier, Sophia-Antipolis, France) for urinary FSH, and Gonal-F (Laboratoires Serono, Boulogne-Billancourt, France) and Puregon (Laboratoires Organon, Puteaux, France) for recombinant FSH. Two different ways of efficacy between u-FSH and r-FSH were considered for the calculations, those reported in Daya's meta-analysis (3.7% in favour of r-FSH for the clinical pregnancy rate per initiated cycle) and in the only double-blind study (Frydman et al., no difference). The annual cost of ART reaches approximately 130 million Euros in France, for the cycles only, and 170 million Euros when including the pregnancy costs. Urinary FSH is much cheaper than recombinant FSH. Whereas the number of administered FSH units was higher in u-FSH, this results in a mean lower cost of 500 Euros per cycle (2422 Euros for u-FSH and 2959 Euros for r-FSH). For one complete year, in France, the potential over cost of recombinant products reaches 24 million Euros when considering only the cycles (128.4 vs. 104.0 million Euros) and 24-31 million Euros when pregnancies and babies (neonatal period) are considered (171.4 vs 140.7 and 147.0 million Euros, respectively). The IVF per baby cost can be estimated at 16 463 Euros for r-FSH and at 14 116 Euros (in case of equivalence between the two drugs) to 15 805 Euros (in case of a difference of 3.7% pregnancy per oocyte recovery) for u-FSH. This gives Public Health lighting to the choices in the matter of ovulation stimulation. It shows the economic impact of the choice in the FSH type.

The effects of levonorgestrel on FSH-stimulated primary rat granulosa cell cultures through gene expression profiling are associated to hormone and folliculogenesis processes.

PubMed

Lira-Albarrán, Saúl; Larrea-Schiavon, Marco F; González, Leticia; Durand, Marta; Rangel, Claudia; Larrea, Fernando

2017-01-05

Levonorgestrel (LNG), a synthetic progestin, is used in emergency contraception (EC). The mechanism is preventing or delaying ovulation at the level of the hypothalamic pituitary unit; however, little knowledge exists on LNG effects at the ovary. The aim of this study was to identify the effects of LNG on FSH-induced 17β-estradiol (E 2 ) production, including LNG-mediated changes on global gene expression in rat granulosa cells (GC). Isolated GC from female Wistar rats were incubated in vitro in the presence or absence of human FSH and progestins. At the end of incubations, culture media and cells were collected for E 2 and mRNA quantitation. The results showed the ability of LNG to inhibit both hFSH-induced E 2 production and aromatase gene expression. Microarray analysis revealed that LNG treatment affects GC functionality particularly that related to folliculogenesis and steroid metabolism. These results may offer additional evidence for the mechanisms of action of LNG as EC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Loss of microRNA-7a2 induces hypogonadotropic hypogonadism and infertility

PubMed Central

Ahmed, Kashan; LaPierre, Mary P.; Denzler, Rémy; Yang, Yinjie; Rülicke, Thomas; Latreille, Mathieu

2017-01-01

MicroRNAs (miRNAs) are negative modulators of gene expression that fine-tune numerous biological processes. miRNA loss-of-function rarely results in highly penetrant phenotypes, but rather, influences cellular responses to physiologic and pathophysiologic stresses. Here, we have reported that a single member of the evolutionarily conserved miR-7 family, miR-7a2, is essential for normal pituitary development and hypothalamic-pituitary-gonadal (HPG) function in adulthood. Genetic deletion of mir-7a2 causes infertility, with low levels of gonadotropic and sex steroid hormones, small testes or ovaries, impaired spermatogenesis, and lack of ovulation in male and female mice, respectively. We found that miR-7a2 is highly expressed in the pituitary, where it suppresses golgi glycoprotein 1 (GLG1) expression and downstream bone morphogenetic protein 4 (BMP4) signaling and also reduces expression of the prostaglandin F2a receptor negative regulator (PTGFRN), an inhibitor of prostaglandin signaling and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion. Our results reveal that miR-7a2 critically regulates sexual maturation and reproductive function by interconnecting miR-7 genomic circuits that regulate FSH and LH synthesis and secretion through their effects on pituitary prostaglandin and BMP4 signaling. PMID:28218624

Metabolic clearance and blood production rates of estradiol in hyperthyroidism.

PubMed

Ridgway, E C; Longcope, C; Maloof, F

1975-09-01

The metabolic clearance rate of 17beta-estradiol (MCR2), the plasma levels of 17beta-estradiol (E2)1, sex-steroid binding globulin (SSBG), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured in 10 hyperthyroid subjects (7 men and 3 women). The blood production rate of 17beta-estradiol (PB2) was calculated for all subjects. Nine of the 10 hyperthyroid subjects had a decreased MCR2 which returned towards normal in 5 of the 6 subjects restudied following therapy. In all 10 subjects the levels of SSBG were increased when they were hyperthyroid and returned toward normal with therapy. It is concluded that the decrease in MCR2 is largely due to the increased binding of 17beta-estradiol to SSBG. In 7 of the 10 hyperthyroid the plasma E2 concentrations were normal whereas 3 had slightly elevated levels. In 8 of the 10 hyperthyroid the PB2 was within the normal range. Only 2 hyperthyroid subjects had slightly elevated PB2. In the 6 subjects who were restudied after therapy, there was no consistent change in PB2 which remained in the normal range in all cases. It is concluded that the MCR2 is decreased in most subjects with hyperthyroidism in association with an increase of SSBG. Despite this change in MCR2 there is no significant change in PB2. The increase in SSBG levels in hyperthyroidism appears to be a direct effect of the elevation of thyroid hormone activity and is not mediated through estrogen.

The anti-oxidant effects of ginger and cinnamon on spermatogenesis dys-function of diabetes rats.

PubMed

Khaki, Arash; Khaki, Amir Afshin; Hajhosseini, Laleh; Golzar, Farhad Sadeghpour; Ainehchi, Nava

2014-01-01

Diabetes rats have been linked to reproductive dysfunction and plant medicine has been shown to be effective in its treatment. Antioxidants have distinctive effects on spermatogenesis, sperm biology and oxidative stress, and changes in anti-oxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. Ginger and cinnamon are strong anti-oxidants and have been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. The present study examined the influence of combined ginger and cinnamon on spermatogenesis in STZ-induced diabetes in male Wistar rats. Animals (n = 80) were allocated randomly into eight groups, 10 each: Group 1: Control rats given only 5cc Normal saline (0.9% NaCl) daily;Group2: rats received ginger (100mg/kg/rat) daily; Group 3: rats received cinnamon (75mg/kg) daily; Group 4: rats received ginger and cinnamon, (100mg/kg/rat ginger and 75mg/kg cinnamon) daily; Group 5: Diabetic control rats received only normal saline. Group 6: Diabetic rats received 100mg/kg/day ginger; Group 7: Diabetic rats received 75mg /kg/ day cinnamon; Group 8: Diabetic rats received ginger and cinnamon (100mg/kg/day and 75mg/kg /day). Diabetes was induced with 55 mg/kg, single intra-peritoneal injection of STZ in all groups. At the end of the experiment (56th day), blood samples were taken for determination of testosterone, LH,FSH, total anti-oxidant capacity, and levels of malondialdehyde, SOD, Catalase and GPX. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis. Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased in ginger and cinnamon and combined ginger and cinnamon treated diabetic rats compared with control groups. Serum testosterone, LH and FSH were higher compared to control group and also serum anti-oxidants (TAC, SOD, GPX and catalase) all were increased at the end of treatment. Combined ginger and cinnamon showed more intense increase in all parameters compare to ginger and cinnamon alone. Most of the results were significant (P<0.05). We concluded that combined ginger and cinnamon have significant beneficial effects on the sperm viability, motility, and serum total testosterone, LH,FSH and serum anti-oxidants' level and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetics.

Potential protective effect of Pistacia lentiscus oil against chlorpyrifos-induced hormonal changes and oxidative damage in ovaries and thyroid of female rats.

PubMed

Chebab, Samira; Mekircha, Fatiha; Leghouchi, Essaid

2017-12-01

The purpose of this study was to evaluate the protective effect of Pistacia lentiscus oil (PLO), known for its antioxidant properties, on chlorpyrifos (CPF)-induced alterations in the thyroid, reproductive hormone levels, and oxidative damage in the ovaries and thyroid of adult Wistar rats. The animals were treated with orally administered PLO (2 mL/kg), CPF (6.75 mg/kg), and a combination of CPF and PLO for 30 days. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (Pg), estradiol (E 2 ), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were assessed using chemiluminescence assay. Malondialdehyde (MDA), protein carbonyl (PC), and reduced glutathione (GSH) levels were examined in the ovaries and thyroid glands. The oil principal volatile compounds detected by gas chromatography analysis were: myrcene, α-pinene and limonene (26.21, 22.66 and 10.33%, respectively). No significant differences were observed between serum concentrations of TSH and FSH in the examined experimental groups. However, serum concentrations of LH, E 2 , Pg, T3, and T4 decreased significantly in CPF-treated rats in comparison with the controls. The body weight and relative weight of ovaries and thyroids in this group were also significantly reduced. The MDA and PC content increased significantly, while the GSH content was markedly depressed in the thyroid and ovaries of rats treated with CPF. Co-administration of PLO and CPF effectively ameliorated the adverse effects; the oxidative damage was reduced and the levels of thyroid and reproductive hormones restored to a normal range. In conclusion, it appears that PLO substantially alleviates the CPF-induced oxidative damage and hormonal alterations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Restoration of Spermatogenesis Using a New Combined Herbal Formula of Epimedium koreanum Nakai and Angelica gigas Nakai in an Luteinizing Hormone-Releasing Hormone Agonist-Induced Rat Model of Male Infertility

PubMed Central

2017-01-01

Purpose We investigated the protective effect of a mixture of 2 herbal extracts, KH-465, which consisted of Epimedium koreanum Nakai and Angelica gigas Nakai, on spermatogenesis in a luteinizing hormone-releasing hormone (LHRH) agonist-induced rat model of male infertility. Materials and Methods Seventy-five 12-week-old male Sprague-Dawley rats were randomly divided into 5 groups, containing 15 rats each: a normal control group that received no treatment and 4 experimental groups (I, II, III, and IV) in which an LHRH agonist was administered for 4 weeks to induce spermatogenic failure. Group I received distilled water, and groups II, III, and IV received 200 mg/kg/day of KH-465, 400 mg/kg/day KH-465, and depo-testosterone for 4 weeks, respectively. Weight changes of the testis and epididymis, sperm count motility, and levels of testosterone (T), free T, follicle-stimulating hormone (FSH), luteinizing hormone (LH), superoxide dismutase (SOD), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were estimated. Results Body, testis, and epididymis weight showed no significant differences among the control and experimental groups. Treatment with KH-465 increased the sperm count and motility. Serum hormone levels of T, free T, and FSH were not significantly different in the experimental groups, while the LH level was higher than in the LHRH agonist-induced control group, but not to a significant extent. Levels of SOD were higher and 8-OHdG were lower in the groups that received KH-465 than in the LHRH agonist-induced control group. Conclusions Our results suggest that KH-465 increased sperm production via reducing oxidative stress and had a positive effect in a male infertility model. PMID:29076302

The effects of chronic administration of pyrimethamine on spermatogenesis and fertility in male rats.

PubMed

Awoniyi, C A; Chandrashekar, V; Hurst, B S; Kim, W K; Schlaff, W D

1993-01-01

The present study examines whether the antifertility effects of pyrimethamine (PYR), an inhibitor of dihydrofolate reductase, are mediated by a reduction in intratesticular testosterone (T) concentrations or whether PYR exerts its effect by a cytotoxic insult to spermatogenic cells that is independent of intratesticular testosterone. Adult male rats were treated daily with 100 mg/kg (n = 16) or 400 mg/kg (n = 16) of PYR in honey for 8 weeks. Control rats (n = 16) received honey without PYR. Eight weeks after treatment, five rats from each PYR-treated group and five control rats were mated with normal cycling female rats, and fertility was assessed. These rats were euthanized after the fertility trial; testis weight, testicular sperm, and epididymal sperm counts were determined, and serum levels of T, LH, FSH, and seminiferous tubule fluid T (STF-T) concentrations were measured by RIA. Testes from three rats per group were perfusion-fixed for histological evaluation. PYR was discontinued in the remaining rats for 8 weeks and similar parameters were evaluated after 8 weeks of recovery. PYR (100 mg/kg/day) treatment for 8 weeks did not have any effects on organ weights, testicular and epididymal sperm counts, and hormone levels when compared to controls. In contrast, PYR (400 mg/kg/day) treatment significantly reduced testis and epididymis weights, testicular and epididymal sperm counts, and fertility. Despite these effects, serum T, LH, FSH, and STF-T concentrations were not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of FSH in two different regimens for ovarian superstimulation prior to ovum pick up and in vitro embryo production in Holstein cows.

PubMed

da Silva, Júlio César Barboza; Ferreira, Roberta Machado; Maturana Filho, Milton; Naves, Julianne de Rezende; Santin, Thiago; Pugliesi, Guilherme; Madureira, Ed Hoffmann

2017-03-01

We aimed with the present study to evaluate the effects of FSH treatment (200 mg) split in four or six administrations on ovarian follicle stimulation and in vitro oocyte competence for embryo production in dairy cows with synchronized follicular wave emergence. On random days of the estrous cycle (Day 0), non-lactating Holstein cows received a progesterone (P4)-releasing intravaginal device and 2 mg estradiol benzoate IM. On Day 3, they received 0.530 mg sodium cloprostenol (PGF2α) IM. Control cows (n = 35) received no further treatments, whereas FSH-treated cows received 200 mg FSH split in four (FSH4 group; n = 33) or six (FSH6 group; n = 33) administration regimens. Starting on Day 4, cows in FSH4 group received 200 mg FSH split in four equivalent doses of 50 mg 12 h apart. Cows in FSH6 group received the same total FSH dose split in six equivalent doses of 33.3 mg 12 h apart, but treatments started on Day 3. On Day 7 AM (36 h of "coasting" period for FSH-treated groups), the P4 devices were removed and cows were subjected to ovum pick up (OPU). Viable oocytes were in vitro fertilized using sexed-sorted semen. Although FSH treatment did not (P > 0.1) increase the total number of follicles (Control, 53.2 ± 4.5 vs. FSH-treated, 51.4 ± 3.1), the two hormonal stimulation regimens, FSH4 and FSH6, increased the number of medium follicles (6-10 mm; 5.2 ± 0.5 vs. 18.1 ± 1.4; P < 0.0001) and reduced the number of small follicles (2-5.9 mm; 46.3 ± 5.1 vs. 31.0 ± 2.4 P < 0.0001). Also, FSH treatment or regimen did not increase (P > 0.1) the number of viable oocytes (Control, 12.6 ± 1.26 vs. FSH-treated, 12.70 ± 1.03), recovery rate (Control, 36.5% vs. FSH-treated, 36%) and the number of in vitro produced blastocyst (Control, 4.1 ± 0.52 vs. FSH-treated 4.3 ± 0.5). We concluded that FSH stimulation protocol proposed herein is effective to stimulate the growth of small antral follicle population prior to OPU, but it was ineffective to improve in vitro oocyte competence for embryo production in non-lactating Holstein cows with synchronized follicular wave emergence. Copyright © 2017 Elsevier Inc. All rights reserved.

Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis.

PubMed

Revelli, Alberto; Poso, Francesca; Gennarelli, Gianluca; Moffa, Federica; Grassi, Giuseppina; Massobrio, Marco

2006-07-18

Both recombinant FSH (r-FSH) and highly-purified, urinary FSH (HP-uFSH) are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce. Two hundred and sixty infertile women (184 with unexplained infertility, 76 with CC-resistant polycystic ovary syndrome) at their first treatment cycle were randomized and included in the study. Ovulation induction was accomplished by daily administration of rFSH or HP-uFSH according to a low-dose, step-up regimen aimed to obtain a monofollicular ovulation. A bi- or tri-follicular ovulation was anyway accepted, whereas hCG was withdrawn and the cycle cancelled when more than three follicles greater than or equal to 18 mm diameter were seen at ultrasound. The primary outcome measure was the cost of therapy per delivered baby, estimated according to a cost-minimization analysis. Secondary outcomes were the following: monofollicular ovulation rate, total FSH dose, cycle cancellation rate, length of the follicular phase, number of developing follicles (>12 mm diameter), endometrial thickness at hCG, incidence of twinning and ovarian hyperstimulation syndrome, delivery rate. The overall FSH dose needed to achieve ovulation was significantly lower with r-FSH, whereas all the other studied variables did not significantly differ with either treatments. However, a trend toward a higher delivery rate with r-FSH was observed in the whole group and also when results were considered subgrouping patients according to the indication to treatment. Considering the significantly lower number of vials/patient and the slight (although non-significant) increase in the delivery rate with r-FSH, the cost-minimization analysis showed a 9.4% reduction in the overall therapy cost per born baby in favor of r-FSH.

[Male hormonal profile in workers exposed to toluene in an industrial packaging plant].

PubMed

Miranda-Figueroa, Genezareth; Paz-Román, María del Pilar; Aguilar-Madrid, Guadalupe; Juárez-Pérez, Cuauhtémoc Arturo; Basurto-Acevedo, Lourdes; Haro-García, Luis

2013-01-01

to identify changes in the male hormonal profile (MHP), consisting of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone, in workers exposed to toluene. cross-sectional study that included 42 workers, formed in two groups: with high and low exposure to toluene (HET and LET, respectively); the hippuric acid in urine, and the serum concentration in FSH, LH, and testosterone were measured. hippuric acid in subjects with LET was 2.53 ± 1.20 g/g creatinine, and with HET: 6.31 ± 3.83 g/g creatinine (p = 0.02). Seric FSH concentration was 5.12 ± 0.77 and 3.55 ± 0.3 mU/mL (p = 0.02) in LET and HET, respectively; LH: 2.66 ± 0.45 and 2.77 ± 0.21 (p = 0.81), and testosterone 3.91 ± 0.34 and 4.86 ± 0.23 ng/mL (p = 0.04). By regression analysis, the correlation coefficient of FSH with hippuric acid was r = -0.33 (p = 0.031), with coefficient of determination of 11 %; the LH correlation coefficient was r = -0.037 (p = 0.88) and 0.05 %, respectively; and the one for testosterone was r = 0.61 (p = 0.0001) and 34 %. in HET group, FSH and LH serum levels diminished; testosterone shows an opposite response, perhaps explained by a different sensitivity of the male gonads exposed to toluene.

Influence of age, strain and season on circadian periodicity of pituitary, gonadal and adrenal hormones in the serum of male laboratory rats.

PubMed

Wong, C C; Döhler, K D; Geerlings, H; von zur Mühlen, A

1983-01-01

The influence of age, strain and season on the circadian pattern of serum levels of LH, FSH, prolactin androgens and corticosterone was studied in five groups of male laboratory rats. Significant 24-hour periodicity was observed for serum levels of corticosterone in all five groups, for androgen levels in four, for prolactin levels in three, for LH levels in two and for FSH levels in one group of rats. There were significant influences of age, strain and season on the temporal patterns and/or on 24-hour mean serum hormone levels. The results indicate that some of the disagreements on existence or nonexistence of circadian rhythms and on rhythm patterns in serum hormone levels may be explained by the fact that animals of different ages or strains had been used or that experiments were performed at different times of the year.

In Utero Exposure to Di( n-butyl)phthalate Induces Morphological and Biochemical Changes in Rats Postpuberty.

PubMed

Okayama, Yuya; Wakui, Shin; Wempe, Michael F; Sugiyama, Mitsuru; Motohashi, Masaya; Mutou, Tomoko; Takahashi, Hiroyuki; Kume, Eisuke; Ikegami, Hiroshi

2017-06-01

Pregnant Sprague-Dawley rats were orally administered di( n-butyl)phthalate (DBP; 100 mg/kg/day) on gestation days (GD) 12 to 21. We investigated the male offspring and probed morphological alterations in Sertoli cells at 7, 9, 14, and 17 weeks of age. Parameters assessed in this study included offspring number, sex ratios, body weights, testis weights, seminiferous tubule (ST) profile numbers and diameters, number of vimentin-labeled Sertoli cells, and both testosterone and follicle-stimulating hormone (FSH) levels. Testicular weight/body weight ratios and the numbers and diameters of ST in maximum transverse testicular sections were statistically similar at weeks 7 and 9; however, at weeks 14 and 17, they were statistically different and displayed higher BrdU-positive Sertoli cells/Sertoli cell ratios in the DBP treatment group. Noteworthily, the serum FSH levels were higher and testicular testosterone levels were lower in the DBP treatment group. To our knowledge, the present study is the first to report that in utero DBP exposure significantly increased Sertoli cell numbers and their cellular proliferation from postpuberty to adulthood, with a significant decrease in testicular testosterone and an increase in FSH.

Pituitary and ovarian hormone activity during the 7-day hormone-free interval of various combined oral contraceptive regimens.

PubMed

Cho, Michael; Atrio, Jessica; Lim, Aaron H; Azen, Colleen; Stanczyk, Frank Z

2014-07-01

The objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). Blood samples were obtained from 62 women. When COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. A more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. This study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Inhibin binding protein in rats: alternative transcripts and regulation in the pituitary across the estrous cycle.

PubMed

Bernard, D J; Woodruff, T K

2001-04-01

Inhibin binding protein (InhBP) and the transforming growth factor-beta (TGF beta) type III receptor, beta glycan, have been identified as putative inhibin coreceptors. Here we cloned the InhBP cDNA in rats and predict that it encodes a large membrane-spanning protein that is part of the Ig superfamily, as has been described for humans. Two abundant InhBP transcripts (4.4 and 1.8 kb) were detected in the adult rat pituitary. The larger transcript encodes the full-length protein while the 1.8-kb transcript (InhBP-short or InhBP-S) corresponds to a splice variant of the receptor. This truncated isoform contains only the N-terminal signal peptide and first two (of 12) Ig-like domains observed in the full-length InhBP (InhBP-long or InhBP-L). InhBP-S does not contain a transmembrane domain and is predicted to be a soluble protein. Beta glycan was also detected in the pituitary; however, it was most abundant within the intermediate lobe. Although we also observed beta glycan immunopositive cells in the anterior pituitary, they rarely colocalized with FSH beta-producing cells. We next examined physiological regulation of the coreceptors across the rat estrous cycle. Like circulating inhibin A and inhibin B levels, pituitary InhBP-L and InhBP-S mRNA levels were dynamically regulated across the cycle and were negatively correlated with serum FSH levels. Expression of both forms of InhBP was also positively correlated with serum inhibin B, but not inhibin A, levels. These data are particularly interesting in light of our in vitro observations that InhBP may function as an inhibin B-specific coreceptor. Pituitary beta glycan mRNA levels did not fluctuate across the cycle nor did they correlate with serum FSH. These observations, coupled with its pattern of expression within the pituitary, indicate that beta glycan likely functions as more than merely an inhibin coreceptor within the pituitary. A direct role for InhBP or beta glycan in regulation of pituitary FSH by inhibin in vivo has yet to be determined, but the demonstration of dynamic regulation of pituitary InhBP and its negative relation to serum FSH across the estrous cycle is an important step in this direction.

The use of gonadotrophin-releasing hormone antagonists in polycystic ovarian disease.

PubMed

Lubin, V; Charbonnel, B; Bouchard, P

1998-12-01

Polycystic ovarian disease (PCOD) is characterized by anovulation, eventually high luteinizing hormone (LH) levels, with increased LH pulse frequency, and hyperandrogenism. As the aetiology of the disease is still unknown, gonadotrophin-releasing hormone (GnRH) antagonists, competitive inhibitors of GnRH for its receptor, are interesting tools in order to study and treat the role of increased LH levels and pulse frequency in this disease. Their administration provokes a rapid decrease in bioactive and immunoactive LH followed by a slower decrease in follicle-stimulating hormone (FSH). In patients with PCOD, the suppression of gonadotrophin secretion eradicates the symptoms of the disease as long as the treatment lasts. Several authors have suggested that increased plasma LH levels have deleterious effects on the fertility of women with PCOD. Indeed, fewer spontaneous pregnancies with more miscarriages are observed when plasma LH levels are high. Assisted reproduction techniques such as in vitro fertilization (IVF) have provided other clues to the role of the LH secretory pattern in women with PCOD. The number of oocytes retrieved, the fertilization rate and the cleavage rate are lower in PCOD patients undergoing IVF and this is inversely correlated with FSH:LH ratio. These abnormalities are corrected when endogenous secretion of LH is suppressed. On the other hand, implantation and pregnancy rates after IVF are similar to those observed in control women. New GnRH antagonists are devoid of side effects and suppress LH secretion within a few hours without a flare-up effect. This action lasts for 10-100 hours. When GnRH antagonists are associated with i.v. pulsatile GnRH, this combination both suppresses the effect of endogenous GnRH and because of the competition for GnRH receptors restores a normal frequency of LH secretion. We have studied two women with PCOD, administering first 10 mg s.c. every 72 hours for 7 days of the GnRH antagonist Nal-Glu, then adding on top i.v. pulsatile GnRH: 10 micrograms/pulse every 90 minutes for 15 days. We thus succeeded in normalizing LH secretion pattern and observed a significant decline in testosterone levels. We failed to induce appropriate ovarian response and ovulation. In conclusion, the combination of GnRH antagonist and GnRH pulsatile treatment can re-establish normal LH secretory pattern in patients with PCOD. The failure to induce ovulation with this regimen suggests the existence of an inherent ovarian defect in women with PCOD.

Possible role of serum testosterone, gonadotropins and prolactin in patients with premature ejaculation.

PubMed

Abu El-Hamd, M; Farah, A

2018-02-01

Premature ejaculation (PE) is the most common male sexual dysfunction. This study aimed to investigate the role of serum testosterone, gonadotropins and prolactin in patients with PE. In a prospective a case-controlled study, it was conducted on 90 male patients with PE and 90 male healthy participants as controls. Patients were evaluated by Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculatory latency time (IELT). Patients with mean IELT values ≤60 s and PEDT total scores ≥11 were considered to have PE. Serum levels of total testosterone (TT), free testosterone (FT), follicle-stimulating hormone (FSH), luteinising hormone (LH) and prolactin (PL) were investigated in patients with PE and controls. There was no statistically significant difference between patients with PE and controls regarding the serum levels of TT, FT, FSH, LH and PL (p value ˃.05). There was no significant correlation between the sex hormones levels (TT, FT, FSH, LH and PL) and (age, body mass index (BMI), IELTS and total PEDT scores of the patients; p value ˃.05). This study concluded that there was no disturbance in serum levels of testosterone, gonadotropins and prolactin in patients with PE and controls. These hormones could not relate to pathogenesis of PE. © 2017 Blackwell Verlag GmbH.

Follicle-stimulating hormone encapsulation in the cholesterol-modified chitosan nanoparticles via molecular dynamics simulations and binding free energy calculations.

PubMed

Yahyaei, Mohammad; Mehrnejad, Faramarz; Naderi-Manesh, Hossein; Rezayan, Ali Hossein

2017-09-30

Follicle-stimulating hormone (FSH) is widely applied in the modern ovarian stimulation techniques. However, it must be administered daily because of its short half-life. Recently, the cholesterol (CS) modified chitosan (CTS) nanogels have attracted significant interest as promising controlled release protein delivery because of their ability to minimize the aggregation and irreversible denaturation of proteins. Herein, we report a molecular dynamics (MD) simulation investigation on the molecular mechanisms of FSH encapsulation in the CS-CTS nanogels. The MD simulations have been performed using the GROMACS software for up to 200ns simulation time. Furthermore, the binding free energy has been calculated by the molecular mechanics [MM] with Poisson-Boltzmann [PB] and surface area solvation (MM/PBSA) method by using the g_mmpbsa tool. Our findings suggest that the main driving force of the formation of the CS-CTS nanogels is the hydrophobic interactions between the CS-CS moieties in water. The results have also indicated that the CS-CTS nanogel formation can occur through the hydrogen bonding in addition to the hydrophobic interactions. The obtained data demonstrate that the FSH encapsulation into the CS-CTS nanogels is a gradual process driven by the hydrophobic interactions between the hydrophobic patch of FSH and the hydrophobic nanodomains of the nanogel. Our results also reveal that except in the hydrophobic patch region, the flexibility of FSH was reduced in the presence of the nanogel. This study provides the elucidation of the nanogel-FSH interactions at the molecular level and presents new perspective for the ideal design and applications of the CS-CTS nanogel in protein delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Ovarian response to recombinant human follicle-stimulating hormone in luteinizing hormone-depleted women: examination of the two cell, two gonadotropin theory.

PubMed

Ben-Chetrit, A; Gotlieb, L; Wong, P Y; Casper, R F

1996-04-01

To evaluate the relative contribution of FSH to ovarian estrogen production. Nonrandomized, prospective study. University of Toronto teaching hospital reproductive biology unit. Five women who had been treated with depot GnRH agonist with hormonal add-back for 4 to 48 months and who were confirmed to be gonadotropin depleted by both bioassay and RIA. Subjects received 75 IU SC recombinant human FSH daily for 7 days followed by 150 IU daily for 7 days and 225 IU daily for the third week. Serum steroid determination and vaginal sonography for follicle size and endometrial thickness were performed serially and follicular fluid hormone levels were measured in two subjects. Bioactive LH and FSH activity were less than the detection limit of the assay (0.1 mIU/mL; conversion factor to SI units, 1.00 for LH and FSH) before recombinant FSH treatment in all five women. In all subjects, at least one preovulatory follicle developed by the end of two to three weeks. Endometrial thickness increased to between 7 and 9 mm in four women. Mean serum E2 in the five subjects increased from 17 pg/mL (range: 5 to 33 pg/mL; conversion factor to SI unit, 3.671) at baseline to 230 pg/mL (range: 37 to 489 pg/mL) at the end of the study. Follicular fluid E2 concentrations ranged from 44,296 to 69,367 pg/mL in the four follicles aspirated. Our results indicate that LH is not necessary for ovarian E2 production. We speculate that the granulosa cells, in the absence of detectable LH bioactivity, can use circulating adrenal androgens or constitutive or FSH-stimulated thecal androgens, to produce intrafollicular E2.

Genetic variations altering FSH action affect circulating hormone levels as well as follicle growth in healthy peripubertal girls.

PubMed

Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian; Main, Katharina M; Juul, Anders

2016-04-01

Do variants of the genes encoding follicle stimulating hormone (FSH) beta subunit (B) and FSH receptor (R) impact circulating reproductive hormone levels and ovarian follicle maturation in healthy peripubertal girls? FSHB and FSHR genetic variants exert, alone or their combination, distinct effects on reproductive hormone levels as well as ovarian follicle maturation in healthy peripubertal girls. FSHB and FSHR genetic variants impact reproductive hormone levels as well as associated pathologies in women. While FSHR c. 2039A>G is known to alter gonadotrophin levels in women, FSHR c.-29G>A has not yet been shown to exert effect and there are conflicting results concerning FSHB c.-211G>T. This population-based study included 633 girls recruited as part of two cohorts, the COPENHAGEN Puberty Study (2006-2014, a cross-sectional and ongoing longitudinal study) and the Copenhagen Mother-Child Cohort (1997-2002, including transabdominal ultrasound (TAUS) of the ovaries in a subset of 91 peripubertal girls). Clinical examinations, including pubertal breast stage (Tanner's classification B1-B5) were performed. Circulating levels of FSH, luteinizing hormone (LH), estradiol, anti-Mullerian hormone (AMH) and inhibin-B were assessed by immunoassays. In a subset of the girls (n = 91), ovarian volume and the number/size of antral follicles were assessed by TAUS. Genotypes were determined by competitive PCR. FSHR c.2039A>G minor alleles were positively associated with serum FSH (β = 0.08, P = 0.004), LH (β = 0.06, P = 0.012) and estradiol (β = 0.06, P = 0.017) (adjusted for Tanner stages). In a combined model, FSHR c.-29G>A and FSHR c.2039A>G alleles were positively associated with FSH levels in early-pubertal girls (B2 + B3, n = 327, r = 0.1, P = 0.02) and in young adolescents (B4 + B5, n = 149, r = 0.2, P = 0.01). Serum AMH and inhibin B levels were not significantly influenced by the single nucleotide polymorphisms (SNPs). Single SNPs were not associated with follicles counts, however, a cumulative minor allele count (FSHB c.-211 G>T and FSHR c.-29G>A) was negatively associated with the number of large follicles (≥5 mm) (n = 91, P = 0.04) (adjusted for Tanner stages). Since we studied girls and young adolescents during pubertal transition, our study may not be fully comparable with previous studies on FSHB and FSHR variants in adult women. The group of young adolescents (Tanner B4 + B5) reflects the endocrine situation in adult women best, however, the group is not large enough to contribute substantially to the conflicting results concerning the influence of FSHB c.-211G>T in adult women. Furthermore, we have no information about the exact day of the menstrual cycle in the subgroup of girls with menarche. The sex-specific interaction of FSHB and FSHR genetic variants and physiological as well as pathological conditions is being increasingly elucidated. The variant triplet set might serve as diagnostic and pharmacogenetic marker. For the first time, we show an additional effect of FSHR c.-29G>A on serum FSH levels in healthy girls. Moreover, morphological data suggest impaired FSH-induced maturation of ovarian follicles in minor allele carriers of FSHB c.-211G>T and FSHR c.-29G>A. This may explain previous findings of delayed pubertal onset in these girls. Funding was provided by the Danish Agency for Science, Technology and Innovation (09-067180), Danish Ministry of the Environment, CeHoS (MST-621-00065), Capital Region of Denmark (December 2011), Ministry of Higher Education and Science (DFF-1331-00113) and EDMaRC (Danish Ministry of Health). A.S.B. was funded from December 2015 by ReproUnion (EU Interreg Öresund-Kattegat-Skagerrak). The authors declare no conflict of interest. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Recombinant versus highly-purified, urinary follicle-stimulating hormone (r-FSH vs. HP-uFSH) in ovulation induction: a prospective, randomized study with cost-minimization analysis

PubMed Central

Revelli, Alberto; Poso, Francesca; Gennarelli, Gianluca; Moffa, Federica; Grassi, Giuseppina; Massobrio, Marco

2006-01-01

Background Both recombinant FSH (r-FSH) and highly-purified, urinary FSH (HP-uFSH) are frequently used in ovulation induction associated with timed sexual intercourse. Their effectiveness is reported to be similar, and therefore the costs of treatment represent a major issue to be considered. Although several studies about costs in IVF have been published, data obtained in low-technology infertility treatments are still scarce. Methods Two hundred and sixty infertile women (184 with unexplained infertility, 76 with CC-resistant polycystic ovary syndrome) at their first treatment cycle were randomized and included in the study. Ovulation induction was accomplished by daily administration of rFSH or HP-uFSH according to a low-dose, step-up regimen aimed to obtain a monofollicular ovulation. A bi- or tri-follicular ovulation was anyway accepted, whereas hCG was withdrawn and the cycle cancelled when more than three follicles greater than or equal to 18 mm diameter were seen at ultrasound. The primary outcome measure was the cost of therapy per delivered baby, estimated according to a cost-minimization analysis. Secondary outcomes were the following: monofollicular ovulation rate, total FSH dose, cycle cancellation rate, length of the follicular phase, number of developing follicles (>12 mm diameter), endometrial thickness at hCG, incidence of twinning and ovarian hyperstimulation syndrome, delivery rate. Results The overall FSH dose needed to achieve ovulation was significantly lower with r-FSH, whereas all the other studied variables did not significantly differ with either treatments. However, a trend toward a higher delivery rate with r-FSH was observed in the whole group and also when results were considered subgrouping patients according to the indication to treatment. Conclusion Considering the significantly lower number of vials/patient and the slight (although non-significant) increase in the delivery rate with r-FSH, the cost-minimization analysis showed a 9.4% reduction in the overall therapy cost per born baby in favor of r-FSH. PMID:16848893

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

PubMed

Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-01-10

To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel.

PubMed

Kaminetsky, Jed; Werner, Michael; Fontenot, Greg; Wiehle, Ronald D

2013-06-01

Clomiphene citrate is employed off-label in men who have low testosterone and for the restoration of sperm counts in men who have used exogenous testosterone. Clomiphene is a mixture of two diastereoisomers: zuclomiphene and enclomiphene. We evaluated enclomiphene citrate in men with secondary hypogonadism. Our aim was to compare oral enclomiphene citrate as an alternative to topical testosterone. Blood levels of total testosterone (TT), estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone binding globulin, thyroid stimulation hormone, prolactin, and insulin-like growth factor 1 IGF-1 were measured at certain times after treatment with each agent. Sperm parameters were determined at the same visits. Free testosterone (FT) was calculated. This was a proof-of-principle, randomized, open-label, fixed dose, active-control, two-center phase IIB study in 12 men with secondary hypogonadism treated previously with topical testosterone. After discontinuation of topical testosterone, morning TT values averaged 165 ± 66 pg/dL. After 3 months, there was a significant rise in men receiving enclomiphene citrate and gel that was sustained for 3 months. At 6 months, TT levels were 545 ± 268 and 525 ± 256 pg/dL for groups receiving the gel and enclomiphene citrate, respectively. Only men in the enclomiphene citrate group demonstrated increased LH and FSH. TT decreased one month posttreatment to pretreatment values. Enclomiphene citrate elevated sperm counts in seven out of seven men at 3 months and six out of six men at 6 months with sperm concentrations in the 75-334 × 10(6) /mL range. The gel was ineffective in raising sperm counts above 20 × 10(6) /mL for all five men at 3 months and raised counts in only two or five men at 6 months. At follow-up, only enclomiphene citrate treatment was associated with elevated sperm counts. Enclomiphene citrate increased testosterone and sperm counts. Concomitant changes in LH and FSH suggest normalization of endogenous testosterone production and restoration of sperm counts through the hypothalamic-pituitary-testicular axis. © 2013 Repros Therapeutics. Journal of Sexual Medicine © 2013 International Society for Sexual Medicine.

Immunization against exon 1 decapeptides from the lutropin/choriogonadotropin receptor or the follitropin receptor as potential male contraceptive.

PubMed

Remy, J J; Couture, L; Rabesona, H; Haertle, T; Salesse, R

1996-11-01

Pituitary gonadotropin hormones lutropin (LH) and follitropin (FSH) control steroidogenesis and gametogenesis in male and female gonads through interaction with G protein-coupled receptors, LHR and FSHR. In the male, LH acts on leydig cells and is mostly responsible for the acquisition of puberty and the production of androgens while FSH, together with androgens, regulates spermatogenesis within Sertoli cells. We have engineered filamentous phages displaying mouse LHR and human FSHR decapeptides chosen in hormone binding regions. Peptides from both receptors displayed on phages belong either to the receptor specific exon 1 (amino acids 18-27) or to the homologous exon 4 (amino acids 98-107). Vaccination of prepubertal BALB/c male mice with hybrid phages using sub-cutaneous or intraperitoneal injections induced immunity against receptors. Anti-receptor immunization produced agonist or antagonist effects depending only on the circulating levels of the antibodies. Both anti-LHR and anti-FSHR vaccines induced efficient as well as reversible male contraception, through different mechanisms: targeting LH receptors inhibited or hyperstimulated Leydig cell testosterone production while targeting FSH receptors did not affect testosterone levels.

Does the Pituitary Gland Volume Change in Polycystic Ovary Syndrome?

PubMed

Bozkurt Koseoglu, Sezen; Dinc Elibol, Funda

2018-05-15

Polycystic ovary syndrome (PCOS) is the commonest cause of menstrual irregularity and hirsutism during reproductive age. We hypothesized in the alterations in the pituitary gland in PCOS. We measured the volume of the pituitary gland in 39 PCOS patients and 42 age-matched healthy controls using 0.35 mm thick T1-weighted sagittal cranial images. Serum levels of estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured on days 3-5 of the menstrual cycle of the participants. There was a significant difference in terms of LH, FSH, and LH/FSH ratio (p < 0.05) between groups. Mean pituitary gland volume (PGV) was 4.1 ± 1.36 mm3 for the study group and 3.4 ± 0.77 mm3 for the control group. PGV was statistically significantly higher in PCOS group than the control group (p < 0.05). There was no correlation between hormone levels and PGVs in groups. Enlarged pituitary volume in PCOS may be due to excessive LH release. © 2018 S. Karger AG, Basel.

Fasting lowers gastrin-releasing peptide and Fsh mRNA in the ovine anterior pituitary gland

USDA-ARS?s Scientific Manuscript database

Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

Fasting lowers gastrin-releasing peptide and FSH mRNA in the ovine anterior pituitary gland

USDA-ARS?s Scientific Manuscript database

Estrogen receptor beta (ER-ß), LH, and FSH are important mediators of reproduction. FSH stimulates follicle recruitment and development. During anorexia, serum concentrations of FSH and LH decrease. Gastrin-releasing peptide (GRP), neuromedin B (NMB), peroxisome proliferator-activated receptor-gamma...

Validation of a noninvasive diagnostic tool to verify neuter status in dogs: The urinary FSH to creatinine ratio.

PubMed

Albers-Wolthers, C H J; de Gier, J; Oei, C H Y; Schaefers-Okkens, A C; Kooistra, H S

2016-09-15

Determining the presence of functional gonadal tissue in dogs can be challenging, especially in bitches during anestrus or not known to have been ovariectomized, or in male dogs with nonscrotal testes. Furthermore, in male dogs treated with deslorelin, a slow-release GnRH agonist implant for reversible chemical castration, the verification of complete downregulation of the hypothalamic-pituitary-gonadal (HPG) axis can be difficult, especially if pretreatment parameters such as the size of the testes or prostate gland are not available. The aims of this study were to validate an immunoradiometric assay for measurement of FSH in canine urine, to determine if the urinary FSH to creatinine ratio can be used to verify the neuter status in bitches and male dogs, as an alternative to the plasma FSH concentration, and to determine if downregulation of the HPG axis is achieved in male dogs during deslorelin treatment. Recovery of added canine FSH and serial dilutions of urine reported that the immunoradiometric assay measures urinary FSH concentration accurately and with high precision. Plasma FSH concentrations (the mean of two samples, taken 40 minutes apart) and the urinary FSH to creatinine ratio were determined before gonadectomy and 140 days (median, range 121-225 days) and 206 days (median, range 158-294 days) after gonadectomy of 13 bitches and five male dogs, respectively, and in 13 male dogs before and 132 days (median, range 117-174 days) after administration of a deslorelin implant. In both bitches and male dogs, the plasma FSH concentration and the urinary FSH to creatinine ratio were significantly higher after gonadectomy, with no overlapping of their ranges. Receiver operating characteristic analysis of the urinary FSH to creatinine ratio revealed a cut-off value of 2.9 in bitches and 6.5 in males to verify the presence or absence of functional gonadal tissue. In male dogs treated with deslorelin, the plasma FSH concentrations and urinary FSH to creatinine ratios were significantly lower after administration of the implant, but their ranges overlapped. We conclude that the urinary FSH to creatinine ratio can be used to verify the neuter status of bitches and male dogs. However, it cannot be used for the assessment of complete downregulation of the HPG axis after administration of a deslorelin implant. The urinary FSH to creatinine ratio is preferable over the plasma FSH concentration because it involves only one sample that can be collected relatively easy and noninvasively. Copyright © 2016 Elsevier Inc. All rights reserved.

The VEGF and PEDF levels in the follicular fluid of patients co- treated with LETROZOLE and gonadotropins during the stimulation cycle.

PubMed

Haas, Jigal; Bassil, Rawad; Gonen, Noa; Meriano, Jim; Jurisicova, Andrea; Casper, Robert F

2018-05-29

Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation. The aim of this study was to compare the VEGF and PEDF levels in the follicular fluids of normal responders treated with letrozole and gonadotropins during the ovarian stimulation with patients treated with gonadotropins only. A single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits. The age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209 nmol/l vs. 3280 nmol/l, p = 0.02) were significantly decreased, and the testosterone levels (246.5 nmol/l vs. 40.7 nmol/l, p < 0.001) were significantly increased in the letrozole group compared to the gonadotropin only group. The progesterone levels (21.4 μmol/l vs. 17.5 p = NS) were comparable between the two groups. The VEGF levels (2992 pg/ml vs. 1812 pg/ml p = 0.02) were significantly increased and the PEDF levels (9.7 ng/ml vs 17.3 ng/ml p < 0.001) were significantly decreased in the letrozole group. Opposite to observations in the mouse, we found that VEGF levels were increased and PEDF levels were decreased in the follicular fluid in patients treated with letrozole during the stimulation cycles. Further investigation is required to determine if patients treated with letrozole during the IVF stimulation protocol are at increased risk for developing OHSS as a result of these findings.

[Anthology of the first clinical studies with hypothalamic hormones: a story of successful international cooperation].

PubMed

Schally, Andrew V; Gual, Carlos

2002-01-01

Our early pioneering clinical trials in Mexico with natural and synthetic thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH) also known as gonadotropin releasing hormone (Gn-RH), were reviewed. Highly purified TRH of porcine origin was shown to stimulate Thyrotropin (TSH) release in hypothyroid cretins. Subsequent tests with synthetic TRH also demonstrated significant increases in plasma TSH in normal men and women as well as in patients with primary hypothyroidism and other endocrine disorders. Even more extensive clinical studies were carried out with highly purified natural porcine LH-RH. Subjects with normal basal serum levels of gonadotropins, low levels (men and women pretreated with steroids) and high levels (e.g. post menopausal women) all responded to LH-RH with a release of LH and FSH. The results of these early studies with the natural LH-RH were confirmed by the use of synthetic LH-RH. These investigations made in Mexico with TRH and LH-RH preceded all other clinical studies by a wide margin. Subsequently various clinical investigations with LH-RH agonists and antagonists were also carried out. All these studies played a major role in introducing hypothalamic-releasing hormones into clinical medicine.

Reproductive responses to photoperiod persist in olfactory bulbectomized Siberian hamsters (Phodopus sungorus).

PubMed

Prendergast, Brian J; Pyter, Leah M; Galang, Jerome; Kay, Leslie M

2009-03-02

In reproductively photoperiodic Syrian hamsters, removal of the olfactory bulbs (OBx) leads to a marked and sustained increase in gonadotrophin secretion which prevents normal testicular regression in short photoperiods. In contrast, among reproductively nonphotoperiodic laboratory strains of rats and mice, bulbectomy unmasks reproductive responses to photoperiod. The role of the olfactory bulbs has been proposed to have opposite effects on responsiveness to photoperiod, depending on the photoperiodicity of the reproductive system; however, Syrian hamsters are the only reproductively photoperiodic rodent species for which the role of the olfactory bulb in reproductive endocrinology has been assessed. This experiment evaluated the role of the olfactory bulbs in the photoperiodic control of reproduction in Siberian hamsters (Phodopus sungorus), an established model species for the study of neural substrates mediating seasonality. Relative to control hamsters housed in long days (15 h light/day), exposure of adult male hamsters to short days (9h light/day) for 8 weeks led to a temporal expansion of the pattern of nocturnal locomotor activity, testicular regression, decreases in testosterone (T) production, and undetectable levels of plasma follicle-stimulating hormone (FSH). Bilateral olfactory bulbectomy failed to affect any of these responses to short days. The patterns of entrainment to long and short days suggests that pre-pineal mechanisms involved in photoperiodic timekeeping are functioning normally in OBx hamsters. The absence of increases in FSH following bulbectomy in long days is incompatible with the hypothesis that the olfactory bulbs provide tonic inhibition of the HPG axis in this species. In marked contrast to Syrian hamsters, the olfactory bulbs of Siberian hamsters play essentially no role in the modulation of tonic gonadotrophin production or gonadotrophin responses to photoperiod.

Prophylactic salpingectomy in premenopausal low-risk women for ovarian cancer: primum non nocere.

PubMed

Morelli, Michele; Venturella, Roberta; Mocciaro, Rita; Di Cello, Annalisa; Rania, Erika; Lico, Daniela; D'Alessandro, Pietro; Zullo, Fulvio

2013-06-01

The objective of this study is to compare ovarian function and surgical outcomes between patients affected by benign uterine pathologies submitted to total laparoscopic hysterectomy (TLH) plus salpingectomy and women in which standard TLH with adnexal preservation was performed. We retrospectively compared data of 79 patients who underwent TLH plus bilateral salpingectomy (group A), with those of 79 women treated by standard TLH without adnexectomy (sTLH) (group B). Ovarian reserve modification, expressed as the difference between 3 months post-operative and pre-operative values of Anti-Müllerian Hormone (AMH), Follicle Stimulating Hormone (FSH), Antral Follicle Count (AFC), mean ovarian diameters and Peak Systolic Velocity (PSV), was recorded for each patient. For each surgical procedure, operative time, variation of hemoglobin level (ΔHb), postoperative hospital stay, postoperative return to normal activity, and complication rate were recorded as secondary outcomes. According to our post-hoc analysis, this equivalence study resulted to have a statistical power of 96.8%. Significant difference was not observed between groups with respect to ΔAMH (p=0.35), ΔFSH (p=0.15), ΔAFC (p=0.09), Δ mean ovarian diameters (p=0.57) and ΔPSV (p=0.61). In addition, secondary outcomes such as operative time (p=0.79), ΔHb (p=0.41), postoperative hospital stay (p=0.16), postoperative return to normal activity (p=0.11) and complication rate also did not show any significant difference. The addition of bilateral salpingectomy to TLH for prevention of ovarian cancer in women who do not carry a BRCA1/2 mutations do not show negative effects on the ovarian function. In addition, no perioperative complications are related to the salpingectomy step in TLH. Copyright © 2013 Elsevier Inc. All rights reserved.

Changes of endocrine and ultrasound markers as ovarian aging in modifying the Stages of Reproductive Aging Workshop (STRAW) staging system with subclassification of mid reproductive age stage.

PubMed

Ding, Ting; Luo, Aiyue; Jiang, Jingjing; Du, Xiaofang; Yang, Shuhong; Lai, Zhiwen; Shen, Wei; Lu, Yunping; Ma, Ding; Wang, Shixuan

2013-01-01

To demonstrate the changes of ovarian aging markers across the Stages of Reproductive Aging Workshop (STRAW) stages and modify it with subclassification of mid reproductive age stage (MR). Healthy females were classified according to the STRAW system. Serum basal FSH, LH, E2, and anti-Müllerian hormone (AMH) were detected, FSH/LH ratio calculated, and antral follicle counts (AFCs) determined in follicular phase. Progression through the whole STRAW stages under MR stage subdivided is associated with elevations in FSH, LH, FSH/LH ratio and decreases in E2, AMH and AFCs (p < 0.001). Both serum AMH and AFCs decreased early (after 25 years) and significantly (p < 0.01) with chronological age in MR stage. 0.982 ng/ml AMH and 3 antral follicles (low level of MR 25-30 years) were set as cutoffs to distinguish MR stage into early mid reproductive age (EMR) and late mid reproductive age (LMR) stages. The women in EMR stage compared with LMR could retrieve more oocytes in IVF treatment (p < 0.05) and has a higher pregnancy chance (57.9%) though not significant. The early and marked fall in serum AMH levels and AFCs suggest fine markers to further categorize and define the MR stage, demonstrating disparate reproductive aging period with reduced ovarian reserve in young age across the STRAW stages.

The effect of active immunization against vasoactive intestinal peptide (VIP) and inhibin on reproductive performance of aging White Leghorn roosters.

PubMed

Avital-Cohen, N; Heiblum, R; Argov, N; Rosenstrauch, A; Chaiseha, Y; Mobarkey, N; Rozenboim, I

2012-01-01

Decreasing fertility in aging domestic roosters is a well-known phenomenon. Aging is manifested by a decrease in plasma testosterone level, testis function, and spermatogenesis, resulting in a low level of fertility. The roles of vasoactive intestinal peptide (VIP) and testicular inhibin in this aging process are not clear. The effects of active immunization against VIP, inhibin, or the combination of both hormones on the reproduction of aging White Leghorn (WL) roosters were assayed. In experiment 1a, 60 White Leghorn roosters (67 wk of age) were divided into 4 groups (n = 15/group). The first group was actively immunized against VIP, the second against inhibin, the third against VIP and inhibin, and the fourth served as a control. Active immunization against VIP decreased semen quality parameters, plasma steroid levels, and gene expression of gonadotropin-releasing hormone-I (GnRH-I), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH receptor, VIP, and prolactin (Prl). Immunization against inhibin increased some of the semen quality parameters and FSH mRNA gene expression but decreased inhibin gene expression. In experiment 1b, at 94 wk of age, we took the actively immunized against VIP group and the control group and divided them into 2 subgroups (n = 7 or 8): the first group was injected with 1 mg of ovine Prl (oPrl) daily for 7 d, and the second group served as a control. Administration of oPrl to previously VIP-immunized birds significantly elevated semen quality parameters. We suggest that VIP, Prl, and inhibin have an important effect on the reproductive axis in aging roosters. Active immunization against VIP-depressed reproductive activity and Prl administration restored their reproduction, indicating that both VIP and Prl are essential for reproduction in aging roosters. Immunization against inhibin improved FSH mRNA gene expression, suggesting a negative role of inhibin on FSH secretion in aging roosters. Not all semen quality parameters increased significantly after immunization against inhibin, even though FSH mRNA gene expression increased, suggesting interference in testicular function in aging roosters.

Social dominance in tilapia is associated with gonadotroph hyperplasia.

PubMed

Golan, Matan; Levavi-Sivan, Berta

2013-10-01

Tilapias are emerging as one of the most important fish in worldwide aquaculture and are also widely used as model fish in the study of reproduction and behavior. During the reproductive season, male tilapia are highly territorial and form spawning pits in which the dominant males court and spawn with available females. Non-territorial males stand a much lower chance of reproducing. Using transgenic tilapia in which follicle stimulating hormone (FSH) gonadotrophs were fluorescently labeled with enhanced green fluorescent protein (EGFP), we studied the effect of social dominance on the hormonal profile and pituitary cell populations in dominant and non-dominant males. Immunofluorescence studies showed that FSH-EGFP-transgenic fish reliably express EGFP in FSH-secreting cells. EGFP expression pattern differed from that of luteinizing hormone. Dominant males had larger gonads as well as higher levels of androgens and gonadotropins in the plasma. Pituitaries of dominant males exhibited higher gonadotropin content and gene expression. Flow cytometry revealed pituitary hyperplasia as well as FSH cell hyperplasia and increased granulation. Taken together, these findings suggest that gonadotroph hyperplasia as well as increased production by individual cells underlie the increased reproductive activity of dominant tilapia males. Copyright © 2013 Elsevier Inc. All rights reserved.

Bone Morphogenetic Protein 15 in the Pro-Mature Complex Form Enhances Bovine Oocyte Developmental Competence

PubMed Central

Sudiman, Jaqueline; Sutton-McDowall, Melanie L.; Ritter, Lesley J.; White, Melissa A.; Mottershead, David G.; Thompson, Jeremy G.; Gilchrist, Robert B.

2014-01-01

Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/− FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/− FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies. PMID:25058588

Bone morphogenetic protein 15 in the pro-mature complex form enhances bovine oocyte developmental competence.

PubMed

Sudiman, Jaqueline; Sutton-McDowall, Melanie L; Ritter, Lesley J; White, Melissa A; Mottershead, David G; Thompson, Jeremy G; Gilchrist, Robert B

2014-01-01

Developmental competence of in vitro matured (IVM) oocytes needs to be improved and this can potentially be achieved by adding recombinant bone morphogenetic protein 15 (BMP15) or growth differentiation factor (GDF9) to IVM. The aim of this study was to determine the effect of a purified pro-mature complex form of recombinant human BMP15 versus the commercially available bioactive forms of BMP15 and GDF9 (both isolated mature regions) during IVM on bovine embryo development and metabolic activity. Bovine cumulus oocyte complexes (COCs) were matured in vitro in control medium or treated with 100 ng/ml pro-mature BMP15, mature BMP15 or mature GDF9 +/- FSH. Metabolic measures of glucose uptake and lactate production from COCs and autofluorescence of NAD(P)H, FAD and GSH were measured in oocytes after IVM. Following in vitro fertilisation and embryo culture, day 8 blastocysts were stained for cell numbers. COCs matured in medium +/- FSH containing pro-mature BMP15 displayed significantly improved blastocyst development (57.7±3.9%, 43.5±4.2%) compared to controls (43.3±2.4%, 28.9±3.7%) and to mature GDF9+FSH (36.1±3.0%). The mature form of BMP15 produced intermediate levels of blastocyst development; not significantly different to control or pro-mature BMP15 levels. Pro-mature BMP15 increased intra-oocyte NAD(P)H, and reduced glutathione (GSH) levels were increased by both forms of BMP15 in the absence of FSH. Exogenous BMP15 in its pro-mature form during IVM provides a functional source of oocyte-secreted factors to improve bovine blastocyst development. This form of BMP15 may prove useful for improving cattle and human artificial reproductive technologies.

The influence of chronic exposure to low frequency pulsating magnetic fields on concentrations of FSH, LH, prolactin, testosterone and estradiol in men with back pain.

PubMed

Woldanska-Okonska, Marta; Karasek, Michal; Czernicki, Jan

2004-06-01

There is widespread public concern that electromagnetic fields might be hazardous. However, studies on the biological effects of magnetic fields (MFs) have not always been consistent. Influence of extremely-low frequency MFs used in physiotherapy on endocrine system was rarely examined. Therefore, the aim of the present study was to investigate the concentrations of some pituitary (FSH, LH, prolactin) and sex (testosterone, estradiol) hormones in men with back pain exposed to magnetic fields applied during magnetotherapy or magnetostimulation over the period of three weeks. The study was performed on 20 men aged 28-62 years (mean+/-SEM: 46.4+/-2.0 years) suffering from chronic low back pain who underwent magnetotherapy (10 patients, mean age+/-SEM: 48.4 years, range: 28-62 years) or subjected to magnetostimulation (10 patients, mean age+/-SEM: 44.3 years, range: 34-52 years) for 15 days (daily at 10:00 h, with weekend breaks). Blood samples were collected at 08:00 before magnetic field application, one day and one month following the application. Concentrations of hormones were measured by micromethod of chemiluminescence. Both magnetotherapy and magnetostimulation lowered levels of prolactin. The levels of LH decreased significantly one month after magnetotherapy in comparison with the baseline whereas following magnetostimulation slight but insignificant increase was observed. Estradiol concentrations were significantly lower one day and one month following magnetosimulation in comparison to the baseline and did not change after magnetotherapy. No statistically significant changes were observed in levels of FSH and testosterone after either magnetotherapy or magnetosimulation at any time examined. Magnetic fields applied in physiotherapy exert no or very subtle effect on concentrations of FSH, LH, prolactin, testosterone, and estradiol in men.

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

PubMed

Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Cui, Mingxuan; Xiong, Shuyu; Ma, Wanlu; Min, Le; Kaiser, Ursula B; Nie, Min; Wu, Xueyan

2017-07-01

The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice. Copyright © 2017 Endocrine Society

Late Complications in acute Leukemia patients following HSCT: A single center experience.

PubMed

Vaezi, Mohammad; Gharib, Cyrous; Souri, Maryam; Ghavamzadeh, Ardeshir

2016-01-01

Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for acute leukemia. As HSCT improves the long-term survival, it is necessary to assess the late-onset complications affecting the quality of life following HSCT. The study included 122 patients (65 male, 57 female) with leukemia (72 AML and 50 ALL) who received transplants from fully- matched siblings, unrelated donors and unrelated cord blood donors between February 2013 and August 2014 in Shariati Hospital. All study participants were over 18 years of age and had the minimum and maximum survival of 2 and 5 years, respectively. Patients who received HLA-haploidentical SCT were excluded from the study. All allogeneic recipients received busulfan and cyclophosphamide as conditioning regimen. Nobody received TBI-based conditioning regimen in this study. Patients were evaluated for cardiovascular, vision, psychological, endocrine, fertility problems and secondary malignancies one year after transplantation. Results : Data were analyzed using SPSS 15.0. Mitral and tricuspid regurgitation (TR/MR) were the most common cardiac complications (n=12, 10.5%).Thirty-nine percent of patients had psychological problems, especially depression (34%). Cataract was observed in 13% of patients and 34% complained of dry eye. Symptomatic pulmonary changes were found in 13 patients (10.6%). None of the HSCT survivors had experienced fertility before study entry. According to LH and FSH levels, 15% and 9% of females had ovarian failure, respectively. Testosterone level was less than normal in 49(84%) men and, according to their FSH and LH level, 20 (41%) had secondary hypogonadism and 29 (59%) had primary gonadal dysfunction. The results showed that patients who received Bu/Cy conditioning regimen experienced fewer late side effects such as cataract formation and hypothyroidism, compared to previous studies using TBI-based conditioning regimen.

Late Complications in acute Leukemia patients following HSCT: A single center experience

PubMed Central

Vaezi, Mohammad; Gharib, Cyrous; Souri, Maryam; Ghavamzadeh, Ardeshir

2016-01-01

Background: Hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for acute leukemia. As HSCT improves the long-term survival, it is necessary to assess the late-onset complications affecting the quality of life following HSCT. Subjects and Methods: The study included 122 patients (65 male, 57 female) with leukemia (72 AML and 50 ALL) who received transplants from fully- matched siblings, unrelated donors and unrelated cord blood donors between February 2013 and August 2014 in Shariati Hospital. All study participants were over 18 years of age and had the minimum and maximum survival of 2 and 5 years, respectively. Patients who received HLA-haploidentical SCT were excluded from the study. All allogeneic recipients received busulfan and cyclophosphamide as conditioning regimen. Nobody received TBI-based conditioning regimen in this study. Patients were evaluated for cardiovascular, vision, psychological, endocrine, fertility problems and secondary malignancies one year after transplantation. Results : Data were analyzed using SPSS 15.0. Mitral and tricuspid regurgitation (TR/MR) were the most common cardiac complications (n=12, 10.5%).Thirty-nine percent of patients had psychological problems, especially depression (34%). Cataract was observed in 13% of patients and 34% complained of dry eye. Symptomatic pulmonary changes were found in 13 patients (10.6%). None of the HSCT survivors had experienced fertility before study entry. According to LH and FSH levels, 15% and 9% of females had ovarian failure, respectively. Testosterone level was less than normal in 49(84%) men and, according to their FSH and LH level, 20 (41%) had secondary hypogonadism and 29 (59%) had primary gonadal dysfunction. Conclusion: The results showed that patients who received Bu/Cy conditioning regimen experienced fewer late side effects such as cataract formation and hypothyroidism, compared to previous studies using TBI-based conditioning regimen. PMID:27047644

Sex steroids in relation to sexual and skeletal maturation in obese male adolescents.

PubMed

Vandewalle, S; Taes, Y; Fiers, T; Van Helvoirt, M; Debode, P; Herregods, N; Ernst, C; Van Caenegem, E; Roggen, I; Verhelle, F; De Schepper, J; Kaufman, J M

2014-08-01

Childhood obesity is associated with an accelerated skeletal maturation. However, data concerning pubertal development and sex steroid levels in obese adolescents are scarce and contrasting. To study sex steroids in relation to sexual and skeletal maturation and to serum prostate specific antigen (PSA), as a marker of androgen activity, in obese boys from early to late adolescence. Ninety obese boys (aged 10-19 y) at the start of a residential obesity treatment program and 90 age-matched controls were studied cross-sectionally. Pubertal status was assessed according to the Tanner method. Skeletal age was determined by an x-ray of the left hand. Morning concentrations of total testosterone (TT) and estradiol (E2) were measured by liquid chromatography-tandem mass spectrometry, free T (FT) was measured by equilibrium dialysis, and LH, FSH, SHBG, and PSA were measured by immunoassays. Genital staging was comparable between the obese and nonobese groups, whereas skeletal bone advancement (mean, 1 y) was present in early and midadolescence in the obese males. Although both median SHBG and TT concentrations were significantly (P < .001) lower in obese subjects during mid and late puberty, median FT, LH, FSH, and PSA levels were comparable to those of controls. In contrast, serum E2 concentrations were significantly (P < .001) higher in the obese group at all pubertal stages. Obese boys have lower circulating SHBG and TT, but similar FT concentrations during mid and late puberty in parallel with a normal pubertal progression and serum PSA levels. Our data indicate that in obese boys, serum FT concentration is a better marker of androgen activity than TT. On the other hand, skeletal maturation and E2 were increased from the beginning of puberty, suggesting a significant contribution of hyperestrogenemia in the advancement of skeletal maturation in obese boys.

Reproductive hormone levels and anthropometry in postmenopausal women with polycystic ovary syndrome (PCOS): a 21-year follow-up study of women diagnosed with PCOS around 50 years ago and their age-matched controls.

PubMed

Schmidt, Johanna; Brännström, Mats; Landin-Wilhelmsen, Kerstin; Dahlgren, Eva

2011-07-01

The hormonal and anthropometric profile of premenopausal women with polycystic ovary syndrome (PCOS) is well described, but there is a lack of data concerning changes in these variables into the postmenopausal period. Our objective was to examine whether PCOS women differ from normal women regarding levels of reproductive hormones, anthropometry, and presence of hirsutism/climacteric symptoms also after menopause. In this prospective study, women with PCOS (61-79 yr) and age-matched controls, examined in 1987, were reinvestigated at a university hospital. Twenty-five PCOS patients (Rotterdam criteria) and 68 controls (randomly allocated from the Gothenburg WHO MONICA study) participated. Reexamination and hormonal measurements were done 21 yr after previous visit. FSH, LH, TSH, thyroid peroxidase antibodies, prolactin, estrone, estradiol, SHBG, androstenedione, total testosterone, dehydroepiandrosterone sulfate, free androgen index, and anthropometry were determined. Presence of climacteric symptoms, hirsutism, and menopausal age were recorded. PCOS women had higher free androgen index (P = 0.001) but lower FSH (P < 0.001) and SHBG (P < 0.01) than controls. Menopausal age, body weight, body mass index, waist to hip ratio, LH, prolactin, androstenedione, dehydroepiandrosterone sulfate, total testosterone, estradiol, and estrone were similar in PCOS and controls. Women with PCOS reported hirsutism more frequently (P < 0.001) but had fewer climacteric symptoms (P < 0.05) and hypothyroidism than controls (P < 0.05). PCOS women differ from controls with regard to levels of certain reproductive hormones also after menopause, but the established premenopausal increase in waist to hip ratio in PCOS patients disappeared after menopause, mainly due to weight gain among controls. A novel finding was the lower prevalence of hypothyroidism in PCOS women.

Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

PubMed

Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

2001-10-01

To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

Sequelae in male rabbits following developmental exposure to p,p'-DDT or a mixture of p,p'-DDT and vinclozolin: cryptorchidism, germ cell atypia, and sexual dysfunction.

PubMed

Veeramachaneni, D N R; Palmer, J S; Amann, R P; Pau, K-Y F

2007-01-01

Rabbit does (7-9 per group) were treated daily per orum from gestation day 15 through post-natal week 4 to provide per kg body wt 25 micaromol (low) or 250 micromol (high) p,p'-DDT or a mixture of DDT and vinclozolin (12.5 and 125 micromol each). Developmental as well as post-pubertal reproductive sequelae of male progeny were studied. Testicular descent in some pups was impaired by DDT. Serum LH or testosterone was not affected. FSH was lower in mixture- but not in DDT-exposed rabbits. Lack of sexual interest, penile erection and ejaculation were observed in some mixture rabbits. Sperm counts were unaffected, but morphologically normal spermatozoa were fewer; nuclear and acrosomal morphogenesis was disrupted. Atypical germ cells resembling carcinoma in situ were found. Also considering data for vinclozolin [Veeramachaneni DNR, Palmer JS, Amann RP, Kane CM, Higuchi TT, Pau K-YF. Disruption of sexual function, FSH secretion, and spermiogenesis in rabbits following developmental exposure to vinclozolin, a fungicide. Reproduction 2006;131:805-16], we concluded that DDT causes cryptorchidism and germ cell atypia, vinclozolin permanently disrupts FSH secretion and sexual function, and the mixture causes the full spectrum of dysgenesis.

Women with clomiphene citrate resistant polycystic ovarian disease: predictors of spontaneous ovulation after laparoscopic ovarian drilling.

PubMed

Abuelghar, Wessam M; Bayoumy, Hassan A; Ellaithy, Mohamed I; Khalil, Marian S

2014-04-01

To evaluate the role of different clinical, biochemical and sonographic factors as predictors of spontaneous ovulation after laparoscopic ovarian drilling (LOD) in women with clomiphene citrate resistant polycystic ovarian disease (CCR-PCOD). This prospective study recruited 251 infertile women with CCR-PCOD. Several clinical, biochemical and sonographic criteria were tested as possible predictors of spontaneous ovulation after LOD using multivariate analysis. Women with higher preoperative levels of LH, FSH and/or androstenedione had significantly higher rates of spontaneous ovulation within the first eight weeks after LOD, but only FSH and androstenedione were found to be independent predictors. Other factors including age, BMI, type of infertility, duration of infertility, menstrual pattern, testosterone level, ovarian volume and SHBG were insignificant predictors. Receiver-operating characteristic (ROC) curves derived from FSH, LH, androstenedione, and a logistic regression model showed that the best cut-off values were 4.1IU/l, 7.8IU/l, 1.2ng/ml, and 0.4897, respectively, with sensitivity of 91.18%, 100%, 73.53%, and 88.24% and specificity of 69.57%, 69.57%, 65.22%, and 73.91% for FSH, LH, androstenedione, and logistic regression model respectively. An extended follow up (9 months after LOD) was conducted for the anovulatory and the non-pregnant ovulatory women, who were treated individually according to their clinical situation. Of these women, 53.5% (69/129) got pregnant, resulting in a cumulative pregnancy rate of 48% (82/171). Of these pregnancies, 16/82 (19.5%) were spontaneous while 35.4% (29/82) and 45.1% (37/82) occurred after ovulation induction by CC and gonadotropins, respectively. This study supports the use of androstenedione, LH and FSH as a simple reliable tool in triaging patients with CCR-PCOD to select the ideal candidates for LOD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily

PubMed Central

Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Hardy, Kate

2017-01-01

Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS. PMID:28324051

Androgen Stimulates Growth of Mouse Preantral Follicles In Vitro: Interaction With Follicle-Stimulating Hormone and With Growth Factors of the TGFβ Superfamily.

PubMed

Laird, Mhairi; Thomson, Kacie; Fenwick, Mark; Mora, Jocelyn; Franks, Stephen; Hardy, Kate

2017-04-01

Androgens are essential for the normal function of mature antral follicles but also have a role in the early stages of follicle development. Polycystic ovary syndrome (PCOS), the most common cause of anovulatory infertility, is characterized by androgen excess and aberrant follicle development that includes accelerated early follicle growth. We have examined the effects of testosterone and dihydrotestosterone (DHT) on development of isolated mouse preantral follicles in culture with the specific aim of investigating interaction with follicle-stimulating hormone (FSH), the steroidogenic pathway, and growth factors of the TGFβ superfamily that are known to have a role in early follicle development. Both testosterone and DHT stimulated follicle growth and augmented FSH-induced growth and increased the incidence of antrum formation among the granulosa cell layers of these preantral follicles after 72 hours in culture. Effects of both androgens were reversed by the androgen receptor antagonist flutamide. FSH receptor expression was increased in response to both testosterone and DHT, as was that of Star, whereas Cyp11a1 was down-regulated. The key androgen-induced changes in the TGFβ signaling pathway were down-regulation of Amh, Bmp15, and their receptors. Inhibition of Alk6 (Bmpr1b), a putative partner for Amhr2 and Bmpr2, by dorsomorphin resulted in augmentation of androgen-stimulated growth and modification of androgen-induced gene expression. Our findings point to varied effects of androgen on preantral follicle growth and function, including interaction with FSH-activated growth and steroidogenesis, and, importantly, implicate the intrafollicular TGFβ system as a key mediator of androgen action. These findings provide insight into abnormal early follicle development in PCOS.

The anti-Müllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH.

PubMed

Sacchi, Sandro; D'Ippolito, Giovanni; Sena, Paola; Marsella, Tiziana; Tagliasacchi, Daniela; Maggi, Elena; Argento, Cindy; Tirelli, Alessandra; Giulini, Simone; La Marca, Antonio

2016-01-01

Anti Müllerian Hormone (AMH) has a negative and inhibitory role in many functions of human granulosa-lutein cells (hGCs) including notoriously the reduction of the aromatase CYP19A1 expression induced by follicle-stimulating hormone (FSH). No data have been provided on the possible role of AMH in modulating the response to luteinizing hormone (LH) (alone or combined with FSH) as well as its effect on other enzymes involved in steroidogenesis including aromatase P450scc. The aim of this study was to investigate the role of AMH as regulator of the basal and stimulated steroids production by hGCs. Primary culture of hGCs were incubated with hormones AMH, LH, and FSH, alone or in combination. The CYP19A1 and P450scc messenger RNA (mRNA) expression, normalized by housekeeping ribosomal protein S7 (RpS7) gene, was evaluated by reverse transcriptase quantitative PCR (RT-qPCR). Each reaction was repeated in triplicate. Negative controls using corresponding amount of vehicle control for each hormone treatment were performed. AMH did not modulate the basal mRNA expression of both aromatase genes at any of the concentrations tested. Meanwhile, the strong mRNA induction of CYP19A1 and P450scc generated by a 24-h gonadotropin treatment (alone and combined) was suppressed by 20 ng/ml AMH added to culture medium. These findings contribute in clarifying the relationship between hormones regulating the early phase of steroidogenesis confirming that AMH is playing a suppressive role on CYP19A1 expression stimulated by gonadotropin in hGCs. Furthermore, a similar inhibitory effect for AMH was observed on P450scc gene expression when activated by gonadotropin treatment.

Expression of nerve growth factor and its receptor, tyrosine kinase receptor A, in rooster testes.

PubMed

Ma, Wei; Wang, Chunqiang; Su, Yuhong; Tian, Yumin; Zhu, Hongyan

2015-10-01

Nerve growth factor (NGF), which is required for the survival and differentiation of the nervous system, is also thought to play an important role in the development of mammalian reproductive tissues. To explore the function of NGF in the male reproductive system of non-mammalian animals, we determined the presence of NGF and its receptor, tyrosine kinase receptor A (TrkA), in rooster testes and investigated the regulation of NGF and TrkA expression by follicle-stimulating hormone (FSH). The mRNA and protein levels of NGF and TrkA in 6-week-old rooster testes were lower than those in 12-, 16- or 20-week age groups; levels were highest in the 16-week group. Immunohistochemistry showed that NGF and TrkA were both detected in spermatogonia, spermatocytes and spermatids. NGF immunoreactivity was observed in Leydig cells and strong TrkA signals were present in Sertoli cells. Meanwhile, FSH increased TrkA transcript levels in rooster testes in a dose-dependent manner. We present novel evidence for the developmental and FSH-regulated expression of the NGF/TrkA system, and our findings suggest that the NGF/TrkA system may play a prominent role in chicken spermatogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.

The use of a combined regimen of GnRH agonist plus a low-dose oral contraceptive improves the spontaneous pulsatile LH secretory characteristics in patients with polycycstic ovary disease after discontinuation of treatment.

PubMed

Genazzani, A D; Battaglia, C; Gamba, O; Petraglia, F; Malavasi, B; Genazzani, A R

2000-05-01

The fertility rate in women with polycystic ovary disease (PCOD) is influenced by the type of treatment received. The present study evaluated the possible correlation between treatment and pulsatile release of gonadotropins. Spontaneous episodic secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and hormonal parameters were monitored before and after 1, 3, and 6 months after treatments suspension. Twenty-four PCOD patients were randomly divided into two groups of 12 subjects. Group A was treated with gonadotropin-releasing hormone (GnRH)-analogue plus oral contraceptive (OC). Group B was treated only with OC. Both groups were treated for 6 months and followed up for 6 months. In all subjects the therapeutic regimens reduced the androgenic milieau and the gonadotropin plasma levels. Spontaneous pulsatile secretion of LH and FSH was significantly modified in both groups, but patients who received the combined regimen showed a significantly greater reduction of LH plasma levels and a significantly greater decrease of LH pulse amplitude throughout the 6 months after treatment suspension. Ferriman-Gallway score and ovarian volumes were significantly reduced in patients who received the combined treatment than in the OC-treated patients. These data support the evidence of a higher efficacy of the combination of GnRH-a + OC than OC alone in restoring a normal and adequate spontaneous episodic gonadotropin discharge and in decreasing Ferriman-Gallway score and ovarian volumes in patients with PCOD.

Cerium oxide nanoparticle elicits oxidative stress, endocrine imbalance and lowers sperm characteristics in testes of balb/c mice.

PubMed

Adebayo, O A; Akinloye, O; Adaramoye, O A

2018-04-01

The toxicity of metallic nanoparticles is a growing concern due to its application in industries and homes. We investigated the toxicity of cerium oxide nanoparticles (CeO 2 NPs) on reproductive system in male balb/c mice. Twenty mice were divided into four groups of five animals each and treated thus: normal saline (control), 100, 200 and 300 μg/kg CeO 2 NPs (i.p.,) thrice in a week for five consecutive weeks. Results showed that CeO 2 NPs significantly reduced the levels of haemoglobin, PCV and RBC count relative to controls. In addition, luteinising and follicle-stimulating hormones (FSH and LH) and prolactin were significantly reduced in the mice. Specifically, CeO 2 NPs at 100 μg/kg decreased testosterone by 23%, while CeO 2 NPs at 200 μg/kg decreased FSH, LH and prolactin by 25%, 26% and 13%, respectively. Testicular malondialdehyde was increased by 103%, 106% and 135% in mice treated with 100, 200 and 300 μg/kg CeO 2 NPs, respectively. CeO 2 NPs caused a significant reduction in activities of antioxidant enzymes and levels of reduced glutathione and total nitric oxide. Moreso, CeO 2 NPs decreased sperm motility and count and increased total sperm abnormality in mice. Histology revealed congestion and degeneration of seminiferous tubules. Overall, CeO 2 NPs induces testicular dysfunction via disruption of antioxidant/oxidant balance and endocrine suppression. © 2017 Blackwell Verlag GmbH.

Ovulation induction: a mini review.

PubMed

Messinis, Ioannis E

2005-10-01

Ovulation induction is the method for treating anovulatory infertility. For patients with hypogonadotrophic hypogonadism, the treatment involves administration of both FSH and LH, while HCG is injected for follicle rupture. Pulsatile GnRH has the same effectiveness as gonadotrophins and the advantage of the low multiple pregnancy rate. In polycystic ovary syndrome (PCOS), the first treatment choice is clomiphene citrate. With this drug, in properly selected patients, the cumulative pregnancy rate approaches that of normal women. Low-dose protocols of FSH are the second line of treatment, effective in inducing monofollicular development. Laparoscopic ovarian drilling can be an alternative but not as a first choice treatment in clomiphene-resistant patients. Other treatments, such as pulsatile GnRH and GnRH agonists, are hardly used today in PCOS. However, in obese women with PCOS, weight loss and exercise should be recommended as the first line of therapy. Newer agents including aromatase inhibitors and insulin sensitizers, although promising, need further evaluation.

Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes

PubMed Central

Nasrolahi, Ozra; Khaneshi, Fereshteh; Rahmani, Fatemeh; Razi, Mazdak

2013-01-01

Background: The global prevalence of diabetes mellitus is on rise. Diabetes-induced oxidative stress has been known to affect liver, pancreas, kidney and reproductive organs pathologically. Honey is a natural product of bee with antioxidant properties. Objective: Current study aimed to analyze the protective effects of Metformin (MF) alone and MF+ natural honey co-administration on diabetes-induced histological derangements in testis of rats. Materials and Methods: Thirty six, mature male Wistar rats were randomly divided into six groups including; control, honey-dosed non-diabetic, diabetes-induced (65 mg/kg, single dose), honey-administrated diabetic (1.0 g/kg/day), Metformin-received diabetic (100 mg/kg/day), Metformin and honey-co-treated diabetic which were followed 40 days. The animals were anesthetized by diethyl ether and the blood samples were collected. The serum levels of testosterone, Insulin, LH and FSH analyzed using antibody enzyme immunoassay method. The testicular tissues were dissected out and underwent to histological analyses. Results: The biochemical analyses revealed that the diabetes resulted in significantly reduced testosterone (p<0.01), LH and FSH (P<0.01, 0.001) levels in serum. Light microscopic analyses showed remarkable (p<0.01) reduction in seminiferous tubules diameter (STD), spermiogenesis index (SPI) and thickness of the epithelium in the diabetic group versus control and co-treated groups. Simultaneous administration of the honey with MF could fairly up-regulate testosterone, LH and FSH levels. The animals in metformin and honey-treated group exhibited with improved tubules atrophy, elevated spermiogenesis index and germinal epithelium thickness. Conclusion: Our data indicated that co-administration of Metformin and honey could inhibit the diabetes-induced damages in testicular tissue. Moreover, the simultaneous administration of metformin and honey up-regulated the diabetes-reduced insulin, LH, FSH and testosterone levels. This article extracted from M.Sc. thesis. (Ozra Nasrolahi) PMID:24639728

[Effect of kuntai capsule on the number of retrieved oocytes, high-quality oocytes and embryos in in vitro fertilization of poor ovarian response patients].

PubMed

Lian, Fang; Jiang, Xiao-Yuan

2014-08-01

To observe the effect of Kuntai Capsule (KC) on the number of retrieved oocytes, the quality of high-quality oocytes and embryos in in vitro fertilization of poor ovarian response (POR) patients. Totally 70 POR patients preparing for in vitro fertilization-embryo transfer (IVF-ET) were randomly assigned to the observation group and the control group, 35 cases in each group. KC was administered to patients in the observation group in the preparation cycle (i.e., three menstrual cycles before IVF-ET) and during the superovulation process. Those in the control group took placebo during this period. Before and after medication the improvement of Shen yin deficiency syndrome (SYDS) was observed in the two groups. The basal follicle-stimulating hormone (bFSH), luteinizing hormone (LH), estradiol (E2), anti-Mullerian hormone (AMH), the ratio of FSH to LH, and antral follicle count (AFC) were observed. Besides, the E2 level of a single ovum on the day of HCG injection, the number of retrieved oocytes, the high-quality oocyte rate, and the high-quality embryos were observed. Compared with the control group, the SYDS, decreased bFSH and LH levels, increased ACF numbers, the E2 level of a single ovum on the day of HCG injection, the number of retrieved oocytes, high-quality oocytes, and high-quality embryos were superior in the observation group (P < 0.05). There was no statistical difference in the decreased FSH/LH level (P > 0.05). E2 and AMH increased after medication of KC in the observation group, while they decreased after administration of placebos in the control group. There was statistical difference in the post-pre treatment difference of E2 and AMH between the two groups (P < 0.05). KC could increase the number of retrieved oocytes, and elevate the quality of occytes and embryos in the IVF-ET.

PIVET rFSH dosing algorithms for individualized controlled ovarian stimulation enables optimized pregnancy productivity rates and avoidance of ovarian hyperstimulation syndrome.

PubMed

Yovich, John L; Alsbjerg, Birgit; Conceicao, Jason L; Hinchliffe, Peter M; Keane, Kevin N

2016-01-01

The first PIVET algorithm for individualized recombinant follicle stimulating hormone (rFSH) dosing in in vitro fertilization, reported in 2012, was based on age and antral follicle count grading with adjustments for anti-Müllerian hormone level, body mass index, day-2 FSH, and smoking history. In 2007, it was enabled by the introduction of a metered rFSH pen allowing small dosage increments of ~8.3 IU per click. In 2011, a second rFSH pen was introduced allowing more precise dosages of 12.5 IU per click, and both pens with their individual algorithms have been applied continuously at our clinic. The objective of this observational study was to validate the PIVET algorithms pertaining to the two rFSH pens with the aim of collecting ≤15 oocytes and minimizing the risk of ovarian hyperstimulation syndrome. The data set included 2,822 in vitro fertilization stimulations over a 6-year period until April 2014 applying either of the two individualized dosing algorithms and corresponding pens. The main outcome measures were mean oocytes retrieved and resultant embryos designated for transfer or cryopreservation permitted calculation of oocyte and embryo utilization rates. Ensuing pregnancies were tracked until live births, and live birth productivity rates embracing fresh and frozen transfers were calculated. Overall, the results showed that mean oocyte numbers were 10.0 for all women <40 years with 24% requiring rFSH dosages <150 IU. Applying both specific algorithms in our clinic meant that the starting dose was not altered for 79.1% of patients and for 30.1% of those receiving the very lowest rFSH dosages (≤75 IU). Only 0.3% patients were diagnosed with severe ovarian hyperstimulation syndrome, all deemed avoidable due to definable breaches from the protocols. The live birth productivity rates exceeded 50% for women <35 years and was 33.2% for the group aged 35-39 years. Routine use of both algorithms led to only 11.6% of women generating >15 oocytes, significantly lower than recently published data applying conventional dosages (38.2%; P<0.0001). When comparing both specific algorithms to each other, the outcomes were mainly comparable for pregnancy, live birth, and miscarriage rate. However, there were significant differences in relation to number of oocytes retrieved, but the mean for both the algorithms remained well below 15 oocytes. Consequently, application of both these algorithms in our in vitro fertilization clinic allows the use of both the rFSH products, with very similar results, and they can be considered validated on the basis of effectiveness and safety, clearly avoiding ovarian hyperstimulation syndrome.

Triple X syndrome and puberty: focus on the hypothalamus-hypophysis-gonad axis.

PubMed

Stagi, Stefano; di Tommaso, Mariarosaria; Scalini, Perla; Lapi, Elisabetta; Losi, Stefania; Bencini, Erica; Masoni, Fabrizio; Dosa, Laura; Becciani, Sabrina; de Martino, Maurizio

2016-06-01

To evaluate the hypothalamus-hypophysis-gonad axis in a cohort of children and adolescents with nonmosaic triple X syndrome. Cross-sectional study with retrospective analysis. University pediatric hospital. Fifteen prepubertal subjects (median age 9.0 years, range 6.9-11.9 years) with nonmosaic triple X syndrome and age- and pubertal-matched control group (30 girls, median age 9.1 y, range 6.9-11.6 years). None. We evaluated FSH, LH, and E2 levels and performed an autoimmunity screening as well as a pelvic ultrasonography and an LH-releasing hormone stimulation test. All triple X patients (with and without pubertal signs) showed a pubertal LH peak level that was significantly different from controls. Triple X patients showed increased basal and peak FSH and LH values compared with control subjects. However, the mean E2 level was significantly lower than control subjects. However, triple X patients showed reduced DHEAS levels and reduced inhibin levels compared with control subjects. Finally, triple X patients had a significantly reduced ovarian volume compared with control subjects, in both prepubertal and pubertal patients. Triple X patients showed premature activation of the GnRH pulse generator, even without puberty signs. Both basal and peak LH and FSH levels were higher than in control subjects, and E2 and inhibin levels and ovarian volume were reduced, which led to a reduced gonadal function. Other studies and a longitudinal evaluation is necessary to better understand the endocrinologic features of these subjects. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Serum Leptin and Ghrelin Levels in Women with Polycystic Ovary Syndrome: Correlation with Anthropometric, Metabolic, and Endocrine Parameters

PubMed Central

Houjeghani, Shiva; Pourghassem Gargari, Bahram; Farzadi, Laya

2012-01-01

Background Polycystic ovary syndrome (PCOS) patients are more prone to abnormal production of some regulatory peptides. In these patients, studies on the serum levels of leptin and ghrelin are controversial. This study aims to investigate serum levels of leptin and ghrelin and their correlation with metabolic and endocrine indices in PCOS. Materials and Methods This case-control study was conducted on 60 women; 30 with PCOS and 30 healthy women whose age and body mass index (BMI) were matched and who were referred to Alzahra Hospital, Tabriz, Iran. Serum levels of leptin, ghrelin, insulin, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), and testosterone were measured. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Descriptive statistics and correlations were performed using SPSS 12.0 for Windows. Results In PCOS women, serum levels of leptin, insulin, HOMA-IR, testosterone, LH, and LH/FSH were significantly higher, while SHBG was lower than in healthy women. Ghrelin and FSH were similar in both groups. Serum levels of leptin correlated with BMI (r=0.85, p<0.001), waist to hip ratio (WHR) (r=0.55, p<0.01), insulin levels (r=0.85, p<0.001) and HOMA-IR (r=0.67, p<0.01), while ghrelin levels had an inverse association with testosterone (r=-0.32, p=0.04). Conclusion The results showed increased leptin levels while ghrelin remained unchanged in PCOS patients. In PCOS patients, leptin positively correlated with BMI, WHR, insulin, and insulin resistance, while ghrelin was only associated with serum testosterone levels. PMID:25493169

Pivagabine decreases stress-related hormone secretion in women with hypothalamic amenorrhea.

PubMed

Genazzani, A D; Stomati, M; Bersi, C; Luisi, S; Fedalti, M; Santuz, M; Esposito, G; Petraglia, F; Genazzani, A R

2000-09-01

Stress-induced neuroendocrine activities influence the regulation of endocrine glands and axes. Weight loss-related hypothalamic amenorrhea is a typical stress-induced physiopathological condition. It is characterized by increased adrenal cortex activation and by reduced GH, LH, FSH and gonadal steroid hormone levels. The aim of the present study was to investigate the effects of pivagabine, a neurotropic drug (1800 mg/day for 7 days) or placebo administration on ACTH, cortisol, GH, LH, FSH and PRL plasma levels in patients with hypothalamic amenorrhea related to weight loss. Hormonal parameters and the pulsatile release of cortisol (6-hour pulsatility, sampling every 10 minutes) were evaluated before and after 7 days of treatment. Pivagabine administration significantly reduced mean plasma ACTH (from 21.7+/-1.7 to 15.4+/-1.2 pg/ml, p<0.05) and cortisol levels (from 12.2+/-0.7 to 9.7+/-0.7 ng/ml, p<0.05) and increased GH levels (from 1.4+/-0.5 to 3.0+/-0.9 ng/ml, p<0.05). A significant reduction of cortisol pulse amplitude was observed (p<0.01) while no change in pulse frequency occurred. No changes were observed in placebo-treated subjects. LH, FSH and PRL levels were not modified by placebo or pivagabine administration. In conclusion, in patients with hypothalamic amenorrhea related to weight loss pivagabine induced a significant decrease of cortisol secretion and an increase of GH release by pivagabine administration, suggesting that this drug exerts a specific neuroendocrine modulatory role.

Ovarian sensitivity index is strongly related to circulating AMH and may be used to predict ovarian response to exogenous gonadotropins in IVF

PubMed Central

2011-01-01

Background Serum anti-Mullerian hormone (AMH) is currently considered the best marker of ovarian reserve and of ovarian responsiveness to gonadotropins in in-vitro fertilization (IVF). AMH assay, however, is not available in all IVF Units and is quite expensive, a reason that limits its use in developing countries. The aim of this study is to assess whether the "ovarian sensitivity index" precisely reflects AMH so that this index may be used as a surrogate for AMH in prediction of ovarian response during an IVF cycle. Methods AMH serum levels were measured in 61 patients undergoing IVF with a "long" stimulation protocol including the GnRH agonist buserelin and recombinant follicle-stimulating hormone (rFSH). Patients were divided into four subgroups according to the percentile of serum AMH and their ovarian stimulation was prospectively followed. Ovarian sensitivity index (OSI) was calculated dividing the total administered FSH dose by the number of retrieved oocytes. Results AMH and OSI show a highly significant negative correlation (r = -0.67; p = 0.0001) that is stronger than the one between AMH and the total number of retrieved oocytes and than the one between AMH and the total FSH dose. Conclusions OSI reflects quite satisfactory the AMH level and may be proposed as a surrogate of AMH assay in predicting ovarian responsiveness to FSH in IVF. Being very easy to calculate and costless, its use could be proposed where AMH measurement is not available or in developing countries where limiting costs is of primary importance. PMID:21824441

Recombinant human follicle-stimulating hormone (r-hFSH) plus recombinant luteinizing hormone versus r-hFSH alone for ovarian stimulation during assisted reproductive technology: systematic review and meta-analysis.

PubMed

Lehert, Philippe; Kolibianakis, Efstratios M; Venetis, Christos A; Schertz, Joan; Saunders, Helen; Arriagada, Pablo; Copt, Samuel; Tarlatzis, Basil

2014-02-20

The potential benefit of adding recombinant human luteinizing hormone (r-hLH) to recombinant human follicle-stimulating hormone (r-hFSH) during ovarian stimulation is a subject of debate, although there is evidence that it may benefit certain subpopulations, e.g. poor responders. A systematic review and a meta-analysis were performed. Three databases (MEDLINE, Embase and CENTRAL) were searched (from 1990 to 2011). Prospective, parallel-, comparative-group randomized controlled trials (RCTs) in women aged 18-45 years undergoing in vitro fertilization, intracytoplasmic sperm injection or both, treated with gonadotrophin-releasing hormone analogues and r-hFSH plus r-hLH or r-hFSH alone were included. The co-primary endpoints were number of oocytes retrieved and clinical pregnancy rate. Analyses were conducted for the overall population and for prospectively identified patient subgroups, including patients with poor ovarian response (POR). In total, 40 RCTs (6443 patients) were included in the analysis. Data on the number of oocytes retrieved were reported in 41 studies and imputed in two studies. Therefore, data were available from 43 studies (r-hFSH plus r-hLH, n=3113; r-hFSH, n=3228) in the intention-to-treat (ITT) population (all randomly allocated patients, including imputed data). Overall, no significant difference in the number of oocytes retrieved was found between the r-hFSH plus r-hLH and r-hFSH groups (weighted mean difference -0.03; 95% confidence interval [CI] -0.41 to 0.34). However, in poor responders, significantly more oocytes were retrieved with r-hFSH plus r-hLH versus r-hFSH alone (n=1077; weighted mean difference +0.75 oocytes; 95% CI 0.14-1.36). Significantly higher clinical pregnancy rates were observed with r-hFSH plus r-hLH versus r-hFSH alone in the overall population analysed in this review (risk ratio [RR] 1.09; 95% CI 1.01-1.18) and in poor responders (n=1179; RR 1.30; 95% CI 1.01-1.67; ITT population); the observed difference was more pronounced in poor responders. These data suggest that there is a relative increase in the clinical pregnancy rates of 9% in the overall population and 30% in poor responders. In conclusion, this meta-analysis suggests that the addition of r-hLH to r-hFSH may be beneficial for women with POR.

A comparison of menotropin, highly-purified menotropin and follitropin alfa in cycles of intracytoplasmic sperm injection

PubMed Central

Esteves, Sandro C; Schertz, Joan C; Verza, Sidney; Schneider, Danielle T; Zabaglia, Silval FC

2009-01-01

Background Over the last several decades, as a result of an evolution in manufacturing processes, a marked development has been made in the field of gonadotropins for ovarian stimulation. Initially, therapeutic gonadotropins were produced from a simple process of urine extraction and purification; now they are produced via a complex system involving recombinant technology, which yields gonadotropins with high levels of purity, quality, and consistency. Methods A retrospective analysis of 865 consecutive intracytoplasmic sperm injection (ICSI) cycles of controlled ovarian hyperstimulation (COH) compared the clinical efficacy of three gonadotropins (menotropin [hMG; n = 299], highly-purified hMG [HP-hMG; n = 330] and follitropin alfa [r-hFSH; n = 236]) for ovarian stimulation after pituitary down-regulation. The endpoints were live birth rates and total doses of gonadotropin per cycle and per pregnancy. Results Laboratory and clinical protocols remained unchanged over time, except for the type of gonadotropin used, which was introduced sequentially (hMG, then HP-hMG, and finally r-hFSH). Live birth rates were not significantly different for hMG (24.4%), HP-hMG (32.4%) and r-hFSH (30.1%; p = 0.09) groups. Total dose of gonadotropin per cycle was significantly higher in the hMG (2685 +/- 720 IU) and HP-hMG (2903 +/- 867 IU) groups compared with the r-hFSH-group (2268 +/- 747 IU; p < 0.001). Total dose of gonadotropin required to achieve clinical pregnancy was 15.7% and 11.0% higher for the hMG and HP-hMG groups, respectively, compared with the r-hFSH group, and for live births, the differences observed were 45.3% and 19.8%, respectively. Conclusion Although similar live birth rates were achieved, markedly lower doses of r-hFSH were required compared with hMG or HP-hMG. PMID:19828024

Comparison of fall prediction by the Hessisch Oldendorf Fall Risk Scale and the Fall Risk Scale by Huhn in neurological rehabilitation: an observational study.

PubMed

Hermann, Olena; Schmidt, Simone B; Boltzmann, Melanie; Rollnik, Jens D

2018-05-01

To calculate scale performance of the newly developed Hessisch Oldendorf Fall Risk Scale (HOSS) for classifying fallers and non-fallers in comparison with the Risk of Falling Scale by Huhn (FSH), a frequently used assessment tool. A prospective observational trail was conducted. The study was performed in a large specialized neurological rehabilitation facility. The study population ( n = 690) included neurological and neurosurgery patients during neurological rehabilitation with varying levels of disability. Around the half of the study patients were independent and dependent in the activities of daily living (ADL), respectively. Fall risk of each patient was assessed by HOSS and FSH within the first seven days after admission. Event of fall during rehabilitation was compared with HOSS and FSH scores as well as the according fall risk. Scale performance including sensitivity and specificity was calculated for both scales. A total of 107 (15.5%) patients experienced at least one fall. In general, fallers were characterized by an older age, a prolonged length of stay, and a lower Barthel Index (higher dependence in the ADL) on admission than non-fallers. The verification of fall prediction for both scales showed a sensitivity of 83% and a specificity of 64% for the HOSS scale, and a sensitivity of 98% with a specificity of 12% for the FSH scale, respectively. The HOSS shows an adequate sensitivity, a higher specificity and therefore a better scale performance than the FSH. Thus, the HOSS might be superior to existing assessments.

Effects of FSH and 17beta-estradiol on the transactivation of estrogen-regulated promoters and cell proliferation in L cells.

PubMed

Pasapera, Ana María; Jiménez-Aguilera, María del Pilar; Chauchereau, Anne; Milgrom, Edwin; Olivares, Aleida; Uribe, Aída; Gutiérrez-Sagal, Rubén; Ulloa-Aguirre, Alfredo

2005-03-01

In the present study, we analyzed human follicle-stimulating hormone (FSH)-induced cell proliferation and transactivation of estrogen-sensitive reporter genes-in L cells stably expressing the human FSH receptor [L-(hFSHR(+)) cells]. In order to dissect the signaling pathways involved in this process, L-(hFSHR(+)) cells were transiently transfected with either the 3X-ERE-TAT-Luc or the ERE-VitA2-TK-CAT reporter genes and treated with FSH or PKA activators (cholera toxin, forskolin and 8-Br-cAMP) in the presence or absence of various kinase inhibitors. We found that FSH and all PKA activators, specifically induced transactivation of both reporter genes. Transactivation of estrogen-sensitive genes by FSH or PKA activators were blocked (approximately 90%) by H89 (PKA inhibitor) and LY294002 but not by Wortmannin (PI3-K inhibitors), 4-OH-tamoxifen, ICI182,780 or SB203580 (p38 MAPK inhibitor); PD98059 (ERK1/2 inhibitor) partially (approximately 30%) blocked the FSH-mediated effect. The combination of FSH and estradiol resulted in a synergistic effect on transactivation as well as on cell proliferation, and this enhancement was attenuated by antiestrogens. We additionally analyzed the participation of the coactivators SRC-1 and cAMP response element binding protein (CREB)-binding protein (CBP) in FSH-evoked estrogen receptor (ER)-dependent transactivation; we found that CBP but not SRC-1 potentiated FSH-induced transcriptional activation of both ER-sensitive reporters, being this effect stronger on the ERE-VitA2-TK-CAT than on the 3X-ERE-TAT-Luc reporter. Thus, in L-(hFSHR(+)) cells FSH induces transcriptional activation of estrogen-sensitive genes through an A-kinase-triggered signaling pathway, using also to a lesser extent the ERK1/2 and p38 pathways. PI3-K is not apparently involved in this FSH-mediated process since LY294002, but not Wortmannin, specifically binds ERs and completely blocks estrogen action. Presumably, CBP cooperates with the ER on genes that contain estrogen responsive elements through mechanisms involving the participation of other proteins and/or basal transcription factors (e.g. CREB), which in turn mediate the transcriptional response of estrogen-sensitive reporter genes to FSH stimulation.

Exposure to Hypoxia at High Altitude (5380 m) for 1 Year Induces Reversible Effects on Semen Quality and Serum Reproductive Hormone Levels in Young Male Adults.

PubMed

He, Jiang; Cui, Jianhua; Wang, Rui; Gao, Liang; Gao, Xiaokang; Yang, Liu; Zhang, Qiong; Cao, Jinjun; Yu, Wuzhong

2015-09-01

This study investigated the effect of hypoxia at high altitude on the semen quality and the serum reproductive hormone levels in male adults. A total of 52 male soldiers were enrolled in this cohort study. They were exposed to hypoxia at high altitude (5380 m) for 12 months when undergoing a service. After exposure, they were followed up for 6 months. The samples of semen and peripheral blood were collected at 1 month before exposure (M0), 6 months of exposure (M6), 12 months of exposure (M12), and 6 months after exposure (M18). The semen quality was assessed with computer-assisted analysis system, and the serum levels of reproductive hormones, including prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone were analyzed by ELISA. Compared with those at M0, total sperm count, sperm density, motility, survival rate, and serum levels of LH, PRL and testosterone were significantly decreased, whereas the liquefaction time was significantly prolonged and serum FSH level was significantly increased at M6 (p<0.05). At M12, total sperm count and sperm density increased, whereas sperm motility, survival rate, and the liquefaction time further decreased. Sperm velocities, progression ratios, and lateral head displacements were also decreased. Serum FSH level decreased while serum LH, PRL, and testosterone levels increased. Compared with those at M6, the changes in these detected parameters of semen and hormone at M12 were significant (p<0.05). At M18, all these detected parameters except testosterone level returned to levels comparable to those before exposure. In conclusion, hypoxia at high altitude causes adverse effects on semen quality and reproductive hormones, and these effects are reversible.

[Unconsciousness due to hyponatremia in a patient with short stature with panhypopituitarism].

PubMed

Notsu, K; Takagi, C; Umaki, I

1995-03-20

An unconscious woman of short stature (141 cm) was admitted to our hospital in March, 1994. She had hyponatremia (120 mEq/l) and had experienced massive bleeding during delivery. No increment of either plasma ACTH or cortisol levels was observed after insulin-induced hypoglycemia. However, urinary 17OHCS levels gradually increased after repeated intramuscular injections of ACTH. Plasma free T3 and free T4 levels were low. Neither plasma TSH nor prolactin (PRL) levels increased after an intravenous injection of TRH. Basal plasma LH, FSH and growth hormone (GH) levels were low and there were no observable responses to any of the stimulation tests. A magnetic resonance image (MRI) of her pituitary gland showed an empty sella. These results showed that she had a panhypopituitarism with primary empty sella. Replacement therapy with glucocorticoid was started and serum sodium levels normalized immediately. Levothyroxine was also administered. The possibility of pituitary dwarfism during her youth and a gradual postpartum reduction of other pituitary hormones may have caused an impairment of the hypothalamo-pituitary-adrenal axis.

Conversion of human choriogonadotropin into a follitropin by protein engineering

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campbell, R.K.; Dean-Emig, D.M.; Moyle, W.R.

1991-02-01

Human reproduction is dependent upon the action of follicle-stimulating hormone (hFSH), luteinizing hormone (hLH), and chorionic gonadotropin (hCG). While the {alpha} subunits of these heterodimeric proteins can be interchanged without effect on receptor-binding specificity, their {beta} subunits differ and direct hormone binding to either LH/CG or FSH receptors. Previous studies employing chemical modifications of the hormones, monoclonal antibodies, or synthetic peptides have implicated hCG {beta}-subunit residues between Cys-38 and Cys-57 and corresponding regions of hLH{beta} and hFSH{beta} in receptor recognition and activation. Since the {beta} subunits of hCG or hLH and hFSH exhibit very little sequence similarity in this region,more » the authors postulated that these residues might contribute to hormone specificity. To test this hypothesis the authors constructed chimeric hCG/hFSH {beta} subunits, coexpressed them with the human {alpha} subunit, and examined their ability to interact with LH and FSH receptors and hormone-specific monoclonal antibodies. Surprisingly, substitution of hFSH{beta} residues 33-52 for hCG{beta} residues 39-58 had no effect on receptor binding or stimulation. However, substitution of hFSH{beta} residues 88-108 in place of the carboxyl terminus of hCG{beta} (residues 94-145) resulted in a hormone analog identical to hFSH in its ability to bind and stimulate FSH receptors. The altered binding specificity displayed by this analog is not attributable solely to the replacement of hCG{beta} residues 108-145 or substitution of residues in the determinant loop located between hCD{beta} residues 93 and 100.« less

Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice.

PubMed

Bernstein, Lori R; Mackenzie, Amelia C L; Lee, Se-Jin; Chaffin, Charles L; Merchenthaler, István

2016-03-01

Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called "egg infertility." A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women.

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis

PubMed Central

Amiri, Mina; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-01-01

Background Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. Objective This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. Methods We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone–binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. Results COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=−0.48; 95% CI −0.81 to −0.15), 6 months (WMD=−2.33; 95% CI −3.48 to −1.18), and 12 months (WMD=−4.70; 95% CI −4.98 to −4.42) and a decrease in LH levels after 3 months (WMD=−3.57; 95% CI −5.14 to −1.99), 6 months (WMD=−5.68; 95% CI −9.57 to −1.80), and 12 months (WMD=−11.60; 95% CI −17.60 to −5.60). Use of COCs containing drospirenone for 6 months decreased FSH (WMD=−0.93; 95% CI −1.79 to −0.08) and LH (WMD=−4.59; 95% CI −7.53 to −1.66) levels. Data for products containing desogestrel were few, but this compound generally had no statistically significant influence on gonadotropin levels similar to that observed with COCs containing cyproterone acetate and drospirenone. Use of COCs was not associated with any significant change in LH-to-FSH ratio. COCs containing cyproterone acetate showed maximum effect on gonadotropin suppression. COCs containing cyproterone acetate significantly decreased estradiol concentrations, whereas those containing drospirenone exhibited no such effect. All COCs demonstrated improvement in androgenic profile and had the same effects on total testosterone and sex hormone–binding globulin concentrations. Progestin compound and treatment duration had no statistically significant effects on changing total testosterone and sex hormone–binding globulin levels. Conclusions COCs containing cyproterone acetate can effectively suppress gonadotropins, leading to a decrease in androgenic parameters. Although different products of COCs could significantly suppress the androgenic profile, it seems that products containing cyproterone acetate are more effective in suppressing gonadotropin and estradiol levels in patients with PCOS. PMID:29695378

Comparing the Effects of Combined Oral Contraceptives Containing Progestins With Low Androgenic and Antiandrogenic Activities on the Hypothalamic-Pituitary-Gonadal Axis in Patients With Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis.

PubMed

Amiri, Mina; Ramezani Tehrani, Fahimeh; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun

2018-04-25

Different products of combined oral contraceptives (COCs) can improve clinical and biochemical findings in patients with polycystic ovary syndrome (PCOS) through suppression of the hypothalamic-pituitary-gonadal (HPG) axis. This systematic review and meta-analysis aimed to compare the effects of COCs containing progestins with low androgenic and antiandrogenic activities on the HPG axis in patients with PCOS. We searched PubMed, Scopus, Google Scholar, ScienceDirect, and Web of Science databases (1980-2017) to identify randomized controlled trials or nonrandomized studies investigating the effect of COCs containing progestins with low androgenic and antiandrogenic activities, including the products containing desogestrel, cyproterone acetate, and drospirenone, on the HPG axis in patients with PCOS. In this meta-analysis, fixed and random effect models were used. Outcomes of interest were weighted mean differences (WMD) of hormonal parameters, including the follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH-to-FSH ratio, estradiol, total testosterone, and sex hormone-binding globulin. Potential sources of heterogeneity were investigated using meta-regression and subgroup analyses. Subgroup analyses were performed based on the used progestin compound and treatment duration. We assessed quality of included studies and their risk of bias using Cochrane guidelines. Publication bias was assessed using Egger test and funnel plot. COC use was significantly associated with a decrease in gonadotropin levels, including FSH and LH. Use of products containing cyproterone acetate was associated with a decrease in FSH levels after 3 months (WMD=-0.48; 95% CI -0.81 to -0.15), 6 months (WMD=-2.33; 95% CI -3.48 to -1.18), and 12 months (WMD=-4.70; 95% CI -4.98 to -4.42) and a decrease in LH levels after 3 months (WMD=-3.57; 95% CI -5.14 to -1.99), 6 months (WMD=-5.68; 95% CI -9.57 to -1.80), and 12 months (WMD=-11.60; 95% CI -17.60 to -5.60). Use of COCs containing drospirenone for 6 months decreased FSH (WMD=-0.93; 95% CI -1.79 to -0.08) and LH (WMD=-4.59; 95% CI -7.53 to -1.66) levels. Data for products containing desogestrel were few, but this compound generally had no statistically significant influence on gonadotropin levels similar to that observed with COCs containing cyproterone acetate and drospirenone. Use of COCs was not associated with any significant change in LH-to-FSH ratio. COCs containing cyproterone acetate showed maximum effect on gonadotropin suppression. COCs containing cyproterone acetate significantly decreased estradiol concentrations, whereas those containing drospirenone exhibited no such effect. All COCs demonstrated improvement in androgenic profile and had the same effects on total testosterone and sex hormone-binding globulin concentrations. Progestin compound and treatment duration had no statistically significant effects on changing total testosterone and sex hormone-binding globulin levels. COCs containing cyproterone acetate can effectively suppress gonadotropins, leading to a decrease in androgenic parameters. Although different products of COCs could significantly suppress the androgenic profile, it seems that products containing cyproterone acetate are more effective in suppressing gonadotropin and estradiol levels in patients with PCOS. ©Mina Amiri, Fahimeh Ramezani Tehrani, Fatemeh Nahidi, Ali Kabir, Fereidoun Azizi. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 25.04.2018.

[Effect of polycystic ovary syndrome treated with the periodic therapy of acupuncture].

PubMed

Yang, Danhong; Zhao, Mei; Tan, Jiahong

2017-08-12

To observe the effects differences for polycystic ovary syndrome (PCOS) between periodic therapy of acupuncture and diane-35 and to explore its mechanism. Sixty patients were randomly assigned into an acupuncture group and a western medication group, 30 cases in each one, 29 patients finally included with one case dropping out respectively. In the acupuncture group, periodic therapy was mainly used at bilateral Sanyinjiao (SP 6), Dahe (KI 12), Guilai (ST 29), Guanyuan (CV 4), Zhongji (CV 3), with different acupoints in the postmenstrual, intermenstrual, premenstrual periods, once every other day, 3 times a week. EA (2 Hz/100 Hz) was used at bilateral Dahe (KI 12) and Guilai (ST 29). If treatment, FSH increased and LH, LH/FSH, T decreased in the two groups (all P <0.05), but T level and the different value before and after treatment in the western medication group were better than those in the acupuncture group (both P <0.05). Periodic therapy of acupuncture is probably one of the effective methods for PCOS, which can improve patients' clinical symptoms, sex hormone level, and menstrual cycle. there was no discomfort during menstrual period, no treatment was given. In the western medication group, diane-35 was prescribed orally for 21 days as a course, with 7 days at interval, one tablet a day. All the treatment was started on the fifth day of the menstrual circle, for continuously 3 months. The indexes were observed before and after treatment, including the menstrual circle, acne score, body mass index (BMI), serum follicle stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH and testosterone (T). The effects of the two groups were compared. The total effective rate was 75.9% (22/29) in the acupuncture group, which was not significantly different from 79.3% (23/29) in the western medication group ( P >0.05). The menstrual cycles were shorter after treatment in the two groups (both P <0.05), with better effect and different value before and after treatment in the acupuncture group (both P <0.05). BMI in the acupuncture group after treatment was lower than that before treatment ( P <0.05) and that after treatment in the western medicine group ( P <0.01), with better different value before and after treatment in the acupuncture group ( P <0.05). The acne scores after treatment decreased in the two groups (both P <0.05), without significant difference after treatment between the two groups ( P >0.05). After treatment,FSH increased and LH,LH/FSH,T decreased in the two groups (all P <0.05),but T level and the different value before and after treatment in the western medication group were better than those in the acupuncture group (both P <0.05). Conclusion Periodic therapy of acupuncture is probably one of the effective methods for PCOS,which can improve patients' clinical symptoms,sex hormone level,and menstrual cycle.

Ovarian and uterine alterations following forced swimming: An immunohistochemical study.

PubMed

Seyed Saadat, Seyedeh Nazanin; Mohammadghasemi, Fahimeh; Ebrahimi, Hannan; Rafati Sajedi, Hanieh; Chatrnour, Gelayol

2016-10-01

Physical exercise is known to be a stressor stimulus that leads to reproductive disruption. The aim of this study was to evaluate the effect of forced swimming on the uterus and ovaries in mice. Adult mice (N=24) were divided into the following three groups: A, control; B, swimming in water (10 o C); and C, swimming in water (23 o C). Swimmers swam for 5 min daily for 5 consecutive days/ wk during 2 wks. An enzyme linked immunosorbent assay was used to determine serum estradiol, follicle stimulating hormone (FSH) and testosterone levels. Immunohistochemistry was performed to study apoptotic cells or estrogen receptor (ER) expression in uterine epithelial cells and ovaries. ANOVA was used for statistical analysis. Swimming in both groups reduced the serum FSH and estradiol levels (p<0.01) without having a significant effect on the serum testosterone level or percentage of apoptosis in ovarian and uterine tissues (p<0.01) compared with controls. A significant reduction in the number of ERs in the uterus and ovaries, and secondary and graafian follicles were observed in groups B and C compared with controls (p<0.01); however the number of primordial and primary follicles were not significantly changed in the ovaries. Forced swimming of 2 wks duration reduces the serum levels of FSH and estradiol without having effects on apoptosis in the ovaries or uteri of mice. Over a long period of time, forced swimming may have an adverse effect on fertility.

Ovarian and uterine alterations following forced swimming: An immunohistochemical study

PubMed Central

Seyed Saadat, Seyedeh Nazanin; Mohammadghasemi, Fahimeh; Ebrahimi, Hannan; Rafati Sajedi, Hanieh; Chatrnour, Gelayol

2016-01-01

Background: Physical exercise is known to be a stressor stimulus that leads to reproductive disruption. Objective: The aim of this study was to evaluate the effect of forced swimming on the uterus and ovaries in mice. Materials and Methods: Adult mice (N=24) were divided into the following three groups: A, control; B, swimming in water (10oC); and C, swimming in water (23oC). Swimmers swam for 5 min daily for 5 consecutive days/ wk during 2 wks. An enzyme linked immunosorbent assay was used to determine serum estradiol, follicle stimulating hormone (FSH) and testosterone levels. Immunohistochemistry was performed to study apoptotic cells or estrogen receptor (ER) expression in uterine epithelial cells and ovaries. ANOVA was used for statistical analysis. Results: Swimming in both groups reduced the serum FSH and estradiol levels (p<0.01) without having a significant effect on the serum testosterone level or percentage of apoptosis in ovarian and uterine tissues (p<0.01) compared with controls. A significant reduction in the number of ERs in the uterus and ovaries, and secondary and graafian follicles were observed in groups B and C compared with controls (p<0.01); however the number of primordial and primary follicles were not significantly changed in the ovaries. Conclusion: Forced swimming of 2 wks duration reduces the serum levels of FSH and estradiol without having effects on apoptosis in the ovaries or uteri of mice. Over a long period of time, forced swimming may have an adverse effect on fertility. PMID:27921086

Ten cases with 46,XX testicular disorder of sex development: single center experience.

PubMed

Akinsal, Emre Can; Baydilli, Numan; Demirtas, Abdullah; Saatci, Cetin; Ekmekcioglu, Oguz

2017-01-01

To present clinical, chromosomal and hormonal features of ten cases with SRY-positive 46,XX testicular disorder of sex development who were admitted to our infertility clinic. Records of the cases who were admitted to our infertility clinic between 2004 and 2015 were investigated. Ten 46,XX testicular disorder of sex development cases were detected. Clinical, hormonal and chromosomal assessments were analized. Mean age at diagnosis was 30.4, mean body height was 166.9cm. Hormonal data indicated that the patients had a higher FSH, LH levels, lower TT level and normal E2, PRL levels. Karyotype analysis of all patients confirmed 46,XX karyotype, and FISH analysis showed that SRY gene was positive and translocated to Xp. The AZFa, AZFb and AZFc regions were absent in 8 cases. In one case AZFb and AZFc incomplete deletion and normal AZFa region was present. In the other one all AZF regions were present. Gonadal development disorders such as SRY-positive 46,XX testicular disorder of sex development can be diagnosed in infertility clinics during infertility workup. Although these cases had no chance of bearing a child, they should be protected from negative effects of testosterone deficiency by replacement therapies. Copyright® by the International Brazilian Journal of Urology.

[Chinese medicinal monomer and compound for 60Co-gamma-induced spermatogenic disturbance in mice].

PubMed

Zhang, Wei-xing; Wang, Hua-li; Wang, Rui; Li, Rui; He, Wei; Zhang, Tian-biao

2010-05-01

To explore the effects of the monomer and compound of the Chinese herbal drugs resveratrol, lycium barbarum polysaccharide (LBP) and icariin on 60Co-gamma-induced spermatogenic disturbance in mice based on the theory of modern Chinese medicine. A total of 105 male Kunming mice were randomly divided into seven groups, with 15 in each. Group A were normally raised and Groups B, C, D, E, F and G irradiated by 60Co-gamma 6 Gy followed by 60Co-gamma 4 Gy at the interval of 7 days. A week later, Groups C, D, E, F and G received intragastrically the suspension of resveratrol, resveratrol + LBP, resveratrol + icariin, resveratrol + LBP + icariin and resveratrol + LBP + icariin + L-carnitine, respectively, at the dose of 80 mg/(kg x d) for 60 days. The general condition, physical signs and body weight changes of the mice were recorded, and 24 hours after the intragastric medication, their testes were harvested to obtain the testicular weight and indexes, the levels of FSH, LH, T and E2 determined by ELISA, the T/E2 ratio calculated, and the histology of the testis tissues observed under the microscope. The testicular indexes of the mice were decreased by radiation-induced damage, but restored to some extent after intragastric medication, especially in Groups E, F and G. The levels of FSH, LH and T were obviously improved by LBP. The T level and testis weight were increased by Icariin. The level of T/E2 was elevated in Groups E, F and G. The best results were achieved in Group F, which exhibited almost complete recovery from reproductive endocrine disorder and spermatogenic damage. The Chinese medicinal monomer is effective for 60Co-gamma-induced spermatogenic disturbance in mice, and the compound suspension of resveratrol + LBP + icariin produces the best result.

Short-term estriol administration modulates hypothalamo-pituitary function in patients with functional hypothalamic amenorrhea (FHA).

PubMed

Genazzani, Alessandro D; Podfigurna-Stopa, Agnieszka; Czyzyk, Adam; Katulski, Krzysztof; Prati, Alessia; Despini, Giulia; Angioni, Stefano; Simoncini, Tommaso; Meczekalski, Blazej

2016-01-01

To evaluate the influence of short-term estriol administration (10 d) on the hypothalamus-pituitary function and gonadotropins secretion in patients affected by functional hypothalamic amenorrhea (FHA). Controlled clinical study on patients with FHA (n = 12) in a clinical research environment. Hormonal determinations and gonadotropin (luteinizing hormone [LH] and FSH) response to a gonadotropin-releasing hormone (GnRH) bolus (10 μg) at baseline condition and after 10 d of therapy with 2 mg/d of estriol per os. Measurements of plasma LH, FSH, prolactin, estradiol, androstenedione, 17α-hydroxyprogesterone, insulin, cortisol, thyroid-stimulating hormone, free triiodothyronine, and free thyroxine. After treatment, the FHA patients showed a statistically significant increase of both LH and FSH plasma levels and the significant increase of their responses to the GnRH bolus. Estriol short-term therapy modulates within 10 d of administration the neuroendocrine control of the hypothalamus-pituitary unit and induces the recovery of both gonadotropins synthesis and secretion in hypogonadotropic patients with FHA.

Hypogonadism in Patients with Sickle Cell Disease: Central or Peripheral?

PubMed Central

Taddesse, A.; Woldie, I.L.; Khana, P.; Swerdlow, P.S.; Chu, J.-W.; Abrams, J.; Abou-Samra, A.-B.

2013-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. PMID:22678347

Hypogonadism in patients with sickle cell disease: central or peripheral?

PubMed

Taddesse, A; Woldie, I L; Khana, P; Swerdlow, P S; Chu, J-W; Abrams, J; Abou-Samra, A-B

2012-01-01

There is conflicting evidence in the literature on the etiology of hypogonadism in patients with sickle cell disease (SCD). A cross-sectional study was done to determine whether hypogonadism in male patients with SCD is due to primary testicular failure or secondary pituitary/hypothalamic dysfunction and assess the association between hypogonadism and serum ferritin levels. Hormonal assessment for serum concentrations of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) was done for 34 men with SCD and their charts were reviewed for relevant clinical variables. Eight men (24%) were classified hypogonadal based on their serum testosterone levels. These men have significantly lower LH (p = 0.001) and FSH (p = 0.01) levels than normogonadal men, indicating a central etiology. There was no significant difference between hypogonadal and normogonadal men with respect to ferritin levels (p = 0.71). Our study indicates a central etiology of hypogonadism in patients with SCD. In this small study ferritin level was not significantly related to hypogonadism. Copyright © 2012 S. Karger AG, Basel.

Interpretation of serum gonadotropin levels in hyperprolactinemia.

PubMed

Abbara, Ali; Clarke, Sophie A; Nesbitt, Alexander; Ali, Sabreen; Comninos, Alexander N; Hatfield, Emma; Martin, Niamh; Sam, Amir; Meeran, Karim; Dhillo, Waljit S

2018-04-16

Background/Aims: Hyperprolactinemia is a common cause of amenorrhea due to hypogonadotropic hypogonadism. Prolactin is hypothesized to impede the reproductive axis through an inhibitory action at the hypothalamus. However, limited data exists to aid the interpretation of serum gonadotropins in the context of hyperprolactinemia. Serum gonadotropin values were reviewed in 243 patients with elevated serum monomeric prolactin due to discrete etiologies at a tertiary reproductive endocrine centre between 2012 and 2015. The cause of hyperprolactinemia was categorized by an experienced endocrinologist / pituitary multidisciplinary team, unless superseded by histology. The most frequently encountered diagnoses were Microprolactinoma (n=88), Macroprolactinoma (n=46), Non-Functioning Pituitary Adenoma (NFPA) (n=72), Drug-Induced Hyperprolactinemia (DIH) (n=22) and Polycystic Ovarian Syndrome (PCOS) (n=15). In patients with prolactinoma and modestly raised serum prolactin levels (<4000 mU/L), increasingly FSH-predominant gonadotropin values were observed with rising prolactin level, consistent with a progressive reduction in hypothalamic GnRH pulsatility. Patients with prolactinoma and higher prolactin values (>4000 mU/L) were more likely to have a reduction in serum levels of both FSH and LH, consistent with direct pituitary gonadotrope dysfunction. Patients with macroadenoma and extremes of serum gonadotropin values (either serum FSH or LH >8 IU/L) were more likely to have NFPA than prolactinoma. Patients with polycystic ovarian syndrome (PCOS) and hyperprolactinemia had LH-predominant secretion in keeping with increased GnRH pulsatility despite a raised prolactin level. The pattern of gonadotropin secretion in patients may reflect the etiology of hyperprolactinemia.
. ©2018S. Karger AG, Basel.

A cost per live birth comparison of HMG and rFSH randomized trials.

PubMed

Connolly, Mark; De Vrieze, Kathleen; Ombelet, Willem; Schneider, Dirk; Currie, Craig

2008-12-01

To help inform healthcare treatment practices and funding decisions, an economic evaluation was conducted to compare the two leading gonadotrophins used for IVF in Belgium. Based on the results of a recently published meta-analysis, a simulated decision tree model was constructed with four states: (i) fresh cycle, (ii) cryopreserved cycle, (iii) live birth and (iv) treatment withdrawal. Gonadotrophin costs were based on highly purified human menopausal gonadotrophin (HP-HMG; Menopur) and recombinant FSH (rFSH) alpha (Gonal-F). After one fresh and one cryopreserved cycle the average treatment cost with HP-HMG was lower than with rFSH (HP-HMG euro3635; rFSH euro4103). The average cost saving per person started on HP-HMG when compared with rFSH was euro468. Additionally, the average costs per live birth of HP-HMG and rFSH were found to be significantly different: HP-HMG euro9996; rFSH euro13,009 (P < 0.0001). HP-HMG remained cost-saving even after key parameters in the model were varied in the probabilistic sensitivity analysis. Treatment with HP-HMG was found to be the dominant treatment strategy in IVF because of improved live birth rates and lower costs. Within a fixed healthcare budget, the cost-savings achieved using HP-HMG would allow for the delivery of additional IVF cycles.

Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: a pilot study

PubMed Central

Cavallini, Giorgio; Biagiotti, Giulio; Bolzon, Elisa

2013-01-01

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone (T)/17-beta-2-oestradiol (E2) ratio <10. Forty-six patients with no chromosomal aberrations were randomized into two groups: 22 received letrozole 2.5 mg per day for 6 months (Group 1: 6 azoospermic+16 cryptozoospermic patients), while 24 received a placebo (Group 2: 5 azoospermic+19 cryptozoospermic patients). The following data were collected: two semen analyses, clinical history, scrotal Duplex scans, body mass index (BMI), Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann–Whitney U test. The relationships between sperm concentration after letrozole administration with respect to FSH, T/E2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration (medians: 400–1.290×106 ml−1; P<0.01) and motility (medians: class A from 2% to 15% P<0.01), FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to T/E2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume. PMID:24121976

Microdose flare protocol with interrupted follicle stimulating hormone and added androgen for poor responders--an observational pilot study.

PubMed

Mitri, Frederic; Behan, Lucy Ann; Murphy, Courtney A; Hershko-Klement, Anat; Casper, Robert F; Bentov, Yaakov

2016-01-01

To investigate whether temporarily withholding FSH and adding androgen could improve follicular response during a microdose flare protocol in women with slow follicular growth or asynchronous follicular development. Observational pilot study. University-affiliated private fertility center. Twenty-six women aged 34-47 years with poor response to stimulation or a previous cancelled IVF cycle and with slow or asynchronous follicular growth during a microdose flare cycle. For 13 women, after initiation of ovarian stimulation using the microdose flare protocol, gonadotropin administration was interrupted and transdermal testosterone gel was added for several days (4.4 ± 1.2 d) starting after cycle day 7 (mean cycle day 10 ± 2.6). FSH, E2, follicular growth, and total number of mature oocytes retrieved were determined for all of the patients. Cycle cancellation rate as well as pregnancy rate following embryo transfer were also documented when applicable. FSH levels declined (25.2 ± 6.5 to 6.8 ± 3.2 IU/L), E2 levels increased (896 ± 687 to 2,163 ± 1,667 pmol/L), and follicular growth improved significantly during gonadotropin interruption and were tracked for 2 days during this time frame. The average number of oocytes retrieved was 5.3 ± 2.6, and the ratio of mature to total oocytes was 4:5. Four of the 13 women in the interruption group conceived following frozen embryo transfer, whereas none in the control group did. The androgen-interrupted FSH protocol may improve follicular response to gonadotropins in cycles that might otherwise be cancelled. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Ovarian function after uterine artery embolization and hysterectomy.

PubMed

Healey, Sarah; Buzaglo, Karen; Seti, Laurent; Valenti, David; Tulandi, Togas

2004-08-01

To evaluate the effect of uterine artery embolization (UAE) and hysterectomy on ovarian function. Prospective case control study (Canadian Task Force classification II-2). University teaching hospital. Eighty-four healthy premenopausal women with symptomatic uterine myoma(s) undergoing UAE or hysterectomy. Patients had blood drawn to measure follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels and underwent transvaginal ultrasound to measure volume of the myoma(s) and uterus on cycle day 3 before the procedures. These measurements were repeated 3 and 6 months after treatment. The main outcome was the differences in serum FSH, LH, E2, and ultrasound findings before and after UAE or hysterectomy. Of the 68 patients who underwent UAE and 16 who underwent hysterectomy, 48 and 13 respectively, completed 6-month follow-up. The mean age of the patients in the UAE group was 44.9 +/- 3.8 years and 43.7 +/- 5.6 years in the hysterectomy group. There was no significant difference in serum FSH before (8.9 +/- 0.7 IU/L) and 6 months after UAE (9.9 +/- 1.0 lU/L), and between the baseline (10.4 +/- 1.8 lU/L) and 6 months posthysterectomy (7.8 +/- 1.8 lU/L). The uterine volume 6 months after UAE (361 +/- 50 mL) was significantly smaller than before UAE(538 +/- 38mL; p =.005, 95% CI 44-241). Compared with baseline (154 +/- 20 mL), the dominant myoma volume was smaller at 6 months after UAE (97 +/- 16 mL; p <.05, 95% CI 1.57-62). Uterine artery embolization is associated with a significant reduction in myoma and uterine volume. Ovarian function at 6 months, as indicated by day 3 FSH levels, is not affected by UAE or hysterectomy.

Recombinant follicle-stimulating hormone: new biotechnology for infertility.

PubMed

Prevost, R R

1998-01-01

The frequency of infertility in developed countries is approximately 8-10%. New drugs are available for assisted reproduction techniques. Two recombinant follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds derived through transfecting nonhuman cell lines with genetic material capable of replicating identical amino acid sequences to human compounds. The cell line used for recombinant (r)-FSH production is the Chinese hamster ovary (CHO). Previously, the only agents that showed benefit in controlled ovulatory stimulation were derived from the urine of menopausal women. Those compounds contain additional substances, such as urinary proteins and various amounts of luteininzing hormone. The amino acid sequence of r-FSH is identical to that of human FSH, but the two recombinant products exist in many different isoforms and differ from each other and from human FSH due to varied carbohydrate side chains. Due to variation in the carbohydrate side chains, follitropin-beta in solution has a higher pH than urine-derived FSH, which enhances receptor affinity and therefore is a greater inducer of folliculogenesis. Follitropin-beta does not cause endogenous production of anti-CHO or anti-FSH antibodies, and is well tolerated.

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice.

PubMed

Wang, Huizhen; Larson, Melissa; Jablonka-Shariff, Albina; Pearl, Christopher A; Miller, William L; Conn, P Michael; Boime, Irving; Kumar, T Rajendra

2014-04-15

FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes.

Acute Gonadotroph and Somatotroph Hormonal Suppression after Traumatic Brain Injury

PubMed Central

Wagner, Justin; Dusick, Joshua R.; McArthur, David L.; Cohan, Pejman; Wang, Christina; Swerdloff, Ronald; Boscardin, W. John

2010-01-01

Abstract Hormonal dysfunction is a known consequence of moderate and severe traumatic brain injury (TBI). In this study we determined the incidence, time course, and clinical correlates of acute post-TBI gonadotroph and somatotroph dysfunction. Patients had daily measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol, growth hormone, and insulin-like growth factor-1 (IGF-1) for up to 10 days post-injury. Values below the fifth percentile of a healthy cohort were considered abnormal, as were non-measurable growth hormone (GH) values. Outcome measures were frequency and time course of hormonal suppression, injury characteristics, and Glasgow Outcome Scale (GOS) score. The cohort consisted of 101 patients (82% males; mean age 35 years; Glasgow Coma Scale [GCS] score ≤8 in 87%). In men, 100% had at least one low testosterone value, and 93% of all values were low; in premenopausal women, 43% had at least one low estradiol value, and 39% of all values were low. Non-measurable GH levels occurred in 38% of patients, while low IGF-1 levels were observed in 77% of patients, but tended to normalize within 10 days. Multivariate analysis revealed associations of younger age with low FSH and low IGF-1, acute anemia with low IGF-1, and older age and higher body mass index (BMI) with low GH. Hormonal suppression was not predictive of GOS score. These results indicate that within 10 days of complicated mild, moderate, and severe TBI, testosterone suppression occurs in all men and estrogen suppression occurs in over 40% of women. Transient somatotroph suppression occurs in over 75% of patients. Although this acute neuroendocrine dysfunction may not be TBI-specific, low gonadal steroids, IGF-1, and GH may be important given their putative neuroprotective functions. PMID:20214417

Whole brain-pituitary in vitro preparation of the transgenic medaka (Oryzias latipes) as a tool for analyzing the differential regulatory mechanisms of LH and FSH release.

PubMed

Karigo, Tomomi; Aikawa, Masato; Kondo, Chika; Abe, Hideki; Kanda, Shinji; Oka, Yoshitaka

2014-02-01

Two types of gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH), are important pituitary hormones for sexual maturation and reproduction, and both of them are centrally regulated by gonadotropin-releasing hormone (GnRH) from the hypothalamus. In mammals, these two gonadotropins are secreted from a single type of gonadotrope. The mechanisms of differential regulation by GnRH of the release of two types of gonadotropins with different secretory profiles are still unknown. In teleosts, however, LH and FSH are secreted from separate cellular populations, unlike in mammals. This feature makes them useful for studying the regulatory mechanisms of LH and FSH secretions independently. Here, we generated transgenic medaka lines that express Ca(2+) indicator protein, inverse-pericam, specifically in the LH or FSH cells. We performed cell-type-specific Ca(2+) imaging of LH and FSH cells, respectively, using the whole brain-pituitary preparations of these transgenic fish in which all neural circuits and GnRH neuronal projection to the pituitary are kept intact. LH and FSH cells showed different Ca(2+) responses to GnRH. The results suggest differential regulation mechanisms for LH and FSH release by GnRH. Moreover, we also succeeded in detecting the effect on LH cells of endogenous GnRH peptide, which was released by electrical stimulation of the axons of GnRH1 neurons. Thus, our newly developed experimental model system using the whole brain-pituitary in vitro preparation of the transgenic medaka is a powerful tool for analyzing the differential regulatory mechanisms of the release of LH and FSH by multisynaptic neural inputs to the pituitary.

The effectiveness of zinc supplementation in men with isolated hypogonadotropic hypogonadism.

PubMed

Liu, Yan-Ling; Zhang, Man-Na; Tong, Guo-Yu; Sun, Shou-Yue; Zhu, Yan-Hua; Cao, Ying; Zhang, Jie; Huang, Hong; Niu, Ben; Li, Hong; Guo, Qing-Hua; Gao, Yan; Zhu, Da-Long; Li, Xiao-Ying

2017-01-01

A multicenter, open-label, randomized, controlled superiority trial with 18 months of follow-up was conducted to investigate whether oral zinc supplementation could further promote spermatogenesis in males with isolated hypogonadotropic hypogonadism (IHH) receiving sequential purified urinary follicular-stimulating hormone/human chorionic gonadotropin (uFSH/hCG) replacement. Sixty-seven Chinese male IHH patients were recruited from the Departments of Endocrinology in eight tertiary hospitals and randomly allocated into the sequential uFSH/hCG group (Group A, n = 34) or the sequential uFSH plus zinc supplementation group (Group B, n = 33). In Group A, patients received sequential uFSH (75 U, three times a week every other 3 months) and hCG (2000 U, twice a week) treatments. In Group B, patients received oral zinc supplementation (40 mg day-1 ) in addition to the sequential uFSH/hCG treatment given to patients in Group A. The primary outcome was the proportion of patients with a sperm concentration ≥1.0 × 106 ml-1 during the 18 months. The comparison of efficacy between Groups A and B was analyzed. Nineteen of 34 (55.9%) patients receiving sequential uFSH/hCG and 20 of 33 (60.6%) patients receiving sequential uFSH/hCG plus zinc supplementation achieved sperm concentrations ≥1.0 × 106 ml-1 by intention to treat analyses. No differences between Group A and Group B were observed as far as the efficacy of inducing spermatogenesis (P = 0.69). We concluded that the sequential uFSH/hCG plus zinc supplementation regimen had a similar efficacy to the sequential uFSH/hCG treatment alone. The additional improvement of 40 mg day-1 oral zinc supplementation on spermatogenesis and masculinization in male IHH patients is very subtle.

R831X mutation of the androgen receptor gene in an adolescent with complete androgen insensitivity syndrome and bilateral testicular hamartomata.

PubMed

Goulis, Dimitrios G; Iliadou, Paschalia K; Papanicolaou, Athanasios; Georgiou, Ioannis; Chatzikyriakidou, Anthi; Gerou, Spiridon; Bondis, Ioannis N; Papadimas, Ioannis

2006-01-01

An 18-year old, phenotypically female individual was examined for primary amenorrhea. Three months before her referral, the patient underwent surgery and a pelvic mass was removed. The physical examination revealed normal female external genitalia, normal breast development, sparse pubic hair and absence of axillary hair. The gynecological examination revealed a short blind vagina pouch and absence of cervix and uterus. Serum testosterone and dihydrotestosterone levels were very high. Karyotype was that of a normal male (46,XY). The transabdominal ultrasound, computed tomography (CT) and Magnetic resonance imaging (MRI) showed absence of uterus and fallopian tubes and revealed testis-like gonads located at the internal opening of the inguinal canal bilaterally. Bilateral gonadectomy was subsequently performed. The pathology report was that of "hamartomatous testes" and associated paratesticular leiomyoma. The clinical, laboratory, imaging, genetic and histological findings confirmed the diagnosis of complete androgen insensitivity syndrome. DNA analysis revealed a R831X mutation in exon 7 of the androgen receptor gene. A Sertoli-cell dynamic test showed elevated basal serum inhibin-B and anti-Müllerian hormone levels without further rise following FSH stimulation. The patient was started on hormone replacement therapy with conjugated estrogens. Complete androgen insensitivity syndrome must be considered in any case of primary amenorrhea. Gonadectomy must be planned to eliminate the risk of gonadal malignancy.

Ovarian follicular development and the follicular fluid hormones and growth factors in normal women of advanced reproductive age.

PubMed

Klein, N A; Battaglia, D E; Miller, P B; Branigan, E F; Giudice, L C; Soules, M R

1996-05-01

Reproductive aging in women (a physiological decline in the function of the hypothalamic-pituitary-ovarian axis) is an infrequently investigated and poorly understood biological phenomenon. Although menstrual irregularity and anovulation are known to precede the menopause, normal women in their fifth decade experience a profound decrease in fertility while still experiencing regular menstrual cycles. To further our understanding of the physiological changes associated with reproductive aging, this study examined the spontaneous development and function of ovarian follicles in normal women, aged 40-45 yr. The subjects were women (n = 21), aged 40-45 yr, who had regular 25- to 35-day ovulatory menstrual cycles, were not infertile, had no medical problems, and met specific criteria for weight, diet, and exercise. The controls were normal women (n = 20), age 20-25 yr, who met the same criteria. The subjects were monitored with daily hormone measurements [LH, FSH, estradiol (E), progesterone (P), and inhibin] and pelvic sonograms from day 1 of their study cycle until the dominant ovarian follicle reached a mean diameter of 15 mm and/or a serum E level of 550 pmol/L or higher was attained. At that time, 10,000 U hCG were given, and a transvaginal sonographic follicle aspiration was performed 32 h later. The follicular fluid (FF) was collected, stored frozen at -70 C, and later analyzed for E, P, testosterone (T), androstenedione, inhibin, insulin-like growth factor I (IGF-I), and IGF-II. The number of cycle days to aspiration was lower (11.6 vs. 15.6 days; P < 0.001) and the early follicular phase mean FSH and mean E levels were higher (9.3 vs. 6.6 mIU/mL and 305 vs. 160 pmol/L; P < 0.01) in the older (O) group compared to the younger group. There was a strong trend toward higher FF mean E (2280 vs. 1931 nmol/L) and lower FF mean T (978 vs. 2361 pmol/L) levels in group O. The E/T ratio was significantly higher (5253 vs. 2408; P < 0.03) in group O. In group O, the mean FF P levels were increased as well (25.1 vs. 18.8 micromol/L; P < 0.01). The serum mean IGF-I (153 vs. 226 ng/mL; P < 0.001) and FF mean IGF-I (113 vs. 158 ng/mL; P < 0.02) levels were significantly decreased in group O. There were no differences between groups in serum or FF IGF-II or inhibin levels. Whether reproductive aging is an intrinsic ovarian process or the ovary is simply responding to exogenous influences, the ovary in general and its follicles in particular are the primary site of the effects of aging. Ovarian follicles in older ovulatory women have some unique features: 1) the follicles are the same size as those in younger women, but form more rapidly; 2) secretion of E and inhibin is not compromised; 3) the concentrations of steroids in the FF are indicative of a healthier follicle, i.e. increased P levels and higher estrogen to androgen ratio; and 4) serum and FF levels of IGF-I are decreased, but there are no differences in IGF-II levels.

Daytime decrease of prolactin levels is associated with PCOS regardless to nutritional status and other hormones levels.

PubMed

Franik, Grzegorz; Madej, Paweł; Guz-Lem, Magdalena; Owczarek, Aleksander; Chudek, Jerzy; Olszanecka-Glinianowicz, Magdalena

2017-05-01

The aim of the study is to analyze daytime changes of prolactin level depending on nutritional status and polycystic ovary syndrome (PCOS). One hundred and fifteen (69 normal weight, 21 overweight and 25 obese) diagnosed with PCOS and 77 (37 normal weight, 18 overweight and 22 obese) women - Non-PCOS without concomitant diseases were enrolled. Body mass and height were measured and BMI was calculated. Serum concentrations of FSH, LH, E2, testosterone, TSH and PRL were determined morning 6.00 a.m. after wake. Second measurement of PRL was performed at 4 p.m. The daytime decrease of prolactin level was higher in PCOS than in Non-PCOS group regardless of nutritional status (normal weight 35.8 ± 26.0 vs. 24.3 ± 15.3 ng/mL; overweight 28.5 ± 25.4 vs. 17.5 ± 8.8 ng/mL and obese 23.2 ± 21.1 vs. 18.4 ± 11.6 ng/ml, respectively). However, in both PCOS and Non-PCOS daytime changes of prolactin level were higher in normal weight than overweight and obese women (35.8 ± 26.0 vs. 28.5 ± 25.4 vs. 23.2 ± 21.1 ng/mL and 24.3 ± 15.3 vs. 17.5 ± 8.8 vs. 18.4 ± 11.6 ng/mL, respectively). The multivariate regression analysis revealed that the daytime changes of prolactin level are proportional to TSH concentration and coexistence of PCOS as well as inversely relative to BMI. In conclusions, our results suggest that overweight and obesity decreased morning PRL level and impaired its daytime decrease, but coexistence of PCOS enlarged its.

Purification and identification of 25-hydroxycholesterol in a reptile: Seasonal variation and hormonal regulation.

PubMed

Singh, Varsha; Priyam, Manisha; Tripathy, Mamta; Rai, Umesh

2017-06-01

The present in vitro study, for the first time, demonstrates the production of 25-hydroxycholestrol (25-HC) by testicular macrophages of a non-mammalian vertebrate. The ether extracts of testicular macrophage-conditioned medium (TMCM) were fractionated on a C18 reversed phase high-performance liquid chromatography (HPLC) column using methanol as the mobile phase. The mass spectrometry (MS) fragmentation pattern of HPLC-purified 25-HC was found to be identical to that of authentic 25-HC. Further, a significant seasonal variation in 25-HC concentration was observed with maximal level in regressed and minimal during breeding phase. To understand the hormonal control of 25-HC production, testicular macrophages from regressed phase testes were incubated with 0.5μg/ml of ovine follicle stimulating hormone (FSH) and 0.1, 1 and 10μg/ml of testosterone (T). FSH considerably enhanced 25-HC production by testicular macrophages. In contrast, T markedly inhibited 25-HC production in a dose-dependent manner. In addition, T significantly inhibited FSH-induced 25-HC production, though pre-treatment with T was more effective as compared to post-treatment with T to FSH. Our findings on production, seasonal variation and hormonal control of 25-HC suggest the functional significance of 25-HC in the testis of reptiles. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of female increased body mass index on in vitro fertilization cycles outcome.

PubMed

Caillon, Hélène; Fréour, Thomas; Bach-Ngohou, Kalyane; Colombel, Agnès; Denis, Marc G; Barrière, Paul; Masson, Damien

2015-01-01

As being overweight can impair female spontaneous fertility or after assisted reproductive technology (ART) cycles, the aim of this study was to compare in vitro fertilization (IVF) outcome according to women's body mass index (BMI). Retrospective study conducted from 2006 to 2009 in the IVF unit of Nantes University Hospital, France. 582 patients undergoing standard infertility workup and controlled ovarian stimulation were categorized according to BMI into two groups: group 1: normal weight (20-24.9 kg/m(2); n=409) and group 2: overweight and obese (≥25 kg/m(2); n=149). Basal hormonal status, smoking habitus, infertility duration, IVF cycle parameters and outcome were recorded. Basal LH, FSH and estradiol levels were higher in group 1 than group 2, but ovarian reserve markers were comparable across the two BMI groups. Higher doses of gonadotropins were required in group 2 to obtain equivalent ovarian response than in group 1. No difference was observed on ovarian response and embryonic parameters. Cycle outcome were not significantly different between both groups, but we found a strong trend towards increasing transfer cancellation and miscarriage rates in group 2. Although overweight and obesity do not compromise ovarian stimulation results whenever adaptation of recombinant FSH doses is made, our data suggest an increased risk of cancellation transfer and miscarriage rate, leading to poorer IVF outcome. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

The use of recombinant human LH (lutropin alfa) in the late stimulation phase of assisted reproduction cycles: a double-blind, randomized, prospective study.

PubMed

Tarlatzis, B; Tavmergen, E; Szamatowicz, M; Barash, A; Amit, A; Levitas, E; Shoham, Z

2006-01-01

The effect of recombinant human LH (r-hLH; lutropin alfa) in women undergoing controlled ovarian stimulation with recombinant human FSH (r-hFSH) prior to IVF was investigated. After down-regulation with the GnRH agonist, buserelin, 114 normo-ovulatory women (aged 18-37 years) received r-hFSH alone until the lead follicle reached a diameter of 14 mm. Patients were then randomized in a double-blind fashion to receive r-hFSH in addition to r-hLH, 75 IU s.c., or placebo daily for a maximum of 10 days prior to oocyte retrieval and IVF. The primary end-point was the number of metaphase II oocytes. There were no significant differences between treatment groups for the primary end-point. Serum estradiol concentrations on the day of HCG administration were significantly higher in the group receiving r-hLH plus r-hFSH than in the group receiving r-hFSH alone (P = 0.0001), but there were no significant differences between the groups in dose and duration of r-hFSH treatment required, oocyte maturation, fertilization rate, pregnancy rate and live birth rate. In this patient population, the addition of r-hLH during the late follicular phase of a long GnRH agonist and r-hFSH stimulation cycle provides no further benefit in terms of oocyte maturation or other end-points.

Exercise-induced stress responses of amenorrheic and eumenorrheic runners.

PubMed

Loucks, A B; Horvath, S M

1984-12-01

The role of stress in exercise-associated amenorrhea was investigated. Sex hormones [FSH, LH, androstenedione (A), testosterone, estrone, and 17 beta-estradiol (E2)], stress hormones [dehydroepiandrosterone, cortisol (F), PRL, norepinephrine, and epinephrine] and psychological status (Profile of Mood States and State-Trait Anxiety Inventory) were measured at rest and in response to a 40-min 80% of maximal aerobic power (VO2max) run in highly trained eumenorrheic (n = 8) and amenorrheic (n = 7) women runners matched for fatness [eumenorrheic, 16.5 +/- 2.3% (+/- SD); amenorrheic, 14.9 +/- 4.8] and maximal aerobic power (eumenorrheic, 58.9 +/- 5.7 ml/kg X min; amenorrheic, 59.8 +/- 4.6). Eumenorrheic runners were tested between days 3 and 8 of the follicular phase. At rest, decreased plasma FSH, LH, and E2 concentrations were found in amenorrheic women [eumenorrheic FSH, 10.5 +/- 4.1 mIU/ml; amenorrheic FSH, 4.9 +/- 1.6 (P less than 0.01); eumenorrheic LH, 14.1 +/- 6.1 mIU/ml; amenorrheic LH, 5.1 +/- 1.7 (P less than 0.01); eumenorrheic E2, 20 +/- 9 pg/ml; amenorrheic E2, 7 +/- 6 (P less than 0.05)]. Other sex and stress hormones and psychological measurements were similar in the two groups and were within the normal range. Ventilatory, cardiovascular, thermoregulatory, and psychological responses to the submaximal run were identical. Among eumenorrheic women, all stress hormones and A increased after exercise, but PRL, F, and A were unchanged among amenorrheic women. Estrone, E2, and testosterone did not change in either group. These observations are inconsistent with a general stress hypothesis of exercise-associated amenorrhea as well as with more specific hyperprolactinemic and hyperandrogenic hypotheses. In amenorrheic women, failure of PRL to increase in response to exercise may be due to their lack of E2, while failure of F and A to increase may indicate reduced adrenal 3 beta-hydroxysteroid dehydrogenase/isomerase activity.

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: a search for the mechanism of action.

PubMed

Nimrod, A

1977-09-01

Cultures of granulosa cells from immature hypophysectomized DES-treated rats were unable to maintain progestin production of more than 48 h in medium without hormone supplementation or in the presence of FSH only. Production of progestin (20alpha-dihydroprogesterone, as measured by radioimmunoassay) remained unimpaired in the presence of androstenedione (Ad) and was markedly increased in the presence of both Ad and FSH. The combined treatment with FSH and Ad during the first 48 h of culture brought about persistent changes in the cultured cells, since progestin accumulation did not decline upon subsequent removal of these hormones during days 3 and 4 of culture. Dibutyryl cyclic AMP (DBC) was able to mimic the changes in steroidogenic capability induced by the combined action of FSH and Ad. The extent of [125I]-FSH binding, FSH-stimulable cAMP accumulation and cyclic 3',5'-nucleotide phosphodiesterase activity were not affected by addition of Ad to the culture medium. Ad synergized with DBC in the stimulation of progestin accumulation in granulosa cell cultures. It is suggested that androgen acts at a step in the regulation of progestin biosynthesis distal to cAMP production.

Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period.

PubMed

Savabieasfahani, Mozhgan; Lee, James S; Herkimer, Carol; Sharma, Tejinder P; Foster, Douglas L; Padmanabhan, Vasantha

2005-01-01

Prenatal exposure of the female sheep to excess testosterone (T) leads to hypergonadotropism, multifollicular ovaries, and progressive loss of reproductive cycles. We have determined that prenatal T treatment delays the latency of the estradiol (E2)-induced LH surge. To extend this finding into a natural physiological context, the present study was conducted to determine if the malprogrammed surge mechanism alters the reproductive cycle. Specifically, we wished to determine if prenatal T treatment 1) delays the onset of the preovulatory gonadotropin surge during the natural follicular phase rise in E2, 2) alters pulsatile LH secretion and the dynamics of the secondary FSH surge, and 3) compromises the ensuing luteal function. Females prenatally T-treated from Day 60 to Day 90 of gestation (147 days is term) and control females were studied when they were approximately 2.5 yr of age. Reproductive cycles of control and prenatally T-treated females were synchronized with PGF2alpha, and peripheral blood samples were collected every 2 h for 120 h to characterize cyclic changes in E2, LH, and FSH and then daily for 14 days to monitor changes in luteal progesterone. To assess LH pulse patterns, blood samples were also collected frequently (each 5 min for 6 h) during the follicular and luteal phases of the cycle. The results revealed that, in prenatally T-treated females, 1) the preovulatory increase in E2 was normal; 2) the latencies between the preovulatory increase in E2 and the peaks of the primary LH and FSH surges were longer, but the magnitudes similar; 3) follicular-phase LH pulse frequency was increased; 4) the interval between the primary and secondary FSH surges was reduced but there was a tendency for an increase in duration of the secondary FSH surge; but 5) luteal progesterone patterns were in general unaltered. Thus, exposure of the female to excess T before birth produces perturbances and maltiming in periovulatory gonadotropin secretory dynamics, but these do not produce apparent defects in cycle regularity or luteal function. To reveal the pathologies that lead to the eventual subfertility arising from excess T exposure during midgestation, studies at older ages must be conducted to assess if there is progressive disruption of neuroendocrine and ovarian function.

Stimulation of in vitro steroidogenesis by pituitary hormones in a turtle (Trachemys scripta) within the temperature-sensitive period for sex determination.

PubMed

White, R B; Thomas, P

1992-12-01

To investigate the possible involvement of pituitary hormones in the regulation of steroidogenesis during reptilian sexual differentiation, we tested the ability of gonadotropin (ovine FSH), adrenocorticotropin (porcine ACTH), and growth hormone (bovine GH) to stimulate in vitro steroidogenesis in embryonic adrenal-kidney-gonad complexes (AKGs) of a turtle, Trachemys scripta, during and after the temperature-sensitive period for sex determination (TSP). Radioimmunoassays were used to measure progesterone, testosterone, estradiol, and corticosterone in incubation media; additionally, immunoreactive ACTH was measured in plasma. Presumptive male and female AKGs were stimulated by both FSH and ACTH at each stage investigated. Secretion of progesterone and corticosterone was usually far greater than that of testosterone or estradiol in both basal and hormone-stimulated incubations. In general, AKGs from presumptive males secreted more progesterone and corticosterone than AKGs from presumptive females. Progesterone and estradiol secretions were stimulated by both FSH and ACTH, but testosterone secretion was stimulated only by ACTH. Corticosterone secretion was strongly stimulated by ACTH. GH failed to significantly stimulate steroid secretion. Plasma ACTH levels were significantly higher in males than in females, and both sexes had significantly higher plasma levels of ACTH after the TSP compared to during the TSP. Our data demonstrate that during the temperature-sensitive period AKGs are responsive to both gonadotropin and ACTH, and that there are significant sex differences in steroidogenesis, sensitivity to gonadotropin and ACTH, and plasma ACTH levels.

The assessment of ovulation by a combination of ultrasound and detailed serial hormone profiles in 35 women with long-standing unexplained infertility.

PubMed

Petsos, P; Chandler, C; Oak, M; Ratcliffe, W A; Wood, R; Anderson, D C

1985-06-01

We have examined for the presence of subtle hormonal abnormalities in women with long-standing unexplained infertility. For a full cycle serum LH, FSH, progesterone and oestradiol levels were measured about three times a week, and serial ultrasound scans of the ovaries made until the time of apparent ovulation. The results on 45 cycles in 35 women with unexplained infertility and in three normal volunteers are presented. Normal ovulatory cycles were defined by a length of 26-32 d, and progressive follicular maturation followed by disappearance or abrupt reduction in size of a follicle within 48 h of the recorded LH peak, followed by progressive and sustained rise in serum progesterone levels to more than 25 nmol/l and a luteal phase length of greater than or equal to 13 d. Thirty spontaneous cycles (28 women) were clearly normal while 15 spontaneous cycles (12 women) were abnormal. Abnormalities included luteinization of an unruptured follicle (eight cycles), absence of follicular development (two cycles), poor follicular development (two cycles), persistence of a large ovarian cyst from the preceeding cycle (two cycles) and one aluteal cycle. Six of the abnormal cycles were characterized hormonally by inappropriate elevation of serum LH levels throughout. If this study had been based only on serial ultrasound scans, all results on abnormal cycles might have been misinterpreted. If it had been conducted only with (multiple) progesterone determinations and the level of greater than 25 nmol/l had been taken as indicative of ovulation nine clearly abnormal cycles would have been considered as normal. We conclude that the combination of the hormonal and ultrasound assessment of ovulation increases our confidence for confirmation of normality and reveals various ovulatory disorders which are possibly due to an endocrinological defect or defects.

Plasticity of the reproductive axis caused by social status change in an african cichlid fish: I. Pituitary gonadotropins.

PubMed

Maruska, Karen P; Levavi-Sivan, Berta; Biran, Jakob; Fernald, Russell D

2011-01-01

Social position in a dominance hierarchy is often tightly coupled with fertility. Consequently, an animal that can recognize and rapidly take advantage of an opportunity to rise in rank will have a reproductive advantage. Reproduction in all vertebrates is controlled by the brain-pituitary-gonad axis, and in males of the African cichlid fish Astatotilapia burtoni, GnRH1 neurons at the apex of this axis are under social control. However, little is known about how quickly social information is transformed into functional reproductive change, or about how socially controlled changes in GnRH1 neurons influence downstream actions of the brain-pituitary-gonad axis. We created an opportunity for reproductively suppressed males to ascend in status and then measured how quickly the perception of this opportunity caused changes in mRNA and protein levels of the pituitary gonadotropins. mRNA levels of the β-subunits of LH and FSH rose rapidly in the pituitary 30 min after suppressed males perceived an opportunity to ascend. In contrast, mRNA levels of GnRH receptor-1 remained unchanged during social transition but were higher in stable dominant compared with subordinate males. In the circulation, levels of both LH and FSH were also quickly elevated. There was a positive correlation between mRNA in the pituitary and circulating protein levels for LH and FSH, and both gonadotropins were positively correlated with plasma 11-ketotestosterone. Our results show that the pituitary is stimulated extremely rapidly after perception of social opportunity, probably to allow suppressed males to quickly achieve reproductive success in a dynamic social environment.

Serum adiponectin and resistin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

PubMed

Olszanecka-Glinianowicz, Magdalena; Kuglin, Dorota; Dąbkowska-Huć, Anna; Skałba, Piotr

2011-01-01

It seems that adipokines participate in disturbances of the function of the hypothalamus-pituitary-ovary axis. The aim of the study was to assess the relationship between plasma adiponectin and resistin levels and insulin resistance and markers of hyperandrogenism in lean and obese PCOS women. Forty-one women with PCOS (22 lean and 19 obese) and 16 healthy lean women were enrolled. Body mass and height were measured and body mass index was calculated. In addition to serum glucose, lipids, androgens and insulin, adiponectin and resistin concentration were assessed in the fasting state. The insulin resistance was calculated based on the HOMA-IR. Similar serum resistin concentrations were found in both PCOS subgroups and controls. The obese PCOS subgroup was characterized by the lowest serum adiponectin level (10.8 ± 8.3, compared with 21.0 ± 15.1 in the normal weight PCOS subgroup and 26.7 ± 12.5 μg/ml in controls). There were no correlations between resistin and adiponectin levels and HOMA-IR values and serum androgen concentrations. Significant positive correlations between adiponectin to resistin ratio and plasma FSH (r = 0.49; p = 0.001) and LH (r = 0.45; p = 0.003) concentrations, and a negative correlation with free androgen index (r = -0.34; p = 0.03) in PCOS group were found. Obese but not normal weight PCOS women have lower adiponectin levels whereas resistin concentration did not differ in normal weight and obese PCOS compared to control subjects. We hypothesize that changes of the relative proportion of adiponectin to resistin, but not circulating adiponectin and resistin levels themselves, may play a role in hormonal disturbances but not in insulin resistance in PCOS. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

[Patients with functional hypothalamic amenorrhea are characterized by low serum inhibin B concentrations].

PubMed

Podfigurna-Stopa, Agnieszka; Luisi, Stefano; Lazzeri, Lucia; Ciani, Valentina; Meczekalski, Błazej; Petraglia, Felice

2010-05-01

Functional hypothalamic disturbances may be the cause of secondary amenorrhea and are related to aberration in both the pattern of pulsatility and amplitude in the release of gonadotropin-releasing hormone (GnRH) in hypothalamus. Inhibin B, as an ovarian peptide plays a crucial role in reproduction function throughout regulation of folliculotropin (FSH) pituitary production and inhibiting GnRH secretion during the menstrual cycle. To measure and estimate serum inhibin B concentration in patients with functional hypothalamic amenorrhea. Material and methods. The study included 41 women suffering from functional hypothalamic amenorrhea. Secondary amenorrhea was defined as the lack of menstruation lasting at least 90 days not due to pregnancy, characterized by low serum concentrations of lutropin (LH < 5 mIU/ml)) and typical for functional hypothalamic disturbances anamnestic investigation. The control group consists of 40 healthy women with normal menstrual cycles and Body Mass Index (BMI between 18.5- 24.9 kg/m2). Medical history, examination and laboratory analysis of LH, FSH, estradiol (E), prolactin, testosterone and inhibin B were performed (ELISA--enzyme-linked immunosorbent assay). There are statistically lower serum inhibin B, FSH, LH, estradiol and prolactin concentrations in patients with functional hypothalamic amenorrhea in comparison to healthy women. Positive correlation between serum concentration of inhibin B and estradiol concentration was found in patients with functional hypothalamic amenorrhea. Patients with functional hypothalamic amenorrhea are characterized by statistical significant decrease in serum inhibin B concentration in comparison to the control group.

Obesity independently influences gonadal function in very long-term adult male survivors of childhood cancer.

PubMed

Blijdorp, Karin; van Dorp, Wendy; Laven, Joop S E; Pieters, Rob; de Jong, Frank H; Pluijm, Saskia M F; van der Lely, Aart Jan; van den Heuvel-Eibrink, Marry M; Neggers, Sebastian J C M M

2014-08-01

Although obesity is associated with gonadal dysfunction in the general population, gonadotoxic treatment might diminish the impact of obesity in childhood cancer survivors (CCS). The aim was to evaluate whether altered body composition is associated with gonadal dysfunction in male CCS, independent of gonadotoxic cancer treatment. Three hundred fifty-one male CCS were included. Median age at diagnosis was 5.9 years (0-17.8) and median age at follow-up 25.6 years (18.0-45.8). Total and non-SHBG-bound testosterone, sex hormone-binding globulin, inhibin B, and follicle-stimulating hormone (FSH) were studied. Potential determinants were BMI, waist circumference, waist-hip ratio, and body composition measures (dual energy X-ray absorptiometry). Non-SHBG-bound testosterone was significantly decreased in survivors with BMI ≥ 30 kg/m(2) (adjusted mean 9.1 nmol/L vs. 10.2 nmol/L, P = 0.015), high fat percentage (10.0 vs. 11.2, P = 0.004), and high waist circumference (>102 cm) (9.0 vs. 11.0, P = 0.020). Survivors with high fat percentage (≥25%) had significantly lower inhibin B/FSH ratios (inhibin B/FSH ratio: β -34%, P = 0.041). Obesity is associated with gonadal dysfunction in male CCS, independent of the irreversible effect of previous cancer treatment. Randomized controlled trials are required to evaluate whether weight normalization could improve gonadal function, especially in obese survivors with potential other mechanisms than lifestyle causing their obesity. Copyright © 2014 The Obesity Society.

Efficacy and safety of follitropin alfa/lutropin alfa in ART: a randomized controlled trial in poor ovarian responders.

PubMed

Humaidan, P; Chin, W; Rogoff, D; D'Hooghe, T; Longobardi, S; Hubbard, J; Schertz, J

2017-03-01

How does the efficacy and safety of a fixed-ratio combination of recombinant human FSH plus recombinant human LH (follitropin alfa plus lutropin alfa; r-hFSH/r-hLH) compare with that of r-hFSH monotherapy for controlled ovarian stimulation (COS) in patients with poor ovarian response (POR)? The primary and secondary efficacy endpoints were comparable between treatment groups and the safety profile of both treatment regimens was favourable. Although meta-analyses of clinical trials have suggested some beneficial effect on reproductive outcomes with r-hLH supplementation in patients with POR, the definitions of POR were heterogeneous and limit the comparability across studies. Phase III, single-blind, active-comparator, randomized, parallel-group clinical trial. Patients were followed for a single ART cycle. A total of 939 women were randomized (1:1) to receive either r-hFSH/r-hLH or r-hFSH. Randomization, stratified by study site and participant age, was conducted via an interactive voice response system. Women classified as having POR, based on criteria incorporating the ESHRE Bologna criteria, were down-regulated with a long GnRH agonist protocol and following successful down-regulation were randomized (1:1) to COS with r-hFSH/r-hLH or r-hFSH alone. The primary efficacy endpoint was the number of oocytes retrieved following COS. Safety endpoints included the incidence of adverse events, including ovarian hyperstimulation syndrome (OHSS). Post hoc analyses investigated safety outcomes and correlations between live birth and baseline characteristics (age and number of oocytes retrieved in previous ART treatment cycles or serum anti-Müllerian hormone (AMH)). The significance of the treatment effect was tested by generalized linear models (Poisson regression for counts and logistic regression for binary endpoints) adjusting for age and country. Of 949 subjects achieving down-regulation, 939 were randomized to r-hFSH/r-hLH (n = 477) or r-hFSH (n = 462) and received treatment. Efficacy assessment: In the intention-to-treat (ITT) population, the mean (SD) number of oocytes retrieved (primary endpoint) was 3.3 (2.71) in the r-hFSH/r-hLH group compared with 3.6 (2.82) in the r-hFSH group (between-group difference not statistically significant). The observed difference between treatment groups (r-hFSH/r-hLH and r-hFSH, respectively) for efficacy outcomes decreased over the course of pregnancy (biochemical pregnancy rate: 17.3% versus 23.9%; clinical pregnancy rate: 14.1% versus 16.8%; ongoing pregnancy rate: 11.0% versus 12.4%; and live birth rate: 10.6% versus 11.7%). An interaction (identified post hoc) between baseline characteristics related to POR and treatment effect was noted for live birth, with r-hFSH/r-hLH associated with a higher live birth rate for patients with moderate or severe POR, whereas r-hFSH was associated with a higher live birth rate for those with mild POR. A post hoc logistic regression analysis indicated that the incidence of total pregnancy outcome failure was lower in the r-hFSH/r-hLH group (6.7%) compared with the r-hFSH group (12.4%) with an odds ratio of 0.52 (95% CI 0.33, 0.82; P = 0.005). Safety assessment: The overall proportion of patients with treatment-emergent adverse events (TEAEs) occurring during or after r-hFSH/r-hLH or r-hFSH use (stimulation or post-stimulation phase) was 19.9% and 26.8%, respectively. There was no consistent pattern of TEAEs associated with either treatment. Despite using inclusion criteria for POR incorporating the ESHRE Bologna criteria, further investigation is needed to determine the impact of the heterogeneity of POR in the Bologna patient population. The observed correlation between baseline clinical characteristics related to POR and live birth rate, as well as the observed differences between groups regarding total pregnancy outcome failure were from post hoc analyses, and the study was not powered for these endpoints. In addition, the attrition rate for pregnancy outcomes in this trial may not reflect general medical practice. Furthermore, as the patient population was predominantly White these results might not be applicable to other ethnicities. In the population of women with POR investigated in this study, although the number of oocytes retrieved was similar following stimulation with either a fixed-ratio combination of r-hFSH/r-hLH or r-hFSH monotherapy, post hoc analyses showed that there was a lower rate of total pregnancy outcome failure in patients receiving r-hFSH/r-hLH, in addition to a higher live birth rate in patients with moderate and severe POR. These findings are clinically relevant and require additional investigation. The benefit:risk balance of treatment with either r-hFSH/r-hLH or r-hFSH remains positive. This study was funded by Merck KGaA, Darmstadt, Germany. P.H. has received honoraria for lectures and unrestricted research grants from Ferring, Merck KGaA and MSD. D.R. is a former employee of EMD Serono, a business of Merck KGaA, Darmstadt, Germany. J.S., J.H. and W.C. are employees of EMD Serono Research and Development Institute, a business of Merck KGaA, Darmstadt, Germany. T.D.'H. and S.L. are employees of Merck KGaA, Darmstadt, Germany. ClinicalTrials.gov identifier: NCT02047227; EudraCT Number: 2013-003817-16. ClinicalTrials.gov: 24 January 2014; EudraCT: 19 December 2013. 30 January 2014. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

A Rare Case of Klinefelter Syndrome Patient with Quintuple Mosaic Karyotype, Diagnosed by GTG-Banding and FISH

PubMed Central

Karimi, Hamideh; Sabbaghian, Marjan; Haratian, Kaveh; Vaziri Nasab, Hamed; Farrahi, Faramarz; Moradi, Shabnam Zari; Tavakolzadeh, Tayebeh; Beheshti, Zahra; Gourabi, Hamid; Meybodi, Anahita Mohseni

2014-01-01

Klinefelter syndrome (KS) is the most common sex chromosomal disorder in men. Most of these patients show the 47,XXY karyotype, whereas approximately 15% of them are mosaics with variable phenotype. A 39-year-old male investigated for primary infertility, was clinically normal with small firm testes and elevated levels of FSH, LH and low level of testosterone. Total azoospermia was confirmed on semen analysis. Testicular histopathology revealed no spermatogenesis and absence of germ cells. Karyotype from whole blood culture showed cells with 47,XXY/46,XX/ 45,X/48,XXXY/ 46,XY mosaicism. The predominant cell line was 47,XXY (83.67%). This was confirmed by fluorescence in situ hybridization (FISH). Also the presence of a small population of cells with the 48,XXXY and 45,X karyotypes was detected by FISH. This case illustrates the utility of FISH as an adjunct to conventional cytogenetics in assess the chromosome copy number in each cell line of a mosaic. PMID:25083188

A Rare Case of Klinefelter Syndrome Patient with Quintuple Mosaic Karyotype, Diagnosed by GTG-Banding and FISH.

PubMed

Karimi, Hamideh; Sabbaghian, Marjan; Haratian, Kaveh; Vaziri Nasab, Hamed; Farrahi, Faramarz; Moradi, Shabnam Zari; Tavakolzadeh, Tayebeh; Beheshti, Zahra; Gourabi, Hamid; Meybodi, Anahita Mohseni

2014-07-01

Klinefelter syndrome (KS) is the most common sex chromosomal disorder in men. Most of these patients show the 47,XXY karyotype, whereas approximately 15% of them are mosaics with variable phenotype. A 39-year-old male investigated for primary infertility, was clinically normal with small firm testes and elevated levels of FSH, LH and low level of testosterone. Total azoospermia was confirmed on semen analysis. Testicular histopathology revealed no spermatogenesis and absence of germ cells. Karyotype from whole blood culture showed cells with 47,XXY/46,XX/ 45,X/48,XXXY/ 46,XY mosaicism. The predominant cell line was 47,XXY (83.67%). This was confirmed by fluorescence in situ hybridization (FISH). Also the presence of a small population of cells with the 48,XXXY and 45,X karyotypes was detected by FISH. This case illustrates the utility of FISH as an adjunct to conventional cytogenetics in assess the chromosome copy number in each cell line of a mosaic.

Ovarian response markers lead to appropriate and effective use of corifollitropin alpha in assisted reproduction.

PubMed

La Marca, Antonio; D'Ippolito, Giovanni

2014-02-01

Corifollitropin alpha is a highly effective gonadotrophin, which maintains multifollicular growth for a week. The advantages of its administration include ease of use of the drug, making the treatment more patient friendly, resulting in a lower level of distress for the patient. At the same time, the pregnancy rate resulting from its use in IVF/intracytoplasmic sperm injection cycles is similar to that found when daily recombinant FSH is administered. The ovarian response to corifollitropin alpha is dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There is a general trend towards a higher ovarian response with an increasing AFC and the number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome following corifollitropin alpha is very similar to the rate reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve at risk of overstimulation, and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Corifollitropin alpha is a highly effective gonadotrophin which maintains multifollicular growth for a week. The ovarian response to corifollitropin was demonstrated to be dependent on clinically established predictors such as baseline FSH, antral follicle count (AFC) and age. There was a general trend toward a higher ovarian response with an increasing AFC and the mean number of oocytes per attempt decreased with increasing baseline FSH and age. Even if the risk of ovarian hyperstimulation syndrome (OHSS) following corifollitropin alpha is very similar to the rate of OHSS reported in literature for young women undergoing IVF, the risk of overstimulation may be reduced by avoiding maximal ovarian stimulation in women anticipated to be hyperresponders. Increasing evidence demonstrates that anti-Müllerian hormone and AFC exhibit a very good diagnostic performance in the prediction of hyperresponse. High basal anti-Müllerian hormone and/or AFC can identify women with enhanced functional ovarian reserve who are at risk of overstimulation if stimulated in IVF cycles and the risk is even higher if maximally stimulated with corifollitropin alpha or high dose of daily recombinant FSH. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

The role of ovarian reserve markers in prediction of clinical pregnancy.

PubMed

Zebitay, Ali G; Cetin, Orkun; Verit, Fatma F; Keskin, Seda; Sakar, M Nafi; Karahuseyinoglu, Sercin; Ilhan, Gulsah; Sahmay, Sezai

2017-05-01

To evaluate the role of ovarian reserve markers in the prediction of clinical pregnancy and embryo transfer accomplishment among poor responder IVF applicants. 304 female poor responder IVF applicants were included in this prospective cohort study conducted at the IVF-unit. Antral follicle count, FSH, LH, E2, AMH and IVF outcomes were compared in pregnant and non-pregnant groups as well as in ET vs. non-ET groups. The number of retrieved oocytes was significantly correlated positively with AMH and AFC, and negatively with FSH and age. Quartiles of FSH and AFC were similar to the rate of pregnancy. Quartiles of AMH (<25%/25-75% and <25%/>75%) were statistically significant. Mean serum levels for AMH were significantly lower in the non-ET group. Our findings seem to indicate that day 3 AMH values can predict ET accomplishment with a sensitivity of 96% and a specificity of 35%. Quartiles of AMH <25% (< 0.21 ng/mL) can predict the IVF results among poor responder IVF applicants. Impact statement Various cut-off values have been determined for day 3 serum AMH values. These values help to determine the groups that are expected to give normal, high or low response to stimulation and decide the treatment options. In contrast to other groups of patients, poor responders cannot reach the embryo transfer stage for several reasons. These are; absence of a mature oocyte after oocyte pick-up, fertilisation failure without male factor or poor embryo quality. In the present study; a cut-off value of 0.33 ng/mL for the prediction of ET accomplishment in poor responder patients was determined with a sensitivity of 96%. Additionally, clinical pregnancy could not be achieved under the value of 0.21 ng/mL day 3 AMH values. It is important to clarify the embryo transfer success of poor responder patients prior to expected treatment success. Pre-treatment counselling for these patients would lessen the disappointment that may develop after treatment. The cost-effectiveness of treatments below these AMH values can be determined by further studies.

Androstenedione response to recombinant human FSH is the most valid predictor of the number of selected follicles in polycystic ovarian syndrome: (a case-control study).

PubMed

Ozyurek, Eser Sefik; Yoldemir, Tevfik; Artar, Gokhan

2017-05-12

We aimed to test the hypothesis that the correlation of the changes in the blood Androstenedione (A 4 ) levels to the number of selected follicles during ovulation induction with low-dose recombinant human follicle stimulating hormone (rhFSH) is as strong as the correlation to changes in the blood Estradiol (E 2 ) levels in polycystic ovary syndrome (PCOS). Prospective Case-control study conducted from October 2014 to January 2016. 61 non-PCOS control (Group I) and 46 PCOS (Group II) patients treated with the chronic low-dose step up protocosl with rhFSH. A 4 , E 2 , progesterone blood levels and follicular growth were monitored.. Univariate and hierarchical multivariable analysis were performed for age, BMI, HOMA-IR, A 4 and E 2 (with the number of selected follicles as the dependent variable in both groups). ROC analysis was performed to define threshold values for the significant determinants of the number of selected follicles to predict cyle cancellations due to excessive ovarian response. The control group (Group I) was comprised of 61 cycles from a group of primary infertile non-PCOS patients, and the study group (Group II) of 46 cycles of PCOS patients. The analysis revealed that the strongest independent predictor of the total number of selected follicles in Group I was the E 2 (AUC) (B = 0.0006[0.0003-0.001]; P < 0.001); whereas for Group II, it was the A 4 (AUC) (B = 0.114[0.04-0.25]; P = 0.01). Optimum thresholds for the A 4 related parameters were defined to predict excessive response within Group II were 88.7%, 3.1 ng/mL and 5.4 ng*days for the percentage increase in A 4 , the maximum A 4 value and area under the curve values for A 4 , respectively. A 4 response to low-dose rhFSH in PCOS has a stronger association with the number of follicles selected than the E 2 reponse. A 4 response preceding the E 2 response is essential for progressive follicle development. Monitoring A 4 rather than E 2 may be more preemptive to define the initial ovarian response and accurate titration of the rhFSH doses. The study was registered as a prospective case-control study in the ClinicalTrials.gov registry with the identifier NCT02329483 .

Honey Attenuates the Detrimental Effects of Nicotine on Testicular Functions in Nicotine Treated Wistar Rats.

PubMed

Kolawole, T A; Oyeyemi, W A; Adigwe, C; Leko, B; Udeh, C; Dapper, D V

2015-12-20

Effect of honey on reproductive functions of male rats exposed to nicotine was examined in this study. Thirty-two adult male wistar rats (n=8/Group) were grouped as Control (distilled water), Nicotine (1.0mg/kg bwt), Honey (100mg/kg bwt) and Nicotine with Honey. The animals were orally treated for 35 days consecutively. Epididymis sperm motility, viability, morphology and counts were estimated, serum Follicle Stimulating Hormone (FSH), Leutinizing Hormone (LH) and Testosterone were assayed using ELISA method and testicular histology were also assessed. Significant reduction in percentage sperm motility, viability, morphology and counts were observed in nicotine group compared to control. Serum FSH, LH and testosterone levels were significantly reduced in nicotine group when compared with the control. There was significant improvement in sperm motility, viability, morphology, counts, FSH, LH and Testosterone in group co-treated with nicotine and honey  relative to nicotine group. Also, the degenerative seminiferous tubule architecture due to nicotine was improved by honey. In conclusion, honey may suppress nicotine toxic effect on reproductive functions in male Wistar rats.

Suppression of LH during ovarian stimulation: analysing threshold values and effects on ovarian response and the outcome of assisted reproduction in down-regulated women stimulated with recombinant FSH.

PubMed

Balasch, J; Vidal, E; Peñarrubia, J; Casamitjana, R; Carmona, F; Creus, M; Fábregues, F; Vanrell, J A

2001-08-01

It has been recently suggested that gonadotrophin-releasing hormone agonist down-regulation in some normogonadotrophic women may result in profound suppression of LH concentrations, impairing adequate oestradiol synthesis and IVF and pregnancy outcome. The aims of this study, where receiver-operating characteristic (ROC) analysis was used, were: (i) to assess the usefulness of serum LH measurement on stimulation day 7 (S7) as a predictor of ovarian response, IVF outcome, implantation, and the outcome of pregnancy in patients treated with recombinant FSH under pituitary suppression; and (ii) to define the best threshold value, if any, to discriminate between women with 'low' or 'normal' LH concentrations. A total of 144 infertile women undergoing IVF/intracytoplasmic sperm injection (ICSI) treatment were included. Seventy-two consecutive patients having a positive pregnancy test (including 58 ongoing pregnancies and 14 early pregnancy losses) were initially selected. As a control non-pregnant group, the next non-conception IVF/ICSI cycle after each conceptual cycle in our assisted reproduction programme was used. The median and range of LH values in non-conception cycles, conception cycles, ongoing pregnancies, and early pregnancy losses, clearly overlapped. ROC analysis showed that serum LH concentration on S7 was unable to discriminate between conception and non-conception cycles (AUC(ROC) = 0.52; 95% CI: 0.44 to 0.61) or ongoing pregnancy versus early pregnancy loss groups (AUC(ROC) = 0.59; 95% CI: 0.46 to 0.70). To assess further the potential impact of suppressed concentrations of circulating LH during ovarian stimulation on the outcome of IVF/ICSI treatment, the three threshold values of mid-follicular serum LH proposed in the literature (<1, < or =0.7, <0.5 IU/l) to discriminate between women with 'low' or 'normal' LH were applied to our study population. No significant differences were found with respect to ovarian response, IVF/ICSI outcome, implantation, and the outcome of pregnancy between 'low' and 'normal' S7 LH women as defined by those threshold values. Our results do not support the need for additional exogenous LH supplementation in down-regulated women receiving a recombinant FSH-only preparation.

Effect of human gonadotropins on spermiation and androgen biosynthesis in the testis of the toad Bufo arenarum (Amphibia, Anura).

PubMed

Pozzi, Andrea Gabriela; Rosemblit, Cinthia; Ceballos, Nora Raquel

2006-01-01

This paper analyzes, in the toad Bufo arenarum, the effect on spermiation and androgen secretion of two human recombinant gonadotropins, human recombinant LH (hrLH) and human recombinant FSH (hrFSH) as well as the well-known spermiation-inducing hormone, human chorionic gonadotropin (hCG). For this purpose, testes were incubated with different concentrations of hrLH (0.01-2.5 microg/ml) and hrFSH (0.05-5 microg/ml), and results were compared with those obtained with 2.5 microg/ml hCG. Spermiation was most efficiently stimulated by hrFSH, which elicited a higher response than either hrLH or hCG. Both hrFSH and hrLH produced a bell-shaped dose-response curve, with a 50% inhibition on spermiation at a concentration twice higher than that necessary to get the highest response. However, none of the gonadotropins yielded a biphasic response on androgen secretion, hrLH producing the highest response at a concentration that evoked a 70% inhibition in the spermiation test. Regarding steroidogenesis, hrLH and hrFSH were more active than hCG. Taken together, the results described in this paper suggest that, in B. arenarum, spermiation and androgen secretion are mediated by different receptors. After comparing the effects of recombinant hormones, we conclude that hrFSH has a greater effect on spermiation than hCG or hrLH.

Follicle-stimulating hormone (FSH), current suicidal ideation and attempt in female patients with major depressive disorder.

PubMed

Kim, Bora; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Soskin, David; Yu, Bum-Hee; Lee, Dongsoo; Lee, Dong-Yun; Park, Hyung-Doo; Jeon, Hong Jin

2013-12-30

Current suicidal ideation and attempts are more commonly found in female patients with major depressive disorder (MDD) than in males. However, little is known about the relationship between activity of female reproductive hormones and suicide. The study population consisted of 490 female MDD patients of age ≥18. They were assessed by the Mini-International Neuropsychiatric Interview. At the same visit, we measured blood Follicle-Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol, progesterone, Adrenocorticotropic Hormone (ACTH), cortisol, thyroid hormones, and prolactin. Blood FSH showed a significant difference among female MDD patients with suicide attempt, those with ideation, and those without within the previous month. Post-hoc analysis also showed that FSH was significantly lower in MDD patients with suicide attempt and ideation than those without, whereas other hormones showed no differences between those with and without attempt. FSH was negatively associated with current suicidality scores after adjustment for age and education years in all age groups. FSH was significantly lower in those with current suicide ideation or attempt than those without in age 45 years or under, but not in other age groups. In conclusion, blood FSH is significantly lower in female MDD patients with current suicide attempt or ideation than those without, especially in age 45 years or under. © 2013 Elsevier Ireland Ltd. All rights reserved.

Hormonal control of spermatogenesis in men: therapeutic aspects in hypogonadotropic hypogonadism.

PubMed

Pitteloud, Nelly; Dwyer, Andrew

2014-05-01

During the first two trimesters of intrauterine life, fetal sex steroid production is driven by maternal human chorionic gonadotropin (hCG). The HPG axis is activated around the third trimester and remains active for the first 6-months of neonatal life. This so-called mini-puberty is a developmental window that has profound effects on future potential for fertility. In early puberty, GnRH secretion is reactivated first at night and then night and day. Pulsatile GnRH stimulates both LH and FSH, which induce maturation of the seminiferous tubules and Leydig cells. Congenital hypogonadotropic hypogonadism (CHH) results from GnRH deficiency. Men with CHH lack the mini-pubertal and pubertal periods of Sertoli Cell proliferation and thus present with prepubertal testes (<4mL) and low inhibin serum levels --reflecting diminished SC numbers. To induce full maturation of the testes, GnRH-deficient patients can be treated with either pulsatile GnRH, hCG or combined gonadotropin therapy (FSH+hCG). Fertility outcomes with each of these regimens are highly variable. Recently, a randomized, open label treatment study (n=13) addressed the question of whether a sequential treatment with FSH alone prior to LH and FSH (via GnRH pump) could enhance fertility outcomes. All men receiving the sequential treatment developed sperm in the ejaculate, whereas 2/6 men in the other group remained azoospermic. A large, multicenter clinical trial is needed to definitively prove the optimal treatment approach for severe CHH. Copyright © 2014. Published by Elsevier Masson SAS.

Concomitant use of FSH and low-dose recombinant hCG during the late follicular phase versus conventional controlled ovarian stimulation for intracytoplasmic sperm injection cycles.

PubMed

Iaconelli, Carla Andrade Rebello; Setti, Amanda Souza; Braga, Daniela Paes Almeida Ferreira; Maldonado, Luiz Guilherme Louzada; Iaconelli, Assumpto; Borges, Edson; Aoki, Tsutomu

2017-12-01

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.

Malignant Brenner tumor. A histologic, morphometrical, immunohistochemical, and ultrastructural study.

PubMed

Seldenrijk, C A; Willig, A P; Baak, J P; Kühnel, R; Rao, B R; Burger, C W; van der Harten, J J; Dijkhuizen, G H; Meijer, C J

1986-08-01

The histologic, morphometric, immunohistochemical, and ultrastructural study of a malignant Brenner tumor in a postmenopausal women presenting with vaginal bleeding is described. A comparison with transitional cell carcinomas is made, and the use of morphometry in grading the urothelial-like epithelium in malignant Brenner tumors is suggested. High preoperative urinary estrogen, low serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and histologically confirmed atypical endometrial hyperplasia suggested a hyperestrogenism. The reduction in urinary estrogen and the increase in serum LH and FSH after tumor removal and the presence of aromatase activity detected in tumor microsomes confirmed that the tumor was synthesizing estrogen. Estrogen receptors were undetectable both by biochemical and histochemical analysis in the tumor.

Superstimulation prior to the ovum pick-up to improve in vitro embryo production in lactating and non-lactating Holstein cows.

PubMed

Vieira, L M; Rodrigues, C A; Castro Netto, A; Guerreiro, B M; Silveira, C R A; Moreira, R J C; Sá Filho, M F; Bó, G A; Mapletoft, R J; Baruselli, P S

2014-07-15

The present study evaluated the efficacy of superstimulation with p-FSH (Folltropin) before the ovum pick-up (OPU) on IVP in lactating and nonlactating Holstein donors. A total of 30 Holstein cows (15 lactating and 15 nonlactating) were blocked by lactation status to one of two groups (control or p-FSH), in a cross-over design. On a random day of the estrous cycle, all cows received an intravaginal progesterone device and 2.0 mg IM of estradiol benzoate (Day 0). Cows in the control group received no further treatment, whereas cows in the p-FSH group received a total dosage of 200 mg of p-FSH on Days 4 and 5 in four decreasing doses 12 hours apart (57, 57, 43, and 43 mg). On Day 7, the progesterone device was removed, and OPU was conducted in both groups (40 hours after the last p-FSH injection in the p-FSH-treated group). There was no difference between groups (P = 0.92) in the numbers of follicles that were aspirated per OPU session (17.2 ± 1.3 vs. 17.1 ± 1.1 in control and p-FSH-treated cows, respectively); however, p-FSH-treated cows had a higher (P < 0.001) percentage of medium-sized follicles (6-10 mm) at the time of the OPU (55.1%; 285/517) than control cows (20.8%; 107/514). Although recovery rate was lower (60.0%, 310/517 vs. 69.8%, 359/514; P = 0.002), p-FSH-treated cows had a higher blastocyst production rate (34.5%, 89/258 vs. 19.8%, 55/278; P < 0.001) and more transferable embryos per OPU session were produced in the p-FSH group (3.0 ± 0.5 vs. 1.8 ± 0.4; P = 0.02). Regardless of treatment, non-lactating cows had a higher blastocyst rate (41.9%, 106/253 vs. 13.4%, 38/283; P = 0.001) and produced more transferable embryos per OPU session (3.5 ± 0.5 vs. 1.3 ± 0.3; P = 0.003) than lactating cows. Thus, superstimulation of Holstein donors with p-FSH before OPU increased the efficiency of IVP. In addition, non-lactating donors had higher percentage of in vitro blastocyst development and produced more embryos per OPU session than lactating cows. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of progestagen-gonadotrophin treatments in estrus synchronization of sheep.

PubMed

Boscos, C M; Samartzi, F C; Dellis, S; Rogge, A; Stefanakis, A; Krambovitis, E

2002-10-15

The main objective of this study was to investigate the effectiveness of certain progestagen-gonadotrophin treatments on synchronization of estrus in sheep. In Experiment I, 30 Chios ewes were treated at the beginning of the breeding season with medroxyprogesterone acetate (MAP) intravaginal sponges for 12 days and a single i.m. treatment of either FSH (Group 1,10 IU, n = 8; Group 2, 5 IU, n = 8; Group 3, 2.5 IU, n = 8) or eCG (Group 4, 400 IU, n = 6) at the time of sponge removal. Ten days after sponge removal laparotomy was performed to record ovarian response. Clinical estrus was observed in more (though not at a significant level) FSH treated than eCG treated sheep (62.5% versus 33.3%). Administration of 400 IU eCG resulted in the highest mean number of CL perewe ovulating (2.8 +/- 0.2), with administration of 10 IU FSH producing the next best results (2.1 +/- 0.3). Statistically significant differences in the mean number of CL per ewe ovulating were found only between ewes in Group 3 (1.7 +/- 0.4) and Group 4 (2.8 +/- 0.2) (P < 0.05). In Experiment II, 53 Chios and 30 Berrichon ewes were treated during the mid-breeding season with MAP intravaginal sponges for 12 days and a single i.m. treatment of either 10 IU FSH (27 Chios and 16 Berrichon ewes) or 400 IU eCG (26 Chios and 14 Berrichon ewes), at the time of sponge removal. Ewes that were in estrus on Days 2-4 and 19-23 after sponge removal were mated to fertile rams. No significant differences were recorded between treatment or breed groups in the proportions of ewes observed in estrus after treatment. In the Berrichon breed, FSH administration resulted in higher lambing rates (93.8% versus 57.1%, P < 0.05) and higher mean number of lambs born per ewe exposed to rams (1.4 +/- 0.2 versus 0.8 +/- 0.2, P < 0.05) than that of eCG. After treatment with eCG, the mean number of lambs born per ewe exposed to rams was higher in the Chios than the Berrichon breed (1.4 +/- 0.2 versus 0.8 +/- 0.2, P < 0.05). After treatment with FSH, the lambing rate was higher in the Berrichon than the Chios breed (93.8% versus 63.0%, P < 0.05). In conclusion, a single FSH treatment (5 or 10 IU) at the end of progestagen treatment appears to be more effective than eCG for the induction of synchronized estrus in sheep at the beginning of the breeding season, with no cases of abnormal ovarian response observed. During the mid-breeding season FSH (10 IU) appears to be equally as effective as eCG (400 IU) in respect of lambing rate and mean number of lambs born per ewe.

Evaluation of ovarian reserve tests in women with systemic lupus erythematosus.

PubMed

Ulug, Pasa; Oner, Gokalp; Kasap, Burcu; Akbas, Emin Murat; Ozcicek, Fatih

2014-07-01

Impact of systemic lupus erythematosus (SLE) on fertility may be negative, and ovarian function can be also reduced by autoimmune oophoritis. In this article, we evaluated the ovarian reserve of pre-menopausal women firstly diagnosed with systemic lupus erythematosus (SLE). This was a prospective controlled study which included twenty women with SLE and twenty healthy women as controls in the reproductive age. Basal levels of FSH, estradiol (E2), and LH on cycle day 3 were measured. All participants underwent transvaginal ultrasonographic examination on the third day of their menstrual periods for the determination of ovarian volume (OV) and total antral follicle count (AFC). A significant difference in FSH, LH, and E2 levels was observed between women with SLE and healthy controls. There was a statistically significant reduction in total AFC and OV in SLE group. Age was associated negatively with AFC, whereas positively with FSH and LH. Menstrual irregularity was significantly higher in SLE patients than control. AFC was the most reliable test to show the menstrual irregularity and negatively correlated each other in women with SLE. In this preliminary study, the first in SLE patients, we illustrated that women with SLE had lower ovarian reserves and higher menstrual irregularity compared with healthy controls according to hormonal and ultrasonographical evaluation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Postnatal Ovary Development in the Rat: Morphologic Study and Correlation of Morphology to Neuroendocrine Parameters

PubMed Central

Picut, Catherine A.; Dixon, Darlene; Simons, Michelle L.; Stump, Donald G.; Parker, George A.; Remick, Amera K.

2014-01-01

Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic–pituitary–gonadal axis matures. During the neonatal stage (postnatal day [PND] 0–7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of “atypical” follicles occurs in the early infantile period (PND 8–14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15–20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their “atypical” appearance. The juvenile stage (PND 21–32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33–37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat. PMID:25107574

Masturbation Frequency and Sexual Function Domains Are Associated With Serum Reproductive Hormone Levels Across the Menopausal Transition

PubMed Central

Zheng, Huiyong; Avis, Nancy E.; Greendale, Gail A.; Harlow, Siobán D.

2015-01-01

Objective: To determine whether reproductive hormones are related to sexual function during the menopausal transition. Design: The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of the menopausal transition located at seven US sites. At baseline, the 3302 community-based participants, aged 42–52, had an intact uterus and at least one ovary and were not using exogenous hormones. Participants self-identified as White, Black, Hispanic, Chinese, or Japanese. At baseline and at each of the 10 follow-up visits, sexual function was assessed by self-administered questionnaires, and blood was drawn to assay serum levels of T, estradiol, FSH, SHBG, and dehydroepiandrosterone sulfate. Main Outcome Measures: Self-reported frequency of masturbation, sexual desire, sexual arousal, orgasm, and pain during intercourse. Results: Masturbation, sexual desire, and arousal were positively associated with T. Masturbation, arousal, and orgasm were negatively associated with FSH. Associations were modest. Estradiol was not related to any measured sexual function domain. Pain with intercourse was not associated with any hormone. Conclusions: Reproductive hormones were associated with sexual function in midlife women. T was positively associated, supporting the role of androgens in female sexual function. FSH was negatively associated, supporting the role of menopausal status in female sexual function. The modest associations in this large study suggest that the relationships are subtle and may be of limited clinical significance. PMID:25412335

Masturbation frequency and sexual function domains are associated with serum reproductive hormone levels across the menopausal transition.

PubMed

Randolph, John F; Zheng, Huiyong; Avis, Nancy E; Greendale, Gail A; Harlow, Siobán D

2015-01-01

To determine whether reproductive hormones are related to sexual function during the menopausal transition. The Study of Women's Health Across the Nation (SWAN) is a multiethnic cohort study of the menopausal transition located at seven US sites. At baseline, the 3302 community-based participants, aged 42-52, had an intact uterus and at least one ovary and were not using exogenous hormones. Participants self-identified as White, Black, Hispanic, Chinese, or Japanese. At baseline and at each of the 10 follow-up visits, sexual function was assessed by self-administered questionnaires, and blood was drawn to assay serum levels of T, estradiol, FSH, SHBG, and dehydroepiandrosterone sulfate. Self-reported frequency of masturbation, sexual desire, sexual arousal, orgasm, and pain during intercourse. Masturbation, sexual desire, and arousal were positively associated with T. Masturbation, arousal, and orgasm were negatively associated with FSH. Associations were modest. Estradiol was not related to any measured sexual function domain. Pain with intercourse was not associated with any hormone. Reproductive hormones were associated with sexual function in midlife women. T was positively associated, supporting the role of androgens in female sexual function. FSH was negatively associated, supporting the role of menopausal status in female sexual function. The modest associations in this large study suggest that the relationships are subtle and may be of limited clinical significance.

Central Effects of Camphor on GnRH and Sexual Hormones in Male Rat

PubMed Central

Shahabi, Sima; Jorsaraei, Seyed Gholam Ali; Moghadamnia, Ali Akbar; Zabihi, Ebrahim; Aghajanpour, Seyed Mohsen; Mousavi Kani, Seyedeh Narges; Pourbagher, Roghieh; Hosseini, Seyed Ahmad; Esmaili, Mohsen; Yoonesi, Ali Asghar; Zarghami, Amin; Alinezhad, Farid

2012-01-01

In Persian traditional medicine is believed that camphor (a crystalline ketone obtained from cinnamomum camphora) is a suppressor of sexual behaviors. This study examined the central effects of camphor on sexual hormones (LH, FSH and testosterone) and GnRH plasma levels in male rat. Male Wistar rats weighing 250-260gr were selected and divided into control (no treatment), sham (ICV injection of EtOH 10%) and treatment (ICV injection of camphor in three doses 4, 20, 40 µg/ 10µl in alcohol) groups. The serum samples were used for assaying of GnRH, LH, FSH and testosterone. There were no significant differences in the levels of hormones between the groups of study. Despite the central administration of camphor in hypothalamus - pituitary - gonad (HPG) axis, no significant differences were seen in sex hormone`s levels compared to the control. With this finding, it can be concluded that camphor may not effectively handle the axis via central pathway. These data recommend further studies of camphor on the HPG axis. PMID:24551777

Changes of blood levels of several hormones, catecholamines, prostaglandins, electrolytes and cAMP in man during emotional stress.

PubMed

Tigranian, R A; Orloff, L L; Kalita, N F; Davydova, N A; Pavlova, E A

1980-01-01

The levels of several hormones (ACTH, GH, TSH, FSH, LH, parathyroid hormone--PTH, insulin, thyroxine--T4, triiodothyronine--T3, cortisol, testosterone, aldosterone, renin), catecholamines (epinephrine, norepinephrine, dopamin), prostaglandins (F1 alpha, F2 alpha, A + E), electrolytes (Na, K, Ca, Mg), cAMP and glucose in blood were measured before and immediately after the examination in 15 male students aged 28 to 35 years. Simultaneously the blood pressure was measured and hemodynamic measures were registered with the aid of echocardiography. A remarkable increase of catecholamines, ACTH, renin, T3, PTH, cAMP, PG F1 alpha, PG F2 alpha and Ca was found before the examination together with the increase of blood pressure. After the examination the levels of catecholamines, renin, aldosterone, T3, PTH, GH, FSH, LH, testosterone, PG A + E, glucose and Ca were found to be increased, while these of insulin, Na, PG F1 alpha, PG F2 alpha were decreased. The decrease of blood pressure was also found.

Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only: a NOPHO-AML study.

PubMed

Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders; Glosli, Heidi; Jahnukainen, Kirsi; Jarfelt, Marianne; Jónmundsson, Guðmundur K; Malmros, Johan; Nysom, Karsten; Hasle, Henrik

2013-12-01

More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings. We included 137 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, who were alive by June 2007. Patients with relapse or treated with HSCT were excluded. AML survivors participated in a physical and biochemical examination (n = 102) and completed a questionnaire (n = 101). One of their siblings completed an identical questionnaire (n = 84). At a median follow-up of 11 years (range 5-25) after diagnosis of AML the survivors (median age 16 years, range 5-36) were either prepubertal or had entered puberty normally. Serum levels of FSH, LH, testosterone, estradiol, sex hormone binding globulin (SHBG), inhibin A and B, and testicular volumes were within normal ranges. Anti-Müllerian hormone (AMH) levels were decreased in 5 of 40 postpubertal females. Mean reported age at menarche was 13.1 (range 11-17) years. Among survivors 15 years of age or older 31% of females reported pregnancies and 9% of males reported pregnancies in their partners, rates comparable with the frequency reported by their siblings. Most AML survivors treated with chemotherapy had normal pubertal development and fertility, however, AMH levels were decreased in 13% of postpubertal females. Longer follow-up is necessary to evaluate possible risk of premature ovarian failure. © 2013 Wiley Periodicals, Inc.

Metabolic and endocrine effects of bisphenol A exposure in market seller women with polycystic ovary syndrome.

PubMed

Vahedi, Mahjoob; Saeedi, Arastoo; Poorbaghi, Seyedeh Leila; Sepehrimanesh, Masood; Fattahi, Mohammadreza

2016-12-01

Bisphenol A (BPA) is one of the synthetic monomer which can be found in the environment. Limited animal and human studies have demonstrated that BPA alters endocrine and or metabolic functions. The aims of the present study were to evaluate serum BPA level in marketing seller women with polycystic ovary syndrome (PCOS) and hormonal and metabolic effects of this exposure compared to a control paired group. In a case-control study, 62 PCOS women who work as marketing sellers and 62 healthy women with similar jobs were included. The two groups were body mass index (BMI)- and age-matched. Serum samples were analyzed for BPA content, fasting blood sugar (FBS), triglyceride, cholesterol, HDL and LDL levels, thyroid stimulating hormone (TSH) concentration, and LH:FSH ratio. Significant higher serum BPA content (0.48 ± 0.08 vs. 0.16 ± 0.04 ng/ml), triglyceride (103.05 ± 13.10 vs. 91.65 ± 12.52 mg/dl), cholesterol (165.05 ± 10.79 vs. 161.21 ± 10.31 mg/dl) levels and LH:FSH ratio (3.64 ± 0.86 vs. 0.62 ± 0.14) and significant lower TSH concentration (1.56 ± 0.68 vs. 2.15 ± 1.09 IU/ml) were detected in case against control group, respectively (P < 0.05). No significant differences were detected in FBS, LDL, and HDL levels between the two groups. Also, there were no significant associations between serum TSH concentration and BPA level neither in case (P = 0.269) nor in control (P = 0.532) groups. In BPA-exposed PCOS women, BPA level was higher than healthy women and this difference maybe the cause of significant differences in levels of triglyceride, cholesterol, TSH, and LH:FSH ratio. These observations confirm the potential role of BPA in PCOS pathophysiology.

Prevalence of hypovitaminosis D, and its association with hypoadiponectinemia and hyperfollistatinemia, in Saudi women with naïve polycystic ovary syndrome.

PubMed

Kensara, Osama Adnan

2018-06-01

The association between vitamin D and polycystic ovary syndrome (PCOS) is an active area of growing research. However, data in Saudi Arabia are scarce. This study aimed to define serum 25-hydroxyvitamin D (25(OH)D) levels among Saudi women with naïve PCOS, and to investigate the associations of their 25(OH)D status with their serum adiponectin and follistatin levels, along with indices of insulin resistance and hormonal deteriorations. In this case-control observational study, 63 women with PCOS and 65 age-and body mass index (BMI)-matched control women were assessed. PCOS was diagnosed based on the revised criteria of Rotterdam. Fasting serum levels of 25(OH)D, adiponectin, follistatin, insulin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), androgen (Δ 4 -androstenedione), estradiol, progesterone, along with fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR) index and lipid profile were measured in both groups. The prevalence of hypovitaminosis D (serum 25(OH)D <30 ng/ml) was higher in PCOS group than control group (77.8% vs. 12.3%). Serum adiponectin and FSH concentrations were significantly lower, while serum follistatin, LH, TT, Δ 4 -androstenedione and insulin levels, as well as FPG and HOMA-IR were significantly higher in PCOS group than control group. In addition, 25(OH)D levels of PCOS women were significantly correlated positively with adiponectin and FSH levels, but negatively with follistatin, HOMA-IR, FPG, LH, testosterone, and Δ 4 -androstenedione levels. Hypovitaminosis D, coexisted and correlated with hypoadiponectinemia and hyperfollistatinemia, is being an alarming risk factor in Saudi women with PCOS. Further investigational and explanatory studies in large size samples are warranted to realize these findings and to improve both diagnostic and treatment tools in Saudi women with PCOS.

In vitro hCG and human recombinant FSH actions on testicular steroidogenesis in the toad Bufo arenarum.

PubMed

Canosa, L F; Ceballos, N R

2002-05-01

In order to study the regulation of testicular steroidogenesis in the toad Bufo arenarum, the effect of gonadotropins (hCG and hrFSH) on steroidogenic enzymes was determined using an in vitro system. 3beta-Hydroxysteroid dehydrogenase/isomerase activity was not affected by any of the gonadotropins, at any of the concentrations used. In contrast, 5alpha-reductase activity was strongly reduced by both hCG and hrFSH. Human chorionic gonadotropin inhibited the activity of cytochrome P450 17alpha-hydroxylase-C(17-20) lyase (P450(c17)), only at the highest concentration used, while hrFSH strongly reduced P450(c17) activity at all the doses assayed. In conclusion, these data suggest that LH (hCG) and FSH regulate steroidogenic enzymes such as 5alphaRed and P450(c17). The results also suggest that FSH could be involved in the regulation of the change in steroidogenesis undergone by the testis during the breeding season. In turn, the inhibition of P450(c17) activity could result in a reduction of androgen production and an increment of C21 steroids. (c) 2002 Elsevier Science (USA).

Gene expression analysis of pig cumulus-oocyte complexes stimulated in vitro with follicle stimulating hormone or epidermal growth factor-like peptides.

PubMed

Blaha, Milan; Nemcova, Lucie; Kepkova, Katerina Vodickova; Vodicka, Petr; Prochazka, Radek

2015-10-06

The gonadotropin-induced resumption of oocyte meiosis in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like peptides, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. Both the gonadotropins and the EGF-like peptides possess the capacity to stimulate resumption of oocyte meiosis in vitro via activation of a broad signaling network in cumulus cells. To better understand the rapid genomic actions of gonadotropins (FSH) and EGF-like peptides, we analyzed transcriptomes of cumulus cells at 3 h after their stimulation. We hybridized aRNA from cumulus cells to a pig oligonucleotide microarray and compared the transcriptomes of FSH- and AREG/EREG-stimulated cumulus cells with untreated control cells and vice versa. The identified over- and underexpressed genes were subjected to functional genomic analysis according to their molecular and cellular functions. The expression pattern of 50 selected genes with a known or potential function in ovarian development was verified by real-time qRT-PCR. Both FSH and AREG/EREG increased the expression of genes associated with regulation of cell proliferation, cell migration, blood coagulation and extracellular matrix remodeling. FSH alone induced the expression of genes involved in inflammatory response and in the response to reactive oxygen species. Moreover, FSH stimulated the expression of genes closely related to some ovulatory events either exclusively or significantly more than AREG/EREG (AREG, ADAMTS1, HAS2, TNFAIP6, PLAUR, PLAT, and HSD17B7). In contrast to AREG/EREG, FSH also increased the expression of genes coding for key transcription factors (CEBPB, FOS, ID1/3, and NR5A2), which may contribute to the differing expression profiles of FSH- and AREG/EREG-treated cumulus cells. The impact of FSH on cumulus cell gene transcription was higher than the impact of EGF-like factors in terms of the number of cell functions affected as well as the number of over- and underexpressed genes. Both FSH and EGF-like factors overexpressed genes involved in the post-ovulatory switch in steroidogenesis and tissue remodelling. However, FSH was remarkably more efficient in the up-regulation of several specific genes essential for ovulation of matured oocytes and also genes that been reported to play an important role in maturation of cumulus-enclosed oocytes in vitro.

Radiotherapy for Rectal Cancer Is Associated With Reduced Serum Testosterone and Increased FSH and LH

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bruheim, Kjersti; Svartberg, Johan; Department of Medicine, University Hospital of North Norway, Tromso

Purpose: It is known that scattered radiation to the testes during pelvic radiotherapy can affect fertility, but there is little knowledge on its effects on male sex hormones. The aim of this study was to determine whether radiotherapy for rectal cancer affects testosterone production. Methods and Materials: All male patients who had received adjuvant radiotherapy for rectal cancer from 1993 to 2003 were identified from the Norwegian Rectal Cancer Registry. Patients treated with surgery alone were randomly selected from the same registry as control subjects. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and sex hormone bindingmore » globulin (SHBG) were analyzed, and free testosterone was calculated (N = 290). Information about the radiotherapy treatment was collected from the patient hospital charts. Results: Serum FSH was 3 times higher in the radiotherapy group than in the control group (median, 18.8 vs. 6.3 IU/L, p <0.001), and serum LH was 1.7 times higher (median, 7.5 vs. 4.5 IU/l, p <0.001). In the radiotherapy group, 27% of patients had testosterone levels below the reference range (8-35 nmol/L), compared with 10% of the nonirradiated patients (p <0.001). Irradiated patients had lower serum testosterone (mean, 11.1 vs. 13.4 nmol/L, p <0.001) and lower calculated free testosterone (mean, 214 vs. 235 pmol/L, p <0.05) than control subjects. Total testosterone, calculated free testosterone, and gonadotropins were related to the distance from the bony pelvic structures to the caudal field edge. Conclusions: Increased serum levels of gonadotropins and subnormal serum levels of testosterone indicate that curative radiotherapy for rectal cancer can result in permanent testicular dysfunction.« less

Induction of a menopausal state alters the growth and histology of ovarian tumors in a mouse model of ovarian cancer.

PubMed

Laviolette, Laura A; Ethier, Jean-François; Senterman, Mary K; Devine, Patrick J; Vanderhyden, Barbara C

2011-05-01

Ovarian cancer is often diagnosed in women after menopause when the levels of the serum gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are increased because of the depletion of growing follicles within the ovary. The ability of FSH and LH to modulate the disease has not been well studied owing to a lack of physiologically relevant models of ovarian cancer. In this study, 4-vinylcyclohexene diepoxide (VCD) was used to deplete ovarian follicles and increase the levels of circulating FSH and LH in the tgCAG-LS-TAg mouse model of ovarian cancer. VCD-induced follicle depletion was performed either before or after induction of the oncogene SV40 large and small T-antigens in the ovarian surface epithelial cells of tgCAG-LS-TAg mice, which was mediated by the intrabursal delivery of an adenovirus expressing Cre recombinase (AdCre). tgCAG-LS-TAg mice injected with AdCre developed undifferentiated ovarian tumors with mixed epithelial and stromal components and some features of sex cord stromal tumors. Treatment with VCD before or after AdCre injection yielded tumors of similar histology, but with the unique appearance of Sertoli cell nests. In mice treated with VCD before the induction of tumorigenesis, the ovarian tumors tended to grow more slowly. The human ovarian cancer cell lines SKOV3 and OVCAR3 responded similarly to increased levels of gonadotropins in a second model of menopause, growing more slowly in ovariectomized mice compared with cycling controls. These results suggest that follicle depletion and increased gonadotropin levels can alter the histology and the rate of growth of ovarian tumors.

Metformin for treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia: a double-blind, randomized, placebo-controlled study.

PubMed

Wu, Ren-Rong; Jin, Hua; Gao, Keming; Twamley, Elizabeth W; Ou, Jian-Jun; Shao, Ping; Wang, Juan; Guo, Xiao-Feng; Davis, John M; Chan, Philip K; Zhao, Jing-Ping

2012-08-01

Data on the treatment of antipsychotic-induced amenorrhea, particularly when occurring with weight gain, are limited. The authors investigated the efficacy and safety of metformin in the treatment of antipsychotic-induced amenorrhea and weight gain in women with first-episode schizophrenia. Eighty-four women (ages 18-40 years) with first-episode schizophrenia who suffered from amenorrhea during antipsychotic treatment were randomly assigned, in a double-blind study design, to receive 1000 mg/day of metformin or placebo in addition to their antipsychotic treatment for 6 months. The primary outcome measures were restoration of menstruation and change in body weight and body mass index (BMI). Secondary outcome measures were changes in levels of prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone; in fasting levels of insulin and glucose; in LH/FSH ratio; and in insulin resistance index. Repeated mixed models with repeated-measures regression analyses and binary logistic regression were used in the analysis. A total of 76 patients completed the 6-month trial. Significantly more patients in the metformin group (N=28, 66.7%) than in placebo group (N=2, 4.8%) resumed their menstruation. Among patients treated with metformin, BMI decreased by a mean of 0.93 and the insulin resistance index by 2.04. In contrast, patients who received placebo had a mean increase in BMI of 0.85. The prolactin, LH, and testosterone levels and LH/FSH ratio decreased significantly in the metformin group at months 2, 4, and 6, but these levels did not change in the placebo group. Metformin was effective in reversing antipsychotic-induced adverse events, including restoration of menstruation, promotion of weight loss, and improvement in insulin resistance in female patients with schizophrenia.

Mechanistic Study on Triptorelin Action in Protecting From 5-FU-Induced Ovarian Damage in Rats.

PubMed

Wang, Ying; Tian, Xiaoyu; Liang, Lingxia; Wang, Yan; Wang, Ruifang; Cheng, Xiaolin; Yan, Zhen; Chen, Yawei; Qi, Pengwei

2014-01-01

Triptorelin, a kind of GnRH agonist, is widely used in the treatment of hormone-responsive cancers in the clinic. This study aimed to discover the underlying mechanism of triptorelin in protection from 5-fluorouracil (5-FU)-induced ovarian damage in Sprague-Dawley rats. In the present study, after using 5-FU to induce ovarian damage in rats, body weight and wet ovaries were weighed, the levels of estradiol (E2), follicle-stimulating hormone (FSH), and anti-Müllerian hormone (AMH) in blood were detected, and the expression of Bcl-2, Bax, and NF-κB was determined. It suggested that, compared to the control, body weight gain, the ratio of ovarian wet weight to body weight, primary follicle numbers, and the levels of AMH were significantly decreased, while the concentration of E2 and FSH was heavily increased following 5-FU administration. In contrast, after coadministration of triptorelin with 5-FU, the ratio of ovarian wet weight to body weight and the levels of AMH were significantly increased, whereas the level of E2 and FSH was decreased significantly when compared with the 5-FU group. Furthermore, at indicated times, 5-FU led to the reduced Bcl-2 and NF-κB expression and increased Bax expression while triptorelin plus 5-FU increased Bcl-2 and NF-κB expression and decreased Bax expression. It was indicated that triptorelin could protect rats from 5-FU-induced ovarian damage by modulation of hormones, Bcl-2, Bax, and NF-κB. These results might highlight the mechanism of triptorelin as a protective agent in clinical chemotherapy for ovarian damage.

Effect of administration of vitamins C and E on fertilization capacity of rats exposed to noise stress.

PubMed

Saki, Ghasem; Jasemi, Majid; Sarkaki, Ali Reza; Fathollahi, Ali

2013-01-01

The aims of this study were to evaluate the effects of administration of Vitamins C and E on fertilization capacity in rats exposed to noise stress. 40 adult male rats were randomly divided into 5 equal groups. Group 1 as controls who were not exposed to noise and groups 2-5 exposed to noise with 90-120 dB intensity and 300-350 Hz frequency from 7 pm to 7 am everyday for 50 days. Group 2 exposed to noise and did not receive Vitamins. Group 3 received vitamin C, Group 4 received Vitamin E. Group 5 received Vitamins C and E concomitantly. After 50 days, serum Follicle-stimulating hormone (FSH), Luteinizing hormone (LH) and testosterone were calculated. Then each rat was left with three female rats for mating. Pregnant females were sacrificed on the 19 th day of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. The level of FSH, LH and testosterone significantly decreased in rats exposed to noise (P < 0.05). By administration of Vitamins in groups 3-5 we observed that the level of hormones significantly increased in compared to group 2 (P < 0.05). The fertilization capacity of male rats in groups 3-5 significantly increased in compared to group 2 (P < 0.05). There was significant difference between groups 1 and 2 in case of fertilization capacity (P = 0.001). The data in this study strongly suggests a negative role for noise stress on level of FSH, LH and testosterone level and also fertilization capacity of male rats. To complement the information it is suggested that this research be done on human samples.

Genome-wide association study of sex hormones, gonadotropins and sex hormone-binding protein in Chinese men.

PubMed

Chen, Zhuo; Tao, Sha; Gao, Yong; Zhang, Ju; Hu, Yanling; Mo, Linjian; Kim, Seong-Tae; Yang, Xiaobo; Tan, Aihua; Zhang, Haiying; Qin, Xue; Li, Li; Wu, Yongming; Zhang, Shijun; Zheng, S Lilly; Xu, Jianfeng; Mo, Zengnan; Sun, Jielin

2013-12-01

Sex hormones and gonadotropins exert a wide variety of effects in physiological and pathological processes. Accumulated evidence shows a strong heritable component of circulating concentrations of these hormones. Recently, several genome-wide association studies (GWASs) conducted in Caucasians have identified multiple loci that influence serum levels of sex hormones. However, the genetic determinants remain unknown in Chinese populations. In this study, we aimed to identify genetic variants associated with major sex hormones, gonadotropins, including testosterone, oestradiol, follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone binding globulin (SHBG) in a Chinese population. A two-stage GWAS was conducted in a total of 3495 healthy Chinese men (1999 subjects in the GWAS discovery stage and 1496 in the confirmation stage). We identified a novel genetic region at 15q21.2 (rs2414095 in CYP19A1), which was significantly associated with oestradiol and FSH in the Chinese population at a genome-wide significant level (p=6.54×10(-31) and 1.59×10(-16), respectively). Another single nucleotide polymorphism in CYP19A1 gene was significantly associated with oestradiol level (rs2445762, p=7.75×10(-28)). In addition, we confirmed the previous GWAS-identified locus at 17p13.1 for testosterone (rs2075230, p=1.13×10(-8)) and SHBG level (rs2075230, p=4.75×10(-19)) in the Chinese population. This study is the first GWAS investigation of genetic determinants of FSH and LH. The identification of novel susceptibility loci may provide more biological implications for the synthesis and metabolism of these hormones. More importantly, the confirmation of the genetic loci for testosterone and SHBG suggests common genetic components shared among different ethnicities.

Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity.

PubMed

Sowers, MaryFran R; Zheng, Huiyong; Greendale, Gail A; Neer, Robert M; Cauley, Jane A; Ellis, Jayne; Johnson, Sarah; Finkelstein, Joel S

2013-07-01

Our objective was to characterize changes in bone resorption in relation to the final menstrual period (FMP), reproductive hormones, body mass index (BMI), and ethnicity. Urinary type I collagen N-telopeptide (NTX), estradiol, and FSH levels were measured annually for up to 8 years spanning the menopause transition in 918 African American, Chinese, Japanese, or Caucasian women. Urinary NTX began to increase sharply about 2 years before the FMP, reaching its peak level about 1 to 1.5 years after the FMP. NTX levels declined modestly from 2 to 6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began increasing rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI <25 kg/m² and smallest in women with BMI >30 kg/m². Increases in NTX were greatest in Japanese women and smallest in African Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.

Association between serum levels of organochlorine pesticides and sex hormones in adults living in a heavily contaminated area in Brazil.

PubMed

Freire, Carmen; Koifman, Rosalina Jorge; Sarcinelli, Paula Novaes; Rosa, Ana Cristina Simões; Clapauch, Ruth; Koifman, Sergio

2014-03-01

Several studies have investigated the effects of organochlorine (OC) pesticides on adverse reproductive outcomes. However, few previous studies explored their effects on sex hormones. To examine the association between serum concentrations of OC pesticides and levels of sex hormones in adult population in a rural area in Brazil heavily contaminated with these pesticides. A cross-sectional study with 304 men and 300 women was undertaken. Wet weight serum concentrations of 19 OC pesticides (dichloro-diphenyl-trichloroethane [DDT] and hexachlorocyclohexane [HCH], among others) were determined in all participants. Testosterone levels were obtained for men and estradiol, progesterone, prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) for women. Associations between OC pesticides and sex hormones were evaluated using linear regression models. Prevalence of women with non-physiological hyperprolactinemia was 4%. After adjusting for serum lipids and confounders, heptachlor and o,p'-DDT concentrations in men were associated with lower testosterone levels, while peri- and postmenopausal women (N=77) showed inverse associations between LH and hexachlorobenzene (HCB), p,p'-DDT, p,p'-DDD (dichloro-diphenyl-dichloroethane), endosulfan 1 and 2, aldrin and mirex, as well as between FSH and p,p'-DDD, endosulfan 1 and aldrin. Premenopausal women (N=210) did not show statistically significant associations between OC pesticides and sex hormones. Inverse associations between OC pesticide concentrations and testosterone in men and LH and FSH in peri-/postmenopausal women, together with the high proportion of women with elevated prolactin, suggest that these OC compounds may have triggered anti-androgenic effects in men and estrogenic effects in women in this population. Copyright © 2013. Published by Elsevier GmbH.

In vitro growth and maturation of isolated caprine preantral follicles: Influence of insulin and FSH concentration, culture dish, coculture, and oocyte size on meiotic resumption.

PubMed

Silva, G M; Brito, I R; Sales, A D; Aguiar, F L N; Duarte, A B G; Araújo, V R; Vieira, L A; Magalhães-Padilha, D M; Lima, L F; Alves, B G; Silveira, L B R; Lo Turco, E G; Rodrigues, A P; Campello, C C; Wheeler, M B; Figueiredo, J R

2017-03-01

The aims of this study were: (1) to evaluate the effect of different insulin concentrations, alone or in combination with either a fixed FSH concentration or increasing FSH concentrations on the in vitro culture of isolated caprine preantral follicles and (2) to analyze the efficiency of two IVM media and maturation culture systems (with or without coculture with in vivo grown oocytes) on the meiosis resumption. Secondary follicles were cultured for 18 days in a basic medium supplemented with low- or high-insulin concentration alone or with a fixed FSH concentration or with increasing FSH concentrations. Oocytes grown in vivo or in vitro were matured alone or cocultured. The high-insulin concentration associated with fixed FSH treatment had higher meiotic resumption rate (P < 0.05) and was the only treatment capable of producing oocytes in metaphase II. The rates of germinal vesicle, germinal vesicle breakdown, metaphase I, metaphase II (MII), meiotic resumption, and oocyte diameter were similar between the maturation media. In conclusion, a basic medium supplemented with 10-μg/mL insulin and 100-μg/mL FSH throughout the culture period improved meiotic resumption rate and produced MII oocytes from caprine preantral follicles cultured in vitro. The MII rate was similar between in vivo and in vitro grown oocytes ≥110 μm. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of early thermal experience on pituitary-gonadal axis in female rats.

PubMed

Kurowicka, Beata; Gajewska, Alina; Franczak, Anita

2006-03-01

The reproductive system fully develops during postnatal stages of life, and as such it may be susceptible to environmental cues such as high temperature. Thus, the purpose of the study was to compare how exposure to 34 degrees Celsius ambient temperature affects pituitary-gonadal axis of immature and adult female rats. Three groups of females at proestrous or metaestrous (n=38) were used in the study. The females were housed in ambient temperature of 34 degrees Celsius (WR group, n=10) or room temperature (CR group, n=16) from birth to adulthood. The females from the third group were acclimated to 34 degrees Celsius as adults (WA group, n=12). In the WR group the onset of puberty was delayed in comparison to the CR group. The plasma PRL level was lower during proestrous and higher during metaestrous in the WR group compared to the CR group. During metaestrous, lower FSH and higher progesterone (P(4)) plasma concentrations were found in the WR females. No changes in LH and oestradiol (E(2)) plasma concentrations were demonstrated. Higher in vitro E(2) and lower P(4) secretions under FSH stimulation were observed in the WR follicles compared to those of the CR group. The WR group also demonstrated higher basal and LH-stimulated luteal in vitro secretion of P(4) than controls. Plasma LH and FSH concentrations during metaestrous were higher in WA females than in the WR group, but PRL level was lower. Follicles of the WA group were unresponsive to FSH with respect to steroid secretion. In addition, LH stimulated luteal E(2) secretion in this group. P(4) release by luteal cells was lower in the WA than in the WR group. We concluded that WR females differ from WA in reproductive system adjustments to rearing temperature and that early thermal experience is more effective in antagonizing the effect of high temperature than acclimation of adult females.

Cimetidine (Tagamet) is a reproductive toxicant in male rats affecting peritubular cells.

PubMed

França, L R; Leal, M C; Sasso-Cerri, E; Vasconcelos, A; Debeljuk, L; Russell, L D

2000-11-01

Cimetidine (Tagamet) is a potent histaminic H2-receptor antagonist, extensively prescribed for ulcers and now available without prescription. Cimetidine is a known testicular toxicant, but its mechanism of action remains uncertain. Rats were treated i.p. with cimetidine either at 50 mg/kg or 250 mg/kg body weight for 59 days. Accessory sex organ weights, but not testis weight, were significantly reduced in the high dose treated groups. FSH levels were significantly elevated in both treated groups, but testosterone levels were unchanged. A high degree of variability characterized testis histology, with most tubules appearing normal and some tubules (15-17%) partially lacking or devoid of germ cells. Morphometry showed that although seminiferous tubule volume was not significantly changed, the volume of peritubular tissue was reduced in the high dose group. There was extensive duplication of the basal lamina, lamina densa in both apparently normal spermatogenic tubules and severely damaged tubules. Apoptotic peritubular myoid cells were also found. TUNEL labeling confirmed extensive apoptotic cell death in peritubular cells, but revealed apoptosis of vascular smooth muscle. Given that 1) peritubular myoid cell apoptosis occurs in apparently normal tubules, that 2) basal lamina disorders are found, and that 3) peritubular cells are lost from the testis, it is suggested that the primary event in cimetidine-related damage is targeted to testicular smooth muscle cells. This is the first in vivo-administered toxicant to be described that targets myoid cells, resulting in abnormal spermatogenesis.

Pituitary response to a dopamine antagonist at different times of the day in normal women.

PubMed

Pérez-López, F R; González-Moreno, C M; Abós, M D; Andonegui, J A; Corvo, R H

1982-08-01

In order to determine whether or not pituitary responsiveness to the dopaminergic antagonist clebopride changes during the nyctohemeral cycle, 10 healthy women with regular cycles were given 1 mg of clebopride orally at 09.00 h and 24.00 h with at least a 5 day interval between each test. In addition, 5 of the women were given a placebo instead of clebopride at midnight to evaluate the spontaneous hormonal changes. During the 24.00 h test the women had significantly higher (P less than 0.05) mean TSH basal levels. Serum prolactin (Prl) increased significantly (P less than 0.001) after clebopride administration while these changes did not occur when placebo was used instead of clebopride at midnight. The Prl response to clebopride was qualitatively similar at 09.00 h and at 24.00 h. Clebopride given at midnight induced a significant increase (P less than 0.05) in serum TSH while this change did not occur when the drug was given at 09.00 h or when placebo was given at midnight. The administration of clebopride resulted in no discernible alternations in serum LH, FSH or GH in either the 09.00 h or the 24.00 h tests. Thus, Prl responses to clebopride were similar in the morning and at midnight, TSH significantly increased after clebopride at midnight whereas this did not occur when the drug was given in the morning, and no significant changes were induced in LH, FSH or GH at the times studied.

Antimüllerian hormone levels and antral follicle counts are not reduced compared with community controls in patients with rigorously defined unexplained infertility.

PubMed

Greenwood, Eleni A; Cedars, Marcelle I; Santoro, Nanette; Eisenberg, Esther; Kao, Chia-Ning; Haisenleder, Daniel J; Diamond, Michael P; Huddleston, Heather G

2017-12-01

To test the hypothesis that women with unexplained infertility demonstrate evidence of diminished ovarian reserve when compared with a population of community controls. Cross-sectional study. Multicenter university-based clinical practices. Study participants included 277 healthy, normo-ovulatory female partners with rigorously defined unexplained infertility randomly selected from a multicenter trial (Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation). Controls included 226 healthy, normo-ovulatory women not seeking treatment for fertility from a community-based cohort (Ovarian Aging study). Serum antimüllerian hormone (AMH) assay at a central laboratory, FSH, fasting serum metabolic testing, transvaginal ultrasonography for antral follicle counts (AFCs), anthropometric measurements. Average AMH, AFC, and AMH/AFC were compared between infertile and control women by age. Analyses of covariance compared these outcomes while controlling for confounders, including age, race, body mass index, smoking history, and study site. In our models, AMH, AFC, and AMH/AFC ovarian reserve indices did not differ between infertile women and community-based controls, after controlling for age, race, body mass index, smoking history, and study site. Currently utilized predictors of ovarian reserve do not discriminate women with rigorously defined unexplained infertility from healthy community-based women of similar demographic characteristics. Contrary to our hypothesis, among women with FSH in the normal range (≤12 IU/L), women with unexplained infertility did not show evidence of decreased ovarian reserve as measured by AMH and AFC. Ovarian reserve markers in isolation may not serve as predictors of future fertility. Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.

How Much Does AMH Really Vary in Normal Women?

PubMed Central

La Marca, Antonio; Grisendi, Valentina; Griesinger, Georg

2013-01-01

Anti-Mullerian Hormone (AMH) is an ovarian hormone expressed in growing follicles that have undergone recruitment from the primordial follicle pool but have not yet been selected for dominance. It is considered an accurate marker of ovarian reserve, able to reflect the size of the ovarian follicular pool of a woman of reproductive age. In comparison to other hormonal biomarkers such as serum FSH, low intra- and intermenstrual cycle variability have been proposed for AMH. This review summarizes the knowledge regarding within-subject variability, with particular attention on AMH intracycle variability. Moreover the impact of ethnicity, body mass index, and smoking behaviour on AMH interindividual variability will be reviewed. Finally changes in AMH serum levels in two conditions of ovarian quiescence, namely contraceptives use and pregnancy, will be discussed. The present review aims at guiding researchers and clinicians in interpreting AMH values and fluctuations in various research and clinical scenarios. PMID:24348558

Enclomiphene citrate stimulates testosterone production while preventing oligospermia: a randomized phase II clinical trial comparing topical testosterone.

PubMed

Wiehle, Ronald D; Fontenot, Gregory K; Wike, Jenny; Hsu, Kuang; Nydell, Jennifer; Lipshultz, Larry

2014-09-01

To determine the effect of enclomiphene citrate in men with secondary hypogonadism. Phase II clinical trial. Community dwelling men making visits to physician offices. Men with secondary hypogonadism. Oral administration of enclomiphene citrate or 1% topical T gel. Luteinizing hormone, FSH, T, and semen analysis. Treatment with enclomiphene citrate resulted in increased morning serum T, E2, and LH levels similar to those obtained with a topical T gel in men with secondary hypogonadism. Follicle-stimulating hormone and LH were increased with enclomiphene, and sperm counts were conserved. Enclomiphene citrate reverses the two hallmarks of secondary hypogonadism, namely, low serum total T and low or inappropriately normal LH while preserving sperm production. NCT01270841 (ClinicalTrials.gov Identifier NCT01270841). Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Restoration and maintenance of spermatogenesis by HCG therapy in patients with hypothalamo-hypophyseal damage.

PubMed

Levalle, O; Bokser, L; Pacenza, N; Aszenmil, G; Fiszlejder, L; Chervin, A; Guitelman, A

1984-01-01

Both gonadotropins are necessary to induce spermatogenesis in man and to recover hypophysectomized males. The patients who suffer from tumoral or traumatic hypothalamo-hypophyseal lesion use to have low endogenous gonadotropins (opposite to hypophysectomized patients), which can produce a minor involution of spermatogenesis. Three patients with postpubertal hypogonadotropic hypogonadism and oligozoospermia were studied. Two of them were operated on for chromophobous adenoma of pituitary, and the other patient had traumatic hypothalamo-hypophyseal lesion. The three patients were treated with 5000 IU HCG/week, associated with testosterone enanthate, in two cases and with bromocryptine in the remaining one. All the patients had normalized spermiogram, but when HCG was interrupted, the sperm count regressed to pretreatment levels in spite of the maintenance of treatment with testosterone or bromocryptine. Minimal amounts of FSH together the testosterone supplied by Leydig cell under the HCG stimulus, are able to recover and maintain the spermatogenesis in these patients.

Early cannabinoid exposure influences neuroendocrine and reproductive functions in male mice: I. Prenatal exposure.

PubMed

Dalterio, S; Steger, R; Mayfield, D; Bartke, A

1984-01-01

Maternal exposure to delta 9-tetrahydrocannabinol (THC), the major psychoactive constituent in marihuana, or to the non-psychoactive cannabinol (CBN) or cannabidiol (CBD) alters endocrine functions and concentrations of brain biogenic amines in their male offspring. Prenatal CBN exposure on day 18 of gestation resulted in decreased plasma FSH levels, testicular testosterone (T) concentrations, and seminal vesicles weights, but increased plasma levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) post-castration in adulthood. Prenatal exposure to THC significantly enhanced the responsiveness of the testes to intratesticular LH injection in vivo and tended to increase human chorionic gonadotropin (hCG)-stimulated T production by decapsulated testes in vitro. In the CBN-exposed mice, hCG-stimulated T production was enhanced, while CBD exposure had no effect. Prenatal THC exposure altered the negative feedback effects of exogenous gonadal steroids in castrated adults, with lower plasma T and FSH levels after 20 micrograms T than in castrated controls. In contrast, CBD-exposed mice had higher levels of LH in plasma post-castration. In CBN-exposed adults, two weeks post-castration the concentration of norepinephrine (NE) and dopamine (DA) in hypothalamus and remaining brain were reduced, while levels of serotonin (5-HT) and its metabolite, 5-HIAA, were elevated compared to that in castrated OIL-controls. Prenatal CBD-exposure also reduced NE and elevated 5-HT and 5-HIAA, but did not affect DA levels post-castration. Concentrations of brain biogenic amines were not influenced by prenatal THC exposure in the present study. A single prenatal exposure to psychoactive or non-psychoactive components of marihuana results in long term alterations in the function of the hypothalamo-pituitary-gonadal axis. Changes in the concentrations of brain biogenic amines may be related to these effects of prenatal cannabinoids on endocrine function in adult male mice.

Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy.

PubMed

Yeap, Bu B; Grossmann, Mathis; McLachlan, Robert I; Handelsman, David J; Wittert, Gary A; Conway, Ann J; Stuckey, Bronwyn Ga; Lording, Douglas W; Allan, Carolyn A; Zajac, Jeffrey D; Burger, Henry G

2016-08-15

This article, Part 1 of the Endocrine Society of Australia's position statement on male hypogonadism, focuses on assessment of male hypogonadism, including the indications for testosterone therapy. (Part 2 will deal with treatment and therapeutic considerations.) Key points and recommendations are:Pathological hypogonadism arises due to diseases of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) or testes (hypergonadotropic hypogonadism). It is a clinical diagnosis with a pathological basis, confirmed by hormone assays.Hormonal assessment is based on measurement of circulating testosterone, luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations. Measurement of sex hormone-binding globulin levels can be informative, but use of calculated free testosterone is not recommended for clinical decision making.Testosterone replacement therapy is warranted in men with pathological hypogonadism, regardless of age.Currently, there are limited data from high-quality randomised controlled trials with clinically meaningful outcomes to justify testosterone treatment in older men, usually with chronic disease, who have low circulating testosterone levels but without hypothalamic, pituitary or testicular disease.Obesity, metabolic syndrome and type 2 diabetes are associated with lowering of circulating testosterone level, but without elevation of LH and FSH levels. Whether these are non-specific consequences of non-reproductive disorders or a correctable deficiency state is unknown, but clear evidence for efficacy and safety of testosterone therapy in this setting is lacking.Glucocorticoid and opioid use is associated with possibly reversible reductions in circulating testosterone level, without elevation of LH and FSH levels. Where continuation of glucocorticoid or opioid therapy is necessary, review by an endocrinologist may be warranted.Changes in management as result of the position statement: Men with pathological hypogonadism should be identified and considered for testosterone therapy, while further research is needed to clarify whether there is a role for testosterone in these other settings.

Iron overload detection using pituitary and hepatic MRI in thalassemic patients having short stature and hypogonadism.

PubMed

Mousa, Amany A; Ghonem, Mohamed; Elhadidy, El Hadidy M; Azmy, Emad; Elbackry, Magda; Elbaiomy, Azza A; Elzehery, Rasha R; Shaker, Gehan A; Saleh, Omyma

2016-05-01

to assess the growth and pubertal development among a group of patients with β-Thalassemia Major (β-TM) and to evaluate the role of the pituitary gland and liver MRI signal intensity (SI) reduction in assessing and predicting the clinical severity of growth and pubertal dysfunctions. Thirty-eight patients with β-TM were examined and divided into two groups: Group I patients were of normal height and puberty and Group II patients had short statures and hypogonadism. Laboratory investigations included serum ferritin, LH, FSH, prolactin, TSH, and basal and dynamic growth hormones. Pituitary and liver MRIs were performed to assess the pituitary to fat (P/F) and liver to muscle (L/M) signal intensities (SI), respectively. Fifteen healthy and sex- and age-matched subjects were included as controls. Both patient groups had significantly elevated serum ferritin and significantly decreased prolactin and IGF1 compared to control subjects. Group II showed a significant reduction in LH, FSH, and IGF1 and a significant increase in ferritin in comparison with Group I and the control group, and it had a highly significant reduction in both P/F and L/M SI in comparison with Group I (p<0.001 and 0.008, respectively). The reduced P/F ratio was significantly correlated with FSH and LH, and a cutoff for a P/F ratio ≥0.94 was obtained to differentiate between Group I and II. MRI in conjunction with the P/F signal intensity ratio is a useful and noninvasive tool for the early diagnosis of pituitary iron overload.

Individualization of controlled ovarian stimulation in vitro fertilization using ovarian reserve markers.

PubMed

Grisendi, Valentina; La Marca, Antonio

2017-06-01

In assisted reproduction technologies (ART) the controlled ovarian stimulation (COS) therapy is the starting point from which a good oocytes retrieval depends. Treatment individualization is based on ovarian response prediction, which largely depends on a woman's ovarian reserve. Anti-Müllerian hormone (AMH) and antral follicle count (AFC) are considered the most accurate and reliable markers of ovarian reserve. A literature search was carried out for studies that addressed the ability of AMH and AFC to predict poor and/or excessive ovarian response in IVF cycles. According to the predicted response to ovarian stimulation (poor- normal- or high-response) is today possible not only to personalize pre-treatment counseling with the couple, but also to individualize the ovarian stimulation protocol, choosing among GnRH-agonists or antagonists for endogenous follicle-stimulating hormone (FSH) suppression and formulating the FSH starting dose most adequate for the single patients. In this review we discuss how to choose the best COS therapy for the single patient, on the basis of the markers-guided ovarian response prediction.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury.

PubMed

Hohl, Alexandre; Ronsoni, Marcelo Fernando; Debona, Rodrigo; Ben, Juliana; Schwarzbold, Marcelo Liborio; Diaz, Alexandre Paim; Thais, Maria Emília Rodrigues de Oliveira; Linhares, Marcelo Neves; Latini, Alexandra; Prediger, Rui Daniel; Pizzol, Felipe Dal; Walz, Roger

2014-01-01

Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. At least one hormonal level abnormality was demonstrated in 3.6-73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8-16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9-16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

Constitutively active follicle-stimulating hormone receptor enables androgen-independent spermatogenesis.

PubMed

Oduwole, Olayiwola O; Peltoketo, Hellevi; Poliandri, Ariel; Vengadabady, Laura; Chrusciel, Marcin; Doroszko, Milena; Samanta, Luna; Owen, Laura; Keevil, Brian; Rahman, Nafis A; Huhtaniemi, Ilpo T

2018-05-01

Spermatogenesis is regulated by the 2 pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). This process is considered impossible without the absolute requirement of LH-stimulated testicular testosterone (T) production. The role of FSH remains unclear because men and mice with inactivating FSH receptor (FSHR) mutations are fertile. We revisited the role of FSH in spermatogenesis using transgenic mice expressing a constitutively strongly active FSHR mutant in a LH receptor-null (LHR-null) background. The mutant FSHR reversed the azoospermia and partially restored fertility of Lhr-/- mice. The finding was initially ascribed to the residual Leydig cell T production. However, when T action was completely blocked with the potent antiandrogen flutamide, spermatogenesis persisted. Hence, completely T-independent spermatogenesis is possible through strong FSHR activation, and the dogma of T being a sine qua non for spermatogenesis may need modification. The mechanism for the finding appeared to be that FSHR activation maintained the expression of Sertoli cell genes considered androgen dependent. The translational message of our findings is the possibility of developing a new strategy of high-dose FSH treatment for spermatogenic failure. Our findings also provide an explanation of molecular pathogenesis for Pasqualini syndrome (fertile eunuchs; LH/T deficiency with persistent spermatogenesis) and explain how the hormonal regulation of spermatogenesis has shifted from FSH to T dominance during evolution.

Recombinant luteinizing hormone priming in multiple follicular stimulation for in-vitro fertilization in downregulated patients.

PubMed

Lisi, F; Caserta, D; Montanino, M; Berlinghieri, V; Bielli, W; Carfagna, P; Carra, M C; Costantino, A; Lisi, R; Poverini, R; Ciardo, F; Rago, R; Marci, R; Moscarini, M

2012-09-01

Follicle development is controlled amongst other factors by pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) that act in synergy in completing follicle maturation. Exogenous gonadotropins, combined with gonadotropin-releasing hormone agonists, have been successfully used in patients with ovulatory disorders undergoing assisted reproduction. There is some evidence of a beneficial role of androgens or LH administration before FSH stimulation. This study was designed to verify whether the addition of LH in the early follicular phase, in downregulated patients undergoing follicular stimulation for assisted reproduction, would add benefits in terms of general outcomes and pregnancy rates. We compared two groups of patients one of which was treated with recombinant FSH (rFSH) alone and the other with rFSH plus recombinant LH (rLH), in the early follicular phase only. The number of eggs recovered was higher in the group treated with FSH only; however, the number of embryos available at transfer was similar in the two groups and, more importantly, the number of Grades I and II embryos was higher in the group pretreated with LH. Similarly, although biochemical pregnancy rate and clinical pregnancy rates were similar in both groups, a beneficial role of LH priming was demonstrated by the higher implantation rate achieved in these patients.

Measurement Differences Between Two Immunoassay Systems for LH and FSH: A Comparison of Roche Cobas e601 vs. Abbott Architect i2000sr.

PubMed

Yin, Lianli; Tang, Yinghua; Chen, Xiang; Sun, Yifan

2018-03-01

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) regulate the growth and reproductive activity of gonadal tissue and determine the concentration of LH is essential for the prediction of ovulation. Collectively, FSH and LH are important measurements to ascertain the causes of infertility as well as diagnosing disorders such as polycystic ovary syndrome and pituitary and gonadal dysfunction. This study compares the correlation between LH and FSH measurements during examination with two different systems, Architect i2000sr (Abbott Laboratories; Lake Bluff, IL, USA) and Cobas e601 (Roche; Geneva, Switzerland), and assesses the differences between these systems. Serum analysis was performed for 95 patients using both the Cobas e601 and Architect i2000sr systems. The method used to compare the systems was Passing-Bablok regression analysis with a Bland-Altman agreement plot. Inter-rater agreement was analyzed using a concordance correlation coefficient. Architect i2000sr and Cobas e601 have strong correlations in their LH and FSH results. However, the Bland-Altman plot shows that LH and FSH measurements in Cobas e601 are about 1.31 times and 1.26 times higher than those in Architect i2000sr, respectively. Passing-Bablok regression analysis also shows significant proportional deviation between them. The difference between the test results for LH and FSH in Cobas e601 and Architect i2000sr indicate that the results from one system cannot be directly used to evaluate the other system.

Corifollitropin alfa versus recombinant follicle-stimulating hormone: an individual patient data meta-analysis.

PubMed

Griesinger, Georg; Boostanfar, Robert; Gordon, Keith; Gates, Davis; McCrary Sisk, Christine; Stegmann, Barbara J

2016-07-01

A meta-analysis was conducted of individual patient data (n = 3292) from three randomized controlled trials of corifollitropin alfa versus rFSH: Engage (150 µg corifollitropin alfa n = 756; 200 IU rFSH n = 750), Ensure (100 µg corifollitropin alfa n = 268; 150 IU rFSH n = 128), and Pursue (150 µg corifollitropin alfa n = 694; 300 IU rFSH n = 696). Women with regular menstrual cycles aged 18-36 and body weight >60 kg (Engage) or ≤60 kg (Ensure), or women aged 35-42 years and body weight ≥50 kg (Pursue), received a single injection (100 µg or 150 µg) of corifollitropin alfa (based on body weight and age) or daily rFSH. The difference (corifollitropin alfa minus rFSH) in the number of oocytes retrieved was +1.0 (95% CI: 0.5-1.5); vital pregnancy rate: -2.2% (95% CI: -5.3%-0.9%); ongoing pregnancy rate: -1.7% (95% CI: -4.7%-1.4%); and live birth rate: -2.0% (95% CI: -5.0%-1.1%). The odds ratio for overall OHSS was 1.15 (95% CI: 0.82-1.61), and for moderate-to-severe OHSS: 1.29 (95% CI: 0.81-2.05). A single dose of corifollitropin alfa for the first 7 days of ovarian stimulation is a generally well-tolerated and similarly effective treatment compared with daily rFSH. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Understanding the interactions of human follicle stimulating hormone with single-walled carbon nanotubes by molecular dynamics simulation and free energy analysis.

PubMed

Mahmoodi, Yasaman; Mehrnejad, Faramarz; Khalifeh, Khosrow

2018-01-01

Interactions of carbon nanotubes (CNTs) and blood proteins are of interest for nanotoxicology and nanomedicine. It is believed that the interactions of blood proteins and glycoproteins with CNTs may have important biological effects. In spite of many experimental studies of single-walled carbon nanotubes (SWCNT) and glycoproteins with different methods, little is known about the atomistic details of their association process or of structural alterations occurring in adsorbed glycoproteins. In this study, we have applied molecular dynamics simulation to investigate the interaction of follicle stimulating hormone (hFSH) with SWCNT. The aim of this work is to investigate possible mechanisms of nanotoxicity at a molecular level. We present details of the molecular dynamics, structure, and free energy of binding of hFSH on the surface of SWCNT. We find that hFSH in aqueous solution strongly adsorbs onto SWCNT via their concave surface as evidenced by high binding free energies for residues in both protein subunits. It was found that hydrophobic, π-cation, and π-π stacking interactions are the main driving forces for the adsorption of the protein at the nanotube surface.

Clomifene citrate or low-dose FSH for the first-line treatment of infertile women with anovulation associated with polycystic ovary syndrome: a prospective randomized multinational study.

PubMed

Homburg, R; Hendriks, M L; König, T E; Anderson, R A; Balen, A H; Brincat, M; Child, T; Davies, M; D'Hooghe, T; Martinez, A; Rajkhowa, M; Rueda-Saenz, R; Hompes, P; Lambalk, C B

2012-02-01

Clomifene citrate (CC) is accepted as the first-line method for ovulation induction (OI) in patients with polycystic ovary syndrome (PCOS) associated with infertility owing to anovulation. Low-dose FSH has been reserved for women failing to conceive with CC. In this RCT, we tested the hypothesis that pregnancy rate (PR) and live birth rates (LBR) are higher after OI with low-dose FSH than with CC as first-line treatment. Infertile women (<40 years old) with PCOS-related anovulation, without prior OI treatment, attending 10 centres in Europe/South America were randomized to OI with either CC (50-150 mg/day for 5 days) or FSH (starting dose 50 IU) for up to three treatment cycles. The primary outcome was clinical PR. Patients (n = 302) were randomized to OI with FSH (n = 132 women; 288 cycles) or CC (n = 123; 310 cycles). Per protocol analysis revealed that reproductive outcome was superior after OI with FSH than with CC with respect to PR per first cycle [30 versus 14.6%, respectively, 95% confidence interval (CI) 5.3-25.8, P = 0.003], PR per woman, (58 versus 44% of women, 95% CI 1.5-25.8, P = 0.03), LBR per woman (52 versus 39%, 95% CI 0.4-24.6, P = 0.04), cumulative PR (52.1 versus 41.2%, P = 0.021) and cumulative LBR (47.4 versus 36.9%, P = 0.031), within three cycles of OI. Pregnancies and live births are achieved more effectively and faster after OI with low-dose FSH than with CC. This result has to be balanced by convenience and cost in favour of CC. FSH may be an appropriate first-line treatment for some women with PCOS and anovulatory infertility, particularly older patients.

Reanalysis of the preoptic afferents and efferents involved in the surge of LH, FSH and prolactin release in the proestrous rat.

PubMed

Kimura, F; Kawakami, M

1978-01-01

In order to elucidate neural pathways concerned with the proestrous surge of LH, FSH and prolactin (Prl) release, brain transection or lesion was made acutely under ether anesthesia between 12.00 and 14.00 h of proestrus, and electrochemical stimulation was done under anesthesia with pentobarbital sodium (31.5 mg/kg b.w.) injected at 13.45 h. Transection which interrupted the connection of septum (SEPT), diagonal band of Broca (DBB) and bed nucleus of stria terminalis (BST) with the preoptic-suprachiasmatic area interfered with ovulation and surge of release of all 3 hormones. Isolation of the basal part of the suprachiasmatic area, including the suprachiasmatic nucleus (SCH), blocked ovulation also. Bilateral lesions in the medial preoptic area (MPO) with platinium-iridium electrode blocked ovulation and the surge of LH and Prl release, but not of FSH. Lesions in the SCH blocked ovulation and the surge of LH, but not of FSH and Prl. In the rat with acute isolation of the basal part of the suprachiasmatic area and SCH, stimulation of the MPO failed to induce ovulation and LH release, but was followed by FSH release. Prl release was not inhibited as in the intact rat. When the rat had the antero-SCH cut, stimulation of the SCH induced LH release but not FSH, and the inhibition on Prl release was pronounced. These findings offer evidence that the limbic-forebrain inputs are necessary for the preoptic integration in order to stimulate the proestrous surge of LH, FSH and Prl release. Furthermore, it is possible that separate pathways from the preoptic area to the medial basal hypothalamus are concerned in the stimulation of individual hormones--a restricted route for LH which may pass through the SCH, a diffuse one for FSH which may pass through either the SCH or anterior hypothalamic area, and a relatively diffuse one for Prl which may pass outside the SCH.

Prevention of microbial hazard on fresh-cut lettuce through adoption of food safety and hygienic practices by lettuce farmers.

PubMed

Oyinlola, Lateefah A; Obadina, Adewale O; Omemu, Adebukunola M; Oyewole, Olusola B

2017-01-01

Lettuce is consumed raw in salads and is susceptible to microbial contamination through environment, agricultural practices, and its morphology, thus, a potential vehicle for food-borne illness. This study investigated the effect of adoption of food safety and hygienic practices by lettuce farmers on the microbial safety of field sourced lettuce in Lagos State, Nigeria. Ten structured questionnaires were administered randomly to 10 lettuce farmers to assess food safety and hygienic practices (FSH). Two farmers who practice FSH and two farmers who do not practice NFSH were finally used for this study. Samples of ready-to-harvest lettuce, manure applied, and irrigation water were obtained for a period of five months (August - December 2013) and analyzed for total plate count (TPC), total coliform count (TCC), Escherichia coli, Listeria spp., Salmonella spp., and Shigella spp . counts. Result of microbial analyses of lettuce samples was compared with international microbiological specification for ready-to-eat foods. Results showed that the range of TPC on lettuce was 6.00 to 8.11 LogCFU/g from FSH farms and TPC of lettuce samples from NFSH farms ranged from 6.66 to 13.64 LogCFU/g. 1.49 to 4.85LogCFU/g were TCC ranges from lettuce samples obtained from FSH farms while NFSH farms had TCC ranging between 3.95 and 10.86 LogCFU/g, respectively. The range of isolated pathogen count on lettuce from FSH and NFSH farms exceeded the international safety standard; there was a significant difference in the microbial count of lettuce from FSH farms and NFSH farms. This study concludes that the lettuce samples obtained did not pass the international microbial safety standards. FSH compliance is a major determinant of the microbial safety of lettuce. Hence, the institution of FSH on farm to improve microbial safety of lettuce produced for public consumption is emphasized.

Economic evaluation of highly purified human menopausal gonadotropin versus recombinant human follicle-stimulating hormone in fresh and frozen in vitro fertilization/intracytoplasmic sperm-injection cycles in Sweden

PubMed Central

Wex, Jaro; Abou-Setta, Ahmed M

2013-01-01

Gonadotropin-releasing hormone-analog type, fertilization method, and number of embryos available for cryopreservation should be incorporated into economic evaluations of highly purified human menopausal gonadotropin (HP-hMG) and recombinant human follicle-stimulating hormone (r-hFSH), as they may affect treatment costs. We searched for randomized trials and meta-analyses comparing HP-hMG and r-hFSH. Meta-analysis showed no significant difference in live births (odds ratio 0.82, 95% confidence interval [CI] 0.66–1.01), but a greater number of oocytes with r-hFSH (mean difference [MD] 1.96, 95% CI 1.02–2.90). Using a cost-minimization model for Sweden, accounting for embryo availability, survival following thawing, and patient dropout, we simulated patients individually for up to three cycles. R-hFSH was found to be cost-saving, at 2,767 kr (95% CI 1,580–4,057) per patient (€315 or $411); baseline savings were 6.43% of the total HP-hMG cost. In fresh cycles only, the savings for r-hFSH were 1,752 kr (95% CI 48–3,658) per patient (€200 or $260). In univariate sensitivity analyses, savings were obtained until the price of r-hFSH increased by 30% or the dosage of HP-hMG decreased by 38%–62% of baseline value. In probabilistic sensitivity analysis, r-hFSH was cost-saving in 100% of the simulated cohort per patient and in 85% per live birth; the respective percentages for fresh cycles only were 97.3% and 73.1%. In conclusion, a greater number of oocytes with r-hFSH allows for more frozen embryo transfers, thereby reducing overall treatment cost. PMID:23966798

Potential role of follicle-stimulating hormone (FSH) and transforming growth factor (TGFβ1) in the regulation of ovarian angiogenesis.

PubMed

Kuo, Shih-Wei; Ke, Ferng-Chun; Chang, Geen-Dong; Lee, Ming-Ting; Hwang, Jiuan-Jiuan

2011-06-01

Angiogenesis occurs during ovarian follicle development and luteinization. Pituitary secreted FSH was reported to stimulate the expression of endothelial mitogen VEGF in granulosa cells. And, intraovarian cytokine transforming growth factor (TGF)β1 is known to facilitate FSH-induced differentiation of ovarian granulosa cells. This intrigues us to investigate the potential role of FSH and TGFβ1 regulation of granulosa cell function in relation to ovarian angiogenesis. Granulosa cells were isolated from gonadotropin-primed immature rats and treated once with FSH and/or TGFβ1 for 48 h, and the angiogenic potential of conditioned media (granulosa cell culture conditioned media; GCCM) was determined using an in vitro assay with aortic ring embedded in collagen gel and immunoblotting. FSH and TGFβ1 increased the secreted angiogenic activity in granulosa cells (FSH + TGFβ1 > FSH ≈ TGFβ1 >control) that was partly attributed to the increased secretion of pro-angiogenic factors VEGF and PDGF-B. This is further supported by the evidence that pre-treatment with inhibitor of VEGF receptor-2 (Ki8751) or PDGF receptor (AG1296) throughout or only during the first 2-day aortic ring culture period suppressed microvessel growth in GCCM-treated groups, and also inhibited the FSH + TGFβ1-GCCM-stimulated release of matrix remodeling-associated gelatinase activities. Interestingly, pre-treatment of AG1296 at late stage suppressed GCCM-induced microvessel growth and stability with demise of endothelial and mural cells. Together, we provide original findings that both FSH and TGFβ1 increased the secretion of VEGF and PDGF-B, and that in turn up-regulated the angiogenic activity in rat ovarian granulosa cells. This implicates that FSH and TGFβ1 play important roles in regulation of ovarian angiogenesis during follicle development. Copyright © 2010 Wiley-Liss, Inc.

A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty

PubMed Central

Arroyo, Armando; Pernasetti, Flavia; Vasilyev, Vyacheslav V.; Amato, Paula; Yen, Samuel S. C.; Mellon, Pamela L.

2010-01-01

Summary We report a 28-year-old-female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS −0.86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X-ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit-1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue. PMID:12153609

Assessment LOPU-IVF in Japanese sika deer (Cervus nippon nippon) and application to Vietnamese sika deer (Cervus nippon pseudaxis) a related subspecies threatened with extinction.

PubMed

Locatelli, Y; Hendriks, A; Vallet, J-C; Baril, G; Duffard, N; Bon, N; Ortiz, K; Scala, C; Maurel, M-C; Mermillod, P; Legendre, X

2012-12-01

In mammals, recovery of oocytes by laparoscopic ovum pick-up (LOPU) coupled with in vitro production (IVP) of embryos represents a promising strategy for both amplification and genetic management of sparse animals from captive endangered wild species. As integrated technique developed mainly for domestic livestock, LOPU-IVP requires several studies to set up protocols for follicular stimulation or optimization of IVP before envisaging successful transposition to wild species. In deer, many endangered subspecies would be potentially concerned by applying such an approach using common subspecies for protocols optimization. The aim of the present study was to assess efficiency of follicle stimulation using ovine FSH (oFSH) for recovery of oocytes by LOPU in common sika deer (Cervus nippon nippon) before transposition of an optimized methodology for IVP of embryos from endangered Vietnamese sika deer hinds (Cervus nippon pseudaxis). In common sika deer, two doses of oFSH (0.25 and 0.5 U) and two frequencies of administration (12 and 24 h) were compared by monitoring of subsequent ovarian response, quality of oocytes recovered by LOPU, and in vitro developmental competence. In a first experiment, the dose of oFSH administered did not significantly affect the total number of follicles aspirated per hind per session (8.6 ± 1.0 vs. 8.2 ± 1.6 with 0.5 vs. 0.25 U oFSH, respectively; not significant). In a second experiment, frequency of 0.25 U oFSH administration did not affect ovarian response. Efficiency of IVP determined on blastocysts rates after in vitro maturation, fertilization, and development in oviduct epithelial cells coculture was increased when FSH was administered at 12-h intervals. Immune response after several follicular stimulations was detected against exogenous oFSH in plasma from the majority of sika deer hinds but was not associated with decreased ovarian response. When 0.25 U oFSH was administered at 12-h intervals to Vietnamese sika deer (N = 4), good quality cumulus oocyte complexes with complete and compact cumulus investments were recovered allowing a high cleavage rate after in vitro maturation and fertilization. Development to the blastocyst stage occurred in a high proportion (30% of oocytes) after coculture with ovine epithelial cells allowing cryobanking of transferable embryos from Vietnamese sika deer. These results confirm that LOPU-IVF after ovarian stimulation with oFSH may be a successful tool for cryobanking transferable embryos from endangered sika deer subspecies. Copyright © 2012 Elsevier Inc. All rights reserved.

Hypoandrogenism in association with diminished functional ovarian reserve.

PubMed

Gleicher, Norbert; Kim, Ann; Weghofer, Andrea; Kushnir, Vitaly A; Shohat-Tal, Aya; Lazzaroni, Emanuela; Lee, Ho-Joon; Barad, David H

2013-04-01

Is diminished functional ovarian reserve (DFOR) associated with low androgen levels? Low androgen levels are associated with DFOR at all ages. Androgen supplementation via dehydroepiandrosterone (DHEA) has been reported to improve functional ovarian reserve (FOR); pregnancy rates in IVF cycles are associated with how well DHEA converts to testosterone (T); and androgen effects through the androgen receptor have been demonstrated in mice to beneficially affect early stages of follicle maturation. In a controlled cohort study we investigated consecutive women presenting to our center with two forms of DFOR, premature ovarian aging/occult primary ovarian insufficiency (POA/OPOI) and physiologic diminished ovarian reserve (DOR). As controls for POA/OPOI patients, infertile women with normal age-specific FOR were recruited. The study involved 140 women with POA/OPOI, defined as age <38 years and abnormally low FOR by age-specific FSH and/or anti-Müllerian hormone (AMH), 166 women with DOR, defined as women age >40 years. Forty-nine control patients <38 years demonstrated normal FOR by FSH and/or AMH. In all three patient groups dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS), total testosterone (TT) and free testosterone (FT) at the time of initial presentation to our fertility center were assessed. In a small subgroup of women early morning cortisol levels were also assessed. DHEAS marginally varied between the three groups (P = 0.04), with older women with DOR actually demonstrating higher levels than controls (P = 0.03). TT differed between the three groups more profoundly (P = 0.005), with women with POA/OPOI demonstrating significantly lower levels than controls (P = 0.009). Adjustment for body mass index, age and race in principle maintained observed differences in TT between groups, while adjustment for FMR1 (fragile X mental retardation 1) genotypes/sub-genotypes eliminated all differences. All three patient groups demonstrated low morning cortisol levels. While results support lower androgen levels in women with DOR, and even more so in women with POA/OPOI, presented data should be viewed as preliminary, considering the known variability of androgen levels and the small number of women in whom morning cortisol levels were available. Especially at young ages DFOR appears associated with significant hypoandrogenism (low T) in comparison with young control patients with normal FOR, raising the question whether this hypoandrogenism originates in adrenals or ovaries. POA/OPOI, thus, phenotypically mimics the polycystic ovary syndrome, where similar questions arise, though in regard to hyperandrogenism. This research was supported by the Foundation for Reproductive Medicine, a not-for-profit medical research foundation and intramural funds from the Center for Human Reproduction. N.G. and D.H.B are members of the Board of the Foundation for Reproductive Medicine. N.G., A.W. and D.H.B. received research support, lecture fees and travel support from a variety of pharmaceutical and medical device companies, none in any way related to the issues discussed in this manuscript. N.G. and D.H.B. are listed as co-inventors on two, already granted US user patents, which claim therapeutic benefits from DHEA supplementation in women with DFOR and DOR: both authors are also listed on additional pending patents in regard to DHEA supplementation and on pending patents, claiming diagnostic and therapeutic benefits from the determination of CGG repeats on the FMR1 gene. N.G. is the owner of the Center for Human Reproduction, where this research was performed.

Vitamin D alters genes involved in follicular development and steroidogenesis in human cumulus granulosa cells.

PubMed

Merhi, Zaher; Doswell, Angela; Krebs, Kendall; Cipolla, Marilyn

2014-06-01

Vitamin D deficiency is common among reproductive-aged women and has a role in female reproduction. This study evaluated the role of 1,25-dihydroxyvitamin D3 (vit D3) in ovarian follicular development and steroidogenesis by using a human granulosa cell (GC) model. Fifty-four women who underwent in vitro fertilization were enrolled. Follicular fluid (FF) and mural and cumulus GCs were collected from small and large follicles. In separate experiments, primary cumulus GCs were cultured with or without vit D3 followed by RT-PCR for mRNA expression levels. The effect of recombinant anti-Mullerian hormone (AMH) on nuclear localization of phospho-Smad 1/5/8 was evaluated in the presence or absence of vit D3 by using immunofluorescence. 25-Hydroxyvitamin D levels in FF as well as cell culture media AMH, progesterone, and estradiol (E2) concentrations were determined by ELISA and RIA. The following were measured: 1) mRNA expression levels; 2) 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme activity; 3) FSH-induced aromatase mRNA and E2 production; and 4) nuclear localization of phospho-Smad 1/5/8. In a multivariate analysis, 25 OH-D levels in FF negatively correlated with AMH and AMH receptor (AMHR)-II mRNA levels in cumulus GCs of small follicles. Compared with women with replete 25-hydroxyvitamin D levels in FF, those with insufficient/deficient levels had a 2-fold increase in AMHR-II mRNA levels in cumulus GCs of small follicles (P = .02). Treatment with vit D3 caused a decrease in AMHR-II and FSH receptor mRNA but an increase in 3-βHSD mRNA levels compared with control (P < .05). Vit D3 enhanced 3-βHSD enzyme activity as assessed by increasing progesterone release; however, vit D3 did not affect FSH-induced aromatase mRNA and E2 production, but it decreased the phosphorylation of Smad 1/5/8 and its nuclear localization. These data suggest that vit D3 alters AMH signaling and steroidogenesis in human cumulus GCs, possibly reflecting a state of GC luteinization potentiation.

Effect of noise stress on male rat fertility, and the protective effect of vitamins C and E on its potential effect.

PubMed

Fathollahi, Ali; Jasemi, Majid; Saki, Ghasem

2013-03-01

To evaluate the effect of noise on the fertility of male rats, and to assess the effect of vitamins C and E on its potential effect. Forty adult male rats were randomly divided into five equal groups. Group 1 (control) was not exposed to noise. Groups 2-5 were exposed to noise of 90-130 dB and 300-350 Hz from 19.00 to 07.00 h every day for 50 days; group 2 received vitamin C and group 3 received vitamin E. Group 4 received vitamins C and E concomitantly and group 5 received no vitamins. After 50 days, the serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH) and testosterone were measured. Each rat was then left for 1 week with three female rats, for mating. Pregnant females were killed humanely after 19 days of pregnancy and evaluated for the presence and number of viable, dead and absorbed fetuses. The mean serum FSH level was statistically significantly different between the control and groups 2 (P < 0.05) and 5 (P < 0.001). The mean serum LH level differed significantly between the control and groups 2 (P = 0.05), 3 (P < 0.05) and 5 (P < 0.001). The mean serum testosterone level was significantly different between the control and group 5 (P < 0.001). Serum FSH, LH and testosterone levels in group 5 were significantly different from all the others (P < 0.001). The pregnancy rates in females mated with groups 1 and 5 were statistically different (P < 0.05). Comparing groups 1-4, there was no difference in the occurrence of abnormal pregnancy (P > 0.05), but group 5 values were significantly different from the others (P < 0.001). These data strongly suggest that noise stress has a significant effect on the fertility of male rats.

Anti-Mullerian Hormone: A Marker of Ovarian Reserve and its Association with Polycystic Ovarian Syndrome.

PubMed

Verma, Anil Kumar; Rajbhar, Sarita; Mishra, Jyoti; Gupta, Mayank; Sharma, Mratunjai; Deshmukh, Geeta; Ali, Wahid

2016-12-01

Anti-Mullerian Hormone (AMH) is a useful endocrine marker for assessing the ovarian reserve. AMH serum level reflects the number of follicles that have made the transition from the primordial pool into the growing follicle pool, and it is not controlled by gonadotropins. The present study was conducted to correlate serum AMH levels with Polycystic Ovarian Syndrome (PCOS) and type of treatment protocol. Serum AMH levels were performed in the early follicular phase (on 2 nd day of menstrual cycle) both in infertile females including PCOS and control women. The results were analyzed in relation to age, Body Mass Index (BMI), ovarian volume, serum Follicle Stimulating Hormone (FSH) levels, Antral Follicle Count (AFC), type of treatment protocols and also in association with PCOS patients. The serum levels of AMH were measured in all the participants on 2 nd day of menstrual cycle using ultra sensitive Enzyme Linked Immunosorbent Assay (ELISA). The plasma AMH levels were significantly higher in women with polycystic ovarian syndrome. The significant association was seen between FSH and AFC with AMH. However, no significant association was observed between AMH levels with age, BMI, ovarian volume and type of treatment protocols. The serum AMH measurement was significantly higher in PCOS patients. No association with type of treatment protocol was obtained.

Relation between sex hormones and hepatocellular carcinoma.

PubMed

El Mahdy Korah, T; Abd Elfatah Badr, E; Mohamed Emara, M; Ahmed Samy Kohla, M; Gamal Saad Michael, G

2016-11-01

Males have higher incidence of hepatocellular carcinoma (HCC) than females. Sex hormones may be a risk factor. The aim was to determine the levels of sex hormones in male and female patients with HCC and cirrhosis versus controls and its possible relationship with HCC. This study was conducted on 90 subjects divided into 40 patients with HCC, 30 patients with liver cirrhosis and 20 apparently healthy subjects complete blood picture, liver function tests. Determination of AFP levels and hormonal assay of oestrogen, progesterone, total testosterone, prolactin, FSH and LH were performed on all subjects. Total testosterone levels were significantly decreased in the two patients groups compared with controls. While oestrogen levels were significantly decreased in the HCC group in comparison with other two groups, prolactin levels were significantly decreased in the HCC group compared with the liver cirrhosis group and increased in the liver cirrhosis group when compared to controls. FSH and LH levels were significantly increased in the HCC group when compared to controls. There is no significant correlation between sex hormones assay and both the size of HCC and degree of cirrhosis in both patient groups. It is concluded that there is no strong relation between sex hormones and HCC when the study was carried out on the levels of sex hormones in patients with HCC. © 2016 Blackwell Verlag GmbH.

Patient preference for a long-acting recombinant FSH product in ovarian hyperstimulation in IVF: a discrete choice experiment.

PubMed

van den Wijngaard, L; Rodijk, I C M; van der Veen, F; Gooskens-van Erven, M H W; Koks, C A M; Verhoeve, H R; Mol, B W J; van Wely, M; Mochtar, M H

2015-02-01

What factors or attributes of a long-acting recombinant FSH (rFSH) or daily-administrated rFSH influence women's preferences IVF? Patients' preferences for rFSH products are primary influenced by the attribute 'number of injections', but a low 'number of injections' is exchanged for a high 'number of injections' at a 6.2% decrease in 'risk of cycle cancellation due to low response' and at a 4.5% decrease in 'chance of OHSS'. Injections of long-acting rFSH have been claimed to be preferred over daily-administrated rFSH injections, but patient preference studies to underpin this assumption have not been performed. A discrete choice experiment (DCE) was created to assess women's preference for long-acting or daily-administrated rFSH under varying attributes of efficiency, safety and burden. The selected attributes were the 'total number of injections', 'chance of ovarian hyperstimulation syndrome (OHSS)' and the 'risk of cycle cancellation due to low response'. Questionnaires were handed out during information gathering sessions in one academic hospital and two teaching hospitals in The Netherlands between April 2011 and April 2012. Women at the start of their first IVF treatment were asked to participate in this patient preference study. Participation was voluntary. We analysed the data by using mixed logit models to estimate the utility of each attribute. Questionnaires (n = 125) were handed out with a response rate of 77% (97/125). Four respondents did not complete the questionnaire. Hence, there were 93 questionnaires available for analysis. All attributes significantly influenced women's preference. Overall, the lower 'number of injections' was preferred above the higher 'number of injections' (mean coefficient 1.25; P < 0.001), while an increase of 1% in 'chance of OHSS' or 5% 'risk of cycle cancellation due to low response' was non-preferred (mean coefficients -0.31 and -0.24, respectively, P < 0.01). The majority of respondents was willing to trade-off a lower 'number of injections' for a higher 'number of injections' when gaining a 6.2% reduction in 'cycle cancellation due to low response', or a 4.5% reduction in 'chance of OHSS'. The generalizability of this DCE is limited in time-span. Women may choose differently when they have previous experience with long-acting rFSH, or when they have to pay for the medication, hospital visits and treatments themselves. The results of this DCE helps us to understand the trade-off women make in their preference for a long-acting rFSH product or a daily-administrated rFSH product in IVF and may support doctors when counselling patients. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Endocrine effects of the tyrosine kinase inhibitor vandetanib in patients treated for thyroid cancer.

PubMed

Brassard, Maryse; Neraud, Barbara; Trabado, Séverine; Salenave, Sylvie; Brailly-Tabard, Sylvie; Borget, Isabelle; Baudin, Eric; Leboulleux, Sophie; Chanson, Philippe; Schlumberger, Martin; Young, Jacques

2011-09-01

The purpose of the study was to assess the endocrine effects of vandetanib, a multikinase inhibitor targeting RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor, in 39 patients with progressive thyroid cancer included in two randomized placebo-controlled trials using vandetanib 300 mg/d. Endocrine samplings were performed at baseline and then every 6 months. We compared differences in endocrine parameters between baseline and on vandetanib therapy or placebo. During vandetanib treatment, several changes were observed. 1) Calcium (P = 0.0004) and vitamin D (P = 0.001) mean replacement doses were increased; calcium level remained unchanged, but serum 25(OH) vitamin D level decreased (P = 0.001); and serum PTH (P = 0.01) and 1,25(OH)(2) vitamin D (P = 0.01) levels increased, suggesting a decreased intestinal absorption of vitamin D or lack of sun exposure as a result of photosensitization. 2) l-T(4) doses were increased (P < 0.0001) to maintain serum TSH within the normal range. 3) In male patients, total testosterone (P = 0.048), bioavailable testosterone (P = 0.03), and SHBG (P = 0.02) levels increased. Serum inhibin B decreased (P = 0.02) and stimulated FSH increased (P = 0.006), suggesting a Sertoli cells insufficiency. 4) Cortisol level increased (P = 0.007) as well as ACTH level (P = 0.03) and cortisol-binding globulin (P = 0.02), but free urinary cortisol levels remained in the normal range. None of these changes were observed in patients randomized to the placebo arm. In patients with locally advanced or metastatic thyroid cancer, the tyrosine kinase inhibitor vandetanib has several endocrine effects. Thyroid hormone, calcium, and vitamin D analog requirements increased, but consequences of the biological alterations on phosphocalcic metabolism and gonadotrope and adrenal functions are unknown.

Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation.

PubMed

Zandvliet, Anthe S; Prohn, Marita; de Greef, Rik; van Aarle, Frank; McCrary Sisk, Christine; Stegmann, Barbara J

2016-07-01

The aim of the present study was to characterize the pharmacokinetic profile of corifollitropin alfa and examine the relationships between dose, intrinsic factors [body weight, body mass index (BMI), age and race] and corifollitropin alfa pharmacokinetics. Data from five phase II and III clinical trials of corifollitropin alfa were evaluated. All subjects included in the analysis received 60 - 180 μg corifollitropin alfa for controlled ovarian stimulation in a gonadotrophin-releasing hormone antagonist protocol followed by daily recombinant follicle stimulating hormone (rFSH) from day 8 onwards. Serum corifollitropin alfa levels (across the entire range of treatment) and total follicle stimulating hormone immunoreactivity levels (up to the start of rFSH treatment) were indicators of drug exposure. The analyses were performed using a nonlinear mixed-effects modelling approach. A total of 2630 subjects were treated with corifollitropin alfa, and 2557 subjects were evaluable for analysis. Body weight, BMI and race (Asian and Black vs. Caucasian) were significant determinants of corifollitropin alfa exposure. Dose-normalized corifollitropin alfa exposure was ~89% higher in women with a body weight of 50 kg vs. 90 kg (in subjects with a similar BMI of 24 kg m(-2) ); 14% higher in women with a BMI of 18 kg m(-2) vs. 32 kg m(-2) (provided they were of similar body weight); and ~15.7% lower in Asian subjects and 13% higher in Black subjects vs. Caucasian subjects. Body weight was the major determinant of corifollitropin alfa exposure; BMI and race (Asian and Black) were also determinants but to a lesser extent and without associated effects on clinical outcomes. Corifollitropin alfa dose adjustment is indicated, based on body weight but not for BMI or race. These recommendations are consistent with the product label. © 2016 The British Pharmacological Society.

Correlation between location of transposed ovary and function in cervical cancer patients who underwent radical hysterectomy.

PubMed

Yoon, Aera; Lee, Yoo-Young; Park, Won; Huh, Seung Jae; Choi, Chel Hun; Kim, Tae-Joong; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo

2015-05-01

The study investigated the association between the location of transposed ovaries and posttreatment ovarian function in patients with early cervical cancer (IB1-IIA) who underwent radical hysterectomy and ovarian transposition with or without adjuvant therapies. Retrospective medical records were reviewed to enroll the patients with early cervical cancer who underwent ovarian transposition during radical hysterectomy at Samsung Medical Center between July 1995 and July 2012. Serum follicle-stimulating hormone (FSH) level was used as a surrogate marker for ovarian function. Twenty-one patients were enrolled. The median age and body mass index (BMI) were 31 years (range, 24-39 years) and 21.3 kg/m² (range, 17.7-31.2 kg/m²), respectively. The median serum FSH level after treatment was 7.9 mIU/mL (range, 2.4-143.4 mIU/mL). The median distance from the iliac crest to transposed ovaries on erect plain abdominal x-ray was 0.5 cm (range, -2.7 to 5.2 cm). In multivariate analysis, posttreatment serum FSH levels were significantly associated with the location of transposed ovaries (β = -8.1, P = 0.032), concurrent chemoradiation (CCRT) as an adjuvant therapy (β = 71.08, P = 0.006), and BMI before treatment (underweight: β = -59.93, P = 0.05; overweight: β = -40.62, P = 0.041). Location of transposed ovaries, adjuvant CCRT, and BMI before treatment may be associated with ovarian function after treatment. We suggest that ovaries should be transposed as highly as possible during radical hysterectomy to preserve ovarian function in young patients with early cervical cancer who might be a candidate for adjuvant CCRT and who have low BMI before treatment.

Maternal sympathetic stress impairs follicular development and puberty of the offspring.

PubMed

Barra, Rafael; Cruz, Gonzalo; Mayerhofer, Artur; Paredes, Alfonso; Lara, Hernán E

2014-08-01

Chronic cold stress applied to adult rats activates ovarian sympathetic innervation and develops polycystic ovary (PCO) phenotype. The PCO syndrome in humans originates during early development and is expressed before or during puberty, which suggests that the condition derived from in utero exposure to neural- or metabolic-derived insults. We studied the effects of maternal sympathetic stress on the ovarian follicular development and on the onset of puberty of female offspring. Timed pregnant rats were exposed to chronic cold stress (4 °C, 3 h/daily from 1000 to 1300 h) during the entire pregnancy. Neonatal rats exposed to sympathetic stress during gestation had a lower number of primary, primordial, and secondary follicles in the ovary and a lower recruitment of primary and secondary follicles derived from the primordial follicular pool. The expression of the FSH receptor and response of the neonatal ovary to FSH were reduced. A decrease in nerve growth factor (NGF) mRNA was found without change in the low-affinity NGF receptor. The FSH-induced development of secondary follicles was decreased. At puberty, estradiol plasma levels decreased without changes in LH plasma levels. Puberty onset (as shown by the vaginal opening) was delayed. Ovarian norepinephrine (NE) was reduced; there was no change in its metabolite, 3-methoxy-4-hydroxyphenylglycol, in stressed rats and no change in NE turnover. The changes in ovarian NE in prepubertal rats stressed during gestation could represent a lower development of sympathetic nerves as a compensatory response to the chronically increased NE levels during gestation and hence participate in delaying reproductive performance in the rat. © 2014 Society for Reproduction and Fertility.

Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

PubMed Central

2012-01-01

Background Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA) were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and molecular pathways mediating ESCC development and provide information potentially useful in designing novel therapeutic interventions for this tumor type. PMID:22280838

Pretreatment and co-administration of oral anti-diabetic agent with clomiphene citrate or rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome.

PubMed

Begum, Mosammat Rashida; Akhter, Sayeba; Ehsan, Mariya; Begum, Mosammat Shahina; Khan, Farzana

2013-05-01

The objective of this study was to explore the result of pretreatment and concomitant use of metformin with clomiphene citrate (CC) and rFSH for ovulation induction in clomiphene-citrate-resistant polycystic ovary syndrome (PCOS). This randomized controlled trial was done in the Dhaka Medical College and Hospital and the Infertility Care and Research Centre, Dhaka, Bangladesh. A total of 165 infertile patients with CC-resistant PCOS who attended for treatment were the target population for this study. Patients were divided into three groups: groups A and B were given metformin and group C was the control. Along with metformin, group A received CC and group B received rFSH. Group C was treated with only rFSH. Metformin was given 1500 mg daily for 4 weeks. Afterwards CC or rFSH were added for induction of ovulation along with metformin. Six ovulatory cycles were assessed. Treatment was terminated when there was no response with maximum dose of CC and rFSH or after six ovulatory cycles without pregnancy or after achieving pregnancy. A P-value of <0.5 was considered as significant. Ovulation (89.09%) and pregnancy (54.55%) rates were higher in group B. Ovulation (74.55%) and pregnancy (29.09%) rates were also satisfactory in group C but a dose of rFSH requirement was significantly higher (P = 0.000). In group A, both ovulation and pregnancy rate were much lower than the other two groups (27.27% and 12.73%, respectively). Use of metformin increases the response of ovulation-inducing agents and can be used safely in PCOS. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Use of letrozole in assisted reproduction: a systematic review and meta-analysis

PubMed Central

Requena, Antonio; Herrero, Julio; Landeras, José; Navarro, Esperanza; Neyro, José L.; Salvador, Cristina; Tur, Rosa; Callejo, Justo; Checa, Miguel A.; Farré, Magí; Espinós, Juan J.; Fábregues, Francesc; Graña-Barcia, María

2008-01-01

BACKGROUND Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78−1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91). CONCLUSIONS Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction. PMID:18812422

Weak evidence of bright light effects on human LH and FSH.

PubMed

Kripke, Daniel F; Elliott, Jeffrey A; Youngstedt, Shawn D; Parry, Barbara L; Hauger, Richard L; Rex, Katharine M

2010-05-11

Most mammals are seasonal breeders whose gonads grow to anticipate reproduction in the spring and summer. As day length increases, secretion increases for two gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH). This response is largely controlled by light. Light effects on gonadotropins are mediated through effects on the suprachiasmatic nucleus and responses of the circadian system. There is some evidence that seasonal breeding in humans is regulated by similar mechanisms, and that light stimulates LH secretion, but primate responses seem complex. To gain further information on effects of bright light on LH and FSH secretion in humans, we analyzed urine samples collected in three experiments conducted for other goals. First, volunteers ages 18-30 years and 60-75 commenced an ultra-short 90-min sleep-wake cycle, during which they were exposed to 3000 lux light for 3 hours at balanced times of day, repeated for 3 days. Urine samples were assayed to explore any LH phase response curve. Second, depressed participants 60-79 years of age were treated with bright light or dim placebo light for 28 days, with measurements of urinary LH and FSH before and after treatment. Third, women of ages 20-45 years with premenstrual dysphoric disorder (PMDD) were treated to one 3-hour exposure of morning light, measuring LH and FSH in urine before and after the treatments. Two of the three studies showed significant increases in LH after light treatment, and FSH also tended to increase, but there were no significant contrasts with parallel placebo treatments and no significant time-of-day treatment effects. These results gave some support for the hypothesis that bright light may augment LH secretion. Longer-duration studies may be needed to clarify the effects of light on human LH and FSH.

Timing of mating and ovarian response in llamas (Lama glama) treated with pFSH.

PubMed

Ratto, M H; Gatica, R; Correa, J E

1997-08-01

The effect of the timing of mating on ovarian response in llamas was evaluated using 20 adult llamas weighing 90-120 kg which had been in oestrus for 5 days and were treated with 20 mg pFSH every 12 h for the following 5 days (total dose: 200 mg of FSH-NIH-P1). They were randomly allocated to Group A (N = 10) and mated immediately at the end of pFSH treatment or to Group B (n = 10) and mated 36 h after the end of pFSH treatment. Llamas of both groups were given hCG (750 iu, i.m.) immediately after mating. A second mating was allowed 12 h later. Ova and embryos were recovered by non-surgical uterine flushing 7 days after the first mating. Ovarian response was immediately evaluated afterwards via laparoscopy. The mean ovulation rate of 4.5 corpora lutea for Group A was significantly lower (P < 0.01) than the mean of 13.8 observed for Group B. The total ovarian response (number of corpora lutea + follicles > 10 mm) was also significantly higher (P < 0.01) in Group B than in Group A. Twenty-seven ova were recovered in each group, corresponding to 60% and 20% (P < 0.01) of the corpora lutea observed in Groups A and B, respectively; however, no significant difference (P > 0.05) in fertilisation rate was observed. The results show that pFSH induces superovulation in llamas treated during oestrus and that a 36-h interval between the end of FSH treatment and mating increases ovulation rate and the total ovarian response but does not affect the number of ova/embryos recovered.

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

PubMed Central

Gourlay, Margaret L.; Specker, Bonny L.; Li, Chenxi; Hammett-Stabler, Catherine A.; Renner, Jordan B.; Rubin, Janet E.

2011-01-01

Purpose Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. Methods We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). Results: FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β= −0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. Conclusions After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight. PMID:22086136

New radioimmunoassay for follicle-stimulating hormone in macaques: ovulatory menstrual cycles. [/sup 125/I tracer technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hodgen, G.D.; Wilks, J.W.; Vaitukaitis, J.L.

A sensitive and specific radioimmunoassay system for macaque follicle-stimulating hormone (mFSH) was developed utilizing an antiserum (H-31) prepared in a rabbit against purified ovine FSH as the immunogen. Sera from castrated female, adult male, and juvenile rhesus monkeys, as well as urinary extracts from castrated rhesus and bonnet monkeys, were used to demonstrate parallelism with a standard of partially purified monkey pituitary gonadotropins (LER-M-907-D). An extract of baboon pituitary tissue also showed parallelism with the reference standard. A highly purified pituitary extract (WP-X-105-28), containing approximately 75 percent macaque luteinizing hormone (mLH) and 1 percent mFSH, was used to demonstrate themore » specificity of this mFSH assay system. Sera and urinary extracts obtained from hypophysectomized monkeys did not show cross-reactivity in the assay. Macaque chorionic gonadotropin (mCG) did not produce an inhibition curve in the assay, as determined from serum samples and urinary extracts collected from pregnant monkeys at the time of peak mCG secretion. Serum concentrations of mFSH were suppressed in ovariectomized monkeys by the administration of ethinyl estradiol for 3 days, but returned to near pretreatment values by 96 h after the last estradiol administration. The determination of serum mFSH concentrations in daily blood samples obtained from 20 rhesus monkeys throughout ovulatory menstrual cycles revealed a pattern similar to that previously reported for the rhesus monkey and the woman. The peak value of serum mFSH during the menstrual cycle coincided with the midcycle surge of mLH in each case. The gonadotropin peaks were preceded by increasing serum concentrations of estradiol and followed by rises in the serum concentrations of progesterone.« less

Bisphenol A and Ovarian Reserve among Infertile Women with Polycystic Ovarian Syndrome.

PubMed

Zhou, Wei; Fang, Fang; Zhu, Wenting; Chen, Zi-Jiang; Du, Yanzhi; Zhang, Jun

2016-12-27

To better understand possible effects of bisphenol A (BPA) exposure on ovarian reserve in women with polycystic ovary syndrome (PCOS), we measured creatinine adjusted urinary BPA (BPA_Cre) concentrations and used regression models to evaluate the association between urinary BPA level and antral follicle count (AFC), antimullerian hormone (AMH), day-3 follicle stimulating hormone levels (FSH) and inhibin B (INHB) in 268 infertile women diagnosed with PCOS. BPA was detected in all women with a median concentration of 2.35 ng/mL (the 25th and 75th percentiles of 1.47 ng/mL and 3.95 ng/mL). A unit increase in BPA_Cre was associated with a significant decrease of 0.34 in AFC (β = -0.34, 95% CI = -0.60, -0.08; p = 0.01). Likewise, BPA was negatively associated with AMH and day-3 FSH levels, but neither of them reached statistical significance. No association was observed between BPA and INHB. Our results suggest that in women with PCOS, BPA may affect ovarian follicles and, therefore, reduce ovarian reserve.

Effect of cortisol on gonadotropin inhibitory hormone (GnIH) in the cinnamon clownfish, Amphiprion melanopus.

PubMed

Choi, Young Jae; Habibi, Hamid R; Kil, Gyung-Suk; Jung, Min-Min; Choi, Cheol Young

2017-04-01

Hypothalamic peptides, gonadotropin-releasing hormone (GnRH) and gonadotropin inhibitory hormone (GnIH), play pivotal roles in the control of reproduction and gonadal maturation in fish. In the present study we tested the possibility that stress-mediated reproductive dysfunction in teleost may involve changes in GnRH and GnIH activity. We studied expression of brain GnIH, GnIH-R, seabream GnRH (sbGnRH), as well as circulating levels of follicle stimulating hormone (FSH), and luteinizing hormone (LH) in the cinnamon clownfish, Amphiprion melanopus. Treatment with cortisol increased GnIH mRNA level, but reduced sbGnRH mRNA and circulating levels of LH and FSH in cinnamon clownfish. Using double immunofluorescence staining, we found expression of both GnIH and GnRH in the diencephalon region of cinnamon clownfish brain. These findings support the hypothesis that cortisol, an indicator of stress, affects reproduction, in part, by increasing GnIH in cinnamon clownfish which contributes to hypothalamic suppression of reproductive function in A. melanopus, a protandrous hermaphroditic fish. Copyright © 2017 Elsevier Inc. All rights reserved.

Costs and outcomes associated with IVF using recombinant FSH.

PubMed

Ledger, W; Wiebinga, C; Anderson, P; Irwin, D; Holman, A; Lloyd, A

2009-09-01

Cost and outcome estimates based on clinical trial data may not reflect usual clinical practice, yet they are often used to inform service provision and budget decisions. To expand understanding of assisted reproduction treatment in clinical practice, an economic evaluation of IVF/intracytoplasmic sperm injection (ICSI) data from a single assisted conception unit (ACU) in England was performed. A total of 1418 IVF/ICSI cycles undertaken there between October 2001 and January 2006 in 1001 women were analysed. The overall live birth rate was 22% (95% CI: 19.7-24.2), with the 30- to 34-year age group achieving the highest rate (28%). The average recombinant FSH (rFSH) dose/cycle prescribed was 1855 IU. Average cost of rFSH/cycle was 646 pound(SD: 219 pound), and average total cost/cycle was 2932 pound (SD: 422 pound). Economic data based on clinical trials informing current UK guidance assumes higher doses of rFSH dose/cycle (1750-2625 IU), higher average cost of drugs/cycle (1179 pound), and higher average total cost/cycle (3266 pound). While the outcomes in this study matched UK averages, total cost/cycle was lower than those cited in UK guidelines. Utilizing the protocols and (lower) rFSH dosages reported in this study may enable other ACU to provide a greater number of IVF/ICSI cycles to patients within given budgets.

[Health economic consequences of the choice of follicle stimulating hormone alternatives in IVF treatment].

PubMed

Poulsen, Peter Bo; Højgaard, Astrid; Quartarolo, Jens Piero

2007-04-02

There is a choice between two types of hormones for stimulation of the follicles in IVF treatment - recombinant FSH and the urine-derived menotrophin. A literature review by NICE (2004) in the United Kingdom documented that the two types of hormones were equally effective and safe, which is why it was recommended to use the cheaper urine-derived hormone. Based on the EISG study (European and Israeli Study Group), the aim was to analyse the health economic consequences of the choice between the two types of hormone in IVF treatment in Denmark. In a prospective cost-effectiveness analysis (health care sector perspective), menotrophin and recombinant FSH (Gonal-F) were compared. Differences in costs were compared with differences in effects of the two alternatives. The total costs for the average patient are lower when using menotrophin compared with recombinant FSH. Furthermore, the cost per clinical pregnancy was lower with menotrophin compared with recombinant FSH hormone. Menotrophin is therefore less expensive both for the patient as well as for the health care sector. The use of menotrophin instead of recombinant FSH can result in savings of up to DKK 16 million on the drug budget--savings that could finance 1,400 additional IVF cycles. The analysis shows that urine-derived menotrophin is a cost-effective alternative to recombinant FSH with a potential for considerable savings for patients as well as the public drug budget.

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial.

PubMed

Hassan, AbdelGany; Shehata, Nesreen; Wahba, Amr

2017-04-01

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5 mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75 IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p = 0.578), cumulative ovulation rate (47% vs. 57%; p = 0.236), miscarriage rate (9% vs. 4%, p > 0.999) or multiple pregnancy rate (0% and 8%, p = 0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.

A new fully human recombinant FSH (follitropin epsilon): two phase I randomized placebo and comparator-controlled pharmacokinetic and pharmacodynamic trials.

PubMed

Abd-Elaziz, Khalid; Duijkers, Ingrid; Stöckl, Lars; Dietrich, Bruno; Klipping, Christine; Eckert, Kelvin; Goletz, Steffen

2017-08-01

What are the differences and similarities of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of the novel recombinant human FSH follitropin epsilon expressed in the human cell line GlycoExpress compared with a Chinese hamster ovary (CHO) derived compound and a urinary derived product? Overall follitropin epsilon, with a fully human glycosylation, shows a comparable PK profile at single-dose as well as multiple-dose administration compared to recombinant CHO-derived FSH as well as urinary derived FSH, whereas the PD properties differ from product to product with follitropin epsilon being most active in PD parameters. Recombinant FSH produced in CHO and FSH obtained from the urine of postmenopausal women show comparable PK and PD properties. However, more recently a comparative study of a recombinant FSH produced in the human cell line PerC6 and a CHO-derived FSH preparation revealed differences in PK and PD properties of the molecule. Both studies were randomized, placebo- and comparator-controlled, single-blind phase I studies in healthy pituitary-suppressed female volunteers aged 18 and 40 years. The single-dose, dose escalation study included 19 women (April 2011 to September 2011) with three ascending dose levels per subject or placebo/comparators with a 14-day washout phase between dosings. The multiple-dose study included 57 women (October 2011 to April 2012) in five cohorts with three dose levels versus placebo and two comparators. Randomization to the respective treatment was performed after successful downregulation of the pituitary gland prior to Investigational Medicinal Product dosing. In the single-dose study, 12 subjects received follitropin epsilon (25, 75, 150 and 300 IU) in three of four possible ascending doses and seven subjects received one dose of two comparators (150 IU Bravelle and 150 IU Gonal-f) and placebo in random order in each treatment period. In the multiple-dose study, 30 subjects received follitropin epsilon (75 IU or 150 IU once daily [QD], or 150 IU every other day [QAD], 10 subjects each) and 27 subjects received 150 IU Gonal-f, 150 IU Bravelle, or placebo for 7 days (11/10/6 subjects). Blood samples for measuring PK as well as PD parameters were collected systematically before, during and after dosing. Adverse events (AEs) and other relevant safety parameters were recorded. Data were summarized using descriptive statistics. The single- and multiple-dose PK parameters maximum concentration (Cmax) and area under the concentration-time curve (AUC0-last) increased in a linear fashion with increasing dose levels of follitropin epsilon. Follitropin epsilon showed PK characteristics comparable to the comparators indicating that well established treatment schemes could be applied. There was a dose-response effect of single and multiple doses of follitropin epsilon on follicular growth, which was shown for the biomarker inhibin B as well as for the mean number and size of follicles. Multiple doses of 75 IU follitropin epsilon given daily, as well as 150 IU follitropin epsilon every second day, showed a follicle growth comparable with 150 IU Gonal-f given daily, while in case of daily administration of 150 IU Bravelle only weak follicle stimulation was observed. Multiple doses of 150 IU follitropin epsilon induced a much higher follicle growth compared to the same dose of Gonal-f. All single and multiple follitropin epsilon doses tested were safe and well tolerated, and overall there were no relevant differences between follitropin epsilon and the comparators in terms of safety. The average number of AEs increased with increasing dose levels. No clinically relevant abnormalities were reported for any of the other safety parameters assessed. No follitropin epsilon anti-drug antibodies were observed. The studies were conducted as a single-blind design. Hormone levels or other parameters assessed in serum are generally not considered as being subject to bias. Other assessments directly performed by the investigators, such as transvaginal ultrasound assessments, may have been subject to personal bias. No prospective calculations of statistical power had been made, as is common practice for first in human and early phase I studies in healthy volunteers. These early development studies showed that follitropin epsilon exhibits comparable PK characteristics, as well as inducing stronger PD effects in terms of follicle growth and serum inhibin B, than the comparators. Follitropin epsilon induced a dose-dependent increase in follicular growth. The results warrant further studies with this new fully human recombinant FSH. The studies were sponsored by GLYCOTOPE GmbH, Berlin, Germany. K.A-E. is an employee of QPS-Netherlands, B.V., which received funding for the studies from Glycotope GmbH; I.D. and C.K. are employees of Dinox B.V., which received funding for the studies from Glycotope GmbH; L.S. and S.G. are employees and shareholders of Glycotope GmbH; B.D. and K.E. are employees of Glycotope GmbH. www.clinicaltrials.gov: NCT01354886 (single-dose); NCT01477073 (multiple-dose). The single-dose trial was registered on 11 May 2011 while the multiple-dose trial was registered on 09 November 2011. First subject was enroled in the single-dose trial in 27 April 2011 and in the multiple-dose trial in 02 October 2011. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Melatonin Promotes Superovulation in Sika Deer (Cervus nippon)

PubMed Central

Wang, Liang; Zhuo, Zhi-Yong; Shi, Wen-Qing; Tan, Dun-Xian; Gao, Chao; Tian, Xiu-Zhi; Zhang, Lu; Zhou, Guang-Bin; Zhu, Shi-En; Yun, Peng; Liu, Guo-Shi

2014-01-01

In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1 ± 2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98 ± 0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p < 0.05). The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p > 0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed. PMID:25007067

Melatonin promotes superovulation in sika deer (Cervus nippon).

PubMed

Wang, Liang; Zhuo, Zhi-Yong; Shi, Wen-Qing; Tan, Dun-Xian; Gao, Chao; Tian, Xiu-Zhi; Zhang, Lu; Zhou, Guang-Bin; Zhu, Shi-En; Yun, Peng; Liu, Guo-Shi

2014-07-08

In this study, the effects of melatonin (MT) on superovulation and reproductive hormones (melatonin, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and PRL) were investigated in female sika deer. Different doses (40 or 80 mg/animal) of melatonin were subcutaneously implanted into deer before the breeding season. Exogenous melatonin administration significantly elevated the serum FSH levels at the time of insemination compared with levels in control animals. During superovulation, the serum LH levels in donor sika deer reached their highest values (7.1±2.04 ng/mL) at the point of insemination, compared with the baseline levels (4.98±0.07 ng/mL) in control animals. This high level of LH was sustained until the day of embryo recovery. In contrast, the serum levels of PRL in the 80 mg of melatonin-treated group were significantly lower than those of control deer. The average number of corpora lutea in melatonin-treated deer was significantly higher than that of the control (p<0.05). The average number of embryos in the deer treated with 40 mg of melatonin was higher than that of the control; however, this increase did not reach significant difference (p>0.05), which may be related to the relatively small sample size. In addition, embryonic development in melatonin-treated groups was delayed.

Are serum levels of vitamin D associated with semen quality? Results from a cross-sectional study in young healthy men.

PubMed

Ramlau-Hansen, Cecilia Høst; Moeller, Ulla Kristine; Bonde, Jens Peter; Olsen, Jørn; Thulstrup, Ane Marie

2011-03-01

To examine the association between low serum vitamin D concentration and estimates of male reproductive function. Cross-sectional study. University hospital. From a Danish pregnancy cohort established in 1984-1987, 347 sons were selected for a study conducted in 2005-2006. Semen parameters and reproductive hormones were related to vitamin D concentrations in 307 men. Semen characteristics and reproductive hormones. A high vitamin D level was unexpectedly associated with lower crude median total sperm count and percentage of normal morphology sperm and a high level of crude median sex hormone-binding globulin and FSH. After adjustment, the associations attenuated to nonsignificant associations, except for sex hormone-binding globulin. Additionally, adjusted free androgen index was lower at higher vitamin D levels, and men with high vitamin D had 11% (95% confidence interval, 1%-20%) lower free androgen index compared with men with low vitamin D. These results do not indicate that low vitamin D is a risk factor for poor semen quality in a population of young healthy men, but we may not have enough men with low vitamin D levels to detect an effect. New studies should include a larger proportion of vitamin D-deficient men. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effects of 3-methyl-4-nitrophenol in diesel exhaust particles on the regulation of testicular function in immature male rats.

PubMed

Li, Chunmei; Taneda, Shinji; Suzuki, Akira K; Furuta, Chie; Watanabe, Gen; Taya, Kazuyoshi

2007-01-01

We investigated the effects of 3-methyl-4-nitrophenol (4-nitro-m-cresol, PNMC) isolated from diesel exhaust particles (DEP) on the reproductive functions of male rats. Twenty-eight-day-old rats were injected subcutaneously with PNMC (1, 10, or 100 mg/kg) daily for 5 days. The weights of the epididymis, seminal vesicle, and Cowper gland were significantly decreased in rats treated with 10 mg/kg PNMC. The plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were significantly increased by PNMC at 100 mg/kg. However, the plasma concentrations of testosterone and immunoreactive (ir)-inhibin were significantly decreased by PNMC at 100 mg/kg. The testosterone content of the testicles was significantly decreased in the group treated with 100 mg/kg PNMC compared with the control group. Furthermore, testicular concentration of ir-inhibin was significantly decreased by PNMC at 1 mg/kg or 100 mg/kg. To investigate the direct effects of PNMC on the secretion of LH and FSH from the anterior pituitary gland, and on the secretion of testosterone from the testes, we exposed cultured anterior pituitary and interstitial Leydig cells to PNMC (10(-6), 10(-5), 10(-4) M) with or without gonadotropin-releasing hormone (GnRH; 10 nM) (for the LH and FSH tests) and human chorionic gonadotropin (hCG; 0.1 IU/mL) (for the testosterone test) for 24 hours. PNMC did not change either the basal or GnRH-stimulated levels of FSH and LH secretion. However, PNMC significantly inhibited both basal and hCG-stimulated testosterone production. These findings suggest that PNMC has a direct effect on the testes of immature male rats, causing a reduction in testosterone secretion.

Diagnosis and Treatment of Diminished Ovarian Reserve in ART Cycles of Women Up to Age 40 Years: The Role of Insurance Mandates

PubMed Central

Butts, Samantha F.; Ratcliffe, Sarah; Dokras, Anuja; Seifer, David B.

2012-01-01

Summary Objective To explore correlates of diminished ovarian reserve (DOR) and predictors of ART treatment outcome in DOR cycles using the SART-CORS database. We hypothesized that state insurance coverage for ART is associated with the prevalence of DOR diagnosis in ART cycles and with treatment outcomes in DOR cycles. Design Cross sectional study using ART cycles between 2004–2007. Setting United States ART registry data. Patients 182,779 fresh, non-donor, initial ART cycles in women up to age 40. Interventions None. Main Outcome Measures Prevalence of DOR and elevated FSH, odds ratio of DOR and elevated FSH in ART mandated vs. non-mandated states, live birth rates. Results Compared to cycles performed in states with mandated ART coverage, cycles in states with no ART mandate were more likely to have DOR (AOR 1.43 95% CI 1.37–1.5, p<0.0001) or elevated FSH (AOR 1.69 95% CI 1.56–1.85, p<0.0001) as the sole reason for treatment. A relationship between lack of mandated ART coverage and increased live birth rates in some, but not all DOR cycles. Conclusions A significant association was observed between lack of mandated insurance for ART and the proportion of cycles treating DOR or elevated FSH. The presence or absence of state mandated ART coverage could impact access to care and the mix of patients that pursue and initiate ART cycles. Additional studies are needed that consider the coalescence of insurance mandates, patient and provider factors, and state level variables on the odds of specific infertility diagnoses and treatment prognosis. PMID:23102859

Androgen receptor CAG repeat polymorphism and hypothalamic-pituitary-gonadal function in Filipino young adult males

PubMed Central

Ryan, Calen P.; McDade, Thomas W; Gettler, Lee T.; Eisenberg, Dan T.A.; Rzhetskaya, Margarita; Hayes, M. Geoffey; Kuzawa, Christopher W.

2016-01-01

Objectives Testosterone (T), the primary androgenic hormone in males, is stimulated through pulsatile secretion of LH and regulated through negative feedback inhibition at the hypothalamus and pituitary. The hypothalamic-pituitary-gonadal (HPG) axis also controls sperm production through the secretion of follicle-stimulating hormone (FSH). Negative feedback in the HPG axis is achieved in part through the binding of T to the androgen receptor (AR), which contains a highly variable trinucleotide repeat polymorphism (AR-CAGn). The number of repeats in the AR-CAGn inversely correlates with transcriptional activity of the AR. Thus, we predicted longer AR-CAGn to be associated with higher T, LH, and FSH levels. Methods We examined the relationship between AR-CAGn and total plasma T, LH, and FSH, as well as 'bioavailable' morning (AM-T) and evening (PM-T) testosterone in 722 young (21.5 ± 0.5 years) Filipino males. Results There was no relationship between AR-CAGn and total T, AM-T, or LH (P > 0.25 for all). We did observe a marginally non-significant (P = 0.066) correlation between AR-CAGn and PM-T in the predicted direction, and a negative correlation between AR-CAGn and FSH (P = 0.005). Conclusions Our results both support and differ from previous findings in this area, and study parameters that differ between our study and others, such as participant age, sample time, and the role of other hormones should be considered when interpreting our findings. While our data point to a modest effect of AR-CAGn on HPG regulation at best, the AR-CAGn may still affect somatic traits by regulating androgenic activity at peripheral tissues. PMID:27417274

Is there a difference in testosterone levels and its regulators in men carrying BRCA mutations?

PubMed Central

Goldberg, Hanan; Grievink, Liat Shavit; Mano, Roy; Ber, Yaara; Ozalbo, Rachely; Tuval, Sivan; Baniel, Jack; Margel, David

2017-01-01

Background Male BRCA mutation carriers are at risk for an early onset aggressive prostate cancer. No data exist on the association of testosterone levels among these patients. We aimed to analyze testosterone and associated hormonal levels among male BRCA carriers and non-carriers. Patients and methods Overall 87 male carriers and 43 non-carriers aged 40-70 were prospectively enrolled. Clinical data were collected and all patients were tested for total testosterone (TT), prostate specific antigen (PSA), follicle stimulating hormone (FSH), luteinizing hormone (LH), free androgen index (FAI), sex hormone binding globulin (SHBG) and prolactin. Multivariate linear regression analysis was performed to predict TT levels. Results The median age, mean BMI, comorbidities, PSA, FSH, LH and SHBG levels in both groups were similar. However, mean TT and FAI were higher in the carriers (16.7 nmol/l vs 13.5 nmol/l, p=0.03 and 39.5 vs 34.8, p=0.05, respectively), while prolactin was significantly lower. Multivariate analysis demonstrated that while BMI was inversely correlated to TT levels in both groups, LH was a predictor only in non-carriers. Conclusions Carriers have higher TT and FAI levels and lower prolactin levels; but LH does not predict their TT levels. Further research in a larger cohort of BRCA carriers with and without prostate cancer should be performed. PMID:29262604

Large, comparative, randomized double-blind trial confirming noninferiority of pregnancy rates for corifollitropin alfa compared with recombinant follicle-stimulating hormone in a gonadotropin-releasing hormone antagonist controlled ovarian stimulation protocol in older patients undergoing in vitro fertilization.

PubMed

Boostanfar, Robert; Shapiro, Bruce; Levy, Michael; Rosenwaks, Zev; Witjes, Han; Stegmann, Barbara J; Elbers, Jolanda; Gordon, Keith; Mannaerts, Bernadette

2015-07-01

To compare corifollitropin alfa with recombinant FSH treatment in terms of the vital pregnancy rate in older patients undergoing IVF. Phase 3 randomized, double-blind, noninferiority trial. Multicenter trial. A total of 1,390 women aged 35-42 years. A single injection of 150 μg of corifollitropin alfa or daily 300 IU of recombinant FSH for the first 7 days then daily recombinant FSH until three follicles reach ≥17 mm in size. Ganirelix was started on stimulation day 5 up to and including the day of recombinant hCG administration. If available, two good quality embryos were transferred on day 3. Vital pregnancy rate (PR), number of oocytes, and live birth rate. Vital PRs per started cycle were 23.9% in the corifollitropin alfa group and 26.9% in the recombinant FSH group, with an estimated difference (95% confidence interval) of -3.0% (-7.4 to 1.4). The mean (SD) number of recovered oocytes per started cycle was 10.7 (7.2) and 10.3 (6.8) in the corifollitropin alfa and the recombinant FSH groups, respectively, with an estimated difference of 0.5 (-0.2 to 1.2). The live birth rates per started cycle were 21.3% in the corifollitropin alfa group and 23.4% in the recombinant FSH group, with an estimated difference (95% confidence interval) -2.3% (-6.5 to 1.9). The incidence of serious adverse events was 0.4% versus 2.7% in the corifollitropin alfa and recombinant FSH groups, respectively, and of ovarian hyperstimulation syndrome (OHSS; all grades) was 1.7% in both groups. Treatment with corifollitropin alfa was proven noninferior to daily recombinant FSH with respect to vital PRs, number of oocytes retrieved, and live birth rates, and was generally well tolerated. NCT01144416. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

MANAGEMENT OF ENDOCRINE DISEASE: The impact of subclinical hypothyroidism on anthropometric characteristics, lipid, glucose and hormonal profile of PCOS patients: a systematic review and meta-analysis.

PubMed

Pergialiotis, Vasilios; Konstantopoulos, Panagiotis; Prodromidou, Anastasia; Florou, Venetia; Papantoniou, Nikolaos; Perrea, Despina N

2017-03-01

Subclinical hypothyroidism (SCH) is encountered in 10-25% of women with PCOS. To date, it remains unclear whether this coexistence influences the severity of metabolic and hormonal profile of these patients. The purpose of our systematic review is to investigate this potential relation. We systematically searched Medline, Scopus, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases together with reference lists from included studies. All prospective and retrospective observational cohort studies that investigated the impact of subclinical hypothyroidism on hormonal and metabolic parameters of PCOS patients were included. The methodological quality of studies was assessed with the Ottawa-Newcastle criteria. Statistical meta-analysis was performed with the RevMan 5.3 software. Twelve studies were finally included in the present review, which enrolled 2341 PCOS patients. Among them, 577 had subclinical hypothyroidism, whereas the remaining 2077 were PCOS women with normal thyroid function. The presence of SCH significantly affected HDL (MD -3.92 mg/dL 95% CI: -6.56, -1.29) and triglycerides levels (26.91 mg/dL 95% CI: -3.79, 50.02). HOMA-IR was also affected (MD 0.82 95% CI: 0.15, 1.50). On the other hand, LDL, fasting glucose and 2-h OGTT were not influenced. Similarly, prolactin, FSH, LH, LH/FSH ratio and sex hormone-binding globulin remained unaffected. Subclinical hypothyroidism does not influence the hormonal profile of women with PCOS. On the other hand, it results in mild metabolic abnormalities, which are not clinically important in a short-term setting. © 2017 European Society of Endocrinology.

Feasibility of corifollitropin alfa/GnRH antagonist protocol combined with GnRH agonist triggering and freeze-all strategy in polycystic ovary syndrome patients.

PubMed

Hwang, Jiann-Loung; Chen, Shee-Uan; Chen, Hen-Ju; Chen, Hsin-Fu; Yang, Yu-Shih; Chang, Chin-Hao; Seow, Kok-Min; Tzeng, Chii-Ruey; Lin, Yu-Hung

2018-06-01

The long-acting corifollitropin alfa is comparable to FSH in terms of pregnancy outcomes in normal responders and poor responders. Corifollitropin alfa has never been studied in polycystic ovary syndrome (PCOS) patients because of concerns of excessive ovarian stimulation and ovarian hyperstimulation syndrome (OHSS). The purpose of the study was to evaluate if corifollitropin alfa can be used in PCOS patients. Forty PCOS patients who were going to undergo in vitro fertilization were enrolled in this study. A single injection of corifollitropin alfa was administered on cycle day 2 or day 3. From stimulation day 8 onwards, daily FSH was administered until the day of final oocyte maturation. Cetrorelix was administered from stimulation day 5 to prevent premature LH surge. Final oocyte maturation was triggered by: acetate. All embryos were cryopreserved and replaced in subsequent cycles. All 40 patients were subjected to oocyte retrieval, and none developed moderate or severe ovarian hyperstimulation syndrome (0%, 95% CI 0-0.088). For each patient, an average of 23.4 (±7.4; 95% CI 21.0-25.7) oocytes were retrieved and a mean of 11.7 (±6.4; 95% CI 9.6-13.8) embryos were frozen. Mean serum estradiol level on the day of GnRHa triggering was 7829.9 pg/ml (±3297; 95% CI 6775-8885). The cumulated ongoing pregnancy rate after 3 frozen-thawed embryo transfers was 75.0% (95% CI 61.6%-88.4%). The results suggest that corifollitropin alfa/GnRH antagonist protocol can be used in PCOS patients, in combination with GnRHa triggering and embryo cryopreservation. Copyright © 2017. Published by Elsevier B.V.

Risk of Hypogonadism From Scatter Radiation During Pelvic Radiation in Male Patients With Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yau, Ivan; Vuong, Te; Garant, Aurelie

Purpose: Recent studies have reported fluctuations in sex hormones during pelvic irradiation. The objective of this study was to observe the effects of radiation on hormonal profiles for two treatment modalities: conventional external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDRBT) given neoadjuvantly for patients with rectal cancer. Methods and Materials: Routine serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were collected from 119 consecutive male patients receiving either EBRT, using 45.0-50.4 Gy in 25-28 fractions with concurrent 5-fluorouracil chemotherapy or HDRBT using 26 Gy in 4 fractions. Results: Thirty patients with initially abnormal profiles were excluded. Profilesmore » included in this study were collected from 51 patients treated with EBRT and 38 patients treated with HDRBT, all of whom had normal hormonal profiles before treatment. Mean follow-up times were 17 months for the entire patient cohort-14 and 20 months, respectively-for the EBRT and HDRBT arms. Dosimetry results revealed a mean cumulative testicular dose of 1.24 Gy received in EBRT patients compared with 0.27 Gy in the HDRBT group. After treatment, FSH and LH were elevated in all patients but were more pronounced in the EBRT group. The testosterone-to-LH ratio was significantly lower (p = 0.0036) in EBRT patients for tumors in the lower third of the rectum. The 2-year hypogonadism rate observed was 2.6% for HDRBT compared with 17.6% for EBRT (p = 0.09) for tumors in the lower two thirds of the rectum. Conclusion: HDRBT allows better hormonal sparing than EBRT during neoadjuvant treatment of patients with rectal cancer.« less

Local anti-fertility effect of inhibin-enriched preparation (IEP) in female hamsters.

PubMed

Bapat, B V; Nandedkar, T D; Sheth, A R

1984-04-01

An inhibin-enriched preparation (IEP) involved in the regulation of follicle stimulating hormone (FSH) is known to play an important role in the normal ovarian cycle. In utero administration of 10 micrograms of IEP on day 3 of pregnancy completely prevented implantation in hamsters. No toxic effect of IEP was observed on the blastocysts as indicated by the dye exclusion test performed with Trypan blue. Thus, the results of the present study indicate an extra-pituitary site of action for the anti-implantation effect of IEP.

Impact of obesity on oral contraceptive pharmacokinetics and hypothalamic-pituitary-ovarian activity

PubMed Central

Edelman, Alison B; Carlson, Nichole E; Cherala, Ganesh; Munar, Myrna Y.; Stouffer, Richard L; Cameron, Judy L; Stanczyk, Frank Z.; Jensen, Jeffrey T

2009-01-01

Objective This study was conducted to determine whether increased body mass index (BMI) affects oral contraceptive (OC) pharmacokinetics and suppression of hypothalamic-pituitary-ovarian (HPO) axis activity. Study design Ovulatory reproductive-age women of normal (< 25 kg/m2; n = 10) and obese (> 30 kg/m2; n = 10) BMI received OCs for two cycles (prospective cohort). Subjects were admitted for two 48-h inpatient stays at the beginning and end of the hormone-free interval. Ethinyl estradiol (EE) and levonorgestrel (LNG) levels were evaluated during both inpatient stays. Gonadotropin pulsatility (FSH and LH) was measured during the second inpatient stay. Estradiol (E2) and progesterone (P) were measured daily during inpatient stays and twice per week in Cycle 2. Results BMI was greater in the obese, compared to the normal BMI group [37.3 kg/m2 (SD 6.0) versus 21.9 kg/m2 (SD 1.6); p < 0.05]. The LNG half-life was significantly longer in the obese group (52.1 ± 29.4 h versus 25.6 ± 9.3 h, p < 0.05) which correlated with a lower maximum LNG concentration on Cycle 2, Day 1 [1.9 ng/mL (SD 0.5) versus 2.5 ng/mL (SD 0.7)] and a longer time to reach steady-state (10 versus 5 days), in obese women. There were no significant differences in volume of distribution between groups. LH pulse parameters did not differ statistically between groups but trended towards greater HPO activity in the obese group. Additionally, more obese (6/10 versus 3/10 normal BMI, p > 0.05) women exhibited E2 levels consistent with development of a dominant follicle, and P levels consistent with ovulation (2/10 versus 1/10) during Cycle 2. Conclusions Compared to women of normal BMI, obese women exhibit differences in OC pharmacokinetics that are associated with greater HPO activity. PMID:19631786

Hypothalamic expression of KiSS-1 system and gonadotropin-releasing effects of kisspeptin in different reproductive states of the female Rat.

PubMed

Roa, J; Vigo, E; Castellano, J M; Navarro, V M; Fernández-Fernández, R; Casanueva, F F; Dieguez, C; Aguilar, E; Pinilla, L; Tena-Sempere, M

2006-06-01

Kisspeptins, products of the KiSS-1 gene with ability to bind G protein-coupled receptor 54 (GPR54), have been recently identified as major gatekeepers of reproductive function with ability to potently activate the GnRH/LH axis. Yet, despite the diversity of functional states of the female gonadotropic axis, pharmacological characterization of this effect has been mostly conducted in pubertal animals or adult male rodents, whereas similar studies have not been thoroughly conducted in the adult female. In this work, we evaluated maximal LH and FSH secretory responses to kisspeptin-10, as well as changes in sensitivity and hypothalamic expression of KiSS-1 and GPR54 genes, in different physiological and experimental models in the adult female rat. Kisspeptin-10 (1 nmol, intracerebroventricular) was able to elicit robust LH bursts at all phases of the estrous cycle, with maximal responses at estrus; yet, in diestrus LH, responses to kisspeptin were detected at doses as low as 0.1 pmol. In contrast, high doses of kisspeptin only stimulated FSH secretion at diestrus. Removal of ovarian sex steroids did not blunt the ability of kisspeptin to further elicit stimulated LH and FSH secretion, but restoration of maximal responses required replacement with estradiol and progesterone. Finally, despite suppressed basal levels, LH and FSH secretory responses to kisspeptin were preserved in pregnant and lactating females, although the magnitude of LH bursts and the sensitivity to kisspeptin were much higher in pregnant dams. Interestingly, hypothalamic KiSS-1 gene expression significantly increased during pregnancy, whereas GPR54 mRNA levels remained unaltered. In summary, our current data document for the first time the changes in hypothalamic expression of KiSS-1 system and the gonadotropic effects (maximal responses and sensitivity) of kisspeptin in different functional states of the female reproductive axis. The present data may pose interesting implications in light of the potential therapeutic use of kisspeptin analogs in the pharmacological manipulation of the gonadotropic axis in the female.

A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom).

PubMed

Conte, F A; Grumbach, M M; Ito, Y; Fisher, C R; Simpson, E R

1994-06-01

We report the features of a new syndrome of aromatase deficiency due to molecular defects in the CYP19 (P450arom) gene in a 46,XX female. At birth, the patient presented with a nonadrenal form of female pseudohermaphrodism. At 17 months of age, laparotomy revealed normal female internal genital structures; the histological appearance of the ovaries was normal. FSH concentrations were markedly elevated at 9.4 ng/mL LER 869, and estrone and estradiol levels were undetectable (< 37 pmol/L). By 14 yr of age, she had failed to exhibit breast development. The clitoris had enlarged to 4 x 2 cm, and pubic hair was Tanner stage IV. The plasma concentration of testosterone was elevated at 3294 pmol/L, as was androstenedione at 9951 pmol/L. Plasma estradiol levels were below 37 pmol/L. ACTH and dexamethasone tests indicated a nonadrenal source of testosterone and androstenedione. Plasma gonadotropin levels were in the castrate range. Pelvic sonography and magnetic resonance imaging showed multiple 4- to 6-cm ovarian cysts bilaterally. Despite increased circulating androgens and clitoral growth, the bone age was 10 yr at chronologic age 14 2/12 yr. Estrogen replacement therapy resulted in a growth spurt, breast development, menarche, suppression of gonadotropin levels, and resolution of the cysts. The clinical findings suggested the diagnosis of P450arom deficiency. Analyses of genomic DNA from ovarian fibroblasts demonstrated two single base changes in the coding region of the P450arom gene, one at 1303 basepairs (C-T), R435C, and the other at 1310 basepairs (G-A), C437Y, in exon 10. The molecular genetic studies indicate that the patient is a compound heterozygote for these mutations. Expression of these mutations showed that the R435C mutation had 1.1% the activity of the wild-type P450arom enzyme, whereas the C437Y mutation demonstrated no activity. The cardinal features of this syndrome are a consequence of P450arom deficiency: 1) the fetal masculinization in this syndrome can be ascribed to defective placental conversion of C19 steroids to estrogens, leading to exposure of the female fetus to excessive amounts of testosterone; 2) the pubertal failure, mild virilization, multicystic ovaries, and hyperstimulation of the ovaries by FSH and LH are the result of the inability of the ovary to aromatize testosterone and androstenedione to estrogens; and 3) the striking delay in bone age at 14 2/12 yr supports the notion that estrogens, in contrast to androgens, are the major sex steroid driving skeletal maturation during puberty. Familial P450arom deficiency, although rare, may be more common than previously suspected.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluation of the effect of follicular stimulating hormone on the in vitro bovine spermatogonial stem cells self-renewal: An experimental study

PubMed Central

Jabarpour, Masoome; Tajik, Parviz

2017-01-01

Background: Spermatogonial stem cells (SSCs) are undifferentiated cells which are highly reproducible and expandable. Several studies have been conducted to reproduce these cells in culture. They used growth factors, hormones and different feeder cells to improve survival and proliferation of SSCs. Objective: This study was conducted to evaluate the effects of follicular stimulating hormone (FSH) on gene expression of fibroblast growth factor (FGF2) and glial cell-derived neurotrophic factor (GDNF) in Sertoli cells. Materials and Methods: Sertoli cells and SSCs were isolated from 3-5 month-old calves. Bovine testicular cells were cultured for 15 days with or without FSH. Identification of these cells was confirmed by immunocytochemistry analysis. Colony formation of SSCs was evaluated using an inverted microscope. The gene expression of FGF2 and GDNF and the gene markers bcl6b, thy-1, and C-kit were evaluated using the quantitative RT-PCR technique. Results: The results indicated that FSH increased colonization of SSCs. the expression of GDNF, FGF2, and markers of undifferentiated spermatogonia was increased following culture in control and FSH groups (p<0.05), this increase was more in FSH group. Conversely, the expression of C-kit was decreased in both groups (p<0.05). Conclusion: The results showed that FSH can increase the self-renewal of SSCs in vitro via upregulation of GDNF and FGF2 expression in Sertoli cells. PMID:29492477

Profile of follitropin alpha/lutropin alpha combination for the stimulation of follicular development in women with severe luteinizing hormone and follicle-stimulating hormone deficiency

PubMed Central

Rinaldi, Leonardo; Selman, Helmy

2016-01-01

A severe gonadotropin deficiency together with chronic estradiol deficiency leading to amenorrhea characterizes patients suffering from hypogonadotropic hypogonadism. Administration of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) to these patients has been shown to be essential in achieving successful stimulation of follicular development, ovulation, and rescue of fertility. In recent years, the availability of both recombinant FSH (rFSH) and recombinant LH (rLH) has provided a new therapeutic option for the stimulation of follicular growth in hypopituitary–hypogonadotropic women (World Health Organization Group I). In this article, we review the data reported in the literature to highlight the role and the efficacy of using recombinant gonadotropins, rFSH and rLH, in the treatment of women with severe LH/FSH deficiency. Although the studies on this issue are limited and the experiences available in the literature are few due to the small number of such patients, it is clearly evident that the recombinant gonadotropins rFSH and rLH are efficient in treating patients affected by hypogonadotropic hypogonadism. The results observed in the studies reported in this review suggest that recombinant gonadotropins are able to induce proper follicular growth, oocyte maturation, and eventually pregnancy in this group of women. Moreover, the clinical use of recombinant gonadotropins in this type of patients has given more insight into some endocrinological aspects of ovarian function that have not yet been fully understood. PMID:27307766

Studies on the synergistic effect of androgen on the stimulation of progestin secretion by FSH in cultured rat granulosa cells: progesterone metabolism and the effect of androgens.

PubMed

Nimrod, A

1977-09-01

Metabolic transformations of progesterone in cultures of granulosa cells from immature hypophysectomized rats treated with diethylstilbestrol were studied in relation to the synergistic action of exogenous androgen and FSH on progestin (progesterone and 20alpha-dihydroprogesterone) accumulation. Androstenedione (Ad; 10 ng/ml) enhanced the sensitivity of rat granulosa cells to this steroidogenic action of FSH, lowering the threshold of the response from greater than 4 ng/ml (FSH alone) to 0.8 ng/ml in the presence of Ad. A synergistic effect with FSH was also shown by various 5alpha-androstane derivatives. They were, however, less effective than the parent delta4-3 keto androstenes. Progesterone underwent extensive 5alpha-reduction during culture, leading to accumulation of endogenous 5alpha-pregnane compounds, and to transformation of labelled progesterone into 5 alpha-reduced radiometabolites. These compounds corresponded in gas-liquid and thin-layer chromatographic behaviour to 3alpha-hydroxy-5alpha-pregnan-20-one, 20alpha-hydroxy-5alpha-pregnan-3-one and 5alpha-pregnane-3alpha,20alpha-diol. The rate of 5alpha-reduction of progestins was not affected by the presence of exogenous Ad (1 microgram/ml), ruling out the possibility that the effect of androgen on progestin accumulation depends on competitive inhibition of 5alpha-reductase. An involvement of androgen of thecal origin in the enhancement of the sensitivity of the FSH-responsive mechanism in granulosa cells is suggested.

Comparison of corifollitropin alfa and daily recombinant follicle-stimulating hormone in poor responder patients undergoing in vitro fertilization cycles.

PubMed

Akarsu, Süleyman; Demir, Sibel; Gode, Funda; Işık, Ahmet Zeki

2017-12-01

The aim of this study was to compare the effect of corifollitropin alfa (CFA) and recombinant follicle-stimulating hormone (rFSH) in poor-responder patients undergoing antagonist cycles. The study was a retrospective analysis of the treatment results of 214 poor responder patients who had been admitted to the In Vitro Fertilization Unit of İzmir Medical Park Hospital between November 2014 and November 2016. Intracytoplasmic sperm injections were performed in 38 patients (group 1) with CFA, and the remaining 176 (group 2) with rFSH for controlled ovarian hyperstimulation. The age, body mass index, anti-müllerian hormone level, duration of infertility, duration of induction and antral follicle number were similar in the two groups. There was no difference in the total aspirated oocyte counts, mature oocyte ratio, fertilization rate, implantation rate, and clinical pregnancy rates between the two groups. The implantation rate was 9/38 (23.6%) in group 1 and 42/176 (23.8%) in group 2, whereas the clinical pregnancy rates were 16.3% and 17.2%, respectively. No difference was found in terms of oocyte count, fertilization rate, implantation rate, and clinical pregnancy rates of CFA or rFSH use in the antagonist cycles in poor-responder patients.

Evaluation of the correlation between insulin like factor 3, polycystic ovary syndrome, and ovarian maldescent.

PubMed

Seyam, Emaduldin; Hefzy, Enas

2018-06-01

The aim of this study was to investigate a proposed correlation between the incidentally discovered undescended ovaries and their confirmed diagnosis as a polycystic ovary disease (PCOD) for all cases included, and to evaluate the role of estimated insulin like factor 3 (INSL3) circulating level in the pathogenesis of both abnormal findings. The study group (A) comprised 35 women whose ovaries had been incidentally found to be undescended during the routine laparoscopy for infertility causes, and all had been diagnosed as PCOD. The control category included two subgroups; subgroup (B) included 35 women group, diagnosed as PCOD but with normally allocated ovaries in the true pelvis, and subgroup (C) included 35 healthy women with regular menses and no signs of hyperandrogenism. Correlations between the level of INSL3 and other PCOD relevant biochemical tests: [e.g. BMI, waist-to-hip ratio (WHR), LH, FSH, androstendione (A), total and free testosterone (T & Ft), DHEA-S, and SHBG] had been also investigated. INSL3 levels were significantly higher in PCOD groups (A) and (B) compared to the healthy fertile control subgroup (C) (80.5 ± 29.4, 65.11 ± 15.6, and 41.11 ± 10.2 pg/mL, respectively), and was highest in group (A). Moreover, we identified a strong correlation between INSL3 and androstenedione (r = 0.42, p = 0.0012), and free (r = 0.42, p = .0123) and total testosterone (r = 0.41, p = .004) in the PCOD (A) and (B) subgroup compared to the levels in subgroup (C). LH was significantly higher in all PCOD women in groups (A&B) (12. 3 ± 3.4, and 11.2 ± 1.4 mIU/L, respectively) compared to those in group (A) (5.7 ± 2.5 mIU/L), with a fair correlation with INSL3. However, there was no statistically significant correlation between INSL3 and FSH, DHEA-S, glucose, basal insulin concentration or HOMA-IR in all PCOD women. The strong positive correlation between INSL3, and high ovarian androgens levels in all PCOD women, which appeared clearly in undescended polycystic ovaries could support the proposed syndrome hypothesis between those abnormal findings.

Staging reproductive aging using Stages of Reproductive Aging Workshop + 10 in black urban African women in the Study of Women Entering and in Endocrine Transition.

PubMed

Jaff, Nicole G; Snyman, Tracy; Norris, Shane A; Crowther, Nigel J

2014-11-01

There has been limited research on accurate staging of the menopausal transition in sub-Saharan African women. Our aim was to assess the usefulness of the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria in staging ovarian aging in black South African women, examining whether obesity has any effect on the menopausal transition. The study enrolled 702 women aged 40 to 60 years. STRAW + 10 criteria were used to categorize the stages of reproductive aging. The Menopause Rating Scale was used to measure the prevalence of vasomotor symptoms. Follicle-stimulating hormone (FSH) and estradiol levels were used as supportive criteria for staging. Human immunodeficiency virus status was assessed using a point-of-care method. Reported age at final menstrual period (FMP) was higher in women interviewed within 4 years of FMP (mean [SD], 49.0 [3.80] y) than in women interviewed 10 years or more after FMP (mean [SD], 42.0 [4.06] y; P < 0.0005). In women within 4 years of FMP, lower body mass index was associated with earlier age at FMP. FSH levels increased and estradiol levels decreased (P < 0.0005 for both trends) across seven staging groups. Human immunodeficiency virus status had no effect on menopause symptoms. Obesity (body mass index ≥35.0 kg/m) was associated with severe vasomotor symptoms. Reporting of age at FMP is unreliable in women interviewed 4 years or more after the event. STRAW + 10 seems accurate in staging reproductive aging, as confirmed by the strong association of FSH and estradiol levels with the menopausal transition stage. STRAW + 10 may be appropriate for use in resource-limited settings in the absence of biomarkers. Biocultural methods may be useful in assessing the menopausal transition in culturally diverse women.

Retarded differentiation of Leydig cells and increased apoptosis of germ cells in the initial round of spermatogenesis of rats with lethal dwarf and epilepsy (lde/lde) phenotypes.

PubMed

Takenaka, Motoo; Yagi, Mio; Amakasu, Kohei; Suzuki, Katsushi; Suzuki, Hiroetsu

2008-01-01

The lde/lde rats show a severe dwarf phenotype with early postnatal lethality and a high incidence of epileptic seizure. Seizures are first detected in this model between 16 and 63 days of age, and mostly begin as wild running and progress to generalized tonic-clonic convulsions. Because our histological examination detected many extracellular vacuoles in the hippocampus and amygdaloid bodies of these animals at 28 days of age, these pathological alterations may be related to the epileptogenesis in lde/lde rats. In addition to these defects, male lde/lde rats have apparently smaller testes with reduced number of germ cells and poorly matured adult-type Leydig cells in comparison with wild-type controls. In the present study, we performed anatomical, histological, and endocrinologic examinations to characterize the testicular phenotype of lde/lde rats at 21, 28, 35, and 56 days of age. Male lde/lde rats showed severely retarded growth of the testes and accessory sex organs. Their seminiferous tubules were significantly smaller and contained markedly fewer germ cells at all time points examined as compared with controls. Significantly fewer Sertoli cells at 21 and 28 days of age, markedly decreased spermatocyte number at 28 days of age, and delayed appearance of spermatids at 56 days of age were observed in the testes of lde/lde rats. More TUNEL (T&T-mediated duTP-biotin nick-end labeling)-positive cells were detected in lde/lde seminiferous tubules, and the largest number of apoptotic cells was recorded at 28 days of age. The increases in 3beta-hydroxysteroid dehydrogenase-positive adult-type Leydig cells and 11beta-hydroxysteroid dehydrogenase-positive mature adult-type Leydig cells were also severely retarded in the testes of lde/lde rats. Consistent with these defects, significantly lower plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were detected in lde/lde males at 28 days of age, and weak immunostaining for FSH and smaller cytoplasm of LH-positive cells were detected in the anterior pituitary lobes of lde/lde males. Despite a normal level of plasma LH after 35 days of age, a significantly lower level of plasma testosterone was detected at 56 days of age. These results indicate that the normal lde allele is related to prepubertal elevations of gonadotropins and normal development of adult-type Leydig cells. Because lde/lde rats experience epileptic seizures during the period when the hypothalamus-pituitary-testicular axis is established, lde/lde rats would be useful as a model for reproductive disorder with pediatric epilepsy.

Protective effects of persian honey, Apis Mellifera Meda Skorikov on side effects of chemotherapy and ischemia/reperfusion induced testicular injury.

PubMed

Gholami, Mohammadreza; Abbaszadeh, Abolfazl; Baharvand, Parastoo; Hasanvand, Afshin; Hasanvand, Amin; Gharravi, Anneh Mohammad

2018-05-23

Introduction The aim of the present study was to survey the protective effect of pretreatment with Persian honey on amelioration of side effects of chemotherapy and ischemia/reperfusion induced testicular injury. Materials and methods Forty adult's male wistar rats were divided into four groups of ischemia-reperfusion (IR), honey + ischemia-reperfusion (HIR), Busulfan (B) and Busulfan intraperitoneally+ honey (BH). The seminiferous tubules were rated for their modified spermatogenesis index (SI) by Johnsons score. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed using the in-situ cell death detection kit. Total serum concentration of Follicle-stimulating hormone (FSH) , Luteinizing hormone (LH) and testosterone was measured using ELISA. All data were expressed as mean ± SD and significance was set at p≤0.05. Results Honey improved SI in the HIR and BH groups and serum levels of FSH and LH in the BH and HIR groups (p<0.001). Also, serum levels of testosterone were significantly higher in BH and HIR groups. But, apoptotic cells in IR and B groups significantly increased (p<0.001), while in HIR and BH groups, the number of apoptotic cells decreased and the positive cells of TUNEL (TdT-mediated dUTP-X nick end labelling) staining were detected in spermatocytes and spermatid. Discussion Pretreatment with honey protect testis against chemotherapy and testicular IR injury, increase FSH and LH and testosterone and decrease the cellular damage and apoptosis. Honey can decrease the side effects of chemotherapy on reproductive system and prevent sterility.

Occult Form of Premature Ovarian Insufficiency in Women with Infertility and Oligomenorrhea as Assessed by Poor Ovarian Response Criteria.

PubMed

Izhar, Rubina; Husain, Samia; Tahir, Suhaima; Husain, Sonia

2017-01-01

The purpose of this study was to evaluate the ability of poor ovarian response criteria to classify women presenting with infertility and oligomenorrhea as having "occult" premature ovarian insufficiency. This was a cross sectional study conducted at Aziz Medical Center, Karachi, Pakistan from 1st August 2015 to 31st July 2016. Women with infertility and oligomenorrhea were included. All eligible women underwent day 2 FSH level and an early follicular phase transvaginal ultrasound to assess the antral follicular count (AFC). All women then underwent the confirmatory test, of Anti-Mullerian Hormone (AMH) level. The main outcome measure was assignment to occult premature ovarian insufficiency (POI) after screening that used the criteria set out in fertility guideline for predicting the likely ovarian response to gonadotrophin stimulation. Another measure was to compare the sensitivity and specificity of the two index criteria, of FSH and AFC, relative to the emerging reference standard, of the AMH criterion. The three criteria together classified 59 (34.91%) women as occult POI in those with oligomenorrhea. The sensitivity, specificity, negative predictive value and positive predictive value of FSH relative to AMH for these women were 77.8%, 95.7%, 90.2% and 89.4%, respectively whereas the same values of AFC relative to AMH were 92.6%, 99.1 %, 96.6% and 98%, respectively. Women with menstrual irregularity and infertility are at a higher risk for satisfying criteria of poor ovarian response irrespective of age. A policy incorporating these surrogate markers can be used to screen these women for occult premature ovarian insufficiency.

Effects of Metformin on Endocrine and Metabolic Parameters in Patients with Polycystic Ovary Syndrome.

PubMed

Zahra, M; Shah, M; Ali, A; Rahim, R

2017-02-01

The present study was designed to evaluate the effects of metformin on metabolic and endocrine parameters in patients with polycystic ovary syndrome (PCOS). The study included 40 patients with PCOS. Patients were divided into 2 groups based on whether they will receive metformin (500 mg 3 times a day, n=20) or placebo (n=20) for 3 consecutive months. Serum concentrations of fasting blood glucose, insulin, HOMA-IR, INSL-3, visfatin, FSH, and LH were measured at baseline and after 3 months of therapy. The key endocrine and metabolic parameters significantly changed after metformin treatment. The systolic and diastolic blood pressures were significantly reduced in the metformin group after treatment compared to placebo (p<0.001). A significant reduction in the size of the right ovary was observed after metformin treatment (p=0.05), while no change was found in the size of left ovary (p>0.12). Moreover, a significant reduction was observed in the serum levels of FSH (p>0.01), LH (p>0.001), and visfatin (p>0.001) after metformin treatment. However, HOMA-IR (which is used to assess insulin resistance) failed to reach the statistical significance (p=0.20). We conclude that metformin treatment in females with PCOS showed significant improvement in systolic and diastolic blood pressures. In addition, an improvement in the hormonal profile in the form of reduction in LH, FSH, and visfatin levels was observed. Thus, therapeutic intervention with metformin could be of clinical importance in high-risk group of young females with PCOS. © Georg Thieme Verlag KG Stuttgart · New York.

Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.

1991-06-01

The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from (1B-3H)androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity inmore » response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures.« less

Lower sperm DNA fragmentation after r-FSH administration in functional hypogonadotropic hypogonadism.

PubMed

Ruvolo, Giovanni; Roccheri, Maria Carmela; Brucculeri, Anna Maria; Longobardi, Salvatore; Cittadini, Ettore; Bosco, Liana

2013-04-01

An observational clinical and molecular study was designed to evaluate the effects of the administration of recombinant human FSH on sperm DNA fragmentation in men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In the study were included 53 men with a non-classical form of hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia. In all patients, sperm DNA fragmentation index (DFI), assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) in situ DNA nick end-labelling (TUNEL) assay, was evaluated before starting the treatment with 150 IU of recombinant human FSH, given three times a week for at least 3 months. Patients' semen analysis and DNA fragmentation index were re-evaluated after the 3-month treatment period. After recombinant human FSH therapy, we did not find any differences in terms of sperm count, motility and morphology. The average DNA fragmentation index was significantly reduced (21.15 vs 15.2, p<0.05), but we found a significant reduction in patients with high basal DFI values (>15 %), while no significant variation occurred in the patients with DFI values ≤ 15 %. Recombinant human FSH administration improves sperm DNA integrity in hypogonadotropic hypogonadism and idiopathic oligoasthenoteratozoospermia men with DNA fragmentation index value >15 % .

[Effect of low-dose or standard-dose conjugated equine estrogen combined with different progesterone on bone density in menopause syndrome women].

PubMed

Zuo, H L; Deng, Y; Wang, Y F; Gao, L L; Xue, W; Zhu, S Y; Ma, X; Sun, A J

2018-04-25

Objective: To explore the effect of low-dose or standard-dose conjugated equine estrogen (CEE) combined with natural progesterone or dydrogesterone on bone density in menopause syndrome women. Methods: Totally 123 patients with menopause syndrome were recruited and randomly assigned to 3 treatment groups: group A (low-dose CEE+progesterone) , group B (standard-dose CEE+progesterone) , group C (standard-dose CEE+dydrogesterone) . Using continuous sequential regimen, the duration of intervention was 12 cycles. The bone mineral density of lumbar 2-4 and neck of femur, the bone metabolic markers, the level of FSH and estradiol were examined just before the drug administration and 12 months after the beginning of experiment. Results: There were 107 cases completed the one year trial. (1) Bone density: after 12 cycles of treatment, there was no significant change in bone density in group A ( P> 0.05) ; lumbar vertebrae of group B and C increased significantly, at 3.0% and 2.1%respectively (all P< 0.05) . The bone density of left femoral neck of group C significantly increased by 2.9% ( P= 0.029) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (2) Bone metabolic markers: after 12 cycles of treatment, the levels of calcium, phosphorus, alkaline phosphatase, Ca/Cr decreased significantly, the difference were statistically significant (all P< 0.05) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . (3) Levels of FSH and estradiol: after 12 cycles of treatment, the levels of FSH in three groups were decreased significantly (all P< 0.01) . The levels of estradiol in three groups were increased significantly (all P< 0.01) . There was no significant difference among the treatment groups at the beginning of experiment ( P> 0.05) . Conclusions: Both low-dose and standard-dose menopause hormone therapy (MHT) could elevate the level of estradiol, reduce bone turnover, prevent bone loss of postmenopausal women effectively. The standard dose of MHT could also increase the density of vertebrae and femoral neck, and generate more clinical benefits.

Longitudinal development of hormone levels and grey matter density in 9 and 12-year-old twins.

PubMed

Brouwer, Rachel M; Koenis, M M G; Schnack, Hugo G; van Baal, G Caroline; van Soelen, Inge L C; Boomsma, Dorret I; Hulshoff Pol, Hilleke E

2015-05-01

Puberty is characterized by major changes in hormone levels and structural changes in the brain. To what extent these changes are associated and to what extent genes or environmental influences drive such an association is not clear. We acquired circulating levels of luteinizing hormone, follicle stimulating hormone (FSH), estradiol and testosterone and magnetic resonance images of the brain from 190 twins at age 9 [9.2 (0.11) years; 99 females/91 males]. This protocol was repeated at age 12 [12.1 (0.26) years] in 125 of these children (59 females/66 males). Using voxel-based morphometry, we tested whether circulating hormone levels are associated with grey matter density in boys and girls in a longitudinal, genetically informative design. In girls, changes in FSH level between the age of 9 and 12 positively associated with changes in grey matter density in areas covering the left hippocampus, left (pre)frontal areas, right cerebellum, and left anterior cingulate and precuneus. This association was mainly driven by environmental factors unique to the individual (i.e. the non-shared environment). In 12-year-old girls, a higher level of circulating estradiol levels was associated with lower grey matter density in frontal and parietal areas. This association was driven by environmental factors shared among the members of a twin pair. These findings show a pattern of physical and brain development going hand in hand.

The utility of the gonadotrophin releasing hormone (GnRH) test in the diagnosis of polycystic ovary syndrome (PCOS).

PubMed

Lewandowski, Krzysztof C; Cajdler-Łuba, Agata; Salata, Ireneusz; Bieńkiewicz, Małgorzata; Lewiński, Andrzej

2011-01-01

Polycystic ovary syndrome (PCOS) is characterised by increased frequency of hypothalamic GnRH pulses leading to a relative increase in LH synthesis by the pituitary. As GnRH stimulation can reveal a relative LH excess, we have endeavoured to assess whether GnRH test might be useful in the diagnosis of PCOS. The study involved 185 subjects: a PCOS group, n = 151, all with oligo- or amenorrhoea, aged (mean ± SD) 24.8 ± ± 5.4 years, BMI 24.5 ± 6.0 kg/m²; and regularly menstruating controls, n = 34, aged 26.6 ± 5.0 years, BMI 24.6 ± 5.5 kg/m². In 121 subjects with PCOS and in 32 controls, serum LH and FSH were measured before (0 minutes) and 30 and 60 minutes after GnRH stimulation (100 μg i.v.). Insulin resistance was assessed by HOMA and Insulin Resistance Index derived from glucose and insulin concentrations during 75 gram oral glucose tolerance test. Women with PCOS had higher testosterone (p = 0.0002), androstendione (p = 0.0021), 17OH-progesterone (p < 0.0001) and were more insulin resistant. Raised concentrations of at least one androgen were, however, found only in 58.1% of women with PCOS. Baseline and stimulated LH concentrations were higher in PCOS (9.09 ± 5.56 vs 4.83 ± 1.71 IU/L, 35.48 ± 31.4 vs 16.30 ± 6.68 IU/L, 33.86 ± 31.8 vs 13.45 ± 5.2 IU/L, at 0, 30 and 60 mins post GnRH, respectively, p < 0.0001). There was no difference in baseline or stimulated FSH concentrations between groups. Relative increases of LH or FSH in comparison to respective baseline values were similar in both groups. There was, however, a marked increase in LH/FSH ratio in PCOS in comparison to controls (LH0 min/FSH(₀ min) 1.59 ± 0.95 vs 0.76 ± 0.2, LH(₃₀ min) /FSH(₃₀ min) 4.07 ± 3.0 vs 1.89 ± 0.79, LH(₆₀ min)/FSH(₆₀ min) 3.56 ± 2.58 vs 1.55 ± 0.63, p < 0.0001 at all time points). Further analysis revealed that LH30 min/FSH(₃₀ min) > 2.11 or LH(₆₀ min)/FSH(₆₀ min) > 1.72 had 78.3% and 87.5% sensitivity and 81.7% and 81.3% specificity for the diagnosis of PCOS, respectively. Women with PCOS have higher baseline and GnRH-stimulated LH concentrations. GnRH stimulation results in an increase in LH/FSH ratio in women with PCOS. Therefore we postulate that this phenomenon might be potentially useful as an additional tool in the diagnosis of PCOS.

[The role of gonadal peptides in clinical investigation].

PubMed

Lahlou, N; Bouvattier, C; Linglart, A; Rodrigue, D; Teinturier, C

2009-01-01

Inhibins, activins, and anti-Mullerian hormone (AMH) are gonadal dimeric peptides produced in ovaries and testes by homologous cells, granulosa cells and Sertoli cells, respectively. The production of inhibins is driven by FSH, that of AMH may indirectly depends on FSH, while it is down regulated, at least in the male, by testosterone. In the past decade, measurements of serum inhibin and AMH have provided useful tools for clinical investigation in gonadal disorders: pseudohermaphroditism, androgen insensitivity, anorchidism, gonadal dysgenesis, disorders of pubertal developpement. Inhibins, activins, and AMH are also reliable markers of gonadal tumors. They are extensively used as indexes of fertility: in the male the production of inhibin B reflects the spermatogenetic activity, in women both inhibin B and AMH levels are correlated with the number of preantral and early antral follicles and reflect the ovarian reserve of follicles available for recruitment.

In vitro production of sheep embryos using laparoscopic folliculocentesis: alternative gonadotrophin treatments for stimulation of oocyte donors.

PubMed

Baldassarre, H; Furnus, C C; De Matos, D G; Pessi, H

1996-02-01

Three different gonadotrophin regimens for the stimulation of donors for laparoscopic folliculocentesis were tested in a total of 142 ewes. The recovered oocytes were subjected to in vitro maturation, fertilization, and culture (IVM/IVF/IVC) for 7 d using standard procedures for sheep. The estrous cycles of all ewes were synchronized using intravaginal sponges containing 60 mg of medroxyprogesterone acetate (MPA) inserted for 14 d. In Experiment 1, all ewes were superovulated with a total dose of 125 IU FSH and 125 IU LH. One-half of the ewes received the gonadotrophin treatment in 4 decreasing doses at 12-h intervals starting 48 h before follicle aspiration (Control), while the other half received the total dose in a single injection at -24 h before collection (Oneshot). There were no significant differences between treatments for recovery rate (81.6 +/- 5.3 vs 77.4 +/- 10.3), cleavage rate (60.6 +/- 20.8 vs 61.4 +/- 23.4), or normal development to the blastocyst stage (20.8 +/- 18.2 vs 13.1 +/- 10.3). However, a higher percentage of ewes produced at least 1 normal blastocyst in the Control group (56.4 vs 31.6%; P < 0.05). In Experiment 2, the control regimen was repeated in half of the ewes, while the remainder were treated with half of the FSH total dose plus 500 IU eCG in a single injection at -24 h before oocyte collection (Oneshot-eCG). The recovery rate (80.9 +/- 5.6 vs 73.3 +/- 15.3), cleavage rate (76.8 +/-19.9 vs 79.7 +/- 22.6), normal development to blastocysts (19.2 +/- 15.3 vs 23.3 +/- 10.7), and percentage of ewes producing at least 1 normal blastocyst (55.9 vs 51.6%) did not differ between treatments. The large variability observed between ewes in the production of normal blastocysts is comparable to that observed with standard MOET procedures, in which a proportion of donors fail to produce good embryos. With the in vitro procedures described here, we were able to produce normal embryos from more than half of the treated ewes, indicating that the technology is useful for the multiplication of genetically valuable animals affected by temporary or irreversible infertility.

[From theory to clinical practice: recombinant FSH in daily practice].

PubMed

Kably Ambe, A; Barrón Vallejo, J; Góngora Rodríguez, A; Carballo Mondragón, E; Anta Jaén, E

1999-08-01

The purpose of the present study is to determine the efficacy of induction ovulation with recombinant FSH in patients treated with in vitro fertilization and embryo transfer (IVF-ET) and basic assisted reproductive techniques (ART). One hundred seven cycles were analyzed. The patients were divided in two groups: Group 1, treated with IVF (n = 12) and group 2, treated with basic ART (n = 95). Only recombinant FSH was utilized for ovulation induction; human corionic gonadotropin (hCG), 10,000 IU, were administered when one or more dominant follicles with diameter > or = 18 mm were presents; oocyte retrieval was performed 34 hour, while intrauterine insemination was practiced at 36 hours after the hCG injection. The pregnancy rate per IVF cycle was 25.0%, and 16.4% for basic ART. It is concluded that ovulation induction with recombinant FSH is a good and efficient alternative for both variations of ART.

Tumor necrosis factor-308 polymorphism increases the embryo implantation rate in women undergoing in vitro fertilization.

PubMed

Vialard, F; El Sirkasi, M; Tronchon, V; Boudjenah, R; Molina-Gomes, D; Bergere, M; Mauduit, C; Wainer, R; Selva, J; Benahmed, M

2013-10-01

Do TNF-308 and -238 polymorphisms impact the embryo implantation rate after in vitro fertilization (IVF) in women without female infertility factor? The presence of the TNF-308A allele is associated with high implantation and multiple pregnancy rates in women without known infertility factors after ovarian hyperstimulation with exogenous FSH. Multiple pregnancies are frequent after the use of Assisted Reproductive Technologies. Single embryo transfer (SET) has been proposed as a simple way to prevent these risks. However, the extension of SET indications to patients not selected based on specific criteria is controversial because of reduced pregnancy rates. To date, the predictive value of the parameters used for SET (age, gynecological history of the patient and uterine characteristics) allows a pregnancy rate of ~30%. The potential predictive value of TNF polymorphisms (-308, rs1800629 and -238, rs361525) on implantation rate was evaluated in 424 women requiring IVF due to male fertility factors. This cohort retrospective study was conducted over 4 years in University-affiliated hospitals. The entire patient group included 424 women undergoing intracytoplasmic sperm injection (ICSI) due to male fertility factors without the contribution of any female factor. From among this group, a selected patient group included 120 women with a normal karyotype, age under 38 years, serum follicle-stimulating hormone (Day-3 FSH) levels below 10 IU/l, a long agonist desensitization protocol associated with recombinant FSH treatment and a Caucasian background. The TNF-238 polymorphism was not associated with implantation rate. In contrast, the presence of the TNF-308A allele was associated with increased Day 3-E2 levels as well as higher implantation and multiple pregnancy rates after fresh embryo transfer in women from the entire and selected patient groups. Moreover, in the selected patient group, the presence of the TNF-308A allele was also associated with a decrease in the miscarriage rate. The benefit of the TNF-308A allele in predicting implantation rates was not observed after the use of frozen embryos. Future studies are needed to evaluate whether the TNF-308A allele might also be a biomarker in women with infertility factors. The TNF-308A allele may represent a good candidate for a potential predictive, non-invasive biomarker in the SET strategy. However, its impact should be evaluated in prospective studies. This study was conducted with financial support from the French Institute for Health and Medical Research (INSERM), Organon France for a FARO (Fond d'Aide à la Recherche Organon) fellowship (to V.T.) and CHU Nice PHRC (PHRC 09-279).There are no competing interests.

Vitamin D Alters Genes Involved in Follicular Development and Steroidogenesis in Human Cumulus Granulosa Cells

PubMed Central

Doswell, Angela; Krebs, Kendall; Cipolla, Marilyn

2014-01-01

Context: Vitamin D deficiency is common among reproductive-aged women and has a role in female reproduction. Objective: This study evaluated the role of 1,25-dihydroxyvitamin D3 (vit D3) in ovarian follicular development and steroidogenesis by using a human granulosa cell (GC) model. Design, Setting, and Participants: Fifty-four women who underwent in vitro fertilization were enrolled. Intervention: Follicular fluid (FF) and mural and cumulus GCs were collected from small and large follicles. In separate experiments, primary cumulus GCs were cultured with or without vit D3 followed by RT-PCR for mRNA expression levels. The effect of recombinant anti-Mullerian hormone (AMH) on nuclear localization of phospho-Smad 1/5/8 was evaluated in the presence or absence of vit D3 by using immunofluorescence. 25-Hydroxyvitamin D levels in FF as well as cell culture media AMH, progesterone, and estradiol (E2) concentrations were determined by ELISA and RIA. Main Outcome Measures: The following were measured: 1) mRNA expression levels; 2) 3β-hydroxysteroid dehydrogenase (3β-HSD) enzyme activity; 3) FSH-induced aromatase mRNA and E2 production; and 4) nuclear localization of phospho-Smad 1/5/8. Results: In a multivariate analysis, 25 OH-D levels in FF negatively correlated with AMH and AMH receptor (AMHR)-II mRNA levels in cumulus GCs of small follicles. Compared with women with replete 25-hydroxyvitamin D levels in FF, those with insufficient/deficient levels had a 2-fold increase in AMHR-II mRNA levels in cumulus GCs of small follicles (P = .02). Treatment with vit D3 caused a decrease in AMHR-II and FSH receptor mRNA but an increase in 3-βHSD mRNA levels compared with control (P < .05). Vit D3 enhanced 3-βHSD enzyme activity as assessed by increasing progesterone release; however, vit D3 did not affect FSH-induced aromatase mRNA and E2 production, but it decreased the phosphorylation of Smad 1/5/8 and its nuclear localization. Conclusion: These data suggest that vit D3 alters AMH signaling and steroidogenesis in human cumulus GCs, possibly reflecting a state of GC luteinization potentiation. PMID:24628555

Disordered follicle development

PubMed Central

Chang, R. Jeffrey; Cook-Andersen, Heidi

2013-01-01

Alterations of ovarian follicle morphology and function have been well documented in women with PCOS. These include increased numbers of growing preantral follicles, failure of follicle growth beyond the mid-antral stage, evidence of granulosa call degeneration, and theca cell hyperplasia. Functional abnormalities include paradoxical granulosa cell hyperresponsiveness to FSH which is clinically linked to ovarian hyperstimulation during ovulation induction. In addition, there is likely a primary theca cell defect that accounts for the majority of excess androgen production in this disorder. The precise mechanisms responsible for altered follicle function are not completely clear. However, several factors appear to influence normal advancement of follicle development as well as impair ovarian steroidogenesis. These include intra- as well as extraovarian influences that distort normal ovarian growth and disrupt steroid production by follicle cells. PMID:22874072

Development of male contraceptive vaccine--a perspective.

PubMed

Moudgal, N R; Jeyakumar, M; Krishnamurthy, H N; Sridhar, S; Krishnamurthy, H; Martin, F

1997-01-01

This paper reviews the recent advances that have occurred in the area of development of a male contraceptive vaccine. The vaccine candidates considered for review are hormone/hormone receptor-based proteins including luteinizing hormone-releasing hormone (LHRH)/LH, follicle stimulating hormone (FSH), as well as LH and FSH receptor proteins. The review also highlights the advances in our basic understanding of gonadotrophin action which have led to development of these vaccines. Focus is mainly on studies in the non-human primate which may be directly relevant to projected studies in the human. The data indicate that the vaccines are well tolerated by the primate (including the human based on limited data) and do not give rise to any known toxic symptoms or immediate health hazards. The response to the immunogen has been uniform and it may be possible to increase antibody titres as well as prolong the immune response by adding acceptable immune stimulators to the adjuvant cocktail and developing better immunization schedules or immunogen delivery systems. Contraceptive vaccines for the male are a feasible proposition and attention should now be focussed on evaluating carefully the bioefficacy of antibodies raised to recombinant ovine FSHbeta or FSH receptor protein fragments in both human and non-human primates. The advantage of the FSH/FSH receptor over the LHRH/LH-based vaccine lies in the fact that the former does not require an exogenous testosterone supplement to maintain accessory gland function, libido etc. The LHRH/LH-based vaccine results in azoospermia, while the FSH vaccine causes the production of low numbers of poor quality spermatozoa which are incapable of impregnating cycling females.

Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

PubMed

Fouda, Usama M; Sayed, Ahmed M

2011-12-01

To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

HP-HMG versus rFSH in treatments combining fresh and frozen IVF cycles: success rates and economic evaluation.

PubMed

Wex-Wechowski, Jaro; Abou-Setta, Ahmed M; Kildegaard Nielsen, Sandy; Kennedy, Richard

2010-08-01

The economic implications of the choice of gonadotrophin influence decision making but their cost-effectiveness in frozen-embryo transfer cycles has not been adequately studied. An economic evaluation was performed comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) using individual patient data (n=986) from two large randomized controlled trials using a long agonist IVF protocol. The simulation model incorporated live birth data and published UK costs of IVF-related medical resources. After treatment for up-to-three cycles (one fresh and up to two subsequent fresh or frozen cycles conditional on availability of cryopreserved embryos), the cumulative live birth rate was 53.7% (95% CI 49.3-58.1%) for HP-HMG and 44.6% (40.2-49.0%) for rFSH (OR 1.44, 95% CI 1.12-1.85; P<0.005). The mean costs per IVF treatment for HP-HMG and rFSH were pound5393 ( pound5341-5449) and pound6269 ( pound6210-6324), respectively (number needed to treat to fund one additional treatment was seven; P<0.001). With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound11,157 ( pound11,089-11,129) and pound14,227 ( pound14,183-14,222) with rFSH (P<0.001). The cost saving using HP-HMG remained after varying model parameters in a probabilistic sensitivity analysis. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

[Chronic active Epstein-Barr virus infection treated with reduced intensity stem cell transplantation].

PubMed

Sakata, Naoki; Sato, Emiko; Sawada, Akihisa; Yasui, Masahiro; Inoue, Masami; Kawa, Keisei

2004-05-01

A 31-year-old woman had been suffering from fever and a sore throat since January 1999, and had a left neck lymphadenopathy in December 1999. Pathological findings of the biopsied lymphnode suggested malignant lymphoma. She was finally diagnosed as having a chronic active Epstein-Barr virus(EBV) infection because of abnormal antibody titers against EBV antigens and an increased EBV load in her peripheral blood. After receiving chemotherapy consisting of CHOP and high dose cytarabine, the amount of the EBV genome decreased below the detection limit before BMT. Therefore, instead of a conventional myeloablative transplant, we performed BMT using reduced-intensity conditioning regimens consisting of fludarabine and melphalan from an HLA-identical sibling donor. After 14 months, the patient remained in complete remission. Menstruation occurred on day 83 following BMT, and the serum level of LH and FSH on day 316 were within normal range. Under these circumstances, RIST seems to be one of the curative treatments for the patients with CAEBV with minimal late side effects.

Ursodeoxycholic acid alleviates cholestasis-induced histophysiological alterations in the male reproductive system of bile duct-ligated rats.

PubMed

Saad, Ramadan A; Mahmoud, Yomna I

2014-12-01

Ursodeoxycholic acid is the most widely used drug for treating cholestatic liver diseases. However, its effect on the male reproductive system alterations associated with cholestasis has never been studied. Thus, this study aimed to investigate the effect of ursodeoxycholic acid on cholestasis-induced alterations in the male reproductive system. Cholestasis was induced by bile duct ligation. Bile duct-ligated rats had higher cholestasis biomarkers and lower levels of testosterone, LH and FSH than did the Sham rats. They also had lower reproductive organs weights, and lower sperm motility, density and normal morphology than those of Sham rats. Histologically, these animals suffered from testicular tubular atrophy, interstitial edema, thickening of basement membranes, vacuolation, and depletion of germ cells. After ursodeoxycholic acid administration, cholestasis-induced structural and functional alterations were significantly ameliorated. In conclusion, ursodeoxycholic acid can ameliorate the reproductive complications of chronic cholestasis in male patients, which represents an additional benefit to this drug. Copyright © 2014 Elsevier Inc. All rights reserved.