Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

PubMed

Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

2016-10-01

Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

Hormone replacement therapy and risk of malignancy.

PubMed

Diamanti-Kandarakis, Evanthia

2004-02-01

The fact that today our concern is oriented towards the risks rather than the benefits of hormone replacement therapy could be the clearest message about our current position. The safety of hormone replacement therapy, an estrogen-progestin combination which has been sympathetic to and supportive of disturbing menopausal symptoms of women, is seriously challenged. Four randomized trials have now reported on the results of hormone replacement therapy in major potentially fatal conditions, in more than 20,000 women studied for about 5 years. The main concern regarding the increased risk of malignancy in healthy postmenopausal women in western countries has been breast cancer. It is estimated to cause an extra case in about six per 1000 users aged 50-59 and 12 per 1000 aged 60-69. Over the same period the estimated risk of endometrial cancer rates are not increased, with a relative risk of 0.76 per 1000 users aged 50-59. Overall, however, the increased incidence of malignancies is greater than any reduction, one per 230 users aged 50-59 and one per 150 aged 60-69. Randomized trials examining other important but rarer malignancies, like ovarian, gall bladder and urinary bladder cancer, are either nonexistent or too small to reliably describe any effects of hormone replacement therapy. Conclusively epidemiological evidence suggests that hormone replacement therapy is associated with a small but substantial increase in breast cancer risk and combined estrogen-progesterone regimens further increase this hazard. Additionally, the evidence from the recent double blind placebo controlled randomized trial on the slight increase in the incidence of adverse cardiovascular events, has turned our orientation away from hormone replacement therapy as a long term therapy in postmenopausal women. In this review, the effort is to approach comprehensively and globally the information on the risks of hormone replacement therapy on several cancer sites.

Molecular evolution of the neurohypophysial hormone precursors in mammals: Comparative genomics reveals novel mammalian oxytocin and vasopressin analogues.

PubMed

Wallis, Michael

2012-11-01

Among vertebrates the neurohypophysial hormones show considerable variation. However, in eutherian mammals they have been considered rather conserved, with arginine vasopressin (AVP) and oxytocin (OT) in all species except pig and some relatives, where lysine vasopressin replaces AVP. The availability of genomic data for a wide range of mammals makes it possible to assess whether these peptides and their precursors may be more variable in Eutheria than previously suspected. A survey of these data confirms that AVP and OT occur in most eutherians, but with exceptions. In a New-World monkey (marmoset, Callithrix jacchus) and in tree shrew (Tupaia belangeri), Pro(8)OT replaces OT, confirming a recent report for these species. In armadillo (Dasypus novemcinctus) Leu(3)OT replaces OT, while in tenrec (Echinops telfairi) Thr(4)AVP replaces AVP. In these two species there is also evidence for additional genes/pseudogenes, encoding much-modified forms of AVP, but in most other eutherian species there is no evidence for additional neurohypophysial hormone genes. Evolutionary analysis shows that sequences of eutherian neurohypophysial hormone precursors are generally strongly conserved, particularly those regions encoding active peptide and neurophysin. The close association between OT and VP genes has led to frequent gene conversion of sequences encoding neurophysins. A monotreme, platypus (Ornithorhynchus anatinus) has genes for OT and AVP, organized tail-to-tail as in eutherians, but in marsupials 3-4 genes are present for neurohypophysial hormones, organized tail-to-head as in lower vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

Endometrial thickness in 1,500 asymptomatic postmenopausal women not on hormone replacement therapy.

PubMed

Hartman, Alex; Wolfman, Wendy; Nayot, Dan; Hartman, Michael

2013-01-01

To determine the normal endometrial thickness (ET) on transvaginal ultrasound (TVUS) of asymptomatic postmenopausal women not on hormone replacement therapy. A subgroup that was determined to be suspicious for having an endometrial polyp was compared with the remainder. This prospective study selected 1,500 consecutive asymptomatic postmenopausal women receiving TVUS assessment from January to August 2010. ET was recorded. Results were divided into those with a normal-appearing lining (n = 1,399) and those suspicious for polyp (n = 101). Results for the entire sample were obtained and the groups were compared using independent samples t tests. Of 1,500 women aged 45-95 years, 77.1% had an ET of ≤4 mm and 92% were ≤5 mm. Independent samples t tests were performed to compare the mean age and mean ET based on polyp status (i.e. with or without a possible polyp). There was a significant difference in mean age, 67.71 vs. 62.36 years (p < 0.01) and mean ET 8.02 vs. 3.40 mm (p < 0.01) between groups. 92% of asymptomatic postmenopausal women not on hormone replacement therapy had an ET of ≤5 mm. The mean ET was 3.71 ± 1.9 mm. However, a significant group, 6.7%, had an endometrial lining suspicious for polyp. These women had a significant increase in mean age and ET. Copyright © 2013 S. Karger AG, Basel.

Effects of female steroid hormones on A-type K+ currents in murine colon.

PubMed

Beckett, Elizabeth A H; McCloskey, Conor; O'Kane, Neil; Sanders, Kenton M; Koh, Sang Don

2006-06-01

Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K(+) channels serve to set the excitability of colonic muscles. We investigated regulation of Kv 4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv 4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause.

Novel double-layer Silastic testicular prosthesis with controlled release of testosterone in vitro, and its effects on castrated rats

PubMed Central

Chen, Hui-Xing; Yang, Shi; Ning, Ye; Shao, Hai-Hao; Ma, Meng; Tian, Ru-Hui; Liu, Yu-Fei; Gao, Wei-Qiang; Li, Zheng; Xia, Wei-Liang

2017-01-01

Testicular prostheses have been used to deal with anorchia for nearly 80 years. Here, we evaluated a novel testicular prosthesis that can controllably release hormones to maintain physiological levels of testosterone in vivo for a long time. Silastic testicular prostheses with controlled release of testosterone (STPT) with different dosages of testosterone undecanoate (TU) were prepared and implanted into castrated Sprague-Dawley rats. TU oil was applied by oral administration to a separate group of castrated rats. Castrated untreated and sham-operated groups were used as controls. Serum samples from every group were collected to measure the levels of testosterone (T), follicle-stimulating hormone and luteinizing hormone (LH). Maximum intracavernous penile pressure (ICPmax) was recorded. The prostates and seminal vesicles were weighed and subjected to histology, and a terminal dexynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) assay was used to evaluate apoptosis. Our results revealed that the weights of these tissues and the levels of T and LH showed significant statistical differences in the oral administration and TU replacement groups compared with the castrated group (P < 0.05). Compared with the sham-operated group, the ICPmax, histology and TUNEL staining for apoptosis, showed no significant differences in the hormone replacement groups implanted with medium and high doses of STPT. Our results suggested that this new STPT could release TU stably through its double semi-permeable membranes with excellent biocompatibility. The study provides a new approach for testosterone replacement therapy. PMID:27174160

Menopause and Ischemic Stroke: A Brief Review

PubMed Central

Shekhar, Shashank; Travis, Olivia K; He, Xiaochen; Roman, Richard J; Fan, Fan

2017-01-01

Ischemic stroke is one of the leading causes of morbidity and mortality worldwide. Females are protected against stroke before the onset of menopause. Menopause results in increased incidence of stroke when compared to men. The mechanisms of these differences remain to be elucidated. Considering that there is a postmenopausal phenomenon and females in general, are living longer sex hormone-dependent mechanisms have been postulated to be the primary factors responsible for the premenopausal protection from stroke and later to be responsible for the higher incidence and increased the severity of stroke after menopause. Animal studies suggest that administration of estrogen and progesterone is neuroprotective and decreases the incidence of stroke. However, the real-world outcomes of hormone replacement therapy have failed to decrease the stroke risk. Despite the multifactorial nature of sex differences in stroke, here, we briefly discuss the pathophysiology of sex steroid hormones, the molecular mechanisms of estrogen receptor-dependent signaling pathways in stroke, and the potential factors that determine the discrepant effects of hormone replacement therapy in stroke. PMID:28936482

Hormonal treatment, mild cognitive impairment and Alzheimer's disease

PubMed Central

Ryan, Joanne; Scali, Jaqueline; Carriere, Isabelle; Ritchie, Karen; Ancelin, Marie-Laure

2008-01-01

A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy trials in non-demented post-menopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer’s disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women’s Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using hormonal replacement therapy compared to controls. Apart from methodological differences, one key short-coming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia. PMID:18072983

Prepubertal Gynecomastia Due to Indirect Exposure to Nonformulary Bioidentical Hormonal Replacement Therapy: A Case Report.

PubMed

De Pinho, Joao Correia; Aghajanova, Lusine; Herndon, Christopher N

2016-01-01

Gynecomastia is a disorder of the endocrine system characterized by an abnormal presence of a palpable unilateral or bilateral enlargement and proliferation of glandular ductal benign breast tissue in male individuals. This case discusses the medical implications of an unregulated, indirect exposure to nonformulary, bioidentical hormone replacement therapy in male children. An 8-year-old boy presented with prepubertal gynecomastia secondary to estrogen exposure from maternal use of bioidentical hormonal replacement therapy (the Wiley protocol). We review the literature on prepubertal gynecomastia secondary to exogenous estrogen exposure, evaluation, clinical surveillance of the pubertal development, and relevant short- and long-term implications. Indirect exposure to nonformulary hormonal replacement in our case report was an etiologic factor in the development of prepubertal gynecomastia. This novel estrogen exposure source has important implications in the differential diagnosis of prepubertal gynecomastia and potential adverse effects secondary to precocious hormonal exposure.

Effects of thyroid hormone manipulation on pre-nuptial molt, luteinizing hormone and testicular growth in male white-crowned sparrows (Zonotrichia leuchophrys gambelii).

PubMed

Pérez, Jonathan H; Meddle, Simone L; Wingfield, John C; Ramenofsky, Marilyn

2018-01-01

Most seasonal species rely on the annual change in day length as the primary cue to appropriately time major spring events such as pre-nuptial molt and breeding. Thyroid hormones are thought to be involved in the regulation of both of these spring life history stages. Here we investigated the effects of chemical inhibition of thyroid hormone production using methimazole, subsequently coupled with either triiodothyronine (T3) or thyroxine (T4) replacement, on the photostimulation of pre-nuptial molt and breeding in Gambel's white-crowned sparrows (Zonotrichia leuchophrys gambelii). Suppression of thyroid hormones completely prevented pre-nuptial molt, while both T3 and T4 treatment restored normal patterns of molt in thyroid hormone-suppressed birds. Testicular recrudescence was blocked by methimazole, and restored by T4 but not T3, in contrast to previous findings demonstrating central action of T3 in the photostimulation of breeding. Methimazole and replacement treatments elevated plasma luteinizing hormone levels compared to controls. These data are partially consistent with existing theories on the role of thyroid hormones in the photostimulation of breeding, while highlighting the possibility of additional feedback pathways. Thus we suggest that regulation of the hypothalamic pituitary gonad axis that controls breeding may be more complex than previously considered. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Growth hormone replacement normalizes impaired fibrinolysis: new insights into endothelial dysfunction in patients with hypopituitarism and growth hormone deficiency.

PubMed

Miljic, D; Miljic, P; Doknic, M; Pekic, S; Stojanovic, M; Cvijovic, G; Micic, D; Popovic, V

2013-12-01

Cardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far. To investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement. Hospital based, interventional, prospective study. Twenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI). Anthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH. At baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to 22.0(9.0-33.0) nmol/l after one month of treatment; p<0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of treatment; p<0.01]. Growth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications. © 2013.

Progesterone

MedlinePlus

... is used as a part of hormone replacement therapy in women who have passed menopause (the change ... hysterectomy (surgery to remove the uterus). Hormone replacement therapy usually includes estrogen, which is used to treat ...

The impact of long-lasting preemptive epidural analgesia before total hip replacement on the hormonal stress response. A prospective, randomized, double-blind study.

PubMed

Al Oweidi, Abdelkarim S; Klasen, Joachim; Al-Mustafa, Mahmoud M; Abu-Halaweh, Sami A; Al-Zaben, Khaled R; Massad, Islam M; Qudaisat, Ibrahim Y

2010-06-01

Recent studies suggest that preemptive analgesia may be effective in reducing postoperative pain. One physiologic explanation may be interference with the endogenous opioid response. We investigated whether long-lasting preoperative preemptive analgesia may have an effect on the hormonal stress response after total hip replacement. 42 patients scheduled for elective hip replacement for coxarthrosis were randomized to receive, on the day before the operation, either 5 ml*h(-1) ropivacaine 0.2% (study group, n = 21) or 5 ml*h(-1) saline (control group, n = 21). Postoperative analgesia was achieved in both groups by patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2%. The main outcome measure was the concentration of authentic beta-endorphin [1-31] in plasma up to 4 days after surgery. Additional parameters included concentrations of adrenocorticotrope hormone and cortisol. Both groups were comparable concerning preoperative parameters and pain scores. Epidural blocks were sufficient in all patients for operative analgesia. Preemptive analgesia was performed for 11-20 hours in both groups and led to significantly decreased pain scores before surgery. Preemptive analgesia with epidural ropivacaine did not lead to decreased concentrations of beta-endorphin [1-31] before the start of surgery or in the postoperative period. Furthermore, no differences could be detected in the time course of beta-endorphin and adrenocorticotrope hormone after surgery. However, cortisol concentrations differed significantly between groups before the operation, but showed a comparable rise after surgery. Differences in postoperative pain after preemptive analgesia do not seem to be due to an altered endogenous opioid response.

Exogenous hormone use, reproductive history and risk of adult myeloid leukaemia.

PubMed

Poynter, J N; Fonstad, R; Blair, C K; Roesler, M; Cerhan, J R; Hirsch, B; Nguyen, P; Ross, J A

2013-10-01

A hormonal aetiology is one explanation for the lower incidence of myeloid leukaemia in women compared with men. In this population-based case-control study, we evaluated associations between exogenous hormone use and reproductive history and myeloid leukaemia, overall and by disease subtype. We observed a suggestive association between oral contraceptive use and acute myeloid leukaemia (odds ratio=0.55, 95% confidence interval=0.32-0.96). Hormone replacement therapy and reproductive factors were not associated with risk. Despite the biological plausibility for a role of oestrogen in leukaemogenesis, other aetiologic factors are likely to explain the differing incidence rates in males and females.

Hypopituitarism.

PubMed

Higham, Claire E; Johannsson, Gudmundur; Shalet, Stephen M

2016-11-12

Hypopituitarism refers to deficiency of one or more hormones produced by the anterior pituitary or released from the posterior pituitary. Hypopituitarism is associated with excess mortality, a key risk factor being cortisol deficiency due to adrenocorticotropic hormone (ACTH) deficiency. Onset can be acute or insidious, and the most common cause in adulthood is a pituitary adenoma, or treatment with pituitary surgery or radiotherapy. Hypopituitarism is diagnosed based on baseline blood sampling for thyroid stimulating hormone, gonadotropin, and prolactin deficiencies, whereas for ACTH, growth hormone, and antidiuretic hormone deficiency dynamic stimulation tests are usually needed. Repeated pituitary function assessment at regular intervals is needed for diagnosis of the predictable but slowly evolving forms of hypopituitarism. Replacement treatment exists in the form of thyroxine, hydrocortisone, sex steroids, growth hormone, and desmopressin. If onset is acute, cortisol deficiency should be replaced first. Modifications in replacement treatment are needed during the transition from paediatric to adult endocrine care, and during pregnancy. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Panhypopituitarism in one identical twin: the effect of hormone replacement].

PubMed

Del Canho, Harrij; van Alfen-van der Velden, Janiëlle; del Canho, Riwka; Otten, Barto

2011-01-01

Panhypopituitarism in childhood is rare. It is even rarer if the disorder appears in a boy with an identical but healthy twin brother. In such a patient it is useful to study the consequences of the hormone disorder and the effect of hormone replacement. A 6-year-old boy saw a paediatrician because of short stature. He was much shorter than his identical twin brother and he had more abdominal fat mass and a smaller penis. Laboratory tests identified hypothyroidism of central origin, in combination with hypocortisolism and growth hormone deficiency. Hormonal replacement resulted in an improvement in growth rate. At the age of 15 years, testosterone therapy was introduced because puberty had not occurred and his growth rate was low. Finally the patient grew a few centimetres taller than his twin brother. In the first year of life, panhypopituitarism has no negative consequences for growth. After this point, growth is clearly delayed. With sufficient replacement growth can completely catch up.

Book review of "The estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins

PubMed Central

Sonnenschein, Carlos

2008-01-01

"The Estrogen elixir: A history of hormone replacement therapy in America" by Elizabeth Siegel Watkins is a thoroughly documented cautionary tale of the information and advice offered to women in the perimenopausal period of their life, and the consequences of exposure to sexual hormones on their health and wellbeing.

Efficacy and safety of bariatric surgery for craniopharyngioma-related hypothalamic obesity: a matched case-control study with 2 years of follow-up.

PubMed

Wijnen, M; Olsson, D S; van den Heuvel-Eibrink, M M; Wallenius, V; Janssen, J A M J L; Delhanty, P J D; van der Lely, A J; Johannsson, G; Neggers, S J C M M

2017-02-01

Hypothalamic obesity is a devastating consequence of craniopharyngioma. Bariatric surgery could be a promising therapeutic option. However, its efficacy and safety in patients with craniopharyngioma-related hypothalamic obesity remain largely unknown. We investigated the efficacy of bariatric surgery for inducing weight loss in patients with craniopharyngioma-related hypothalamic obesity. In addition, we studied the safety of bariatric surgery regarding its effects on hormone replacement therapy for pituitary insufficiency. In this retrospective matched case-control study, we compared weight loss after bariatric surgery (that is, Roux-en-Y gastric bypass and sleeve gastrectomy) between eight patients with craniopharyngioma-related hypothalamic obesity and 75 controls with 'common' obesity during 2 years of follow-up. We validated our results at 1 year of follow-up in a meta-analysis. In addition, we studied alterations in hormone replacement therapy after bariatric surgery in patients with craniopharyngioma. Mean weight loss after bariatric surgery was 19% vs 25% (difference -6%, 95% confidence of interval (CI) -14.1 to 4.6; P=0.091) at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity compared with control subjects with 'common' obesity. Mean weight loss was 25% vs 29% (difference -4%, 95% CI -11.6 to 8.1; P=0.419) after Roux-en-Y gastric bypass and 10% vs 20% (difference -10%, 95% CI -14.1 to -6.2; P=0.003) after sleeve gastrectomy at 2 years of follow-up in patients with craniopharyngioma-related hypothalamic obesity vs control subjects with 'common' obesity. Our meta-analysis demonstrated significant weight loss 1 year after Roux-en-Y gastric bypass, but not after sleeve gastrectomy. Seven patients with craniopharyngioma suffered from pituitary insufficiency; three of them required minor adjustments in hormone replacement therapy after bariatric surgery. Weight loss after Roux-en-Y gastric bypass, but not sleeve gastrectomy, was comparable between patients with craniopharyngioma-related hypothalamic obesity and control subjects with 'common' obesity at 2 years of follow-up. Bariatric surgery seems safe regarding its effects on hormone replacement therapy.

Successful Pregnancies After Adequate Hormonal Replacement in Patients With Combined Pituitary Hormone Deficiencies.

PubMed

Correa, Fernanda A; Bianchi, Paulo H M; Franca, Marcela M; Otto, Aline P; Rodrigues, Rodrigo J M; Ejzenberg, Dani; Serafini, Paulo C; Baracat, Edmundo Chada; Francisco, Rossana P V; Brito, Vinicius N; Arnhold, Ivo J P; Mendonca, Berenice B; Carvalho, Luciani R

2017-10-01

Women with hypopituitarism have lower pregnancy rates after ovulation induction. Associated pituitary hormone deficiencies might play a role in this poorer outcome. We evaluated fertility treatment and pregnancy outcomes in five women with childhood-onset combined pituitary hormone deficiencies (CPHD). Five women with CPHD were referred for fertility treatment after adequacy of hormone replacement was determined. Patients were subjected to controlled ovarian stimulation (COS) for timed intercourse, intrauterine insemination, or in vitro fertilization, according to the presence or absence of other infertility factors (male or tubal). All women became pregnant. The number of COS attempts until pregnancy was achieved varied between 1 and 5. The duration of COS resulting in at least one dominant follicle varied between 9 and 28 days, and total gonadotropin consumed varied between 1200 and 3450 IU. Two patients with severely suppressed basal gonadotropin levels since an early age had a cancelled COS cycle. All pregnancies were singleton except one (monochorionic twin gestation). The gestational ages at birth ranged from 35 weeks to 39 weeks and 4 days; three patients underwent cesarean section, and two had vaginal deliveries. Only one newborn was small for gestational age (delivered at 35 weeks). Adequate hormonal replacement prior to ovarian stimulation resulted in successful pregnancies in patients with childhood-onset CPHD, indicating that hormone replacement, including growth hormone, is an important step prior to fertility treatments in these patients.

Psychological well-being and the dyadic relationship of Chinese menopausal women (and their spouses) attending hormone replacement clinics.

PubMed

Lam, P M; Cheung, G W Y; Shek, D T L; Lee, D T S; Haines, C; Chung, T K H

2004-04-01

This survey examined the general health and the marital relationship of 122 Chinese menopausal women and their spouses attending hormone replacement clinics. Climacteric symptoms of the participants were assessed by the modified Greene Climacteric Scale (GCS). The psychological well-being of the participants and their spouses was assessed by the 12-item Chinese General Health Questionnaire (GHQ), and their marital quality was assessed by the Chinese Dyadic Adjustment Scale (DAS). The GCS scores of our cohort were significantly higher than that of a community-based sample of menopausal Chinese women. About one-third of the participants and one-fifth of their spouses suffered from reduced psychological well-being. Although the DAS total scores of the participants and their spouses were comparable to those of the adjusted couples in a younger population, the affectional DAS subscores were significantly lower. The GCS scores of the menopausal women were significantly positively correlated with their GHQ scores but negatively correlated with their DAS scores. In summary, the menopausal women attending the hormonal replacement clinics, especially those with more dimacteric symptoms, suffered from significant psychiatric morbidity and marital maladjustment. The psychological dimension of the menopause should never be neglected.

Increased fat deposition in injured skeletal muscle is regulated by sex-specific hormones

PubMed Central

McHale, Matthew J.; Sarwar, Zaheer U.; Cardenas, Damon P.; Porter, Laurel; Salinas, Anna S.; Michalek, Joel E.; McManus, Linda M.

2012-01-01

Sex differences in skeletal muscle regeneration are controversial; comparisons of regenerative events between sexes have not been rigorously defined in severe injury models. We comprehensively quantified inflammation and muscle regeneration between sexes and manipulated sex-specific hormones to determine effects on regeneration. Cardiotoxin injury was induced in intact, castrated and ovariectomized female and male mice; ovariectomized mice were replaced with low- or high-dose 17-β estradiol (E2) or progesterone (P4). Extent of injury was comparable between intact mice, but females were more efficient in removal of necrotic debris, despite similar tissue levels of inflammatory cells and chemokines. Myofiber size during regeneration was equivalent between intact mice and after castration or ovariectomy (OVX) but was decreased (P < 0.001) in ovariectomized mice with high-dose E2 replacement. Intermuscular adipocytes were absent in uninjured muscle, whereas adipocyte area was increased among regenerated myofibers in all groups. Interestingly, intermuscular fat was greater (P = 0.03) in intact females at day 14 compared with intact males. Furthermore, castration increased (P = 0.01) and OVX decreased adipocyte accumulation. After OVX, E2, but not P4, replacement decreased (P ≤ 0.03) fat accumulation. In conclusion, sex-dependent differences in regeneration consisted of more efficient removal of necrosis and increased fat deposition in females with similar injury, inflammation, and regenerated myofiber size; high-dose E2 decreased myofiber size and fat deposition. Adipocyte accumulation in regenerating muscle was influenced by sex-specific hormones. Recovery following muscle injury was different between males and females, and sex-specific hormones contributed to these differences, suggesting that sex-specific treatments could be beneficial after injury. PMID:22116509

Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause

PubMed Central

Sullivan, Shannon D.; Sarrel, Philip M.; Nelson, Lawrence M.

2016-01-01

Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychological impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective hormone replacement therapy options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, ~50 years. We address special populations of women with POI, including women with Turner Syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women. PMID:27912889

Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment.

PubMed

Yang, Hongbo; Wang, Linjie; Qiu, Xiaonan; Yan, Kemin; Gong, Fengying; Zhu, Huijuan; Pan, Hui

2018-04-25

Recombinant human growth hormone (rhGH) replacement therapy is usually stopped after linear growth completion in patients with growth hormone deficiency. In patients with multiple pituitary hormone deficiency (MPHD), the long-term effects of discontinuation of rhGH replacement are unknown. In this study, the anthropometric and metabolic parameters of 24 male patients with adult growth hormone deficiency (AGHD) due to MPHD in childhood after cessation of rhGH therapy for a mean of 7.1 years were measured and compared with 35 age-matched controls. Body composition was evaluated by bioelectrical impedance analysis (BIA). In the AGHD group, body mass index (BMI) was significantly increased and 29.2% had obesity. The AGHD group had a 17.7 cm increase in waist circumference (WC). The fat free mass (FFM) was significantly lower in the AGHD group. Both the fat mass (FM) and percentage of fat mass (FM%) were significantly increased in the AGHD group. Both the systolic blood pressure (BP) and diastolic pressure were significantly lower in AGHD group. The lipid profile was generally similar in both groups, except for a decrease of high density lipoprotein-cholesterol (HDL-C) in the AGHD group. There was significant hyperuricemia in the AGHD group. Cessation of rhGH leads to a significant increase of FM in early adulthood in male patients with childhood-onset MPHD (CO-MPHD).

Successful Pregnancies After Adequate Hormonal Replacement in Patients With Combined Pituitary Hormone Deficiencies

PubMed Central

Bianchi, Paulo H. M.; Franca, Marcela M.; Otto, Aline P.; Rodrigues, Rodrigo J. M.; Ejzenberg, Dani; Serafini, Paulo C.; Baracat, Edmundo Chada; Francisco, Rossana P. V.; Brito, Vinicius N.; Arnhold, Ivo J. P.; Mendonca, Berenice B.

2017-01-01

Context: Women with hypopituitarism have lower pregnancy rates after ovulation induction. Associated pituitary hormone deficiencies might play a role in this poorer outcome. Objective: We evaluated fertility treatment and pregnancy outcomes in five women with childhood-onset combined pituitary hormone deficiencies (CPHD). Patients and Methods: Five women with CPHD were referred for fertility treatment after adequacy of hormone replacement was determined. Patients were subjected to controlled ovarian stimulation (COS) for timed intercourse, intrauterine insemination, or in vitro fertilization, according to the presence or absence of other infertility factors (male or tubal). Results: All women became pregnant. The number of COS attempts until pregnancy was achieved varied between 1 and 5. The duration of COS resulting in at least one dominant follicle varied between 9 and 28 days, and total gonadotropin consumed varied between 1200 and 3450 IU. Two patients with severely suppressed basal gonadotropin levels since an early age had a cancelled COS cycle. All pregnancies were singleton except one (monochorionic twin gestation). The gestational ages at birth ranged from 35 weeks to 39 weeks and 4 days; three patients underwent cesarean section, and two had vaginal deliveries. Only one newborn was small for gestational age (delivered at 35 weeks). Conclusion: Adequate hormonal replacement prior to ovarian stimulation resulted in successful pregnancies in patients with childhood-onset CPHD, indicating that hormone replacement, including growth hormone, is an important step prior to fertility treatments in these patients. PMID:29264457

Panhypopituitarism after multisystem trauma.

PubMed

Wiechecka, Joanna; Krzewska, Aleksandra; Droń, Izabela; Beń-Skowronek, Iwona

2013-01-01

The pituitary gland plays a key role in hormonal regulation in the organism, contributing to maintenance of balance of basic vital functions. To emphasise the need for assessment of pituitary function after head injury, as correct diagnosis and hormone replacement therapy prove to be a life-saving therapy accelerating the recovery process. A healthy, normally developing 9-year-old girl, a child of young and healthy parents, was struck by a falling tree. The results of severe head trauma included adrenal crisis, hypothyroidism, and diabetes insipidus as manifestations of damage to the anterior and posterior pituitary gland. Administration of hormone replacement therapy, i.e. hydrocortisone, L-thyroxine, and desmopressin greatly improved the patient´s condition and facilitated effective rehabilitation. Determination of pituitary hormones in children after severe head injury should be an important part of diagnosis allowing identification of an early stage of acute hypopituitarism and acceleration of recovery through hormone replacement therapy.

Ventilatory, metabolic, and thermal responses to hypercapnia in female rats: effects of estrous cycle, ovariectomy, and hormonal replacement.

PubMed

Marques, Danuzia A; de Carvalho, Débora; da Silva, Glauber S F; Szawka, Raphael E; Anselmo-Franci, Janete A; Bícego, Kênia C; Gargaglioni, Luciane H

2015-07-01

The aim of this study was to examine how estrous cycle, ovariectomy, and hormonal replacement affect the respiratory [ventilation (V̇e), tidal volume, and respiratory frequency], metabolic (V̇o2), and thermoregulatory (body temperature) responses to hypercapnia (7% CO2) in female Wistar rats. The parameters were measured in rats during different phases of the estrous cycle, and also in ovariectomized (OVX) rats supplemented with 17β-estradiol (OVX+E2), with a combination of E2 and progesterone (OVX+E2P), or with corn oil (OVX+O, vehicle). All experiments were conducted on day 8 after ovariectomy. The intact animals did not present alterations during normocapnia or under hypercapnia in V̇e, tidal volume, respiratory frequency, V̇o2, and V̇e/V̇o2 in the different phases of the estrous cycle. However, body temperature was higher in female rats on estrus. Hormonal replacement did not change the ventilatory, thermoregulatory, or metabolic parameters during hypercapnia, compared with the OVX animals. Nevertheless, OVX+E2, OVX+E2P, and OVX+O presented lower hypercapnic ventilatory responses compared with intact females on the day of estrus. Also, rats in estrus showed higher V̇e and V̇e/V̇o2 during hypercapnia than OVX animals. The data suggest that other gonadal factors, besides E2 and P, are possibly involved in these responses. Copyright © 2015 the American Physiological Society.

Pituitary apoplexy

MedlinePlus

... body's sex glands produce little or no hormones) Hypothyroidism (thyroid gland does not make enough thyroid hormone) ... other missing hormones are not replaced, symptoms of hypothyroidism and hypogonadism may develop.

An audit of growth hormone replacement for GH-deficient adults in Scotland.

PubMed

Philip, Sam; Howat, Isobel; Carson, Maggie; Booth, Anne; Campbell, Karen; Grant, Donna; Patterson, Catherine; Schofield, Christopher; Bevan, John; Patrick, Alan; Leese, Graham; Connell, John

2013-04-01

Guidelines on the clinical use of growth hormone therapy in adults were issued by the UK National Institute for Clinical Excellence (NICE) in August 2003. We conducted a retrospective clinical audit on the use of growth hormone (GH) in Scotland to evaluate the use of these guidelines and their impact on clinical practice. The audit had two phases. In phase I, the impact of NICE criteria on specialist endocrine practice in starting and continuing GH replacement was assessed. In phase II, the reasons why some adults in Scotland with growth hormone deficiency were not on replacement therapy were evaluated. A retrospective cross-sectional case note review was carried out of all adult patients being followed up for growth hormone deficiency during the study period (1 March 2005 to 31 March 2008). Phase I of the audit included 208 patients and phase II 108 patients. Sellar tumours were the main cause of GH deficiency in both phases of the audit. In phase I, 53 patients (77%) had an AGHDA-QoL score >11 documented before commencing GH post-NICE guidance, compared with 35 (25%) pre-NICE guidance. Overall, only 39 patients (18%) met the full NICE criteria for starting and continuing GH (pre-NICE, 11%; post-NICE, 35%). Phase II indicated that the main reasons for not starting GH included perceived satisfactory quality of life (n = 47, 43%), patient reluctance (16, 15%) or a medical contraindication (16, 15%). Although the use of quality of life assessments has increased following publication of the NICE guidelines, most adults on GH in Scotland did not fulfil the complete set of NICE criteria. The main reason for not starting GH therapy in adult GH-deficient patients was perceived satisfactory quality of life. © 2012 Blackwell Publishing Ltd.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

PubMed

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T 4 ) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy

PubMed Central

Wada, Keisuke; Kobayashi, Hironori; Moriyama, Aisa; Haneda, Yasuhiro; Mushimoto, Yuichi; Hasegawa, Yuki; Onigata, Kazumichi; Kumori, Koji; Ishikawa, Noriyoshi; Maruyama, Riruke; Sogo, Tsuyoshi; Murphy, Lynne; Taketani, Takeshi

2017-01-01

Abstract. Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth. Neonatal jaundice was noted but temporarily improved with phototherapy. Jaundice recurred at 2 mo of age. Elevated direct bilirubin (D-Bil) and liver dysfunction were found but cholangiography showed no signs of biliary atresia (BA). Liver biopsy findings showed giant cell formation of hepatocytes with hypoplastic bile ducts. Subsequent magnetic resonance imaging (MRI) of the head revealed a hypoplastic pituitary gland with an ectopic posterior lobe, and the patient was diagnosed with congenital CPHD based on decreased secretion of cortisol and GH by the pituitary anterior lobe load test. D-Bil levels promptly improved after hydrocortisone (HDC) replacement. We subsequently began replacement with levothyroxine (L-T4) and GH, and liver histology showed normal interlobular bile ducts at 8 mo old. This is the first case report of proven histological improvement after hormone replacement therapy. This suggested that pituitary-mediated hormones, especially cortisol, might be involved in the development of the bile ducts. PMID:29026274

American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients--2002 update.

PubMed

Petak, Steven M; Nankin, Howard R; Spark, Richard F; Swerdloff, Ronald S; Rodriguez-Rigau, Luis J

2002-01-01

In these clinical practice guidelines, specific recommendations are made for determining the most effective methods of diagnosing and treating hypogonadism in adult male patients. The target populations for these guidelines include the following: (1) men with primary testicular failure requiring testosterone replacement (hypergonadotropic hypogonadism); (2) male patients with gonadotropin deficiency or dysfunction who may have received testosterone replacement therapy or treatment for infertility (hypogonadotropic hypogonadism); and (3) aging men with symptoms relating to testosterone deficiency who could benefit from testosterone replacement therapy. Initial hormonal evaluation generally consists of a testosterone determination, in conjunction with a free testosterone or sex hormone-binding globulin level, inpatients with clear symptoms and signs but normal-range total testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels. Other possible tests include semen analysis, pituitary imaging studies, genetic studies, bone densitometry, testicular ultrasonography,testicular biopsy, and specialized hormonal dynamic testing. Therapeutic options generally consist of testosterone replacement by injections, patches, or topically applied gel in hypergonadotropic patients and in hypogonadotropic patients not interested in fertility. In hypogonadotropic patients interested in fertility, gonadal stimulation option scan be considered, including human chorionic gonadotropin stimulation therapy with or without human menopausal gonadotropin (or follicle-stimulating hormone) or gonadotropin-releasing hormone pump therapy. These therapies may be combined with assisted reproductive technologies such as in vitro fertilization with intracytoplasmic sperm injection, which may allow pregnancy to occur with very low numbers of sperm.

Factors associated with mortality of myxedema coma: report of eight cases and literature survey.

PubMed

Yamamoto, T; Fukuyama, J; Fujiyoshi, A

1999-12-01

High-dose thyroid hormone replacement has been recommended for treatment of myxedema coma (MC) while questions of safety of the therapy and of efficacy of low-dose thyroid hormone replacement have not been systematically addressed. We treated 8 patients with MC in a period of 18 years, the first 3 with high-dose intravenous injections of levotriiodothyronine (LT3) and the other 5 patients with a smaller amount of either LT3 or levothyroxine (LT4). Two of the first 3 patients died of pneumonia and the other 5 recovered despite pulmonary abnormalities at the outset. To find factors associated with fatal outcome after treatment, the MEDLINE database was searched for MC cases with data of thyroid hormone replacement and outcome within 1 month of therapy. Clinical data for our 5 patients and 82 cases from the MEDLINE search were pooled and factors associated with mortality were sought among age, gender, presence of cardiac or pulmonary complications, and doses of thyroid hormone by multiple logistic regression analysis. It revealed that greater age, cardiac complications, and high-dose thyroid hormone replacement (LT4 > or = 500 microg/d or LT3 > or = 75 microg/d) were significantly associated with a fatal outcome within 1 month of treatment. Elderly MC patients can be treated with low-dose hormone replacement. A bolus of 500 microg LT4, especially by mouth or via nasogastric tube, appears to be tolerated by younger patients (< 55 years) without cardiac complication. The conclusion remains to be confirmed in more patients.

The Language of Journalism in Treatments of Hormone Replacement News

ERIC Educational Resources Information Center

MacDonald, Susan Peck

2005-01-01

Researchers studying science communication have criticized the sensationalism that often appears in journalistic accounts of science news. This article looks at the linguistic sources of that sensationalism by analyzing the journalistic coverage of the Women's Health Initiative (WHI) study of hormone replacement research, which was abruptly…

Induction of a hypothyroid state during juvenile development delays pubertal reactivation of the neuroendocrine system governing luteinising hormone secretion in the male rhesus monkey (Macaca mulatta).

PubMed

Mann, D R; Bhat, G K; Stah, C D; Pohl, C R; Plant, T M

2006-09-01

The present study aimed to determine the influence of thyroid status on the timing of the pubertal resurgence in gonadotrophin-releasing hormone pulse generator activity [tracked by circulating luteinising hormone (LH) levels] in male rhesus monkeys. Six juvenile monkeys were orchidectomised and then treated with the antithyroid drug, methimazole, from 15-19 months until 36 months of age, at which time thyroxine (T(4)) replacement was initiated. Four additional agonadal monkeys served as controls. Blood samples were drawn weekly for hormonal assessments. Body weight, crown-rump length and bone age were monitored at regular intervals. By 8 weeks of methimazole treatment, plasma T(4) had fallen sharply, and the decline was associated with a plasma thyroid-stimulating hormone increase. In controls, plasma LH levels remained undetectable until the pubertal rise occurred at 29.3 +/- 0.2 months of age. This developmental event occurred in only half of the methimazole-treated animals before 36 months of age when T(4) replacement was initiated. The hypothyroid state was associated with a profound arrest of growth and bone maturation, but increased body mass indices and plasma leptin levels. T(4) replacement in methimazole-treated monkeys was associated with the pubertal rise in LH in the remaining three animals and accelerated somatic development in all six animals. Although pubertal resurgence in LH secretion occurred at a later chronological age in methimazole-treated animals compared to controls, bone age, crown-rump length and body weight at that time did not differ between groups. There were no long-term differences in plasma prolactin between groups. We conclude that juvenile hypothyroidism in male primates causes a marked delay in the pubertal resurgence of LH secretion, probably occasioned at the hypothalamic level. Whether this effect is meditated by an action of thyroid hormone directly on the hypothalamus or indirectly as a result of the concomitant deficit in somatic development remains to be determined.

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism

PubMed Central

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K.; Vivekanandan, Muthupillai

2016-01-01

Background: Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. Materials and Methods: This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Results: Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. Conclusions: The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations. PMID:27042409

Effect of steroid replacement on thyroid function and thyroid autoimmunity in Addison's disease with primary hypothyroidism.

PubMed

Sahoo, Jaya Prakash; Selviambigapathy, Jayakumar; Kamalanathan, Sadishkumar; Nagarajan, K; Vivekanandan, Muthupillai

2016-01-01

Steroid replacement without thyroxine supplementation normalizes thyroid function test (TFT) in some but not all Addison's disease patients with primary hypothyroidism. Both autoimmune and nonautoimmune mechanisms contribute to this improvement in TFT. However, the documentation of the change in thyroid autoimmunity after cortisol replacement is very limited in the literature. The aim of this study was to determine the effect of steroid replacement on TFT and anti-thyroid peroxidase antibody (anti-TPO-Ab) titer in Addison's disease with primary hypothyroidism. This observational study was conducted in a tertiary care center in South India. Six Addison's disease patients with primary hypothyroidism, who were only on steroid replacement, were included in the study. Low serum cortisol (<83 nmol/L) with high plasma adrenocorticotropic hormone (>22 pmol/L) and/or hyperpigmentation of skin/mucous membranes was considered as the diagnostic criteria for Addison's disease. Primary hypothyroidism (both overt and subclinical) was defined as high thyroid stimulating hormone (TSH) with/without low free thyroxine (fT4). TFT and anti-TPO-Ab were performed before and after steroid replacement in all of them. Poststeroid replacement, there was a normalization of TSH in all but one subjects. In overt hypothyroidism patients, fT4 also normalized. The improvement in TFT was not associated with decreasing titer of the anti-TPO-Ab in all six patients. However, there was a significant difference in TSH after steroid replacement compared to the baseline status. The concept of normalization of primary hypothyroidism with cortisol replacement in patients with Addison's disease should be recognized to avoid iatrogenic thyrotoxicosis caused by thyroxine replacement. Both autoimmune and nonautoimmune mechanisms contribute to these alterations.

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.

PubMed

Bagattini, Brunella; Cosmo, Caterina Di; Montanelli, Lucia; Piaggi, Paolo; Ciampi, Mariella; Agretti, Patrizia; Marco, Giuseppina De; Vitti, Paolo; Tonacchera, Massimo

2014-11-01

Levothyroxine (l-T4) is commonly employed to correct hormone deficiency in children with congenital hypothyroidism (CH) and in adult patients with iatrogenic hypothyroidism. To compare the daily weight-based dosage of the replacement therapy with l-T4 in athyreotic adult patients affected by CH and adult patients with thyroid nodular or cancer diseases treated by total thyroidectomy. A total of 36 adult patients (27 females and nine males) aged 18-29 years were studied; 13 patients (age: 21.5±2.1, group CH) had athyreotic CH treated with l-T4 since the first days of life. The remaining 23 patients (age: 24±2.7, group AH) had hypothyroidism after total thyroidectomy (14 patients previously affected by nodular disease and nine by thyroid carcinoma with clinical and biochemical remission). Patient weight, serum free thyroid hormones, TSH, thyroglobulin (Tg), anti-Tg, and anti-thyroperoxidase antibodies were measured. Required l-T4 dosage was evaluated. At the time of the observations, all patients presented free thyroid hormones within the normal range and TSH between 0.8 and 2 μIU/ml. Patients had undetectable Tg and anti-thyroid antibodies. The daily weight-based dosage of the replacement therapy with l-T4 to reach euthyroidism in patients of group CH was significantly higher than that in those of group AH (2.16±0.36 vs 1.73±0.24 μg/kg, P<0.005). Patients of group CH treated with l-T4 had significantly higher serum TSH levels than patients of group AH (P=0.05) as well as higher FT4 concentrations. To correct hypothyroidism, patients of group CH required a daily l-T4 dose/kg higher than group AH patients, despite higher levels of TSH. The different requirement of replacement therapy between adult patients with congenital and those with surgical athyroidism could be explained by a lack of thyroid hormones since fetal life in CH, which could determine a different set point of the hypothalamus-pituitary-thyroid axis. © 2014 European Society of Endocrinology.

Diagnosis and Treatment of Hypopituitarism

PubMed Central

2015-01-01

Hypopituitarism is a chronic endocrine illness that caused by varied etiologies. Clinical manifestations of hypopituitarism are variable, often insidious in onset and dependent on the degree and severity of hormone deficiency. However, it is associated with increased mortality and morbidity. Therefore, early diagnosis and prompt treatment is necessary. Hypopituitarism can be easily diagnosed by measuring basal pituitary and target hormone levels except growth hormone (GH) and adrenocorticotropic hormone (ACTH) deficiency. Dynamic stimulation tests are indicated in equivocal basal hormone levels and GH/ACTH deficiency. Knowledge of the use and limitations of these stimulation tests is mandatory for proper interpretation. It is necessary for physicians to inform their patients that they may require lifetime treatment. Hormone replacement therapy should be individualized according to the specific needs of each patient, taking into account possible interactions. Long-term endocrinological follow-up of hypopituitary patients is important to monitor hormonal replacement regimes and avoid under- or overtreatment. PMID:26790380

HISTORICAL AND CURRENT PERSPECTIVE IN THE USE OF THYROID EXTRACTS FOR THE TREATMENT OF HYPOTHYROIDISM.

PubMed

Hennessey, James V

2015-10-01

To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies. A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature. A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products. The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.

Ovariectomy and 17β-estradiol replacement in rats and mice: a visual demonstration.

PubMed

Ström, Jakob O; Theodorsson, Annette; Ingberg, Edvin; Isaksson, Ida-Maria; Theodorsson, Elvar

2012-06-07

Estrogens are a family of female sexual hormones with an exceptionally wide spectrum of effects. When rats and mice are used in estrogen research they are commonly ovariectomized in order to ablate the rapidly cycling hormone production, replacing the 17β-estradiol exogenously. There is, however, lack of consensus regarding how the hormone should be administered to obtain physiological serum concentrations. This is crucial since the 17β-estradiol level/administration method profoundly influences the experimental results. We have in a series of studies characterized the different modes of 17β-estradiol administration, finding that subcutaneous silastic capsules and per-oral nut-cream Nutella are superior to commercially available slow-release pellets (produced by the company Innovative Research of America) and daily injections in terms of producing physiological serum concentrations of 17β-estradiol. Amongst the advantages of the nut-cream method, that previously has been used for buprenorphine administration, is that when used for estrogen administration it resembles peroral hormone replacement therapy and is non-invasive. The subcutaneous silastic capsules are convenient and produce the most stable serum concentrations. This video article contains step-by-step demonstrations of ovariectomy and 17β-estradiol hormone replacement by silastic capsules and peroral Nutella in rats and mice, followed by a discussion of important aspects of the administration procedures.

The emergence of levothyroxine as a treatment for hypothyroidism.

PubMed

Hennessey, James V

2017-01-01

To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies. A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified. Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines. The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.

Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy?

PubMed

Tigas, S; Idiculla, J; Beckett, G; Toft, A

2000-12-01

There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves' disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves' disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves' disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement.

Successful Pregnancies and Deliveries in a Patient With Evolving Hypopituitarism due to Pituitary Stalk Transection Syndrome: Role of Growth Hormone Replacement

PubMed Central

Yoshizawa, Miyako; Ieki, Yasuhiko; Takazakura, Eisuke; Fukuta, Kaori; Hidaka, Takao; Wakasugi, Takanobu; Shimatsu, Akira

2017-01-01

We herein report a 31-year-old Japanese woman with evolving hypopituitarism due to pituitary stalk transection syndrome. She had a history of short stature treated with growth hormone (GH) in childhood and had hypothyroidism and primary amenorrhea at 20 years old. Levothyroxine replacement and recombinant follicle stimulating hormone-human chorionic gonadotropin (FSH-hCG) therapy for ovulation induction were started. GH replacement therapy (GHRT) was resumed when she was 26 years old. She developed mild adrenocortical insufficiency at 31 years old. She succeeded in becoming pregnant and delivered twice. GHRT was partially continued during pregnancy and stopped at the end of the second trimester without any complications. PMID:28250299

The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis

PubMed Central

Felix-Patrício, Bruno; Miranda, Alexandre F.; Medeiros, Jorge L.; Gallo, Carla B. M.; Gregório, Bianca M.; de Souza, Diogo B.; Costa, Waldemar S.; Sampaio, Francisco J. B.

2017-01-01

ABSTRACT Purpose: To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. Materials and Methods: 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Results: Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Conclusion: Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations. PMID:28379662

The prostate after castration and hormone replacement in a rat model: structural and ultrastructural analysis.

PubMed

Felix-Patrício, Bruno; Miranda, Alexandre F; Medeiros, Jorge L; Gallo, Carla B M; Gregório, Bianca M; Souza, Diogo B; Costa, Waldemar S; Sampaio, Francisco J B

2017-01-01

To evaluate if late hormonal replacement is able to recover the prostatic tissue modified by androgenic deprivation. 24 rats were assigned into a Sham group; an androgen deficient group, submitted to bilateral orchiectomy (Orch); and a group submitted to bilateral orchiectomy followed by testosterone replacement therapy (Orch+T). After 60 days from surgery blood was collected for determination of testosterone levels and the ventral prostate was collected for quantitative and qualitative microscopic analysis. The acinar epithelium height, the number of mast cells per field, and the densities of collagen fibers and acinar lumen were analyzed by stereological methods under light microscopy. The muscle fibers and types of collagen fibers were qualitatively assessed by scanning electron microscopy and polarization microscopy. Hormone depletion (in group Orch) and return to normal levels (in group Orch+T) were effective as verified by serum testosterone analysis. The androgen deprivation promoted several alterations in the prostate: the acinar epithelium height diminished from 16.58±0.47 to 11.48±0.29μm; the number of mast cells per field presented increased from 0.45±0.07 to 2.83±0.25; collagen fibers density increased from 5.83±0.92 to 24.70±1.56%; and acinar lumen density decreased from 36.78±2.14 to 16.47±1.31%. Smooth muscle was also increased in Orch animals, and type I collagen fibers became more predominant in these animals. With the exception of the densities of collagen fibers and acinar lumen, in animals receiving testosterone replacement therapy all parameters became statistically similar to Sham. Collagen fibers density became lower and acinar lumen density became higher in Orch+T animals, when compared to Sham. This is the first study to demonstrate a relation between mast cells and testosterone levels in the prostate. This cells have been implicated in prostatic cancer and benign hyperplasia, although its specific role is not understood. Testosterone deprivation promotes major changes in the prostate of rats. The hormonal replacement therapy was effective in reversing these alterations. Copyright® by the International Brazilian Journal of Urology.

Regulation of extrarenal potassium homeostasis by adrenal hormones in rats.

PubMed

Bia, M J; Tyler, K A; DeFronzo, R A

1982-06-01

The effect of chronic (7-10 days) adrenal insufficiency on extrarenal potassium tolerance was examined by infusing potassium into rats after acute nephrectomy. The increment in plasma potassium concentration was significantly higher in glucocorticoid-replaced adrenalectomized rats versus controls (max delta PK 3.59 +/-0.11 vs. 2.93 +/- 0.08 meq/liter; P less than 0.001). The impairment in extrarenal potassium tolerance in adrenalectomized rats could not be attributed to acidemia, hypotension, changes in plasma insulin or glucose concentration, or potassium retention prior to study. Acute replacement with aldosterone resulted in significant improvement in the rise in plasma potassium after KCl (max delta PK 3.18 +/- 0.06 meq/liter; P less than 0.005 compared with aldosterone-deficient adrenalectomized rats but higher than in controls, P less than 0.02). If given on a chronic basis, aldosterone replacement led to a complete correction of the defect (max delta PK = 2.89 +/- 0.08 meq/liter). Acute epinephrine replacement in adrenalectomized rats also returned potassium tolerance to normal (max delta PK = 3.02 +/- 0.10 meq/liter). The results demonstrate that extrarenal potassium tolerance is impaired in chronic adrenal insufficiency and suggest that both aldosterone and epinephrine deficiency may contribute to the defect, since replacement with either hormone returns potassium tolerance toward normal. Accordingly, both aldosterone and epinephrine have important extrarenal mechanisms of action.

The influence of hormonal replacement and growth hormone treatment on the lipids in Turner syndrome.

PubMed

Irzyniec, Tomasz Jerzy; Jeż, Wacław

2014-03-01

Women with Turner syndrome (TS) have a risk of developing cardiovascular diseases. We assessed the lipid and carbohydrate metabolism in TS-women in the context of current hormone replacement therapy (HRT) and growth hormone (GH) treatment during childhood. The information were collected from medical documentation and anamnesis of 165 TS-women (24.9 ± 7.7 yr) between 1995 and 2011. The patients underwent a pituitary-gonadal axis assessment together with measurements of total cholesterol (TC), high- (HDL) and low- (LDL) density lipoproteins, triglycerides (TG), and glucose levels. Only 58% of women were using HRT. No differences were found in the levels of the lipid components and glucose in women who were undergoing HRT compared to those without it. Compared to TS-women without (n  =  113), prior GH treatment in 34 TS-women positively influenced the lipid parameters: TC 5.0 ± 1.1 versus 4.6 ± 0.9 mmol/l (p = 0.03), HDL 1.5 ± 0.5 versus 1.4 ± 0.4 mmol/l (p > 0.05), LDL 3.3 ± 0.9 versus 2.9 ± 0.7 mmol/l (p = 0.03), and TG 1.1 ± 0.6 versus 0.8 ± 0.3 g/l (p = 0.009), respectively. (1) HRT does not affect lipid metabolism in TS-women. (2) The use of GH in TS-children favorably influences their lipid profile in adulthood.

Hormone therapy alters the composition of the vaginal microflora in ovariectomized rats.

PubMed

Bezirtzoglou, E; Voidarou, Ch; Papadaki, A; Tsiotsias, A; Kotsovolou, O; Konstandi, M

2008-05-01

The aim of the present study was to evaluate the alterations that may take place in the bacterial genital tract flora in the absence of ovarian hormones. The role of hormone replacement therapy was also assessed. For this purpose, various bacteria were identified from the vaginal flora of ovariectomized and sham operated female rats, following the Bergey's manual criteria. The data of this study showed that substantial differences exist in the vaginal bacterial microflora between ovariectomized and normal cyclic rats. Ovariectomy was associated with a lower total bacterial load that may be due mainly to the absence of Lactobacillus. Anaerobic bacteria were also absent. Streptococcus and Enterococcus were also not favored in an environment lacking the ovarian hormones. In contrast, C. perfringens, Bacteroides, S. epidermidis, and S. aureus were detected in high numbers in ovariectomized rats. In terms of the impact of hormone replacement therapy on vaginal flora, only estradiol (EE2) restored Lactobacillus levels in ovariectomized rats, whereas all hormonal schemes used brought Streptococcus, Clostridium lec (-), and C. perfringens, the spore and vegetative forms, close to those detected in normal cyclic female rats. In conclusion, ovarian hormones appeared to be regulatory factors that favor the presence of a broad variety of bacteria, which are members of the normal genital tract flora. On the other hand, ovariectomy modifies the vaginal microbial profile, and hormone replacement therapy based mainly on schemes containing EE2 could alleviate this disturbance.

Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison's disease.

PubMed

Molnár, Ágnes; Kövesdi, Annamária; Szücs, Nikolette; Tóth, Miklós; Igaz, Péter; Rácz, Károly; Patócs, Attila

2016-08-01

Glucocorticoid substitution is essential in patients with chronic primary adrenocortical insufficiency (Addison's disease) and both over-treatment and inadequate dosage have deleterious effects. Individual sensitivity to glucocorticoids is partly genetically determined. To test the hypothesis whether the well-characterized SNPs of the GR and HSD11B1 genes may modulate the individual sensitivity to exogenous glucocorticoids and may influence clinical and/or laboratory parameters and the glucocorticoid substitution dosage in patients with Addison's disease. 68 patients with primary adrenocortical insufficiency were involved. Clinical and laboratory data, as well as the dosage of the hormone replacement therapy were collected. Peripheral blood DNA was isolated, and the GR and HSD11B1 SNPs were examined using allele-specific PCR or Taqman assay on Real Time PCR. The allele frequency of the GR N363S polymorphism was higher in patients compared to the control group and the disease appeared significantly earlier in patients harbouring the GR A3669G compared to noncarriers. These patients had higher ACTH level measured at the time of diagnosis. Homozygous BclI carriers had higher body mass index (BMI) and lower total hydrocortisone equivalent supplementation dose needed than heterozygous or noncarriers. The BMI and weight gain during hormone replacement therapy were also higher in carriers of the HSD11B1 rs4844880 treated with glucocorticoids other than dexamethasone. The BclI polymorphism of the GR gene and the rs4844880 of the HSD11B1 gene may contribute to weight gain and may affect the individual need of glucocorticoid substitution dose in these patients. © 2016 John Wiley & Sons Ltd.

Hormone replacement therapy: short-term versus long-term use.

PubMed

Rousseau, Mary Ellen

2002-01-01

Midwives manage health care of women throughout the life cycle including prescribing hormone replacement therapy (HRT). This article presents a history of research on the use of HRT, as well as risks and benefits. Older research on the effects of HRT on heart disease, osteoporosis, and breast cancer is included. The results and recommendations of the Women's Health Initiative are examined.

Prader-Willi syndrome: A primer for clinicians

PubMed Central

2011-01-01

The advent of sensitive genetic testing modalities for the diagnosis of Prader-Willi syndrome has helped to define not only the phenotypic features of the syndrome associated with the various genotypes but also to anticipate clinical and psychological problems that occur at each stage during the life span. With advances in hormone replacement therapy, particularly growth hormone children born in circumstances where therapy is available are expected to have an improved quality of life as compared to those born prior to growth hormone. This manuscript was prepared as a primer for clinicians-to serve as a resource for those of you who care for children and adults with Prader-Willi syndrome on a daily basis in your practices. Appropriate and anticipatory interventions can make a difference. PMID:22008714

The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

PubMed

Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

2004-11-01

To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function.

PubMed

Perakakis, Nikolaos; Upadhyay, Jagriti; Ghaly, Wael; Chen, Joyce; Chrysafi, Pavlina; Anastasilakis, Athanasios D; Mantzoros, Christos S

2018-05-09

We have previously demonstrated that the adipose tissue derived hormone leptin controls reproductive function by regulating the hypothalamic-pituitary-gonadal axis in response to energy deficiency. Here, we evaluate the activins-follistatins-inhibins (AFI) axis during acute (short-term fasting in healthy people) and chronic energy deficiency (women with hypothalamic amenorrhea due to strenuous exercise [HA]) and investigate their relation to leptin and reproductive function in healthy subjects and subjects with HA. The AFI axis was investigated in: a) A double-blinded study in healthy subjects having three randomly assigned admissions, each time for four days: in the isocaloric fed state, complete fasting with placebo treatment, complete fasting with leptin replacement, b) A case-control study comparing women with HA vs healthy controls, c) An open-label interventional study investigating leptin treatment in women with HA over a period of up to three months, d) A randomized interventional trial investigating leptin treatment vs placebo in women with HA for nine months. The circulating levels of activin A, activin B, follistatin and follistatin-like 3 change robustly in response to acute and chronic energy deficiency. Leptin replacement in acute energy deprivation does not affect the levels of these hormones suggesting an independent regulation by these two hormonal pathways. In chronic energy deficiency, leptin replacement restores only activin B levels, which are in turn associated with an increase in the number of dominant follicles. We demonstrate for the first time that the AFI axis is affected both by acute and chronic energy deficiency. Partial restoration of a component of the axis, i.e. activin B only, through leptin replacement is associated with improved reproductive function in women with HA. Copyright © 2018. Published by Elsevier Inc.

Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation.

PubMed

Groban, L; Lin, M; Kassik, K A; Ingram, R L; Sonntag, W E

2011-04-01

The primary goal of growth hormone (GH) replacement is to promote linear growth in children with growth hormone deficiency (GHD). GH and insulin-like growth factor-1 (IGF-1) are also known to have roles in cardiac development and as modulators of myocardial structure and function in the adult heart. However, little is known about cardiac diastolic function in young adults with childhood onset GH deficiency in which GH treatment was discontinued following puberty. The aim of the study was to evaluate the effects of long standing GHD and peri-pubertal or continuous GH replacement therapy on diastolic function in the adult dwarf rat. The dwarf rat, which possesses a mutation in a transcription factor necessary for development of the somatotroph, does not exhibit the normal peri-pubertal rise in GH around day 28 and was used to model childhood or early-onset GHD (EOGHD). In another group of male dwarfs, GH replacement therapy was initiated at 4 weeks of age when GH pulsatility normally begins. Ten weeks after initiation of injections, GH-treated dwarf rats were divided into 2 groups; continued treatment with GH for 12 weeks (GH-replete) or treatment with saline for 12 weeks. This latter group models GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Saline-treated heterozygous (HZ) rats were used as age-matched controls. At 26 weeks of age, cardiac function was assessed using invasive or noninvasive (conventional and tissue Doppler) indices of myocardial contractility and lusitropy. Systolic function, as determined by echocardiography, was similar among groups. Compared with HZ rats and GH-replete dwarfs, the EOGHD group exhibited significant reductions in myocardial relaxation and increases in left ventricular filling pressure, indicative of moderate diastolic dysfunction. This was further associated with a decrease in the cardiac content of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), one of the important cardiac calcium regulatory proteins. Dwarfs supplemented with GH during the peri-adolescence stage, but not beyond (AOGHD), exhibited a subtle prolongation in the deceleration time to early filling. In contrast, continual GH replacement preserved diastolic function such that the cardiac phenotype of the GH-replete dwarfs resembled that of their age-matched HZ counterpart. Our data indicate that GHD during adolescence leads to overt diastolic dysfunction in early adulthood and this is prevented by continual GH replacement therapy. Since discontinuation of GH replacement following adolescence only mitigated the lusitropic deficits that were observed in untreated dwarfs, GH treatment into adulthood could be beneficial. Copyright © 2011 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.

Persistent osteopenia in ballet dancers with amenorrhea and delayed menarche despite hormone therapy: a longitudinal study.

PubMed

Warren, Michelle P; Brooks-Gunn, Jeanne; Fox, Richard P; Holderness, Claire C; Hyle, Emily P; Hamilton, William G; Hamilton, Linda

2003-08-01

To investigate the role of estrogen deprivation and replacement in amenorrheic and nonamenorrheic dancers on hormone therapy and calcium. Clinical, placebo-controlled, randomized trial study.Healthy volunteers in an academic research environment. Fifty-five dancers (mean age: 22.0 +/- 4.6, age at menarche: 14.7 +/- 2.3 years), including 24 amenorrheics. Amenorrheics were randomized in a controlled trial to receive placebo or Premarin, 0.625 mg for 25 days monthly, with Provera, 10 mg, for 10 of these 25 days (hormone therapy) for 2 years. These women were compared to normally menstruating controls. The study participants also received 1250 mg of calcium per day. Bone mineral density (BMD) measured at the foot, wrist, and lumbar spine. Our overall results showed no difference in BMD between the treated or placebo groups, indicating that hormone therapy did not change or normalize BMD when compared to normals. Five patients (all on placebo) who resumed menses during the study showed an increase in BMD without normalization. These findings suggest that mechanisms other than hypoestrogenism may be involved with the osteopenia associated with exercise-induced amenorrhea.

Bias in Observational Studies of Prevalent Users: Lessons for Comparative Effectiveness Research From a Meta-Analysis of Statins

PubMed Central

Danaei, Goodarz; Tavakkoli, Mohammad; Hernán, Miguel A.

2012-01-01

Randomized clinical trials (RCTs) are usually the preferred strategy with which to generate evidence of comparative effectiveness, but conducting an RCT is not always feasible. Though observational studies and RCTs often provide comparable estimates, the questioning of observational analyses has recently intensified because of randomized-observational discrepancies regarding the effect of postmenopausal hormone replacement therapy on coronary heart disease. Reanalyses of observational data that excluded prevalent users of hormone replacement therapy led to attenuated discrepancies, which begs the question of whether exclusion of prevalent users should be generally recommended. In the current study, the authors evaluated the effect of excluding prevalent users of statins in a meta-analysis of observational studies of persons with cardiovascular disease. The pooled, multivariate-adjusted mortality hazard ratio for statin use was 0.77 (95% confidence interval (CI): 0.65, 0.91) in 4 studies that compared incident users with nonusers, 0.70 (95% CI: 0.64, 0.78) in 13 studies that compared a combination of prevalent and incident users with nonusers, and 0.54 (95% CI: 0.45, 0.66) in 13 studies that compared prevalent users with nonusers. The corresponding hazard ratio from 18 RCTs was 0.84 (95% CI: 0.77, 0.91). It appears that the greater the proportion of prevalent statin users in observational studies, the larger the discrepancy between observational and randomized estimates. PMID:22223710

Quality of life in congenital, untreated, lifetime isolated growth hormone deficiency.

PubMed

Barbosa, Jorge A R; Salvatori, Roberto; Oliveira, Carla R P; Pereira, Rossana M C; Farias, Catarine T; Britto, Allan V de O; Farias, Natália T; Blackford, Amanda; Aguiar-Oliveira, Manuel H

2009-07-01

Impaired quality of life (QoL) is commonly described as being associated with growth hormone (GH) deficiency (GHD), and beneficial effects of GH replacement therapy on QoL have been reported. However, most studies examined heterogeneous cohorts of patients GHD of varying etiologies, severities and age of onset. Most of these patients miss other pituitary hormones, whose replacement can also influence QoL. We studied the QoL of a homogeneous cohort of 20 adults with isolated GH deficiency (IGHD) due to the same mutation in the GH-releasing hormone receptor gene (IGHD, 10 men) using the Life Satisfaction Hypopituitarism Module (QLS-H), and compared them with 20 matched controls residing in the same community (CO, 10 men). Additionally, the IGHD group was evaluated after 6 months of treatment with bi-monthly depot GH, and after 12 months from its interruption. There was no difference in the total score of QoL (TSQoL) or in any of the nine categories that composes the questionnaire between IGHD and CO. Similar results were obtained when data were analyzed by sex. GH treatment only increased satisfaction with physical endurance, but did not cause an increase in the TSQoL. We conclude that in this unique population congenital, untreated, lifetime IGHD does not reduce QoL, and treatment with GH for 6 months only causes improvement in satisfaction with physical resistance.

Clinical Features of Early and Late Postoperative Hypothyroidism After Lobectomy.

PubMed

Park, Suyeon; Jeon, Min Ji; Song, Eyun; Oh, Hye-Seon; Kim, Mijin; Kwon, Hyemi; Kim, Tae Yong; Hong, Suck Joon; Shong, Young Kee; Kim, Won Bae; Sung, Tae-Yon; Kim, Won Gu

2017-04-01

Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur. We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC). This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up. Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001). Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery. Copyright © 2017 by the Endocrine Society

What is the optimal bone-preserving strategy for patients with Addison's disease?

PubMed

Lee, Paul; Greenfield, Jerry R

2015-08-01

Addison's disease is associated with low bone mineral density and increased risk of hip fractures. Causes are multifactorial, contributed by underlying adrenocortical hormonal deficiency, associated autoimmune endocrinopathies, electrolyte disturbances and, in some patients, supraphysiologic glucocorticoid replacement. Recent realization of physiologic cortisol production rate has revised downwards glucocorticoid replacement dosages. Meanwhile, new research has emerged suggesting complex interplay between sodium and calcium homoeostasis under the influence of mineralocorticoid and parathyroid hormone that may impact bone health. As the prevalence of Addison's disease is rising, and osteoporosis and fractures are associated with significant morbidity and increased mortality, attention to bone preservation in Addison's disease is of clinical relevance and importance. We suggest an approach to bone health in Addison's disease integrating physiologic adrenocortical hormonal replacement with electrolyte and mineral homoeostasis optimization. © 2015 John Wiley & Sons Ltd.

Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism?

PubMed

Biondi, Bernadette; Wartofsky, Leonard

2012-07-01

Levothyroxine therapy is the traditional lifelong replacement therapy for hypothyroid patients. Over the last several years, new evidence has led clinicians to evaluate the option of combined T(3) and T(4) treatment to improve the quality of life, cognition, and peripheral parameters of thyroid hormone action in hypothyroidism. The aim of this review is to assess the physiological basis and the results of current studies on this topic. We searched Medline for reports published with the following search terms: hypothyroidism, levothyroxine, triiodothyronine, thyroid, guidelines, treatment, deiodinases, clinical symptoms, quality of life, cognition, mood, depression, body weight, heart rate, cholesterol, bone markers, SHBG, and patient preference for combined therapy. The search was restricted to reports published in English since 1970, but some reports published before 1970 were also incorporated. We supplemented the search with records from personal files and references of relevant articles and textbooks. Parameters analyzed included the rationale for combination treatment, the type of patients to be selected, the optimal T(4)/T(3) ratio, and the potential benefits of this therapy on symptoms of hypothyroidism, quality of life, mood, cognition, and peripheral parameters of thyroid hormone action. The outcome of our analysis suggests that it may be time to consider a personalized regimen of thyroid hormone replacement therapy in hypothyroid patients. Further prospective randomized controlled studies are needed to clarify this important issue. Innovative formulations of the thyroid hormones will be required to mimic a more perfect thyroid hormone replacement therapy than is currently available.

The Role of Androgens and Estrogens on Healthy Aging and Longevity

PubMed Central

Dillon, E. Lichar; Urban, Randall J.; Sheffield-Moore, Melinda

2012-01-01

Aging is associated with a loss of sex hormone in both men (andropause) and women (menopause). In men, reductions in testosterone can trigger declines in muscle mass, bone mass, and in physical function. In women, the impact of the loss of sex hormones, such as estradiol, on bone is well elucidated, but evidence is limited on whether the loss of estradiol negatively affects muscle mass and physical function. However, deficiencies in multiple anabolic hormones have been shown to predict health status and longevity in older persons. Thus, consideration should be given as to whether targeted hormone replacement therapies may prove effective at treating clinical conditions, such as age-related sarcopenia, cancer cachexia, and/or acute or chronic illnesses. If initiated carefully in the appropriate clinical population, hormone replacement therapies in men and women may prevent and reverse muscle and bone loss and functional declines and perhaps promote healthy aging and longevity. PMID:22451474

Pituitary Dysfunction from an Unruptured Ophthalmic Internal Carotid Artery Aneurysm with Improved 2-year Follow-up Results: A Case Report.

PubMed

Qi, Meng; Ye, Ming; Li, Meng; Zhang, Peng

2018-01-01

Internal carotid artery (ICA) supraclinoid segment aneurysms extending into the sellar region and leading to pituitary dysfunction are a rare occurrence. To date, long-term follow up of pituitary function 2 years post-treatment has never been reported. Herein, we present a case of pituitary dysfunction due to an unruptured ophthalmic segment internal carotid artery aneurysm and report improved 2-year follow-up results. A 76-year-old male presented with disturbed consciousness due to hyponatremia, which was caused by hypoadrenocorticism resulting from pituitary dysfunction complicated by hypogonadism and hypothyroidism. Computed tomography angiography revealed an intracranial aneurysm of the ophthalmic segment of the right ICA with an intrasellar extension. Thus, digital subtraction angiography and coil embolization were performed, followed by hormone replacement therapy. A 2-year follow-up revealed a partial improvement in the pituitary function, including complete restoration of thyroid-stimulating hormone level and other thyroid hormones levels, and partial restoration of testosterone levels, followed by discontinuation of thyroid hormone replacement therapy. However, the mechanisms of such pituitary dysfunction and the effects of various treatments, including clipping and coiling, on different hormones of pituitary function recovery remain unclear. A long-term follow-up of >2 years may elucidate the pituitary function recovery post-treatment and provide a medication adjustment for hormone replacement therapy.

Androgens and bone health.

PubMed

Hansen, K A; Tho, S P

1998-01-01

Osteoporosis is one of the most common metabolic bone diseases in the adult population and its prevalence will continue to rise as our population grows older. In both sexes, hypogonadism is associated with accelerated loss of bone and development of osteoporosis. Adrenal and gonadal androgen levels decline with advancing age in both sexes. Androgens act by either directly binding to androgen receptors, or by aromatization of androgens to estrogens and subsequently interacting with estrogen receptors. Both pathways are important for skeletal health. Direct androgen binding to an androgen receptor may play a more important role in early skeletal development and determination of sexual dimorphic traits. While bone remodeling, which is important in maintaining healthy bone through life, is primarily stimulated by estrogen, studies in the rat and human support the complex action of androgens and estrogens in bone modeling and remodeling, and hence the development and maintenance of healthy bone. In postmenopausal females, the addition of androgens to hormone replacement therapy results in significant additional improvement in bone mineral density compared to estrogen replacement alone. Accumulating evidence indicate that androgens play an important role in the health of bone and the potential benefit of adding these agents to hormone replacement regimens.

Hypoparathyroidism: clinical features, skeletal microstructure and parathyroid hormone replacement

PubMed Central

Rubin, Mishaela R.; Bilezikian, John P.

2013-01-01

Objective Hypoparathyroidism is a disorder in which parathyroid hormone is deficient in the circulation due most often to immunological destruction of the parathyroids or to their surgical removal. The objective of this work was to define the abnormalities in skeletal microstructure as well as to establish the potential efficacy of PTH(1-84) replacement in this disorder. Subjects and methods Standard histomorphometric and μCT analyses were performed on iliac crest bone biopsies obtained from patients with hypoparathyroidism. Participants were treated with PTH(1-84) for two years. Results Bone density was increased and skeletal features reflected the low turnover state with greater BV/TV, Tb. Wi and Ct. Wi as well as suppressed MS and BFR/BS as compared to controls. With PTH(1-84), bone turnover and bone mineral density increased in the lumbar spine. Requirements for calcium and vitamin D fell while serum and urinary calcium concentrations did not change. Conclusion Abnormal microstructure of the skeleton in hypoparathyroidism reflects the absence of PTH. Replacement therapy with PTH has the potential to correct these abnormalities as well as to reduce the requirements for calcium and vitamin D. PMID:20485912

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

Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D.

In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R{sub d}) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R{sub d}. In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportalmore » replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using (3-{sup 3}H)glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R{sub d}.« less

Foot length before and during insulin-like growth factor-I treatment of children with laron syndrome compared to human growth hormone treatment of children with isolated growth hormone deficiency.

PubMed

Silbergeld, Aviva; Lilos, Pearl; Laron, Zvi

2007-12-01

To compare foot length deficits between patients with Laron syndrome (LS) (primary growth hormone [GH] insensitivity) and congenital isolated GH deficiency (IGHD) and their response to replacement therapy with insulin-like growth factor-I (IGF-I) and hGH, respectively. Data for the study were collected from the records of nine children with LS (3 M, 6 F) 7.8 +/- 4.8 years old (mean +/- SD), and nine children with IGHD (3 M, 6 F), 3.8 +/- 3.3 years old. Fifteen non-treated adult patients with LS were also included in the study. Measurements of foot length were recorded without treatment and monitored during 9 years of treatment in the children and in the untreated adult patients. For statistical analysis the non-parametric Mann-Whitney U test was used. With almost similar basal values in growth deficit and pre-treatment growth velocities, the achievements towards norms after 9 years of treatment were greater in the patients with IGHD than in the patients with LS: foot length reached -1.4 +/- 0.8 vs. -3.3 +/- 1.0 SDS (mean +/- SD), and body height -2.2 +/- 1.0 vs. -3.9 +/- 0.5 SDS. The difference between the two groups could be due to the initiation of replacement therapy in the patients with IGHD at a younger age. Adult foot size of untreated patients with LS is small but less retarded than the height deficit. Both IGF-I and hGH are potent growth stimulating hormones of linear growth and acrae as exemplified by foot growth.

Hormone Replacement Therapy: MedlinePlus Health Topic

MedlinePlus

... Cancer Institute) Also in Spanish Menopause: Medicines to Help You (Food and Drug Administration) ... Hormone Therapy for the Primary Prevention of Chronic Conditions (U.S. Preventive Services Task Force) - ...

Mucinous cystadenocarcinoma of the pancreas developing during hormone replacement therapy.

PubMed

Tanaka, Shinji; Kawamura, Toru; Nakamura, Noriaki; Teramoto, Kenichi; Arii, Shigeki

2007-05-01

Hormone replacement therapy (HRT) containing estrogens is generally used to relieve climacteric symptoms and to prevent osteoporosis and coronary heart disease [1], however, there has been increasing evidence of the HRT as the risk of hormone-dependent neoplasms including breast cancer [2], uterine endometrial cancer [3], ovarian cancer [4], and even lung cancer [5]. Noteworthy is mucinous cyst neoplasms (MCNs) of the pancreas, characterized by mucin-producing columnar epithelium supported by "ovarian-like" mesenchymal stroma, occur mostly in females expressing estrogen receptors [6, 7]. Although several reports regarding the closed relationship between MCNs and pregnancy [8, 9] might imply potential sex hormone-dependency of the MCNs [10], no correlation has been reported. This is the first case report of malignant MCN developing during continuous HRT after hysterectomy.

Hormone replacement therapy in young women with primary ovarian insufficiency and early menopause.

PubMed

Sullivan, Shannon D; Sarrel, Philip M; Nelson, Lawrence M

2016-12-01

Primary ovarian insufficiency (POI) is a rare but important cause of ovarian hormone deficiency and infertility in women. In addition to causing infertility, POI is associated with multiple health risks, including bothersome menopausal symptoms, decreased bone density and increased risk of fractures, early progression of cardiovascular disease, psychologic impact that may include depression, anxiety, and decreased perceived psychosocial support, potential early decline in cognition, and dry eye syndrome. Appropriate hormone replacement therapy (HRT) to replace premenopausal levels of ovarian sex steroids is paramount to increasing quality of life for women with POI and ameliorating associated health risks. In this review, we discuss POI and complications associated with this disorder, as well as safe and effective HRT options. To decrease morbidity associated with POI, we recommend using HRT formulations that most closely mimic normal ovarian hormone production and continuing HRT until the normal age of natural menopause, ∼50 years. We address special populations of women with POI, including women with Turner syndrome, women with increased risk of breast or ovarian cancer, women approaching the age of natural menopause, and breastfeeding women. Published by Elsevier Inc.

Controversial endocrine interventions for the aged.

PubMed

Leow, M K S; Loh, K C

2006-07-01

Specific endocrine changes occur with the ageing process. The last decade has witnessed significant progress in the basic and clinical science of ageing, thereby rejuvenating the interest in anti-ageing medicine, especially that of hormone replacement, by medical professionals and the lay public. However, endocrine manipulation as a therapeutic strategy for ageing is still evolving as continuing research attempts to answer the many questions of what it can achieve at the risk of incurring unknown long-term adverse effects. The current day doctor is confronted with a host of options, and will benefit from a synopsis of the latest evidence before making the most appropriate decision for aged patients seeking hormonal replacement therapy as a means to counter the effects of ageing. This review aims to give a rapid overview of the endocrine profile of geriatric population and the studies on the more controversial hormonal replacement therapies for the aged.

Future possibilities in the prevention of breast cancer: Luteinizing hormone-releasing hormone agonists

PubMed Central

Spicer, Darcy V; Pike, Malcolm C

2000-01-01

The cyclic production of estrogen and progesterone by the premenopausal ovary accounts for the steep rise in breast cancer risk in premenopausal women. These hormones are breast cell mitogens. By reducing exposure to these ovarian hormones, agonists of luteinizing hormone-releasing hormone (LHRH) given to suppress ovarian function may prove useful in cancer prevention. To prevent deleterious effects of hypoestrogenemia, the addition of low-dose hormone replacement to the LHRH agonist appears necessary. Pilot data with such an approach indicates it is feasible and reduces mammographic densities. PMID:11250719

International Comparison of Adult Height in Children with Growth Hormone Deficiency and Limitations of Growth Hormone Treatment in Japan.

PubMed

Tanaka, Toshiaki

2017-03-01

The approved therapeutic dose of growth hormone (GH) for growth hormone deficiency (GHD) varies depending on the country. Japan has the lowest therapeutic dose globally, with a single dose of 0.175 mg/kg/week. GH treatment for GHD is considered as a replacement therapy and in fact, a dose of 0.175 mg/kg/week is slightly higher than GH secretion in prepubertal healthy children but nearly the same as that of pubertal children. Although the same growth rate as that of healthy children is expected in response to replacement therapy, the catch-up growth observed for the first 1 to 2 years of GH treatment was misinterpreted as an effect of the GH replacement therapy. The real effect of the GH replacement therapy was the growth rate appeared after more than 3 years of GH therapy, when patients showed nearly the same growth rate as healthy children. Therefore, children with GHD can have a higher growth rate than healthy children only for the first 1 to 2 years of GH therapy, after which their growth rate begins to wane. In the United States and Europe, the various therapeutic doses and high-dose treatment are accepted and the SD score of adult height after treatment is higher than that in Japan. The improvement degree of the height SD score and the adult height SD score with GH therapy are lower in Japan compared with other countries that administer a similar therapeutic dose. This suggests that the response to GH can be affected by race. Actual comparison of the response to GH between Japanese and Caucasian patients using KIGS (Pharmacia International Growth Database) data showed that both the short-term response and the effect on adult height were reduced in Japanese patients. As there is a strong positive correlation between adult height and height at the onset of puberty, treatment methods that can increase pubertal growth will be considered in the future for patients with GDH who enter puberty with short stature. Copyright© of YS Medical Media ltd.

Hormonal development therapy (HDT) in hypogonadism in long-term view.

PubMed

Heinz, Marlene

2010-04-01

Since the 1960s, oestrogen deficiency in hypogonadism in girls has been successfully treated by a sort of analogous application of the menopausal hormone replacement therapy (HRT) scheme, here however, to induce and support sexual development in puberty and adolescence. The essential distinction between goals, ways and means of the two distinct hormonal treatments caused by menopause and by hypogonadism in puberty also suggests that the latter treatment is more characteristic of defining hormonal development therapy (HDT). Moreover, specific HDT in hypogonadism is essential for longitudinal growth of girls, functions of female reproductive system, bone and lipid metabolism and the immune, central nervous and cardiovascular systems. By contrast, the aim of menopausal replacement therapy in elderly women is treating negative effects of physiological loss of oestrogens as hot flush, lacks of female well-being and osteoporosis, while in hypogonadal girls there is of course nothing that might be replaced eventually. Especially in cases of absolute oestrogen deficiency, as in Turner syndrome and in other cases of premature ovarian failure, HDT has to be started at the age of expected puberty. An international consensus suggests possibly lifelong HDT for the lasting support of female development and functions. However, neither reliable studies about possible risks and side effects of continuous hormonal therapy in adult women with hypogonadismus nor a more precise consensus have emerged yet. Emphasising the term HDT particularly aims at putting more effort in getting over these paucities simultaneously. Indications, hormonal therapy, dosage, application and timing in puberty are described in this article. Aspects of long-term hormonal treatment are critically discussed. Copyright 2010 Elsevier Ltd. All rights reserved.

Steroids, reproductive endocrine function, and affect. A review.

PubMed

Frye, C A

2009-12-01

Although the effects of estrogen (E2) on mood have been studied for some time, there is controversy over the utility of hormone replacement therapy (HRT). Administration of E2 and/or other steroid hormones (e.g., progestogens, androgens, etc.) may be able to reduce increased anxiety and depression that is present with the onset of menopause. However, some studies indicate that E2 replacement does not significantly improve anxiety and/or depressive symptoms in all postmenopausal subjects. More recent data suggests that the efficacy of HRT could be based on a number of factors, including variety of E2-replacements available, the timing during or after menopause when HRT is initiated, and/or effects of other steroid hormones, such as progestogens and androgens. Notably, little attention has been paid to the possible synergistic effects of E2 that may require progestogens and/or androgens to produce positive outcomes in mood. Additionally, steroid hormones have a number of effects that influence anxiety and depression across the lifespan. As such, dose, timing, and combination of steroid replacement may explain these differences in behavioral outcome. With the increasing peri- to postmenopausal population, many women can expect to live nearly half their lifetime in a postmenopausal state. Therefore, examining these ambiguous findings is of critical importance. This review will focus on a synthesis of the available information regarding findings from animal and human studies in terms of effects of steroid hormones across the lifespan, different HRT options and their subsequent interactions in the brain and/or the hypothalamic-pituitary-adrenal axis, and effects on anxiety and depression.

Reversible Hypopituitarism Associated with Intravascular Large B-Cell Lymphoma: Case Report of Successful Immunochemotherapy.

PubMed

Sawada, Yusuke; Ishii, Sumiyasu; Koga, Yasuhiko; Tomizawa, Taku; Matsui, Ayako; Tomaru, Takuya; Ozawa, Atsushi; Shibusawa, Nobuyuki; Satoh, Tetsurou; Shimizu, Hiroaki; Hirato, Junko; Yamada, Masanobu

2016-03-01

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of diffuse large B-cell lymphoma. There have been only a limited number of reports regarding pituitary dysfunction associated with IVLBCL. We present a 71-year-old woman with hypopituitarism without any hypothalamic/pituitary abnormalities as assessed by magnetic resonance imaging. She presented with edema, abducens palsy, and elevated levels of lactate dehydrogenase and soluble interleukin-2 receptor. Provocative testing showed that the peaks of luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone and adrenocorticotropic hormone were evoked to normal levels by simultaneous administration of luteinizing hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone, but the responses of these four pituitary hormones showed a delayed pattern. She was diagnosed with IVLBCL with cerebrospinal invasion by pathological findings of the bone marrow, skin, and cerebrospinal fluid. She achieved hematological remission after immunochemotherapy. Pituitary function was also restored without hormonal replacement, and the improvement of the pituitary function was confirmed by dynamic testing. We reviewed the literature with respect to hypopituitarism associated with IVLBCL. There were less than 20 case reports and most of the patients died. Endocrinological course was described in only two cases, and both of them required hormonal supplementation. To our knowledge, this is the first case of hypopituitarism induced by IVLBCL that was successfully managed by immunochemotherapy alone. This case suggests that early diagnosis and treatment of IVLBCL might improve anterior pituitary function and enable patients to avoid hormone replacement therapy.

Does postmenopausal hormone replacement therapy affect intraocular pressure?

PubMed

Abramov, Yoram; Borik, Sharon; Yahalom, Claudia; Fatum, Muhammad; Avgil, Gadiel; Brzezinski, Amnon; Banin, Eyal

2005-08-01

To assess the effects of postmenopausal hormone replacement therapy (HRT) on intraocular pressure (IOP). This was a cross-sectional controlled study, including 107 women aged 60 to 80 years receiving HRT and 107 controls who have never received HRT. All subjects underwent IOP assessment and funduscopic photography for cup-to-disc (C/D) ratios, and completed questionnaires regarding personal and family history of glaucoma, hormone replacement therapy, lifetime estrogen and progesterone exposure, and cardiovascular risk factors. Main Outcome Measures included IOP, prevalence of increased IOP, and C/D ratios. The groups did not differ in mean IOP (15.3 versus 15.3 mm Hg), mean vertical (0.18 versus 0.21) and horizontal (0.17 versus 0.14) C/D ratios, and in prevalence of increased IOP (15% versus 14%), C/D ratio (7% versus 7%), or glaucoma (9% versus 11%). A personal history of ischemic heart disease was the only risk factor associated with increased IOP (O.R. = 4.63, P = 0.003). Lifetime estrogen and progesterone exposure, including pregnancies, deliveries, menstruation years, and the use of oral contraceptives did not significantly affect the risk for increased IOP. Hormone replacement therapy and lifetime estrogen and progesterone exposure do not seem to affect IOP or the risk for increased IOP. A personal history of ischemic heart disease may be associated with a higher risk for this disorder.

Massive pericardial effusion without cardiac tamponade due to subclinical hypothyroidism (Hashimoto's disease).

PubMed

Papakonstantinou, Panteleimon E; Gourniezakis, Nikolaos; Skiadas, Christos; Patrianakos, Alexandros; Gikas, Achilleas

2018-05-01

Hypothyroidism is a significant cause of pericardial effusion. However, large pericardial effusions due to hypothyroidism are extremely rare. Hormone replacement therapy is the cornerstone of treatment for hypothyroidism and regular follow-up of patients after initiation of the therapy is indicated. Herein, the case of a 70-year-old woman with a massive pericardial effusion due to Hashimoto's disease is presented. A 70-year-old female from a rural village on the island of Crete, Greece, was admitted to our hospital due to a urinary tract infection. She was under hormone replacement therapy with levothyroxine 100 µg once a day for Hashimoto's disease. Two years previously, the patient had had an episode of pericarditis due to hypothyroidism and had undergone a computed tomography-guided pericardiocentesis. The patient did not have regular follow-up and did not take the hormone replacement therapy properly. On admission, the patient's chest X-ray incidentally showed a possible pericardial effusion. The patient was referred for echocardiography, which revealed a massive pericardial effusion. Beck's triad was absent. Thyroid hormones were consistent with subclinical hypothyroidism: thyroid-stimulating hormone (TSH) 30.25 mIU/mL (normal limits: 0.25-3.43); free thyroxin 4 0.81 ng/dL (normal limits: 0.7-1.94). The patient had a score of 5 on the scale outlined by the European Society of Cardiology (ESC) position statement on triage strategy for cardiac tamponade and, despite the absence of cardiac tamponade, a pericardiocentesis was performed after 48 hours. The patient was treated with 125 µg levothyroxine orally once daily. This was a rare case of an elderly female patient from a rural village with chronic massive pericardial effusion due to subclinical hypothyroidism without cardiac tamponade. Hypothyroidism should be included in the differential diagnosis of pericardial effusion, especially in a case of unexplained pericardial fluid. Initiation of hormone replacement therapy should be personalised in elderly patients. TSH levels >10 mU/L usually require therapy with levothyroxine in order to prevent adverse events. Rural patients usually do not have regular follow-up after the initiation of hormone replacement therapy. Pericardial effusions due to hypothyroidism grow slowly and subclinical hypothyroidism rarely shows signs and symptoms and can be underdiagnosed. The ESC position statement on triage strategy for pericardial diseases is a valuable clinical tool to estimate the necessity for pericardial drainage in such cases.

Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria.

PubMed

Kranz, Georg S; Seiger, Rene; Kaufmann, Ulrike; Hummer, Allan; Hahn, Andreas; Ganger, Sebastian; Tik, Martin; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

2017-04-15

Sex steroid hormones such as estradiol and testosterone are known to have organizing, as well as activating effects on neural tissue in animals and humans. This study investigated the effects of transgender hormone replacement therapy on white matter microstructure using diffusion tensor imaging. Female-to-male and male-to-female transgender participants were measured at baseline, four weeks and four months past treatment start and compared to female and male controls. We observed androgenization-related reductions in mean diffusivity and increases in fractional anisotropy. We also observed feminization-related increases in mean diffusivity and reductions in fractional anisotropy. In both transgender participants and controls, hormonal fluctuations were correlated with changes in white matter microstructure. Although the present study does not preclude regression to the mean as a potential contributing factor, the results indicate that sex hormones are - at least in part - responsible for white matter variability in the human brain. Studies investigating the effects of sex hormones on adult human brain structure may be an important route for greater understanding of the psychological differences between females and males. Copyright © 2017 Elsevier Inc. All rights reserved.

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)

Hormone Replacement Therapy: Can It Cause Vaginal Bleeding?

MedlinePlus

... hormone therapy for menopause symptoms, and my monthly menstrual periods have returned. Is this normal? Answers from ... Advertising and sponsorship opportunities Reprint Permissions A single copy of these materials may be reprinted for noncommercial ...

Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression

PubMed Central

Sohn, Seo Young; Joung, Ji Young; Cho, Yoon Young; Park, Sun Mi; Jin, Sang Man; Chung, Jae Hoon

2015-01-01

Background There are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH). Methods We retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up. Results Significant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods. Conclusion Female DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT. PMID:26248858

Reproductive age modulates the impact of focal ischemia on the forebrain as well as the effects of estrogen treatment in female rats

PubMed Central

Selvamani, Amutha; Sohrabji, Farida

2009-01-01

While human observational studies and animal studies report a neuroprotective role for estrogen therapy in stroke, the multicenter placebo-controlled Women's Health Initiative (WHI) study concluded that hormone therapy increased the risk for stroke in postmenopausal women. The present study therefore tested the hypothesis that estrogen replacement would increase the severity of a stroke-like injury in females when this replacement occurs after a prolonged hypoestrogenic period, such as the menopause or reproductive senescence, but not when given to females that were normally cycling immediately prior to the hormone replacement. Two groups of female rats were used: multiparous females with normal but lengthened estrus cycles (mature adults), and older multiparous females currently in a persistent acyclic state (reproductive senescent). Animals were either used intact, or were bilaterally ovariectomized and immediately replaced with a 17β-estradiol pellet or control pellet. Animals were subject to a forelimb placing test (a test for sensorimotor deficit) and thereafter to middle cerebral artery occlusion (MCAo) by stereotaxic injection of the vasoconstrictive peptide endothelin-1, adjacent to the MCA. One week after stroke, behavioral tests were performed again. Cortical and striatal infarct volume, measured from brain slices, was significantly greater in intact reproductive senescent females as compared to intact mature adults. Furthermore, estrogen treatment to ovariectomized mature adult females significantly reduced the cortical infarct volume. Paradoxically, estrogen treatment to ovariectomized reproductive senescent females significantly increased cortical and striatal infarct volumes as compared to control pellet replaced senescent females. Significant post-stroke behavioral deficit was observed in all groups on the side contralateral to the lesion, while senescent females also exhibited deficits on the ipsilateral side, in the cross-midline forelimb placement test. Using an animal model that approximates the natural ovarian aging process, these findings strongly support the hypothesis that the effectiveness of estrogen therapy in protecting brain health may depend critically on the time of initiation with respect to a female's reproductive status. PMID:18829137

Regulation of vernal migration in Gambel's white-crowned sparrows: Role of thyroxine and triiodothyronine.

PubMed

Pérez, Jonathan H; Furlow, J David; Wingfield, John C; Ramenofsky, Marilyn

2016-08-01

Appropriate timing of migratory behavior is critical for migrant species. For many temperate zone birds in the spring, lengthening photoperiod is the initial cue leading to morphological, physiological and behavior changes that are necessary for vernal migration and breeding. Strong evidence has emerged in recent years linking thyroid hormone signaling to the photoinduction of breeding in birds while more limited information suggest a potential role in the regulation of vernal migration in photoperiodic songbirds. Here we investigate the development and expression of the vernal migratory life history stage in captive Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) in a hypothyroidic state, induced by chemical inhibition of thyroid hormone production. To explore possible variations in the effects of the two thyroid hormones, triiodothyronine and thyroxine, we subsequently performed a thyroid inhibition coupled with replacement therapy. We found that chemical inhibition of thyroid hormones resulted in complete abolishment of mass gain, fattening, and muscle hypertrophy associated with migratory preparation as well as resulting in failure to display nocturnal restlessness behavior. Replacement of thyroxine rescued all of these elements to near control levels while triiodothyronine replacement displayed partial or delayed rescue. Our findings support thyroid hormones as being necessary for the expression of changes in morphology and physiology associated with migration as well as migratory behavior itself. Copyright © 2016 Elsevier Inc. All rights reserved.

Myxedema coma and cardiac ischemia in relation to thyroid hormone replacement therapy in a 38-year-old Japanese woman.

PubMed

Taguchi, Takafumi; Iwasaki, Yasumasa; Asaba, Koichi; Takao, Toshihiro; Hashimoto, Kozo

2007-12-01

Although thyroid hormone deficiency, either clinical or subclinical, is an established risk factor for cardiovascular disease, coronary ischemia in a premenopausal woman in her 30s is relatively rare. A 38-year-old woman was referred to our hospital with severe breathlessness and depressed consciousness. Physical examination found facial, abdominal, and pretibial edema; coarse hair, hoarse voice, and dry skin; engorged jugular veins; a distant heart sound; and reduced bilateral entry of air into the chest. Laboratory examinations revealed severe hypothyroidism, hyperlipidemia, and elevated serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125). A computed tomography scan showed massive pleural and pericardial effusions. After 3 months of levothyroxine replacement therapy (initial dose: 12.5 microg/d; maintenance dose: 125 microg/d), all abnormal laboratory values associated with hypothyroidism returned to within normal ranges, with the exception of a transient and paradoxical rise in serum thyroid-stimulating hormone levels. However, 3 weeks after the initiation of therapy, the patient reported intermittent chest pains during the course of therapy, and a coronary artery angiogram revealed diffuse stenosis of all 3 branches. The patient underwent coronary artery bypass grafting, with subsequent improvement in coronary perfusion. Careful cardiovascular evaluation is recommended before the start of thyroid hormone replacement therapy. In addition, care should be taken in the interpretation of serum biomarkers of malignancy (eg, CEA, CA125) in patients with myxedema, as values may be elevated in a hypothyroid state. Long-standing hypothyroidism may be associated with severe coronary atherosclerosis, even in a relatively young, premenopausal woman. The potential adverse cardiovascular effects of thyroid hormone must be considered during replacement therapy, even in relatively young patients.

The Role of Sex Hormone Replacement Therapy on Self-Perceived Competence in Adolescents with Delayed Puberty.

ERIC Educational Resources Information Center

Schwab, Jacqueline; Kulin, Howard E.; Susman, Elizabeth J.; Finkelstein, Jordan W.; Chinchilli, Vernon M.; Kunselman, Susan J.; Liben, Lyye S.; D'Arcangelo, M. Rose; Demers, Lawrence M.

2001-01-01

Examined role of sex steroids in development of self-perceived competence among adolescents receiving hormone therapy for delayed puberty. Found that hormone treatments had a significant positive effect for both males and females in perceived job competence. Significant positive effects were also obtained for perceptions of romantic appeal and…

Treatable Bedridden Elderly―Recovery from Flexion Contracture after Cortisol Replacement in a Patient with Isolated Adrenocorticotropic Hormone Deficiency

PubMed Central

Tanaka, Takamasa; Terada, Norihiko; Fujikawa, Yoshiki; Fujimoto, Takushi

2016-01-01

Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder with diverse clinical presentations. A 79-year-old man was bedridden for six months due to flexion contractures of the bilateral hips and knees, along with hyponatremia. He was diagnosed with IAD based on the results of endocrine tests. After one month of corticosteroid replacement, he recovered and was able to stand up by himself. Although flexion contracture is a rare symptom of IAD, steroid replacement therapy may be effective, even for seemingly irreversibly bedridden elderly patients. In bedridden elderly patients with flexion contractures, we should consider and look for any signs of adrenal insufficiency. PMID:27746435

Treatable Bedridden Elderly -Recovery from Flexion Contracture after Cortisol Replacement in a Patient with Isolated Adrenocorticotropic Hormone Deficiency.

PubMed

Tanaka, Takamasa; Terada, Norihiko; Fujikawa, Yoshiki; Fujimoto, Takushi

Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder with diverse clinical presentations. A 79-year-old man was bedridden for six months due to flexion contractures of the bilateral hips and knees, along with hyponatremia. He was diagnosed with IAD based on the results of endocrine tests. After one month of corticosteroid replacement, he recovered and was able to stand up by himself. Although flexion contracture is a rare symptom of IAD, steroid replacement therapy may be effective, even for seemingly irreversibly bedridden elderly patients. In bedridden elderly patients with flexion contractures, we should consider and look for any signs of adrenal insufficiency.

Pituitary cell differentiation from stem cells and other cells: toward restorative therapy for hypopituitarism?

PubMed

Willems, Christophe; Vankelecom, Hugo

2014-01-01

The pituitary gland, key regulator of our endocrine system, produces multiple hormones that steer essential physiological processes. Hence, deficient pituitary function (hypopituitarism) leads to severe disorders. Hypopituitarism can be caused by defective embryonic development, or by damage through tumor growth/resection and traumatic brain injury. Lifelong hormone replacement is needed but associated with significant side effects. It would be more desirable to restore pituitary tissue and function. Recently, we showed that the adult (mouse) pituitary holds regenerative capacity in which local stem cells are involved. Repair of deficient pituitary may therefore be achieved by activating these resident stem cells. Alternatively, pituitary dysfunction may be mended by cell (replacement) therapy. The hormonal cells to be transplanted could be obtained by (trans-)differentiating various kinds of stem cells or other cells. Here, we summarize the studies on pituitary cell regeneration and on (trans-)differentiation toward hormonal cells, and speculate on restorative therapies for pituitary deficiency.

The contraception needs of the perimenopausal woman.

PubMed

Hardman, Sarah M R; Gebbie, Ailsa E

2014-08-01

Perimenopausal women have low fertility but must still be advised to use contraception until natural sterility is reached if they are sexually active. Patterns of contraceptive use vary in different countries worldwide. Long-acting reversible contraceptive methods offer reliable contraception that may be an alternative to sterilisation. Hormonal methods confer significant non-contraceptive benefits, and each individual woman should weigh up the benefits and risks of a particular method. No method of contraception is contraindicated by age alone, although combined hormonal contraception and injectable progestogens are not recommended for women over the age of 50 years. The intrauterine system has particular advantages as a low-dose method of effective hormonal contraception, which also offers control of menstrual dysfunction and endometrial protection in women requiring oestrogen replacement. Condoms are recommended for personal protection against sexually transmitted infections in new relationships. Standard hormone replacement therapy is not a method of contraception. Copyright © 2014 Elsevier Ltd. All rights reserved.

Management of hyper and hypo thyroid conditions

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

Locke, W.

1982-03-01

In hyperthyroidism, the primary objective of therapy is to reduce secretion of thyroid hormone, which can be accomplished in various ways. The stimulus to hypersecretion can be removed in some causes of hyperthyroidism; in others, hormone synthesis and release can be inhibited by drugs such as thioamides, adrenergic blocking agents, or possibly lithium or glucocorticoids. Radioactive iodine is indicated for primary therapy of uncomplicated hyperthyroidism due to Graves' disease in persons over 30 years of age (myxedema may be a complication) and for treatment of autonomous thyroid adenoma in patients who are not suitable candidates for surgery. Surgical ablation ismore » preferred for some causes of hyperthyroidism but may induce postoperative hypothyroidism. Hypothyroidism due to thyroid failure usually presents few therapeutic difficulties and can be managed simply by long-term hormone replacement. Before hormone replacement is prescribed for secondary or tertiary hypothyroidism, the other pituitary functions should be assessed.« less

Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline.

PubMed

Fleseriu, Maria; Hashim, Ibrahim A; Karavitaki, Niki; Melmed, Shlomo; Murad, M Hassan; Salvatori, Roberto; Samuels, Mary H

2016-11-01

To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults. The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline. The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.

Re-framing the representation of women in advertisements for hormone replacement therapy.

PubMed

Whittaker, R

1998-06-01

This article examines and presents examples of contemporary advertising within the medical and health professions that continue the process and organisation of knowledge about women and their reproductive bodies. It draws on feminist and poststructural perspectives to inform a critical evaluation of the visual representations of menopausal women and hormone replacement therapy. These representations work to construct certain definitions of the feminine that sustain and support existing contradictory cultural meanings and values about menopause. I argue that the images continue to misrepresent and define what forms of femininity and sexual gender are desirable and acceptable for menopausal women. The article addresses the problems of gender discrimination and bias within the advertising industry, and illustrates the ways in which readers of visual texts may be influenced by stereotypic assumptions concerning a woman's lived experience of menopause. It illustrates how specific symbolic images directed towards men and women for hormone replacement therapy, testosterone deficiency and sexual dysfunction influence the viewer's decision making and action responses.

Analysis of therapeutic growth hormone preparations: report of an interlaboratory collaborative study on growth hormone assay methodologies.

PubMed

Bristow, A F; Jeffcoate, S L

1992-09-01

Recombinant DNA-derived human growth hormone (somatotropin) is widely used to treat growth hormone-deficient children. The potency of this product is determined by in-vivo bioassay in hypophysectomized rats, which is imprecise, costly and invasive, and there have been suggestions that it could safely be replaced with in-vitro or physico-chemical alternatives. In this report we present the results of a collaborative study designed to test this proposal. Somatotropin was modified by mild or severe proteolysis, mild or severe oxidation or treatment at high pH, and compared in a multi-centre collaborative study with unmodified somatotropin or with dimerized somatotropin. Participating laboratories included manufacturers and national control laboratories, and pharmacopoeial bioassays were compared with in-house in-vitro and physico-chemical bioassays. Although performing adequately with untreated somatotropin, for degraded samples the in-vivo bioassays were relatively unresponsive to changes in the growth hormone molecule. In contrast, the physico-chemical assays, in particular the reverse-phase HPLC, performed with a high degree of selectivity. We conclude that in the case of somatotropin, the in-vivo bioassay can be removed from the routine product specification with an acceptable degree of security. This however does not obviate the requirement rigorously to demonstrate biological activity in-vivo during product development, nor may the conclusions of this study be applied to other therapeutic recombinant proteins without similar collaborative investigations.

Pelvic floor dysfunction--does menopause duration matter?

PubMed

Trutnovsky, Gerda; Guzman-Rojas, Rodrigo; Martin, Andrew; Dietz, Hans P

2013-10-01

To explore the effect of menopause and hormone replacement therapy on pelvic organ prolapse and pelvic floor muscle function. The records of patients who attended a tertiary urogynaecological center were reviewed retrospectively. A standardised interview included menopausal age, i.e. years since last period or onset of menopausal symptoms, current or previous hormone use. The clinical examination included prolapse assessment (POP-Q) and palpation of the levator ani muscle. 4D transperineal ultrasound, supine and after voiding, was performed in all patients. Volume data sets were analysed for pelvic organ descent and measures of contractility and distensibility of the pelvic floor at a later date, blinded to all clinical data. Of 311 women seen during the inclusion period, 65% were postmenopausal. Current systemic or local hormone use was reported by 7% and 6%, respectively. 163 women (52%) reported prolapse symptoms with a mean bother of 5.7/10. Significant pelvic organ prolapse was found on clinical examination (POP-Q stage≥2) in 77%, and diagnosed on ultrasound in 61%. On multivariate analysis, controlling for calendaric age, parity and levator avulsion, there was no evidence for menopausal age as an independent predictor of any symptom and sign of pelvic organ prolapse and pelvic floor muscle function. Local oestrogen use and past or present hormone replacement therapy had no detectable effect on any pelvic floor parameter. Hormone deficiency following menopause is unlikely to play a major role in pelvic organ support and levator ani function. Hence, both do not appear to be substantially influenced by local or systemic hormone replacement therapy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Influence of growth hormone replacement on neurological and psychomotor development. Case report.

PubMed

Motta, Felipe; Eisencraft, Adriana Pasmanik; Crisostomo, Lindiane Gomes

2018-05-14

The height response to the use of growth hormone in short height cases has already been confirmed in the literature. The influence of the insulin-like growth factor 1 (GH-IGF1) axis components on development, function, regeneration, neuroprotection, cognition, and motor functions has been evaluated in experimental studies and in adults with central nervous system lesions. However, there is still little research on the clinical impact of hormone replacement on neurological and psychomotor development. This report presents the case of a patient with excellent weight-height recovery and, even more surprisingly, neurological and psychomotor development in response to use of growth hormone. The result strengthens the correlation between experimental and clinical findings related to cerebral plasticity response to growth hormone in children. A preterm male patient with multiple health problems during the neonatal and young infancy period, who for six years presented with a relevant deficit in growth, bone maturation, and neurological and psychomotor development. At six years of age, he had low stature (z-score -6.89), low growth rate, and low weight (z-score -7.91). He was incapable of sustaining his axial weight, had not developed fine motor skills or sphincter control, and presented with dysfunctional swallowing and language. Supplementary tests showed low IGF-11 levels, with no changes on the image of the hypothalamus-pituitary region, and bone age consistent with three-year-old children - for a chronological age of six years and one month. Growth hormone replacement therapy had a strong impact on the weight-height recovery as well as on the neurological and psychomotor development of this child.

Effect of Penetration Enhancers on the Percuaneous Delivery of Hormone Replacement Actives.

PubMed

Trimble, John O; Light, Bob

2017-01-01

Transdermal compositions for hormone replacement are comprised of exogenous hormones that are biochemically similar to those produced endogenously by the ovaries or elsewhere in the body. In this work, estradiol, estriol, and testosterone were loaded in transdermal vehicles, prepared using one of three selected penetration enhancer mixtures: Vehicle 1 (olive oil and oleic acid), Vehicle 2 (isopropyl palmitate and lecithin), and Vehicle 3 (isopropyl myristate and lecithin). The influence of penetration enhancers on transdermal delivery was evaluated using Franz-type diffusion cells and Normal Human 3D Model of Epidermal Tissue. Results showed that drug delivery is affected by the penetration enhancer used in the transdermal composition. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Sex hormones and headache.

PubMed

Silberstein, S D

2000-01-01

The normal female life cycle is associated with a number of hormonal milestones: menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex hormones. Menarche marks the onset of menses and cyclic changes in hormone levels. Pregnancy is associated with rising noncyclic levels of sex hormones, and menopause with declining noncyclic levels. Hormonal contraceptive use during the reproductive years and hormone replacement in menopause are therapeutic hormonal interventions that alter the levels and cycling of sex hormones. These events and interventions may cause a change in the prevalence or intensity of headache. The menstrual cycle is the result of a carefully orchestrated sequence of interactions between the hypothalamus, pituitary, ovary, and endometrium, with the sex hormones acting as modulators and effectors at each level. Estrogen and progestins have potent effects on central serotonergic and opioid neurons, modulating both neuronal activity and receptor density. The primary trigger of Menstrually-related migraine (MM) appears to be the withdrawal of estrogen rather than the maintenance of sustained high or low estrogen levels. However, changes in the sustained estrogen levels with pregnancy (increased) and menopause (decreased) appear to affect headaches. Headaches associated with OC use or menopausal hormonal replacement therapy may be related, in part, to periodic discontinuation of oral sex hormone preparations. The treatment of migraine associated with changes in sex hormone levels is frequently difficult and the patients are often refractory to therapy. Based on what is known of the pathophysiology of migraine, we have attempted to provide a logical approach to the treatment of headaches that are associated with menses, menopause, and OCs using abortive and preventive medications and hormonal manipulations. Considerable evidence suggests a link between estrogen and progesterone, the female sex hormones, and migraine. (Silberstein and Merriam, 1997; Lipton and Stewart, 1993; Epstein et al., 1975; Goldstein and Chen, 1982; Selby and Lance, 1960) Although no gender difference is apparent in prepubertal children, with migraine occurring equally in 4p. 100 of boys and girls, (Goldstein and Chen, 1982, Waters and O'Connor, 1971) migraine occurs more frequently in adult women (18p. 100) than in men (6p. 100). (Lipton and Stewart, 1993) Migraine develops most frequently in the second decade, with the peak incidence occurring with adolescence. (Selby and Lance, 1960; Epstein et al., 1975) Menstrually-related migraine (MM) begins at menarche in 33p. 100 of affected women (Epstein et al. , 1975). MM occurs mainly at the time of menses in many migrainous women, and exclusively with menses (true menstrual migraine [TMM]) in some (Epstein et al., 1975). Menstrual migraine can be associated with other somatic complaints arising before and often persisting into menses, such as nausea, backache, breast tenderness, and cramps and like them appears to be the result of falling sex hormone levels (Silberstein and Merriam, 1997; American Psychiatric Association, 1994). In addition, premenstrual migraine can be associated with premenstrual dysphoric disorder (PDD), also called "premenstrual syndrome" (PMS), which is distinct from the physical symptoms of the perimenstrual period and is probably not directly driven by declining progesterone levels (Mortola, 1998). Migraine occurring during (rather than prior to) menstruation is usually not associated with PMS (Silberstein and Merriam, 1997). Migraine may worsen during the first trimester of pregnancy and, although many women become headache-free during the last two trimesters, 25p. 100 have no change in their migraine (Silberstein, 1997). MM typically improves with pregnancy, perhaps due to sustained high estrogen levels (Silberstein, 1997). Hormonal replacement with estrogens can exacerbate migraine and oral contraceptives (OCs) can change its character and frequency

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

PubMed

Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

2015-09-01

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.

The effect of chronic estrogen application on bile and gallstone composition in women with cholelithiasis.

PubMed

Sieron, Dominik; Czerny, Boguslaw; Sieron-Stoltny, Karolina; Karasiewicz, Monika; Bogacz, Anna; Seremak-Mrozikiewicz, Agnieszka; Kotrych, Daniel; Boron, Dariusz; Mrozikiewicz, Przemyslaw

2016-03-01

Chronic application of third generation progestagens as contraceptives or hormone replacement therapy (HRT) could influence the serum lipid profile, and consequently the bile and gallstone composition. The aim of this study was to determine components of serum, bile and gallstones in women of reproductive age or postmenopausal women using hormonal third generation for at least two years. We enrolled 101 Caucasian women with cholelithiasis. The study included 45 women of reproductive age and 56 postmenopausal women who were divided into subgroups receiving or not exogenous female hormones. In patients we determined serum levels of 17β-estradiol, triglycerides, HDL and LDL cholesterol as well as composition of gallstones and bile. The postmenopausal women showed a significant reduction in the concentration of bile acids in serum while the application of HRT caused an increase in their contents. Serum total and LDL cholesterol in postmenopausal women was higher than in women without hormonal contraception and postmenopausal patients with HRT. Moreover, women taking the exogenous hormones showed a reduced content of calcium ions in both serum, bile and gallstones. Our observations confirm that the chronic use of oral contraceptives and hormone replacement therapy cause an increase in bile lithogenity.

Treatment with Growth Hormone for Adults with Growth Hormone Deficiency Syndrome: Benefits and Risks

PubMed Central

Díez, Juan J.; Sangiao-Alvarellos, Susana; Cordido, Fernando

2018-01-01

Pharmacological treatment of growth hormone deficiency (GHD) in adults began in clinical practice more than 20 years ago. Since then, a great volume of experience has been accumulated on its effects on the symptoms and biochemical alterations that characterize this hormonal deficiency. The effects on body composition, muscle mass and strength, exercise capacity, glucose and lipid profile, bone metabolism, and quality of life have been fully demonstrated. The advance of knowledge has also taken place in the biological and molecular aspects of the action of this hormone in patients who have completed longitudinal growth. In recent years, several epidemiological studies have reported interesting information about the long-term effects of GH replacement therapy in regard to the possible induction of neoplasms and the potential development of diabetes. In addition, GH hormone receptor polymorphism could potentially influence GH therapy. Long-acting GH are under development to create a more convenient GH dosing profile, while retaining the excellent safety, efficacy, and tolerability of daily GH. In this article we compile the most recent data of GH replacement therapy in adults, as well as the molecular aspects that may condition a different sensitivity to this treatment. PMID:29562611

Prevalence and Predictors of Overweight and Obesity in Patients with Pituitary Dysfunctions.

PubMed

Harbeck, Birgit; Danneberg, Sven; Rahvar, Amir-Hossein; Monig, Heiner; Haas, Christian S

2016-01-01

Patients with hypothalamic-pituitary disorders (HPD) may be of increased risk to develop overweight and obesity, thereby fostering cardiovascular events. However, it remains unclear if patients with pituitary dysfunctions per se have an increased risk of becoming obese. The objective of this study was to evaluate prevalence and to identify possible predictors of overweight and obesity in patients with pituitary dysfunctions. A total of 121 out-patients having various causes for HPD were assessed for height and body weight; body mass index (BMI) was calculated and correlated with clinical features. Patients were divided into various subgroups depending on underlying conditions and therapeutic modalities. Most of the HPD patients were overweight or obese with males being significantly more affected. Of interest, patients with macroadenomas suffered significantly more often from overweight and obesity than individuals with microadenomas (73.4% vs. 43.5%, p= 0.006). Increased BMI (≥25 kg/m2) tended to be more common in patients with prolactinomas (70.0%), hormone deficiencies (76.1%) and hormone replacement therapies (76.6%) than in a healthy population. In conclusion, we showed that patients with HPD: (i) frequently suffer from overweight and obesity; (ii) prevalence of overweight and obesity however is comparable to that in the general population; (iii) only patients with macroadenomas seem to have a significantly higher risk; (iv) hormone deficiencies and hormonal replacement therapy may foster weight gain and (v) radiation and surgical tumour therapy per se do not seem to be additional risk factors for weight gain. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of hormones on lipids and lipoproteins

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

Krauss, R.M.

1991-12-01

Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men andmore » are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.« less

Hormone replacement therapy in women with systemic lupus erythematosus and risk of cardiovascular disease.

PubMed

Hochman, J; Urowitz, M B; Ibañez, D; Gladman, D D

2009-04-01

We sought to determine the impact of hormone replacement therapy (HRT) on the occurrence of coronary artery disease (CAD) in women with systemic lupus erythematosus (SLE). Women in the University of Toronto lupus database who had taken HRT with no history of CAD were compared with all post-menopausal female patients with no history of HRT or CAD. Chi-squared and t-tests were used to compare the risk factors of CAD and Kaplan-Meier curve, log rank test and proportional hazard model with time-dependent covariates were used to compare the time from entry into the clinic to occurrence of CAD. A total of 114 HRT-user patients with no history of CAD were compared with 227 post-menopausal non-HRT user SLE controls. The groups were similar with respect to lupus anticoagulant, antiphospholipid antibody, cumulative steroid dose and classic cardiac risk factors. A similar percentage of patients developed CAD in the control (13.7%) and HRT (11.4%) groups. There was no difference in the time to development of CAD. In the multivariate analysis, HRT was not a risk factor for CAD. Only age (P = 0.0001, HR = 1.11, 95% CI = 1.05, 1.17) and SLEDAI-2K (P = 0.0001, HR = 1.10, 95% CI = 1.05, 1.16) were significantly associated with the risk of CAD. In this small group of patients with SLE, HRT alone did not appear to predispose to CAD.

The effects of progesterone selection on psychological symptoms in hormone replacement therapy.

PubMed

Caglayan, Emel Kiyak; Kara, Mustafa; Etiz, Sema; Kumru, Pinar; Aka, Nurettin; Kose, Gultekin

2014-01-01

The aim of this study is to evaluate the effects of hormone replacement therapy using dienogest and medroxyprogesterone acetate on psychological symptoms in perimenopausal and postmenopausal women. A total of 73 patients who sought treatment at the menopause units of the authors' gynecology and obstetrics clinics between of November 2003 and October 2004 complaining of vasomotor symptoms were included in the study prospectively. The cases were divided into two groups: Group I (37 patients) was given 2 mg estradiol valerate and 2 mg dienogest, and Group II (36 patients) was given 2 mg estradiol valerate and 10 mg medroxyprogesterone acetate. The groups' results in months 0 and 6 were compared through the evaluation of vasomotor and psychological symptom levels. No significant difference was found between the groups when the initial levels of vasomotor and psychological symptom subtypes were compared (p = 0.16). It was observed that all the psychological symptoms decreased in the 6th month in the group using dienogest in comparison with the initial situation, and that psychological symptoms increased in the group using medroxyprogesterone acetate in the evaluation performed in the 6th month compared with the initial levels. It was also found out that there was a statistically significant difference between the two groups when compared in terms of these symptoms (p < 0.0001). While the use of dienogest normalizes the general psychological situation and sleep, it was observed that the use of medroxyprogesterone acetate (MPA) worsens the general psychological situation.

Late pubertal growth spurt in a girl with growth hormone deficiency: Is Kaufmann therapy effective in a girl with short stature who responds poorly to growth hormone therapy and estrogen-replacement therapy?

PubMed

Yasuda, Katsuhiko

2017-05-01

A Japanese senior high school girl aged 18 years and 5 months with growth hormone deficiency was referred for primary amenorrhea. Her height was 1.36 m, and her bodyweight was 23.5 kg. She had received daily growth hormone therapy from the age of 5 years. Growth hormone therapy was discontinued at the age of 16 years and 11 months, and estrogen-replacement therapy (ERT) was started to stimulate secondary sexual characteristics. Although ERT was performed until the age of 18 years and 11 months, genital bleeding did not occur. ERT was changed to Kaufmann therapy, and the first genital bleeding occurred 1 year and 4 months later. Finally, regular medically induced menses occurred at the age of 21 years and 10 months. Her height increased by 9 cm in 1 year after the initiation of menstrual bleeding. Kaufmann therapy was associated not only with menstrual bleeding but also with growth spurt. © 2017 Japan Society of Obstetrics and Gynecology.

What is the best approach to tailoring hydrocortisone dose to meet patient needs in 2012?

PubMed

Debono, Miguel; Ross, Richard J

2013-05-01

Cortisol is an essential stress hormone and replacement with oral hydrocortisone is lifesaving in patients with adrenal insufficiency. Cortisol has a diurnal rhythm regulated by the central body clock and this rhythm is a metabolic signal for peripheral tissue clocks. Loss of cortisol rhythmicity is associated with fatigue, depression and insulin resistance. A general principle in endocrinology is to replace hormones to replicate physiological concentrations; however, the pharmacokinetics of oral immediate-release hydrocortisone make it impossible to fully mimic the cortisol rhythm and patients still have an increased morbidity and mortality despite replacement. Traditionally, physicians have replaced hydrocortisone with a total daily dose based on the diurnal 24-h cortisol production rate with hydrocortisone given twice or thrice daily, with the highest dose first thing in the morning. Monitoring treatment and dose titration has been much debated with some clinicians using cortisol day curves and others relying on clinical symptoms. The main challenge is that there is no established biomarker of cortisol activity. In addressing the clinical question, we have taken the view that an understanding of the cortisol circadian rhythm and hydrocortisone pharmacokinetics is essential when tailoring hydrocortisone dose. Using this approach, we have developed a thrice daily, weight-related, dosing regimen and a pharmacokinetic and clinical method to monitor treatment. Our argument for replicating the cortisol circadian rhythm is based on the observation that disruption of the rhythm is associated with ill health, and the few studies that have compared different treatment regimens. Further studies are required to definitively test the benefits of replacing the cortisol circadian rhythm in patients with adrenal insufficiency. © 2012 Blackwell Publishing Ltd.

Apocrine sweat gland obstruction by antiperspirants allowing transdermal absorption of cutaneous generated hormones and pheromones as a link to the observed incidence rates of breast and prostate cancer in the 20th century.

PubMed

McGrath, Kris G

2009-06-01

Breast and prostate cancer share similarities and likely represent homologous cancers in females and males, respectively. The role of hormones such as testosterone and estrogen in carcinogenesis is well established. Despite worldwide research efforts, the pathogenesis of these diseases is largely not well understood. Personal care products containing estrogens or xenoestrogens have raised concern as a breast cancer risk, especially in young African-American women. In the United States (US) there is a parallel rise in the incidence in breast and prostate cancer compared to selected non-hormone dependent tumors. Observed US and global breast and prostate cancer incidence increases were occurring before exogenous hormone replacement and xenoestrogen exposure were commonplace. An unintentional, inadvertent, and long term hormone exposure may occur from transdermal absorption of sex hormones and pheromones (androgens) from axillary apocrine sweat gland obstruction by aluminum-based antiperspirants. The global rise in antiperspirant use parallels rises in breast and prostate cancer incidence and mortality rates. A multi-disciplinary literature based set of evidence is presented on how such a link is possible, to prompt confirmatory investigations in the pursuit of unmet needs in breast and prostate cancer etiology and prevention.

Potent agonists of growth hormone-releasing hormone. Part I.

PubMed

Zarandi, M; Serfozo, P; Zsigo, J; Bokser, L; Janaky, T; Olsen, D B; Bajusz, S; Schally, A V

1992-03-01

Analogs of the 29 amino acid sequence of growth hormone-releasing hormone (GH-RH) with agmatine (Agm) in position 29 have been synthesized by the solid phase method, purified, and tested in vitro and in vivo. The majority of the analogs contained desaminotyrosine (Dat) in position 1, but a few of them had Tyr1, or N-MeTyr1. Some peptides contained one or more additional L- or D-amino acid substitutions in positions 2, 12, 15, 21, 27, and/or 28. Compared to the natural sequence of GH-RH(1-29)NH2, [Dat1,Ala15]GH-RH(1-28)Agm (MZ-3-191) and [D-Ala2,Ala15]GH-RH(1-28)Agm (MZ-3-201) were 8.2 and 7.1 times more potent in vitro, respectively. These two peptides contained Met27. Their Nle27 analogs, [Dat1,Ala15,Nle27]GH-RH(1-28)Agm(MZ-2-51), prepared previously (9), and [D-Ala2,Ala15,Nle28]GH-RH(1-28)Agm(MZ-3-195) showed relative in vitro potencies of 10.5 and 2.4, respectively. These data indicate that replacement of Met27 by Nle27 enhanced the GH-releasing activity of the analog when the molecule contained Dat1-Ala2 residues at the N-terminus, but peptides containing Tyr1-D-Ala2 in addition to Nle27 showed decreased potencies. Replacement of Ser28 with Asp in multi-substituted analogs of GH-RH(1-28)Agm resulted in a decrease in in vitro potencies compared to the parent compound. Thus, the Ser28-containing MZ-2-51, and [Dat1,Ala15,D-Lys21,Nle27]GH-RH(1-28)Agm, its Asp28 homolog (MZ-3-149), possessed relative activities of 10.5 and 5.6, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

A cluster of inflammatory breast cancer (IBC) in an office setting: additional evidence of the importance of environmental factors in IBC etiology.

PubMed

Duke, Tina J; Jahed, Nasreen C; Veneroso, Carmela C; Da Roza, Ricardo; Johnson, Owen; Hoffman, Daniel; Barsky, Sanford H; Levine, Paul H

2010-11-01

We investigated a cluster of three cases of inflammatory breast cancer (IBC) diagnosed within 10 months in an office setting of 24 people. Information about medical history, pregnancy history, family history of breast cancer, oral contraceptive use/hormone replacement therapy, exposure to possible oncogenic agents and tumor promoters were obtained to determine whether there were differences in risk factors for IBC between cases and controls. The physical environment and location of the cases' office raised concern about air and water quality as well as radiation as being contributory risk factors for developing IBC. Of the three women with IBC, two had high exposures to pesticides/herbicides, all three used oral contraceptives and two used hormone replacement therapy at the time of diagnosis, two had a family history of breast cancer, and two were obese. Among fifteen controls four had pesticide/herbicide exposure, one had a family history of breast cancer, nine used oral contraceptives, seven used hormone replacement therapy, and five were obese. No specific environmental causes were established for this cluster. Several promoting factors have been suggested that could result in subclinical breast cancer emerging as IBC. Among them are exogenous hormones and exposure to herbicides/pesticides.

[Lipoprotein (a) in an urban population of Venezuela: Evidence that estrogenic deprivation increase in lipoprotein (a) levels is transitory].

PubMed

Bermúdez Pirela, V; Cabrera de Bravo, M; Mengual Moreno, E; Cano Ponce, C; Leal González, E; Lemus Antepaz, M; Amell de Díaz, A; Sorell Gómez, L

2007-07-01

Lipoprotein (a) [Lp (a)] is an independent risk factor for coronary artery disease and normal serum levels of this particle is not known in our country. Thus, the aim of this study was to determine plasma Lp (a) concentration in a population sample of Maracaibo. Fifth hundred out-patients, consulting at Centro de Investigaciones Endocrino-Metabólicas "Dr. Félix Gómez" were randomly underwent to venipunction to obtain a fasting blood simple to assess Lp (a) by a ELISA assay. No significantly differences were found when compared by sex or age separately, higher levels in Lp (a) was found in female 40-44 year group (median: 20,9 mg/dl). Thus, female population was divided in two sub-groups: < 40 years (median: 13 mg/dl) 40 yr and more (median: 16 mg/dl), finding higher Lp (a) levels in the second group (p < 0,02). Hormonal replace therapy was assessed by age, resulting that women subjected this approach shows lower levels of Lp (a) (p < 0,01), except in 60-64 year group. Lp (a) in a Maracaibo was within normal levels. Hormonal replace therapy diminishes Lp (a) concentration in menopausal women, but in menopausal women without hormonal therapy Lp (a) levels experienced a sustained decrease to normal levels in a age-depended manner.

Generalized Resistance to Thyroid Hormone Associated with a Mutation in the Ligand-Binding Domain of the Human Thyroid Hormone Receptor β

NASA Astrophysics Data System (ADS)

Sakurai, Akihiro; Takeda, Kyoko; Ain, Kenneth; Ceccarelli, Paola; Nakai, Akira; Seino, Susumu; Bell, Graeme I.; Refetoff, Samuel; Degroot, Leslie J.

1989-11-01

The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine --> cytosine replacement in the codon for amino acid 340 resulted in a glycine --> arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor β gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor β gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

Revisiting the Cutaneous Impact of Oral Hormone Replacement Therapy

PubMed Central

Piérard, Gérald E.; Humbert, Philippe; Berardesca, Enzo; Gaspard, Ulysse; Hermanns-Lê, Trinh; Piérard-Franchimont, Claudine

2013-01-01

Menopause is a key point moment in the specific aging process of women. It represents a universal evolution in life. Its initiation is defined by a 12-month amenorrhea following the ultimate menstrual period. It encompasses a series of different biologic and physiologic characteristics. This period of life appears to spot a decline in a series of skin functional performances initiating tissue atrophy, withering, and slackness. Any part of the skin is possibly altered, including the epidermis, dermis, hypodermis, and hair follicles. Hormone replacement therapy (oral and nonoral) and transdermal estrogen therapy represent possible specific managements for women engaged in the climacteric phase. All the current reports indicate that chronologic aging, climacteric estrogen deficiency, and adequate hormone therapy exert profound effects on various parts of the skin. PMID:24455744

[Social and healthy circumstances of women's decision about applying hormonal replacement therapy].

PubMed

Zołnierczuk-Kieliszek, Dorota U; Kulik, Teresa B; Pacian, Anna B; Stefanowicz, Agata

2006-01-01

The aim of the study was to evaluate the frequency of hormonal replacement therapy (HRT) application among Polish women aged 40-65, patients of five selected health care institutions located in south-eastern Poland and to determine the most significant factors that influence women's decision to initiate HRT. The next purpose was to establish how the women learned about the possibility of receiving HRT. Women, who never decided to take sex hormones, were asked about the reasons of such decision. The study comprised a group of 1033 women aged 40-65 years living in south-eastern Poland, the patients of various hospital wards and outpatient clinics. The study was conducted from January 2003 to December 2004 using categorized interview technique. The interview questionnaire was constructed by the authors. The statistical analysis was performed on the basis of the chi2 test of independence; log-linear analysis and Pareto's analysis were also used. Research result analysis proves that 30.5% of the examined women have used HRT currently or in the past. The sociodemographic and healthy variables that showed positive correlation with receiving hormonal treatment by midlife women were: age 51-65 years, the presence of climacteric ailments, the absence of monthly bleedings, possessing of permanent life partner and good self-estimation of one's financial status. It was not revealed that better educated women more frequently decide to take HRT. The main sources of women's knowledge about HRT were the mass media and health service employees. Among the reasons for not taking up hormonal treatment the most significant were: lack or small intensification of menopausal ailments as well as the fear of side effects of hormonal replacement therapy.

Cardiovascular disease in menopause: does the obstetric history have any bearing?

PubMed

Mahendru, Amita A; Morris, Edward

2013-09-01

Cardiovascular disease remains a leading cause of morbidity and mortality in menopausal women in spite of the overall reduction in age-adjusted mortality from the disease in the last few years. It is now clear that mechanisms of cardiovascular disease in menopausal women are similar to men and rather than midlife acceleration of cardiovascular disease in women, the final impact of cardiovascular disease in later life may be a reflection of cardiovascular changes during reproductive years as a result of woman's obstetric history. A decade after the Women's Health Initiative trial, there is upcoming evidence to suggest that hormone replacement therapy in young recently menopausal women has a cardioprotective effect. Cardiovascular changes during normal pregnancy or pregnancy complications such as preeclampsia may affect a woman's long-term cardiovascular health. Therefore, it is plausible that the cardioprotective benefit of hormone replacement therapy depends on occult pre-existing cardiovascular risks in women in relation to their previous obstetric history. In this review, we describe the cardiovascular changes during and after pregnancy in obstetric complications such as recurrent miscarriage, preeclampsia, intrauterine growth restriction, preterm labour and gestational diabetes; existing evidence regarding their association with cardiovascular disease later in life, and hypothesize possible mechanisms. Our aim is to improve the understanding and highlight the importance of including obstetric history in risk assessment in menopausal women and individualizing their risks before prescribing hormone replacement therapy. Future research in risk benefit assessment of hormone replacement therapy should also account for a woman's background cardiovascular risk in the light of her obstetric history.

Growth arrest despite growth hormone replacement, post-craniopharyngioma surgery.

PubMed Central

DeVile, C J; Hayward, R D; Neville, B G; Grant, D B; Stanhope, R

1995-01-01

Children with growth failure, whether secondary to an endocrinopathy such as growth hormone deficiency or secondary to neurological handicap with poor nutrient intake, grow at a subnormal rate but it is most unusual for a child to have complete growth arrest. PMID:7745571

Estrogen, aging and the cardiovascular system

PubMed Central

Stice, James P.; Lee, Jennifer S.; Pechenino, Angela S.; Knowlton, Anne A.

2014-01-01

Estrogen is a powerful hormone with pleiotropic effects. Estrogens have potent antioxidant effects and are able to reduce inflammation, induce vasorelaxation and alter gene expression in both the vasculature and the heart. Estrogen treatment of cultured cardiac myocytes and endothelial cells rapidly activates NFκB, induces heat-shock protein (HSP)-72, a potent intracellular protective protein, and protects cells from simulated ischemia. In in vivo models, estrogens protect against ischemia and trauma/hemorrhage. Estrogens may decrease the expression of soluble epoxide hydrolase, which has deleterious effects on the cardiovascular system through metabolism of epoxyeicosatrienoic acids. Natural (endogenous) estrogens in premenopausal women appear to protect against cardiovascular disease and yet controlled clinical trials have not indicated a benefit from estrogen replacement postmenopause. Much remains to be understood in regards to the many properties of this powerful hormone and how changes in this hormone interact with aging-associated changes. The unexpected negative results of trials of estrogen replacement postmenopause probably arise from our lack of understanding of the many effects of this hormone. PMID:19371207

[Issues related to secondary osteoporosis associated with growth hormone deficiency in adulthood].

PubMed

Kužma, Martin; Jackuliak, Peter; Killinger, Zdenko; Vaňuga, Peter; Payer, Juraj

Growth hormone (GH) increases linear bone growth through complex hormonal reactions, mainly mediated by insulin like growth factor 1 (IGF1) that is produced mostly by hepatocytes under influence of GH and stimulates differentiation of epiphyseal prechondrocytes. IGF1 and GH play a key role in the linear bone growth after birth and regulation of bone remodelation during the entire lifespan. It is known that adult GH deficient (GHD) patients have decreased BMD and increased risk of low-impact fractures. Most data gathered thus far on the effect of GH replacement on bone status comprise the measurement of quantitative changes of bone mass. Some animal studies with GHD showed that the bone microarchitecture, measured using computed tomography methods, is significantly compromised and improve after GH replacement. However, human studies did not show significantly decreased bone microarchitecture, but limited methodological quality does not allow firm conclusions on this subject.Key words: bone mass - bone quality - fracture - growth hormone - IGF1.

Psychomotor retardation in a girl with complete growth hormone deficiency.

PubMed

Dayal, Devi; Malhi, Prabhjot; Kumar Bhalla, Anil; Sachdeva, Naresh; Kumar, Rakesh

2013-01-01

Infants with complete growth hormone deficiency may suffer from psychomotor retardation in addition to severe growth failure. Without replacement therapy, they may have a compromised intellectual potential manifesting as learning disabilities and attention-deficit disorders in later life. In this communication, we discuss an infant who showed improvement in physical growth after growth hormone therapy but her psychomotor skills did not improve probably due to late start of treatment. There is a need to start growth hormone therapy as early as possible in infants with complete growth hormone deficiency to avoid adverse effects on psychomotor and brain development.

Muscle performance after the menopause.

PubMed

Sirola, Joonas; Rikkonen, Toni

2005-06-01

The timing of the menopause transition has remained fairly constant throughout history. It represents a milestone in female health and, after passing through it, women experience increased musculoskeletal and cardiovascular morbidity. Muscle performance is an important determinant of functional capacity and quality of life among the elderly and is also involved in the maintenance of balance. Therefore, good muscle strength can prevent fragility fractures and lessen the burden of osteoporosis. Muscle strength begins to decline during the perimenopausal years and this phenomenon seems to be partly estrogen dependent. Randomized controlled trials have indicated that hormone replacement therapy may prevent a decline in muscle performance, although the exact mechanism of estrogen-dependent sarcopenia remains to be clarified. Exercises have been shown to improve postmenopausal muscle performance and hormone replacement therapy may also potentiate these beneficial effects. Improvement or maintenance of muscle strength alone, however, may not be considered as a primary indication for long-term hormone replacement therapy in view of current knowledge of its risks and benefits. Work history and educational background may be associated with postmenopausal muscle performance, which itself has unique associations with skeletal and cardiovascular diseases.

[Influence of replacement growth hormone therapy (hGH) on pituitary-thyroid and pituitary-adrenal systems in prepubertal children with GH deficiency].

PubMed

Vyshnevs'ka, O A; Bol'shova, O V

2013-06-01

Today, the most pathogenic therapy of GH deficiency is hGH replacement therapy. Replacement hGH therapy a highly effective method of growth correction in children with GH deficiency, but further investigations are necessary for timely detection of disturbances of other organs and systems. The authors reported that hGH therapy supressed thyroid and adrenal functions. Besides, most patients with GH deficiency have multiple defficiency of pituitary hormones (both TSH and ACTH), so hGH therapy can enhances hypothyroidism and hypoadrenalism. In the Department of Pediatric Endocrinology of the Institute of Endocrinology and Metabolism a great experience was accumulated in the treatment of GH deficiency children and in the study of the efficacy and safety of this treatment.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA L II): relationship between vascular events and the use of hormone replacement therapy in postmenopausal women.

PubMed

Fernández, Mónica; Calvo-Alén, Jaime; Bertoli, Ana M; Bastian, Holly M; Fessler, Barri J; McGwin, Gerald; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S

2007-10-01

To examine the influence of hormone replacement therapy (HRT) in the occurrence of vascular arterial and venous thrombotic events in postmenopausal women with systemic lupus erythematosus (SLE). SLE women aged > or =16 years, disease duration < or =5 years from LUMINA, a multiethnic, longitudinal outcome study, were included. Menopause was defined at disease onset as the presence of amenorrhea >6 months and/or oophorectomy, and/or increased follicle stimulating hormone values, and/or HRT use regardless of the presence or absence of climacteric symptoms (hot flashes). Patients were divided into HRT ever users and nonusers. Patients with positive antiphospholipid antibodies (n = 9) or vascular arterial events (n = 1) occurring before HRT use were excluded. The occurrence of vascular arterial and venous thrombotic events was compared between HRT users and HRT nonusers and its role examined by logistic regression after adjusting for "confounding by indication" using propensity score or logistic regression analyses. Seventy-two postmenopausal women, 32 (44%) HRT users and 40 (56%) HRT nonusers, were studied. HRT use was associated with fewer vascular arterial but not venous thrombotic events (P = 0.021) in the univariable analyses. However, after adjusting for the propensity score, HRT use was no longer significant (P = 0.064). Comparable results were obtained by logistic regression. HRT use was not associated with the occurrence of vascular arterial events in the LUMINA patients. HRT use in women with SLE should be individualized, but our data suggest its use may be safe if antiphospholipid antibodies are not present or vascular arterial events have not previously occurred.

The Impact of Bariatric Surgery on Thyroid Function and Medication Use in Patients with Hypothyroidism.

PubMed

Zendel, Alex; Abu-Ghanem, Yasmin; Dux, Joseph; Mor, Eyal; Zippel, Douglas; Goitein, David

2017-08-01

Bariatric surgery (BS) is effective in treating obesity and its associated comorbidities. However, there is a paucity of data on the effect of BS on thyroid function in hypothyroid patients, specifically in those treated with thyroid hormone replacement therapy (THR). The aim of this study was to assess the effect of BS on thyroid function and on THR dosage in patients with hypothyroidism. A retrospective analysis of prospectively collected data of all hypothyroid patients who underwent BS between 2010 and 2014 was performed. Data collected included demographic and anthropometric measurements, as well as changes in thyroid hormone levels and THR dosage up to a year from surgery. During the study period, 93 hypothyroid patients (85 females, 91%), 83 of which treated with replacement thyroid hormone, underwent BS. Laparoscopic sleeve gastrectomy was performed in 77 (82.8%) and Roux-en-Y gastric bypass in 16 patients. Average age and body mass index (BMI) were 46.6 ± 11.2 years and 43.7 ± 6.4 kg/m 2 , respectively. Mean BMI and thyroid-stimulating hormone (TSH) significantly deceased after 6 and 12 months following surgery whereas mean free T4 levels remained stable. TSH decrease was directly correlated to baseline TSH but not to BMI reduction. One year after surgery, 11 patients (13.2%) did not require THR, while the rest required a significantly lower average dose (P < 0.02). There is a favorable effect of BS on the hypothyroid bariatric population. This includes improvement of thyroid function and reduction of thyroid medication dosages. Further studies are required to evaluate an influence of THR absorption and compare different types of bariatric surgeries.

Growth hormone distribution kinetics are markedly reduced in adults with growth hormone deficiency.

PubMed

Catalina, Pablo F; Páramo, Concepción; Andrade, Maria Amalia; Mallo, Federico

2007-03-01

Growth hormone (GH) circulating levels are highly dependent not only on GH secretion rate from the pituitary, but also on the hormone distribution in the compartments of the body and elimination phenomena. In adult GH-deficient patients these factors become critical nowadays, especially when recombinant human GH (rhGH) is available for replacement therapy. In the present study, we assess the influence of both distribution and elimination phenomena on GH pharmacokinetics in adult GH-deficient patients. We used a four-step methodology following a compartmental approach after an intravenous bolus of recombinant GH in adult GH-deficient patients. We found that GH kinetics are clearly explained by a bi-exponential, two-compartmental model in GH-deficient patients, similarly than in normal or diabetic subjects, as previously shown. We have also observed a marked delay in the whole GH elimination process in GH-deficient patients compared to normal adult subjects, as revealed by metabolic clearance ratio (MCR), elimination constant from central compartment (k(10)), and mean resident time in the body (MRT). Interestingly, such a delay appear to be caused by deep changes in the distribution phase (Mtt(1)- mean transit time-1; T(1/2alpha)- GH half-life at distribution phase), while the elimination phenomenon remains unaltered. Our results emphasize the relevance of distribution phenomena in GH pharmacokinetics, and indicates that studies avoiding data from the GH distribution phase, such as those carried out in steady-state conditions, or those using noncompartmental models, could easily miss relevant information. Our data should be taken into consideration when establishing the appropriate dosage for GH replacement treatments in GH-deficient patients, and calculations should include GH distribution kinetics.

ITALIAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS STATEMENT-REPLACEMENT THERAPY FOR PRIMARY HYPOTHYROIDISM: A BRIEF GUIDE FOR CLINICAL PRACTICE.

PubMed

Guglielmi, Rinaldo; Frasoldati, Andrea; Zini, Michele; Grimaldi, Franco; Gharib, Hossein; Garber, Jeffrey R; Papini, Enrico

2016-11-01

Hypothyroidism requires life-long thyroid hormone replacement therapy in most patients. Oral levothyroxine (LT4) is an established safe and effective treatment for hypothyroidism, but some issues remain unsettled. The Italian Association of Clinical Endocrinologists appointed a panel of experts to provide an updated statement for appropriate use of thyroid hormone formulations for hypothyroidism replacement therapy. The American Association of Clinical Endocrinologists' protocol for standardized production of clinical practice guidelines was followed. LT4 is the first choice in replacement therapy. Thyroid-stimulating hormone (TSH) should be maintained between 1.0 and 3.0 mIU/L in young subjects and at the upper normal limit in elderly or fragile patients. Achievement of biochemical targets, patient well-being, and adherence to treatment should be addressed. In patients with unstable serum TSH, a search for interfering factors and patient compliance is warranted. Liquid or gel formulations may be considered in subjects with hampered LT4 absorption or who do not allow sufficient time before or after meals and LT4 replacement. Replacement therapy with LT4 and L-triiodothyronine (LT3) combination is generally not recommended. A trial may be considered in patients with normal values of serum TSH who continue to complain of symptoms of hypothyroidism only after co-existent nonthyroid problems have been excluded or optimally managed. LT3 should be administered in small (LT4:LT3 ratio, 10:1 to 20:1) divided daily doses. Combined therapy should be avoided in elderly patients or those with cardiac risk factors and in pregnancy. LT4 therapy should be aimed at resolution of symptoms of hypothyroidism, normalization of serum TSH, and improvement of quality of life. In selected cases, the use of liquid LT4 formulations or combined LT4/LT3 treatment may be considered to improve adherence to treatment or patient well-being. AACE = American Association of Clinical Endocrinologists FT3 = free triiodothyronine FT4 = free thyroxine LT3 = levotriiodothyronine LT4 = levothyroxine MeSH = medicine medical subject headings QoL = quality of life TSH = thyroid-stimulating hormone.

Sleeve gastrectomy leads to easy management of hormone replacement therapy and good weight loss in patients treated for craniopharyngioma.

PubMed

Trotta, Manuela; Da Broi, Joël; Salerno, Angelo; Testa, Rosa M; Marinari, Giuseppe M

2017-03-01

The aim of this study is to investigate the effects of sleeve gastrectomy on hormone replacement therapy and on hypothalamic obesity in patients affected by craniopharyngioma with post-surgical pan-hypopituitarism. A retrospective review of three patients, treated for hypothalamic obesity with laparoscopic sleeve gastrectomy, who have previously undergone surgery for craniopharyngioma in their childhood, was done. Patients' mean age and BMI were 22.3 years (range 21-24) and 49.2 kg/m 2 (range 41.6-58.1), respectively. The mean time of delay between neurosurgery and bariatric surgery was 12.3 years (range 6-16). There were no major complications or deaths. At 24 months follow-up, the mean BMI was 35.3 kg/m 2 (range 31.2-40.6). No hydrocortisone and sex steroids dose changes were observed, while levothyroxine was decreased in two patients. Growth hormone replacement therapy was increased in two patients, whereas it was started in one patient. Desmopressin was significantly decreased in all of them. Patients with surgically induced pan-hypopituitarism after craniopharyngioma who become obese, can expect good results from sleeve gastrectomy: this procedure does not have significant negative effects on hormone substitution and leads to a good stabilization of body weight in a mid-term follow-up.

Conversion of autoimmune hypothyroidism to hyperthyroidism.

PubMed

Furqan, Saira; Haque, Naeem-ul; Islam, Najmul

2014-08-03

Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

Conversion of autoimmune hypothyroidism to hyperthyroidism

PubMed Central

2014-01-01

Background Graves’ disease and Hashimoto’s thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. Case presentation We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. Conclusion High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone. PMID:25086829

Mission Connect Mild TBI Translational Research Consortium

DTIC Science & Technology

2015-07-01

stimulation testing, such as with the glucagon stimulation test (GST) is the only way to make a definitive diagnosis of growth hormone deficiency. The normal...2011) "Serum IGF-1 concentrations in a sample of patients with traumatic brain injury as a diagnostic marker of growth hormone secretory response to...Masel Annual Report 2015 Page4 • A paper entitled: The Effects of Growth Hormone Replacement Therapy on Cognition after Traumatic Brain Injury

Hypothyroidism: causes, killers, and life-saving treatments.

PubMed

Dubbs, Sarah B; Spangler, Ryan

2014-05-01

Hypothyroidism is a very common, yet often overlooked disease. It can have a myriad of signs and symptoms, and is often nonspecific. Identification requires analysis of thyroid hormones circulating in the bloodstream, and treatment is simply replacement with exogenous hormone, usually levothyroxine (Synthroid). The deadly manifestation of hypothyroidism is myxedema coma. Similarly nonspecific and underrecognized, treatment with exogenous hormone is necessary to decrease the high mortality rate. Copyright © 2014 Elsevier Inc. All rights reserved.

Language Profile in Congenital Hypothyroid Children Receiving Replacement Therapy.

PubMed

Soliman, Hend; Abdel Hady, Aisha Fawzy; Abdel Hamid, Asmaa; Mahmoud, Heba

2016-01-01

The aim of this work was to evaluate receptive and expressive language skills in children with congenital hypothyroidism receiving early hormonal replacement treatment before the age of 3 months and to identify any subtle areas of weaknesses in their language development to check the necessity for future language intervention. The study was conducted on 30 hypothyroid children receiving hormonal replacement. They were subdivided into group I (5-8 years 11 months; 12 cases) and group II (9-12 years 11 months; 18 cases). All patients were subjected to a protocol of assessment applied in the Diabetes, Endocrine and Metabolism Pediatric Unit (DEMPU) and evaluation of language skills by the REAL scale. The younger group reached average Arabic language scores, while the older group showed moderate language delay. Early replacement therapy supports language development in young children. However, longitudinal and follow-up studies are required to identify difficulties presenting at older ages that may affect children in the academic settings. © 2016 S. Karger AG, Basel.

Hypothyroidism and Mortality among Dialysis Patients

PubMed Central

Rhee, Connie M.; Alexander, Erik K.; Bhan, Ishir

2013-01-01

Summary Background and objectives Hypothyroidism is highly prevalent among ESRD patients, but its clinical significance and the benefits of thyroid hormone replacement in this context remain unclear. Design, setting, participants, & measurements This study examined the association between hypothyroidism and all-cause mortality among 2715 adult dialysis patients with baseline thyrotropin levels measured between April of 2005 and April of 2011. Mortality was ascertained from Social Security Death Master Index and local registration systems. The association between hypothyroidism (thyrotropin greater than assay upper limit normal) and mortality was estimated using Cox proportional hazards models. To reduce the risk of observing reverse-causal associations, models included a 30-day lag between thyrotropin measurement and at-risk time. Results Among 350 (12.9%) hypothyroid and 2365 (87.1%) euthyroid (assay within referent range) patients, 917 deaths were observed during 5352 patient-years of at-risk time. Hypothyroidism was associated with higher mortality. Compared with thyrotropin in the low-normal range (0.4–2.9 mIU/L), subclinical hypothyroidism (thyrotropin >upper limit normal and ≤10.0 mIU/L) was associated with higher mortality; high-normal thyrotropin (≥3.0 mIU/L and ≤upper limit normal) and overt hypothyroidism (thyrotropin >10.0 mIU/L) were associated with numerically greater risk, but estimates were not statistically significant. Compared with spontaneously euthyroid controls, patients who were euthyroid while on exogenous thyroid replacement were not at higher mortality risk, whereas patients who were hypothyroid were at higher mortality risk. Sensitivity analyses indicated that effects on cardiovascular risk factors may mediate the observed association between hypothyroidism and death. Conclusions These data suggest that hypothyroidism is associated with higher mortality in dialysis patients, which may be ameliorated by thyroid hormone replacement therapy. PMID:23258793

Comparison of the therapeutic effects of tri-iodothyronine and methylprednisolone during early sepsis in laboratory animals.

PubMed

Coskun, F; Saylam, B; Kulah, B; Dolapci, I; Sungur, A; Ozer, M Vasfi

2012-01-01

Despite major advances, the treatment of sepsis is still a challenging problem for surgeons. This study was aimed to compare the therapeutic effects of methylprednisolone and tri-iodothyronine replacement therapy during an early sepsis. Forty male Wistar albino rats weighing 300-340 g were divided into the Control, CLP, CLP/MP, CLP/T3 and CLP/MP/T3 groups. The Control group underwent a sham operation. Only cecal ligation and puncture was performed in the CLP group. The CLP/MP groups received an intramuscular injection of (MP) methylprednisolone (30 mg/kg) at one and half hour before CLP. The CLP/T3 group was given an intraperitoneal (IP) injection of tyroid hormone (T3) 0.4 µg/100 g immediately after CLP. The CLP/MP/T3 group was given IM injection of MP 30 mg/kg before CLP and IP injection of T3 0.4 µg/100 g after CLP. Hemavet changes, blood cultures, peritoneal bacteria content, hormonal alterations and histopathologic changes of intestinal, lung and liver tissue were used to asses the possible therapeutic effects of MP and T3 during early sepsis. A septic insult resulted in significant alterations on hemavet values, free T3, free T4 and cortisol levels, peritoneal bacteria content and intestinal lung and liver tissue samples of the CLP group. Hemavet changes and peritoneal inflammation findings were significantly limited in the CLP/T3 and CLP/MP/T3 groups. Histopathologic changes had no significant difference between the groups during an early sepsis. Compared to the MP replacement therapy, therapeutic effects of T3 replacement therapy have been found significantly more promising (Tab. 1, Fig. 10, Ref. 49).

Structural similarity of ghrelin derivatives to peptidyl growth hormone secretagogues.

PubMed

Matsumoto, M; Kitajima, Y; Iwanami, T; Hayashi, Y; Tanaka, S; Minamitake, Y; Hosoda, H; Kojima, M; Matsuo, H; Kangawa, K

2001-06-15

Ghrelin is a 28-amino acid residue endogenous growth hormone secretagogue. Intensive investigations revealed that the N-terminus tetrapeptide, having octanoyl group at Ser(3), is the minimum active core. In this study, we further explored the structure-function relationships of the active N-terminus portion of ghrelin using a Ca(2+) mobilization assay. The smallest and most potent ghrelin derivative we have found so far is 5-aminopentanoyl-Ser(Octyl)-Phe-Leu-aminoethylamide, showing comparable activity to the natural molecule. In the process of modifying the active core, the ghrelin-derived short analogues emerged structurally close to peptidyl growth hormone secretagogues. The N-terminus modification suggested that Gly(1)-Ser(2) unit works as a spacer, forming adequate distance between N(alpha)-amino group and n-octanoyl group. Replacement of 3rd and 4th amino acid residues to D-isomer suggested that the N-terminal dipeptide contributes to shape the biologically active geometry by effecting conformation of residues in positions 3 and 4. Copyright 2001 Academic Press.

Preparation and characterization of marine sponge collagen nanoparticles and employment for the transdermal delivery of 17beta-estradiol-hemihydrate.

PubMed

Nicklas, Martina; Schatton, Wolfgang; Heinemann, Sascha; Hanke, Thomas; Kreuter, Jörg

2009-09-01

Transdermal administration of estradiol offers advantages over oral estrogens for hormone replacement therapy regarding side effects by bypassing the hepatic presystemic metabolism. The objective of this study was to develop nanoparticles of Chondrosia reniformis sponge collagen as penetration enhancers for the transdermal drug delivery of 17beta-estradiol-hemihydrate in hormone replacement therapy. Collagen nanoparticles were prepared by controlled alkaline hydrolysis and characterized using atomic force microscopy and photon correlation spectroscopy. Estradiol-hemihydrate was loaded to the nanoparticles by adsorption to their surface, whereupon a drug loading up to 13.1% of sponge collagen particle mass was found. After incorporation of drug-loaded nanoparticles in a hydrogel, the estradiol transdermal delivery from the gel was compared with that from a commercial gel that did not contain nanoparticles. Saliva samples in postmenopausal patients showed significantly higher estradiol levels after application of the gel with nanoparticles. The area under the curve (AUC) for estradiol time-concentration curves over 24 hours was 2.3- to 3.4-fold higher and estradiol levels 24 hours after administration of estradiol were at least twofold higher with the nanoparticle gel. The hydrogel with estradiol-loaded collagen nanoparticles enabled a prolonged estradiol release compared to a commercial gel and yielded a considerably enhanced estradiol absorption. Consequently, sponge collagen nanoparticles represent promising carriers for transdermal drug delivery.

Fourth-Generation Progestins Inhibit 3β-Hydroxysteroid Dehydrogenase Type 2 and Modulate the Biosynthesis of Endogenous Steroids

PubMed Central

Louw-du Toit, Renate; Perkins, Meghan S.; Snoep, Jacky L.; Storbeck, Karl-Heinz; Africander, Donita

2016-01-01

Progestins used in contraception and hormone replacement therapy are synthetic compounds designed to mimic the actions of the natural hormone progesterone and are classed into four consecutive generations. The biological actions of progestins are primarily determined by their interactions with steroid receptors, and factors such as metabolism, pharmacokinetics, bioavailability and the regulation of endogenous steroid hormone biosynthesis are often overlooked. Although some studies have investigated the effects of select progestins on a few steroidogenic enzymes, studies comparing the effects of progestins from different generations are lacking. This study therefore explored the putative modulatory effects of progestins on de novo steroid synthesis in the adrenal by comparing the effects of select progestins from the respective generations, on endogenous steroid hormone production by the H295R human adrenocortical carcinoma cell line. Ultra-performance liquid chromatography/tandem mass spectrometry analysis showed that the fourth-generation progestins, nestorone (NES), nomegestrol acetate (NoMAC) and drospirenone (DRSP), unlike the progestins selected from the first three generations, modulate the biosynthesis of several endogenous steroids. Subsequent assays performed in COS-1 cells expressing human 3βHSD2, suggest that these progestins modulate the biosynthesis of steroid hormones by inhibiting the activity of 3βHSD2. The Ki values determined for the inhibition of human 3βHSD2 by NES (9.5 ± 0.96 nM), NoMAC (29 ± 7.1 nM) and DRSP (232 ± 38 nM) were within the reported concentration ranges for the contraceptive use of these progestins in vivo. Taken together, our results suggest that newer, fourth-generation progestins may exert both positive and negative physiological effects via the modulation of endogenous steroid hormone biosynthesis. PMID:27706226

A case-control study of hormonal exposures as etiologic factors for ALS in women: Euro-MOTOR.

PubMed

Rooney, James P K; Visser, Anne E; D'Ovidio, Fabrizio; Vermeulen, Roel; Beghi, Ettore; Chio, Adriano; Veldink, Jan H; Logroscino, Giancarlo; van den Berg, Leonard H; Hardiman, Orla

2017-09-19

To investigate the role of hormonal risk factors for amyotrophic lateral sclerosis (ALS) among women from 3 European countries. ALS cases and matched controls were recruited over 4 years in Ireland, Italy, and the Netherlands. Hormonal exposures, including reproductive history, breastfeeding, contraceptive use, hormonal replacement therapy, and gynecologic surgical history, were recorded with a validated questionnaire. Logistic regression models adjusted for age, education, study site, smoking, alcohol, and physical activity were used to determine the association between female hormones and ALS risk. We included 653 patients and 1,217 controls. Oral contraceptive use was higher among controls (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.84), and a dose-response effect was apparent. Hormone replacement therapy (HRT) was associated with a reduced risk of ALS only in the Netherlands (OR = 0.57, 95% CI 0.37-0.85). These findings were robust to sensitivity analysis, but there was some heterogeneity across study sites. This large case-control study across 3 different countries has demonstrated an association between exogenous estrogens and progestogens and reduced odds of ALS in women. These results are at variance with previous findings, which may be partly explained by differential regulatory, social, and cultural attitudes toward pregnancy, birth control, and HRT across the countries included. Our results indicate that hormonal factors may be important etiologic factors in ALS; however, a full understanding requires further investigation. © 2017 American Academy of Neurology.

Growth hormone (GH) and atherosclerosis: changes in morphology and function of major arteries during GH treatment.

PubMed

Pfeifer, M; Verhovec, R; Zizek, B

1999-04-01

Patients with hypopituitarism have increased carotid artery intima-media thickness and reduced arterial distensibility. The effect of 2 years of growth hormone (GH) replacement therapy on these parameters was studied in 11 GH-deficient men (age range, 24-49 years) with hypopituitarism and compared with 12 healthy, age-matched men with no evidence of pituitary or vascular disease. Before treatment the intima-media of the common carotid arteries and the carotid bifurcations were significantly thicker in patients (P < 0.001) than in the control group. Treatment with GH normalized the intima-media thickness of the common carotid artery within 6 months and of the carotid bifurcation within 3 months. The changes in intima-media thickness of the carotid artery were negatively correlated with changes in serum levels of insulin-like growth factor I during treatment. There was a significant improvement in flow-mediated, endothelium-dependent dilation of the brachial artery at 3 months, which was sustained at 6, 18 and 24 months of GH treatment (P < 0.05). Thus, GH replacement therapy in GH-deficient men reverses early morphological and functional atherosclerotic changes in major arteries, and may reduce rates of vascular morbidity and mortality.

Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis.

PubMed

Wu, Olivia; Robertson, Lindsay; Twaddle, Sara; Lowe, Gordon; Clark, Peter; Walker, Isobel; Brenkel, Ivan; Greaves, Mike; Langhorne, Peter; Regan, Lesley; Greer, Ian

2005-10-01

Laboratory testing for the identification of heritable thrombophilia in high-risk patient groups have become common practice; however, indiscriminate testing of all patients is unjustified. The objective of this study was to evaluate the cost-effectiveness of universal and selective history-based thrombophilia screening relative to no screening, from the perspective of the UK National Health Service, in women prior to prescribing combined oral contraceptives and hormone replacement therapy, women during pregnancy and patients prior to major orthopaedic surgery. A decision analysis model was developed, and data from meta-analysis, the literature and two Delphi studies were incorporated in the model. Incremental cost-effectiveness ratios (ICERs) for screening compared with no screening was calculated for each patient group. Of all the patient groups evaluated, universal screening of women prior to prescribing hormone replacement therapy was the most cost-effective (ICER 6824 pounds). In contrast, universal screening of women prior to prescribing combined oral contraceptives was the least cost-effective strategy (ICER 202,402 pounds). Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism was more cost-effective than universal screening in all the patient groups evaluated.

GH therapy in transition age: state of the art and future perspectives.

PubMed

Cappa, M; Caruso, M; Saggese, G; Salerno, M C; Tonini, G

2015-03-01

Growth hormone (GH) has been recently approved by the Italian Health Authorities for use in transition patients with childhood onset-growth hormone deficiency (CO-GHD). GH in addition to promote linear growth influences several key metabolic processes. In particular, in the transition period, from late adolescent to early adulthood, GH plays an important role in the achievement of a complete somatic development including body composition, muscle mass maturation, full skeletal mineralization and reproductive maturation, as well as in the prevention of metabolic and cardiovascular risk. Therefore, GH replacement should be restarted if a GH stimulation test at the re-evaluation fulfills established criteria. Endocrinologists experienced in the care of GHD adolescent patients held a workshop in Rome, Italy in July 2012 to review in detail the literature data and compare experiences of five Italian endocrinological centers on the negative consequences of interrupting GH treatment and the positive effects of continued GH replacement on intermediary metabolism, heart, muscle, pubertal development, and bone. The aim of the meeting was to delineate the state of the art on GH therapy in transition age and provide suggestions to pediatric and adult endocrinologists for a smooth transition care.

Advances in bioanalytical techniques to measure steroid hormones in serum.

PubMed

French, Deborah

2016-06-01

Steroid hormones are measured clinically to determine if a patient has a pathological process occurring in the adrenal gland, or other hormone responsive organs. They are very similar in structure making them analytically challenging to measure. Additionally, these hormones have vast concentration differences in human serum adding to the measurement complexity. GC-MS was the gold standard methodology used to measure steroid hormones clinically, followed by radioimmunoassay, but that was replaced by immunoassay due to ease of use. LC-MS/MS has now become a popular alternative owing to simplified sample preparation than for GC-MS and increased specificity and sensitivity over immunoassay. This review will discuss these methodologies and some new developments that could simplify and improve steroid hormone analysis in serum.

Testosterone replacement therapy: role of pituitary and thyroid in diagnosis and treatment

PubMed Central

Crawford, Megan

2016-01-01

Crosstalk among hormones characterizes endocrine function, and assessment of the hypogonadal man should take that into consideration. In men for whom testosterone deficiency is a concern, initial evaluation should include a thorough history and physical exam in which other endocrinopathies are being considered. Hypogonadism can be associated with both pituitary and thyroid dysfunction, for which appropriate biochemical evaluation should be undertaken in certain clinical scenarios. If low serum testosterone is confirmed measurement of luteinizing and follicle stimulating hormones (LH and FSH respectively) is essential to establish whether the hypogonadism is primary or secondary. In secondary hypogonadism measurement of prolactin is always necessary, and measurement of other pituitary hormones, along with pituitary imaging, may be indicated. Checking thyroid function may also be enlightening, and can raise additional therapeutic considerations. Correction of other pituitary axes may attenuate the need for testosterone replacement therapy in some cases. PMID:28078216

Effects of Anorexia Nervosa on the Endocrine System.

PubMed

Baskaran, Charumathi; Misra, Madhusmita; Klibanski, Anne

2017-03-01

Anorexia nervosa (AN) is characterized by severe undernutrition associated with alterations in multiple endocrine axes, which are primarily adaptive to the state of caloric deprivation. Hormonal changes include growth hormone (GH) resistance with low insulin like growth factor-1 (IGF-1) levels, hypothalamic hypogonadism, relative hypercortisolemia and changes in appetite regulating hormones, including leptin, ghrelin, and peptide YY. These alterations contribute to abnormalities in bone metabolism leading to low bone mass, impaired bone microarchitecture, and increased risk for fracture, and may also negatively impact cognition, emotions and mood. The best strategy to improve all biologic outcomes is weight and menstrual recovery. Physiological estrogen replacement improves bone accrual rates and measures of trait anxiety in adolescents with AN. Other therapies including testosterone and IGF-1 replacement, and use of DHEA with oral estrogen-progesterone combination pills, bisphosphonates and teriparatide have also been studied to improve bone outcomes. Copyright© of YS Medical Media ltd.

An AOP-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish

EPA Science Inventory

Within the field of chemical safety assessment, there is a desire to replace costly whole organism testing with more efficient and cost-effective alternatives based on in vitro test systems. Disruption of thyroid hormone signaling via inhibition of enzymes called deiodinases is o...

Effects of Physiologic Testosterone Replacement on Quality of Life, Self-Esteem, and Mood in Women with Primary Ovarian Insufficiency

PubMed Central

Guerrieri, Gioia M.; Martinez, Pedro E.; Klug, Summer P.; Haq, Nazli A.; Vanderhoof, Vien H.; Koziol, Deloris E.; Popat, Vaishali B.; Kalantaridou, Sophia N.; Calis, Karim A.; Rubinow, David R.; Schmidt, Peter J.; Nelson, Lawrence M.

2014-01-01

Objective Low androgen levels occur in women with primary ovarian insufficiency(POI) and could contribute to mood and behavioral symptoms in this condition. We examined the effects of physiologic testosterone (T) replacement therapy added to standard estrogen/progestin replacement therapy (EPT) on quality of life, self-esteem, and mood in women with POI. Methods 128 women with 46XX spontaneous POI participated in a 12 month randomized, placebo-controlled, parallel-design investigation of the efficacy of T augmentation of EPT. Quality of life, self-esteem, and mood symptoms were evaluated with standardized rating scales and a structured clinical interview. Differences in outcome measures between the T and placebo treatments were analyzed by Wilcoxon rank-sum tests. Results No differences were found in baseline characteristics including serum hormone levels(P >0.05). Baseline mean(SD) CES-D scores were 10.7(8.6)(T) and 9.2(7.8)(placebo) (P = 0.35). After 12 months of treatment, measures of quality of life, self-esteem, and the presence of mood symptoms did not differ between treatment groups. Serum T levels achieved physiologic levels in the T group and were significantly higher compared to placebo (P < 0.001). Baseline T levels were not associated with either adverse or beneficial clinical effects. Conclusions The 150 microgram T patch achieves physiologic hormone levels in women with POI. Our findings suggest that augmentation of standard EPT with physiologic testosterone replacement in young women with POI neither aggravates nor improves baseline reports of quality of life, or self-esteem and had minimal effect on mood. Other mechanisms might play a role in the altered mood that accompanies this disorder. PMID:24473536

The effects of growth hormone deficiency and growth hormone replacement therapy on intellectual ability, personality and adjustment in children.

PubMed

Puga González, B; Ferrández Longás, A; Oyarzábal, M; Nosas, R

2010-06-01

Traditionally, it has been assumed that intellectual development in children with growth hormone deficiency (GHD) is distributed between ranges of a normal population based on the observation that it does not differ substantially from that of children of the same age. Nevertheless, few studies have investigated this assumption. This Spanish Collaborative study was prospectively planned with two main purposes: to study a possible influence of GHD on intelligence quotient (IQ), personality traits and adaptative capacity and to study the evolution of these parameters during substitution therapy with growth hormone (GH). Although the overall intellectual ability of children with GHD is comparable to that of a normal reference population, some areas such the motor-component scale (evaluated by McCarthy test) and performance IQ (evaluated by WISC-R) were below the mean at the beginning of the study, showing significant improvement during therapy. Emotional adjustment (normal at study start) also improved significantly during treatment. Females showed better adjustment capacity before and during GH therapy. Longer studies with an increased number of cases are needed to confirm these effects of GHD and its treatment in children.

Hormone Replacement Therapy and Physical Function in Healthy Older Men. Time to Talk Hormones?

PubMed Central

Giannoulis, Manthos G.; Martin, Finbarr C.; Nair, K. Sreekumaran; Umpleby, A. Margot

2012-01-01

Improving physical function and mobility in a continuously expanding elderly population emerges as a high priority of medicine today. Muscle mass, strength/power, and maximal exercise capacity are major determinants of physical function, and all decline with aging. This contributes to the incidence of frailty and disability observed in older men. Furthermore, it facilitates the accumulation of body fat and development of insulin resistance. Muscle adaptation to exercise is strongly influenced by anabolic endocrine hormones and local load-sensitive autocrine/paracrine growth factors. GH, IGF-I, and testosterone (T) are directly involved in muscle adaptation to exercise because they promote muscle protein synthesis, whereas T and locally expressed IGF-I have been reported to activate muscle stem cells. Although exercise programs improve physical function, in the long-term most older men fail to comply. The GH/IGF-I axis and T levels decline markedly with aging, whereas accumulating evidence supports their indispensable role in maintaining physical function integrity. Several studies have reported that the administration of T improves lean body mass and maximal voluntary strength in healthy older men. On the other hand, most studies have shown that administration of GH alone failed to improve muscle strength despite amelioration of the detrimental somatic changes of aging. Both GH and T are anabolic agents that promote muscle protein synthesis and hypertrophy but work through separate mechanisms, and the combined administration of GH and T, albeit in only a few studies, has resulted in greater efficacy than either hormone alone. Although it is clear that this combined approach is effective, this review concludes that further studies are needed to assess the long-term efficacy and safety of combined hormone replacement therapy in older men before the medical rationale of prescribing hormone replacement therapy for combating the sarcopenia of aging can be established. PMID:22433122

Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement.

PubMed

Rohayem, Julia; Drechsel, Hendrik; Tittel, Bettina; Hahn, Gabriele; Pfaeffle, Roland; Huebner, Angela

2016-01-01

Growth hormone (GH) has been used to treat children with GH deficiency (GHD) since 1966. Using a combined retrospective and cross-sectional approach, we explored the long-term outcomes of patients with GHD, analysed factors influencing therapeutic response, determined persistence into adulthood, investigated pituitary morphology, and screened for mutations in causative genes. The files of 96 GH-deficient children were reviewed. In a subset of 50 patients, re-assessment in adulthood was performed, including GHRH-arginine testing, pituitary magnetic resonance imaging (MRI), and mutational screening for the growth hormone-1 gene (GH1) and the GHRH receptor gene (GHRHR) in isolated GHD (IGHD), and HESX1, PROP1, POU1F1, LHX3, LHX4, and GLI2 in multiple pituitary hormone deficiency (MPHD) patients. GH was started at a height SDS of -3.2 ± 1.4 in IGHD patients and of -4.1 ± 2.1 in MPHD patients. Relative height gain was 0.3 SDS/year, absolute gain 1.6 SDS, and 1.2/2.6 SDS in IGHD/MPHD, respectively. Mid-parental target height was reached in 77%. Initial height SDS, bone age retardation and duration of GH replacement were correlated with height SDS gain. GHD persisted into adulthood in 19 and 89% of subjects with IGHD and MPHD, respectively. In 1/42 IGHD patients a GH1 mutation was detected; PROP1 mutations were found in 3/7 MPHD subjects. Anterior pituitary hypoplasia, combined with posterior pituitary ectopy and pituitary stalk invisibility on MRI, was an exclusive finding in MPHD patients. GH replacement successfully corrects the growth deficit in children with GHD. While the genetic aetiology remains undefined in most cases of IGHD, PROP1 mutations constitute a major cause for MPHD. Persistence of GHD into adulthood is related to abnormal pituitary morphology. © 2016 S. Karger AG, Basel.

Sex steroids and the GH axis: Implications for the management of hypopituitarism.

PubMed

Birzniece, Vita; Ho, Ken K Y

2017-02-01

Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Sex hormones exert profound effect on the secretion and action of GH. Estrogens stimulate the secretion of GH, but inhibit the action of GH on the liver, an effect that occurs when administered orally. Estrogens suppress GH receptor signaling by stimulating the expression proteins that inhibit cytokine receptor signaling. This effect of estrogens is avoided when physiological doses of estrogens are administered via a non-oral route. Estrogen-like compounds, such as selective estrogen receptor modulators, possess dual properties of inhibiting the secretion as well as the action of GH. In contrast, androgens stimulate GH secretion, driving IGF-1 production. In the periphery, androgens enhance the action of GH. The differential effects of estrogens and androgens influence the dose of GH replacement in patients with hypopituitarism on concomitant treatment with sex steroids. Where possible, a non-oral route of estrogen replacement is recommended for optimizing cost-benefit of GH replacement in women with GH deficiency. Adequate androgen replacement in conjunction with GH replacement is required to achieve the full anabolic effect in men with hypopituitarism. Copyright © 2017 Elsevier Ltd. All rights reserved.

[The reproductive system in Prader-Willi syndrome].

PubMed

Eldar-Geva, Talia; Hirsch, Harry J; Gross-Tsur, Varda

2015-03-01

Prader-Willi syndrome (PWS) is a genetic syndrome caused by the lack of expression of imprinted genes located on paternal chromosome 15q11-q13, characterized by endocrine defects, an insatiable appetite, short stature, cognitive and behavioral difficulties and dysmorphic features. Nearly all PWS males and most PWS women show clinical and/or laboratory evidence of hypogonadism, affecting their habitus, health and quality of life. Until recently, hypogonadism in PWS was generally considered to be of centrall, hypothalamic origin. However, recent studies have shown that primary gonadal dysfunction is the major contributor to hypogonadism in this condition, while severe gonadotropin deficiency is rare. Despite clinical and laboratory evidence of hypogonadism, young adult PWS men and women have sexual and romantic interests and aspirations. Pregnancies have been reported in a few women with genetically documented PWS. Fertility has not been reported in PWS men. Recognition of these interests is essential for physicians and caregivers in order to offer proper anticipatory guidance, psychological and sex education and counseling. Individual variations in pubertal development, reproductive hormone profiles, bone-mineral density and individual appeal need to be considered when recommending sex hormone replacement in this population. Testosterone should be considered in most hypogonadal PWS males, considering possible side effects. Hormone replacement may be indicated in PWS women with decreasing bone mineral density or in PWS women who wish to have regular menses. Contraception should be considered in women with normal inhibin B levels. Hormone replacement is likely to improve bone density, quality of life and body image.

Differential effects of raloxifene and estrogen on body composition in growth hormone-replaced hypopituitary women.

PubMed

Birzniece, Vita; Meinhardt, Udo J; Gibney, James; Johannsson, Gudmundur; Armstrong, Nicola; Baxter, Robert C; Ho, Ken K Y

2012-03-01

GH deficiency causes reduction in muscle and bone mass and an increase in fat mass (FM), the changes reversed by GH replacement. The beneficial effects of GH on fat oxidation and protein anabolism are attenuated more markedly by raloxifene, a selective estrogen receptor modulator, compared with 17β-estradiol. Whether this translates to a long-term detrimental effect on body composition is unknown. Our objective was to compare the effects of 17β-estradiol and raloxifene on FM, lean body mass (LBM), and bone mineral density (BMD) during GH replacement. This was an open-label randomized crossover study. Sixteen hypopituitary women received GH (0.5 mg/d) replacement for 24 months. One group received 17β-estradiol (2 mg/d) for the first 6 months before crossover to raloxifene (60 mg/d) for the remaining 18 months; the other received the reversed sequence. Serum IGF-I and IGF-binding protein-3 concentrations, and FM, LBM, lumbar spine and femoral neck BMD were analyzed at baseline and at 6, 12, and 24 months within and between subjects. GH therapy significantly increased mean IGF-I during 17β-estradiol and raloxifene cotreatments equally, but elevated IGF-binding protein-3 to a greater extent during raloxifene cotreatment. GH cotreatment with 17β-estradiol increased LBM and lumbar spine and femoral neck BMD and reduced FM to a greater extent than with raloxifene. In hypopituitary women, raloxifene at therapeutic doses significantly attenuated the beneficial effects of GH on body composition compared with 17β-estradiol. Raloxifene has no metabolic advantage over 17β-estradiol during GH replacement.

The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors.

PubMed

Woodmansee, W W; Gordon, D F; Dowding, J M; Stolz, B; Lloyd, R V; James, R A; Wood, W M; Ridgway, E C

2000-07-01

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth. Somatostatin has been implicated as a synergistic factor in the inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.

Stability of Proteins in Carbohydrates and Other Additives during Freezing: The Human Growth Hormone as a Case Study.

PubMed

Arsiccio, Andrea; Pisano, Roberto

2017-09-21

Molecular dynamics is here used to elucidate the mechanism of protein stabilization by carbohydrates and other additives during freezing. More specifically, we used molecular dynamics simulations to obtain a quantitative estimation of the capability of various cryoprotectants to preserve a model protein, the human growth hormone, against freezing stresses. Three mechanisms were investigated, preferential exclusion, water replacement, and vitrification. Model simulations were finally validated upon experimental data in terms of the ability of excipients to prevent protein aggregation. Overall, we found that the preferential exclusion and vitrification mechanisms are important during the whole freezing process, while water replacement becomes dominant only toward the end of the cryoconcentration phase. The disaccharides were found to be the most efficient excipients, in regard to both preferential exclusion and water replacement. Moreover, sugars were in general more efficient than other excipients, such as glycine or sorbitol.

Hypopituitarism in the elderly in the presence of elevated thyroid stimulating hormone levels.

PubMed Central

Beringer, T.; McClements, B.; Weir, I.; Gilmore, D.; Kennedy, L.

1988-01-01

Two cases of primary hypothyroidism with hypopituitarism in elderly patients are reported. The elevated levels of thyroid stimulating hormone led to delay in the recognition of accompanying pituitary failure. Elderly patients should not be commenced on thyroxine replacement therapy until the possibility of hypopituitarism and cortisol deficiency has been excluded. PMID:3256811

An AOP-based alternative testing strategy to predict the impact of thyroid hormone disruption on swim bladder inflation in zebrafish (poster)

EPA Science Inventory

Within the field of chemical safety assessment, there is a desire to replace costly whole organism testing with more efficient and cost-effective alternatives based on in vitro test systems. Disruption of thyroid hormone signaling via inhibition of enzymes called deiodinases is o...

Informing women about hormone replacement therapy: the consensus conference statement

PubMed Central

Mosconi, Paola; Donati, Serena; Colombo, Cinzia; Mele, Alfonso; Liberati, Alessandro; Satolli, Roberto

2009-01-01

Background The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/benefits. Methods We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: a literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. Results Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone therapy" should be the preferred definition. Conclusion This CC led to the identification of specific information drawbacks. Women are exposed to messages that are often partial, non evidence-based nor transparently developed. The structured and participative methodology of this CC allowed a multidisciplinary perspective and a substantial lay people input. PMID:19480688

Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study.

PubMed

Close, Helen; Mason, James M; Wilson, Douglas; Hungin, A Pali S

2012-05-29

Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT). Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD) remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. 51,182 menopausal women were identified using the UK General Practice Research Database between 1995-2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs) were calculated for GORD and proton-pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18-1.89). Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03-1.74). Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01-2.22). This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance.

Primary hypothyroidism in the community: Lower daily dosages of levothyroxine replacement therapy for Asian patients.

PubMed

Tan, Ngiap Chuan; Chew, Rong Quan; Koh, Yi Ling Eileen; Subramanian, Reena Chandini; Sankari, Usha; Meyappan, Meykkumar; Cho, Li Wei

2017-02-01

The goal of treatment in patients with primary hypothyroidism is to attain euthyroidism guided by the stipulated thyroid-stimulating hormone (TSH) levels range so as to minimize any potential long-term adverse effects. However, various factors may result in their Levothyroxine (T4) under and over-replacement.Our study aimed to evaluate the mean daily dose of L-T4 replacement for Asian patients with primary hypothyroidism. The secondary aims were to determine the proportion of those who were either over or under-replaced, and the factors associated with their thyroid function status and replacement adherence.Data collected using questionnaire survey from targeted patients managed in a typical public primary care center in Singapore: socio-demographic characteristics, clinical parameters, laboratory investigations, mean daily L-T4-replacement doses, and replacement regimens. The thyroid status of patients was classified based on thyroid function investigations.Complete data of 229 patients were analyzed. A total of 59.8% of patients had TSH within the normal range, 27.5% and 12.7% were under and over-replaced, respectively. About 60% of Asian patients with primary hypothyroidism achieved normal TSH status requiring average of 1.1 μg of daily L-T4/kgBW (kg body weight). Subjects who were over-replaced had a higher daily L-T4 dose/kgBW when compared to the euthyroid and the under replaced groups. Those with L-T4 over-replacement were largely due to excessive dosage. Patients who were younger, from lower socioeconomic strata, and higher BMI were more likely to be over or under-replaced.Majority of Asian patients with hypothyroidism required replacement of 1.1 μg of daily L-T4/kgBW. Their thyroid status was influenced by demographic and dosing factors.

Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy

DTIC Science & Technology

2011-06-01

tract length to male fertility (Davis-Dao et al., 2007) and in hypogonadal men to response to testosterone replacement (Zitzmann et al., 2004...changing, as occurs in development and aging, or clinically, as when hormone is replaced in hypogonadal men or ablated in prostate cancer treatment

Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

PubMed Central

Auger, Catherine J.; Coss, Dylan; Auger, Anthony P.; Forbes-Lorman, Robin M.

2011-01-01

Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems. PMID:21368111

Liquid L-thyroxine versus tablet L-thyroxine in patients on L- thyroxine replacement or suppressive therapy: a meta-analysis.

PubMed

Laurent, Irakoze; Tang, Siying; Astère, Manirakiza; Wang, Kan Ran; Deng, Shuhua; Xiao, Ling; Li, Qi Fu

2018-03-23

To compare the effectiveness of liquid L-T4 (L-thyroxine) and tablet L-T4 in patients on L-T4 replacement or suppressive therapy. The Cochrane Library, PubMed, Embase, and Web of Science databases were searched to identify relevant articles. All prospective or randomized controlled studies (RCTs) comparing liquid L-T4 and tablet L-T4 in patients on L-T4 replacement or suppressive therapy were included in the analysis. Overall, the initial search of the four databases identified 1278 published studies; of these, eight studies were ultimately included in the meta-analysis. TSH (thyroid stimulating hormone) levels were significantly suppressed in patients on liquid L-T4 compared with those on tablet L-T4, in patients on L-T4 suppressive therapy with L-T4 malabsorption (Mean Difference (MD) = -2.26, 95% Confidence Interval (CI): -3.59, -0.93; P = 0.0009)). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 suppressive therapy without malabsorption (MD = 0.08, 95% CI: -0.31, 0.47; P = 0.69). TSH levels were significantly normalized in patients on liquid L-T4 compared with those on tablet L-T4, in Patients on L-T4 replacement therapy with L-T4 malabsorption (MD = -3.20, 95% CI: -5.08, -1.32; P = 0.0009). However, liquid L-T4 and tablet L-T4 did not show a statistically significant difference in patients on L-T4 replacement therapy without malabsorption (MD = 0.91, 95% CI: -0.03, 1.86; P = 0.06). Liquid L-T4 is more efficient than tablet L-T4 in patients on L-T4 replacement or suppressive therapy with malabsorption. No significant differences were observed in patients without malabsorption. Further studies should be conducted to verify these findings.

Effects of sex steroids on muscarinic sties in the rat brain

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

Al-Dahan, M.I.

1986-03-01

The level of binding sites for (/sup 3/H)scopolamine in the rat hypothalamus and amygdala (but not elsewhere in the brain) is modified by hormonal status. In females, there is an inverse relation between the level of sites and estrogen (E/sub 2/) and progesterone (P) concentration. Binding is high in metoestrous (Met) and in ovariectomized (Ovx) animals but low in proestrous (Pro). Hormone replacement in ovariectomized animals lowers the level of the sites. Castration (Cast) of males reduces the level of sites but subsequent testosterone (T) treatment restores normal levels. The results support a role of hormones in sexual behavior viamore » alteration in levels of muscarinic receptors: male hormone increases and female hormones decrease receptor levels.« less

The timing hypothesis and hormone replacement therapy: a paradigm shift in the primary prevention of coronary heart disease in women. Part 2: comparative risks.

PubMed

Hodis, Howard N; Mack, Wendy J

2013-06-01

A major misperception concerning postmenopausal hormone replacement therapy (HRT) is that the associated risks are large in magnitude and unique to HRT, but over the past 10 years, sufficient data have accumulated so that the magnitude and perspective of risks associated with the primary coronary heart disease prevention therapies of statins, aspirin, and postmenopausal HRT have become more fully defined. Review of randomized controlled trials indicates that the risks of primary prevention therapies and other medications commonly used in women's health are of similar type and magnitude, with the majority of these risks categorized as rare to infrequent (<1 event per 100 treated women). Evidence-based data show that the risks of postmenopausal HRT are predominantly rare (<1 event per 1,000 treated women) and certainly no greater than other commonly used medications in women's health, including statins and aspirin. These risks, including breast cancer, stroke, and venous thromboembolism are common across medications and are rare, and even rarer when HRT is initiated in women younger than 60 or who are less than 10 years since menopause. In Part 1 of this series, the sex-specificity of statins and aspirin and timing of initiation of HRT as modifiers of efficacy in women were reviewed. Herein, the comparative risks of primary prevention therapies in women are discussed. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

Protein metabolism in Turner syndrome and the impact of hormone replacement therapy.

PubMed

Gravholt, Claus Højbjerg; Riis, Anne Lene; Møller, Niels; Christiansen, Jens Sandahl

2007-09-01

Studies have documented an altered body composition in Turner syndrome (TS). Body fat is increased and muscle mass is decreased. Ovarian failure necessitates substitution with female hormone replacement therapy (HRT), and HRT induces favourable changes in body composition. It is unknown how HRT affects protein metabolism. To test whether alterations in body composition before and after HRT in TS are a result of altered protein metabolism. We performed a randomized crossover study with active treatment (HRT in TS and oral contraceptives in controls) or no treatment. We studied eight women (age 29.7 +/- 5.6 (mean +/- SD) years) with TS, verified by karyotype, and eight age-matched controls (age 27.3 +/- 4.9 years). All subjects underwent a 3-h study in the postabsorptive state. Protein dynamics of the whole body and of the forearm muscles were measured by an amino acid tracer dilution technique using [(15)N]phenylalanine and [(2)H(4)]tyrosine. Substrate metabolism was examined by indirect calorimetry. Energy expenditure was comparable among TS and controls, and did not change during active treatment. Whole-body phenylalanine and tyrosine fluxes were similar in the untreated situations, and did not change during active treatment. Amino acid degradation and protein synthesis were similar in all situations. Muscle protein breakdown was similar among groups, and was not affected by treatment. Muscle protein synthesis rate and forearm blood flow did not differ among groups or due to treatment. Protein metabolism in TS is comparable to controls, and is not affected by HRT.

Hormone replacement therapy after a diagnosis of breast cancer: cancer recurrence and mortality.

PubMed

Durna, Eva M; Wren, Barry G; Heller, Gillian Z; Leader, Leo R; Sjoblom, Peter; Eden, John A

2002-10-07

To determine whether hormone replacement therapy (HRT) after treatment for breast cancer is associated with increased risk of recurrence and mortality. Retrospective observational study. Postmenopausal women diagnosed with breast cancer and treated by five Sydney doctors between 1964 and 1999. Times from diagnosis to cancer recurrence or new breast cancer, to death from all causes and to death from primary tumour were compared between women who used HRT for menopausal symptoms after diagnosis and those who did not. Relative risks (RRs) were determined from Cox regression analyses, adjusted for patient and tumour characteristics. 1122 women were followed up for 0-36 years (median, 6.08 years); 154 were lost to follow-up. 286 women used HRT for menopausal symptoms for up to 26 years (median, 1.75 years). Compared with non-users, HRT users had reduced risk of cancer recurrence (adjusted relative risk [RR], 0.62; 95% CI, 0.43-0.87), all-cause mortality (RR, 0.34; 95% CI, 0.19-0.59) and death from primary tumour (RR, 0.40; 95% CI, 0.22-0.72). Continuous combined HRT was associated with a reduced risk of death from primary tumour (RR, 0.32; 95% CI, 0.12-0.88) and all-cause mortality (RR, 0.27; 95% CI, 0.10-0.73). HRT use for menopausal symptoms by women treated for primary invasive breast cancer is not associated with an increased risk of breast cancer recurrence or shortened life expectancy.

Preliminary development of a new individualised questionnaire measuring quality of life in older men with age-related hormonal decline: the A-RHDQoL

PubMed Central

McMillan, Carolyn V; Bradley, Clare; Giannoulis, Manthos; Martin, Finbarr; Sönksen, Peter H

2003-01-01

Background There is increasing interest in hormone replacement therapy to improve health and quality of life (QoL) of older men with age-related decline in hormone levels. This paper reports the preliminary development and evaluation of the psychometric properties of a new individualised questionnaire, the A-RHDQoL, measuring perceived impact of age-related hormonal decline on QoL of older men. A-RHDQoL design was based on the HDQoL for people with growth hormone (GH) deficiency and the ADDQoL (for diabetes). Methods Internal consistency reliability and some aspects of validity of the A-RHDQoL were investigated in a cross-sectional survey of 128 older men (age range: 64 – 80 yrs), being screened for inclusion in a trial of GH and testosterone (T) replacement, and who completed the A-RHDQoL once. Respondents rated personally applicable life domains for importance and impact of their hormonal decline. A single overview item measured present QoL. Serum levels of Insulin-like Growth Factor-I and total T were measured. Results Of the 24 A-RHDQoL domains, 21 were rated as relevant and important for older men. All domains were perceived as negatively impacted by hormonal decline. The most negatively impacted domains were: memory (-4.54 ± 3.02), energy (-4.44 ± 2.49), sex life (-4.34 ± 3.08) and physical stamina (-4.29 ± 2.41), (maximum range -9 to +9). The shorter 21-domain A-RHDQoL had high internal consistency reliability (Cronbach's alpha coefficient = 0.935, N = 103) and applicable domains could be weighted and summed into an overall Average Weighted Impact score. The questionnaire was acceptable to the majority of respondents and content validity was good. The single overview item measuring present QoL correlated significantly with total T levels [r = 0.26, p <0.01, N = 114]. Conclusion The new 21-item A-RHDQoL is an individualised questionnaire measuring perceived impact of age-related hormonal decline on the QoL of older men. The internal consistency reliability and content validity of the A-RHDQoL are established, but the measure is at an early stage of its development and its sensitivity to change and other psychometric properties need now to be evaluated in clinical trials of hormone replacement in older men. PMID:14613571

An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk

DTIC Science & Technology

2007-04-01

active learning techniques in Introduction to Epidemiology Ongoing5 W81XWH-06-1-0312 Reding, Kerryn 7 TASK STATUS of FUTURE TASKS Task 3...Apply for and obtain IRB renewal Ongoing task Task 4: Training-related Work (Months 13-36) a. Present research findings on active learning at

Hormonal treatment and flight feather molt in immature Sandhill Cranes

USGS Publications Warehouse

Gee, G.F.; Lewis, J.C.

1982-01-01

Molt, the production of a new generation of feathers, is a poorly understood physiological phenomenon in nondomestic birds. Often in large birds like geese, flight is restricted by clipping the primary remiges on 1 wing and flight is restored after the molt when the primaries are replaced. A similar technique would be desirable for use with cranes conditioned for release to the native habitat. However, immature sandhill cranes (Grus canadensis) did not appear to replace their primaries annually; therefore, we studied their flight feather molt (from 4 months to 3.5 years of age) and attempted to influence molting. Under natural conditions tail feathers (rectrices) were replaced annually and all secondaries replaced in 2.5-year-old birds. However, replacement of primaries in immature sandhill cranes appears to be a gradual process beginning the 2nd year; about 33% of the original primaries (present at 10 months of age) persisted in the 3.5-year-oId birds. Pulling out the primaries of immature sandhill cranes induces the growth of new primaries, as is true of many other birds. However, the new primaries were incapable of supporting flight, fell out repeatedly, and those that remained were often deformed. Pulling the primaries, under the influence of tranquilizers and anesthetics to relax the feather papillae, also did not induce normal growth of the replacement primaries. Progesterone (including excessively high doses), thyroxine, and follicle stimulating hormone, although effective in inducing feather replacement in domestic poultry, had no effect on crane molt.

Are thyroid nodules associated with sex-related hormones? A cross-sectional SPECT-China study.

PubMed

Chen, Yi; Chen, Yingchao; Wang, Ningjian; Chen, Chi; Nie, Xiaomin; Li, Qin; Han, Bing; Xia, Fangzhen; Zhai, Hualing; Jiang, Boren; Shen, Zhoujun; Lu, Yingli

2017-08-03

Little is known about the association between thyroid nodules (TNs) and endogenous sex hormones. We aimed to investigate the relationship between TNs and sex-related hormones among men in China. The data were obtained from a cross-sectional study Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China study, 2014-2015) based on the population. In total, 4024 men over 18 years of age who were not using hormone replacement therapy and who underwent complete assays of the serum total testosterone (T), oestradiol (E 2 ), follicle-stimulating hormone (FSH), luteinising hormone (LH) and sex hormone-binding globulin (SHBG) levels as well as thyroid ultrasonography (US) enrolled in this study. Of the 4024 participants (54.15±13.08 years old), 1667 participants (41.4%) had TNs. Men with TN(s) (TN(+) group) had significantly lower levels of total T and SHBG and higher E 2 /T levels compared with the men without TN(s) (TN(-) group) (p<0.05). The TN prevalence decreased with the quartiles of the SHBG level (p<0.05). Binary logistic analysis showed that lower quartiles of SHBG had a greater risk of TN(s) (all p for trend <0.05). This association persisted in the fully adjusted model (p for trend=0.017), in which, for the lowest compared with the highest quartile of SHBG, the OR of TN(s) was 1.42 (95% CI 1.07 to 1.89). No statistically significant association was found between sex-related hormones and US characteristics associated with malignancy (nodule >10 mm, microcalcification and a 'taller' than 'wider' shape). TNs are highly prevalent in men in China. A lower SHBG level was significantly associated with TN among men. The potential role of SHBG in the pathogenesis of the TN remains to be elucidated. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Phytoestrogens in the treatment of menopause].

PubMed

Remport, Júlia; Blázovics, Anna

2017-08-01

In previous centuries many women did not even live until their menopause years due to poor economic conditions, deficiencies of medicine, epidemics and wars. Nowadays in the developed countries, people live until they are 75-80 years old, and with the expansion of average age, the number of people affected by menopause and the years spent in that state increase. Nowadays women spend one third of their lives in the menopausal stage. The only effective way to treat unpleasant symptoms for centuries was with the use of herbs, and the knowledge about them spread through oral tradition. In the 20th century, this therapeutic form was pushed into the background by the development of synthetic drug production and the introduction of hormone replacement therapy. Thanks to the influence of media in the 20th century, women began to have the social need for preserving their beauty and youth for as long as they could. Hormone replacement therapy enjoyed great popularity because women were temporarily relieved of their life quality-impairing menopausal symptoms, but years later it turned out that hormone replacement therapy could pose serious risks. A distinct advantage of herbal therapy is the more advantageous side-effect-profile opposite the used synthetics in hormone replacement therapy. Women are therefore happy to turn to valuable and well-tried natural therapies, which have been used for thousands of years. There is growing interest in herbal remedies. Studying the effects of phytoestrogens has now become an active area for research. However, the results of studies in animals and humans are controversial, some sources suggest that phytoestrogens are effective and safe, other authors claim that they are ineffective in menopause or they have particularly dangerous properties, and cannot be recommended to everyone. It is important to address this issue for the sake of health, mental health and safety of women, and so it is necessary to assess the benefits and the risks before applying them. Orv Hetil. 2017; 158(32): 1243-1251.

The Conundrum of Estrogen Receptor Oscillatory Activity in the Search for an Appropriate Hormone Replacement Therapy

PubMed Central

Della Torre, Sara; Biserni, Andrea; Rando, Gianpaolo; Monteleone, Giuseppina; Ciana, Paolo; Komm, Barry

2011-01-01

By the use of in vivo imaging, we investigated the dynamics of estrogen receptor (ER) activity in intact, ovariectomized, and hormone-replaced estrogen response element-luciferase reporter mice. The study revealed the existence of a long-paced, noncircadian oscillation of ER transcriptional activity. Among the ER-expressing organs, this oscillation was asynchronous and its amplitude and period were tissue dependent. Ovariectomy affected the amplitude but did not suppress ER oscillations, suggesting the presence of tissue endogenous oscillators. Long-term administration of raloxifene, bazedoxifene, combined estrogens alone or with basedoxifene to ovariectomized estrogen response element-luciferase mice showed that each treatment induced a distinct spatiotemporal profile of ER activity, demonstrating that the phasing of ER activity among tissues may be regulated by the chemical nature and the concentration of circulating estrogen. This points to the possibility of a hierarchical organization of the tissue-specific pacemakers. Conceivably, the rhythm of ER transcriptional activity translates locally into the activation of specific gene networks enabling ER to significantly change its physiological activity according to circulating estrogens. In reproductive and nonreproductive organs this hierarchical regulation may provide ER with the signaling plasticity necessary to drive the complex metabolic changes occurring at each female reproductive status. We propose that the tissue-specific oscillatory activity here described is an important component of ER signaling necessary for the full hormone action including the beneficial effects reported for nonreproductive organs. Thus, this mechanism needs to be taken in due consideration to develop novel, more efficacious, and safer hormone replacement therapies. PMID:21505049

[Benefits and risks of growth hormone in adults with growth hormone deficiency].

PubMed

Díez, Juan J; Cordido, Fernando

2014-10-21

Adult growth hormone (GH) deficiency is a well-recognized clinical syndrome with adverse health consequences. Many of these may improve after replacement therapy with recombinant GH. This treatment induces an increase in lean body mass and a decrease in fat mass. In long-term studies, bone mineral density increases and muscle strength improves. Health-related quality of life tends to increase after treatment with GH. Lipid profile and markers of cardiovascular risk also improve with therapy. Nevertheless, GH replacement therapy is not without risk. According to some studies, GH increases blood glucose, body mass index and waist circumference and may promote long-term development of diabetes and metabolic syndrome. Risk of neoplasia does not appear to be increased in adults treated with GH, but there are some high-risk subgroups. Methodological shortcomings and difficulties inherent to long-term studies prevent definitive conclusions about the relationship between GH and survival. Therefore, research in this field should remain active. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Pubertal induction in hypogonadism: Current approaches including use of gonadotrophins.

PubMed

Zacharin, Margaret

2015-06-01

Primary disorders of the gonad or those secondary to abnormalities of the hypothalamic pituitary axis result in hypogonadism. The range of health problems of childhood and adolescence that affect this axis has increased, as most children now survive chronic illness, but many have persisting deficits in gonadal function as a result of their underlying condition or its treatment. An integrated approach to hormone replacement is needed to optimize adult hormonal and bone health, and to offer opportunities for fertility induction and preservation that were not considered possible in the past. Timing of presentation ranges from birth, with disorders of sexual development, through adolescent pubertal failure, to adult fertility problems. This review addresses diagnosis and management of hypogonadism and focuses on new management strategies to address current concerns with fertility preservation. These include Turner syndrome, and fertility presevation prior to childhood cancer treatment. New strategies for male hormone replacement therapy that may impinge upon future fertility are emphasized. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prevalence of right atrial non-pulmonary vein triggers in atrial fibrillation patients treated with thyroid hormone replacement therapy.

PubMed

Kim, Ki-Hun; Mohanty, Sanghamitra; Mohanty, Prasant; Trivedi, Chintan; Morris, Eli Hamilton; Santangeli, Pasquale; Bai, Rong; Al-Ahmad, Amin; Burkhardt, John David; Gallinghouse, Joseph G; Horton, Rodney; Sanchez, Javier E; Bailey, Shane; Hranitzky, Patrick M; Zagrodzky, Jason; Kim, Soo G; Di Biase, Luigi; Natale, Andrea

2017-08-01

Thyroid hormone (TH) is known to enhance arrhythmogenicity, and high-normal thyroid function is related with an increased recurrence of atrial fibrillation (AF) after catheter ablation. However, the impact of thyroid hormone replacement (THR) on AF ablation is not well known. This study evaluated 1163 consecutive paroxysmal AF patients [160 (14%) on THR and 1003 (86%) without THR] undergoing their first catheter ablation. A total of 146 patients on THR and 146 controls were generated by propensity matching, based on calculated risk factor scores, using a logistic model (age, sex, body mass index, and left atrium size). The presence of non-pulmonary vein (PV) triggers was disclosed by a high-dose isoproterenol challenge (up to 30 μg/min) after PV isolation. Clinical characteristics were not different between the groups. When compared to the control, non-PV triggers were significantly greater in the THR patients [112 (77%) vs. 47 (32%), P < 0.001], and most frequently originated from the right atrium (95 vs. 56%, P < 0.001). Other sources of non-PV triggers were the interatrial septum (25 vs. 11%, P = 0.002), coronary sinus (70 vs. 52%, P = 0.01), left atrial appendage (47 vs. 34%, P = 0.03), crista terminalis/superior vena cava (11 vs. 8%, P = 0.43), and mitral valve annulus (7 vs. 5%, P = 0.45) (THR vs. control), respectively. After mean follow-up of 14.7 ± 5.2 months, success rate was lower in patients on THR therapy [94 (64.4%)] compared to patients not receiving THR therapy [110 (75.3%), log-rank test value = 0.04]. Right atrial non-PV triggers were more prevalent in AF patients treated with THR. Elimination of non-PV triggers provided better arrhythmia-free survival in the non-THR group.

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed

Arisaka, O; Hall, R; Hughes, I A

1983-10-08

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism.

Current medical management of endocrine-related male infertility

PubMed Central

Ring, Joshua D; Lwin, Aye A; Köhler, Tobias S

2016-01-01

Male factor contributes to 50%–60% of overall infertility but is solely responsible in only 20% of couples. Although most male factor infertility is ascertained from an abnormal semen analysis, other male factors can be contributory especially if the sample returns normal. Male infertility can be due to identifiable hormonal or anatomical etiologies that may be reversible or irreversible. This manuscript will highlight existing guidelines and our recommendations for hormone evaluation for male infertility and empiric therapies including multivitamins, estrogen receptor modulators (clomiphene), estrogen conversion blockers (anastrozole), and hormone replacement. PMID:27098657

Spontaneous endocrine cure of gigantism due to pituitary apoplexy.

PubMed Central

Arisaka, O; Hall, R; Hughes, I A

1983-01-01

An 11 year old, tall boy presented with symptoms typical of pituitary apoplexy. A large necrotic and haemorrhagic tumour was removed, which was shown to be an adenoma secreting growth hormone and prolactin. Subsequent treatment comprised cranial irradiation and hormone replacement. Eighteen months after operation growth was static and plasma growth hormone and prolactin concentrations were undetectable. Treatment of pituitary apoplexy should comprise excision of the tumour and postoperative irradiation; such treatment after early recognition of the condition offers the best chance of preserving normal pituitary function in children with gigantism. PMID:6311318

Quality of life in patients with hypopituitarism.

PubMed

Crespo, Iris; Santos, Alicia; Webb, Susan M

2015-08-01

Quality of life (QoL) is impaired in patients with adults with growth hormone deficiency (AGHD) of any cause, especially if additional hypopituitarism is present, and improves after replacement therapy with recombinant human growth hormone (rhGH). This review includes relevant publications since 2013. Recent findings confirm that most patients with AGHD who improve their QoL after rhGH therapy experience persistent effects for years, if replacement therapy is maintained. Sometimes, however, QoL may not normalize completely, especially if it is caused by a craniopharyngioma (because of concomitant neuropsychological comorbidities that affect autonomy and cognitive function), or functional pituitary tumours, i.e., in Cushing's disease, in which chronic brain exposure to hypercortisolism is associated with more depression, anxiety, loss of memory and emotional distress. Another group in which QoL and energy rarely normalize despite improving after rhGH is hypopituitarism because of traumatic brain injury. Worse QoL is seen in patients who also suffer insomnia, depression, negative illness perceptions and are treated in a rural (compared with an urban) healthcare environment. Better QoL after rhGH is seen in AGHD patients who are not depressed, after successful surgery, living in Europe (rather than the USA), with poorer baseline QoL scores, less obesity and no impaired vision. Further improvement of QoL may be possible with individualized psychosocial interventions.

Low external pH replaces 2,4-D in maintaining and multiplying 2,4-D-initiated embryogenic cells of carrot

NASA Technical Reports Server (NTRS)

Smith, D. L.; Krikorian, A. D.

1990-01-01

A mixed culture comprised of both embryonic globules and nonembryogenic callus was derived from seedling hypocotyls of Daucus carota cv. Scarlet Nantes on 2,4-D- containing medium using well-established methods. Then the mixed cultures were transferred to, and serially subcultured on, a hormone-free medium near pH 4. The medium contained 1 mM NH4+ as the sole nitrogen source. When cultured in this way, embryonic globules were able to multiply without development into later embryo stages. Nonembryogenic callus did not survive. Continuous culture of embryonic globules on this low pH hormone-free medium yielded cultures consisting entirely of preglobular stage proembryos (PGSPs). PGSP cultures have been maintained as such with continuous multiplication for nearly 2 years without loss of embryogenic potential. These hormone-free-maintained PGSPs continue their development to later embryo stages when cultured on the same hormone-free medium buffered at pH 5.8. We show that hormone-free medium near pH 4 can replace 2,4-D in its ability to sustain multiplication of 2,4-D-initiated embryogenic cells of carrot at an acceptable growth rate without their development into later embryo stages. This procedure provides selective conditions that do not permit the growth of non-embryogenic cells while providing an adequate environment for embryogenic cell proliferation and should prove invaluable in studying habituation.

Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men.

PubMed

Brambilla, Donald J; O'Donnell, Amy B; Matsumoto, Alvin M; McKinlay, John B

2007-12-01

Estimates of intraindividual variation in hormone levels provide the basis for interpreting hormone measurements clinically and for developing eligibility criteria for trials of hormone replacement therapy. However, reliable systematic estimates of such variation are lacking. To estimate intraindividual variation of serum total, free and bioavailable testosterone (T), dihydrotestosterone (DHT), SHBG, LH, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEAS), oestrone, oestradiol and cortisol, and the contributions of biological and assay variation to the total. Paired blood samples were obtained 1-3 days apart at entry and again 3 months and 6 months later (maximum six samples per subject). Each sample consisted of a pool of equal aliquots of two blood draws 20 min apart. Men aged 30-79 years were randomly selected from the respondents to the Boston Area Community Health Survey, a study of the health of the general population of Boston, MA, USA. Analysis was based on 132 men, including 121 who completed all six visits, 8 who completed the first two visits and 3 who completed the first four visits. Day-to-day and 3-month (long-term) intraindividual standard deviations, after transforming measurements to logarithms to eliminate the contribution of hormone level to intraindividual variation. Biological variation generally accounted for more of total intraindividual variation than did assay variation. Day-to-day biological variation accounted for more of the total than did long-term biological variation. Short-term variability was greater in hormones with pulsatile secretion (e.g. LH) than those that exhibit less ultradian variation. Depending on the hormone, the intraindividual standard deviations imply that a clinician can expect to see a difference exceeding 18-28% about half the time when two measurements are made on a subject. The difference will exceed 27-54% about a quarter of the time. Given the level of intraindividual variability in hormone levels found in this study, one sample is generally not sufficient to characterize an individual's hormone levels but collecting more than three is probably not warranted. This is true for clinical measurements and for hormone measurements used to determine eligibility for a clinical trial of hormone replacement therapy.

Regulation of Estrogen Receptor α Expression in the Hypothalamus by Sex Steroids: Implication in the Regulation of Energy Homeostasis.

PubMed

Liu, Xian; Shi, Haifei

2015-01-01

Sex differences exist in the complex regulation of energy homeostasis that utilizes central and peripheral systems. It is widely accepted that sex steroids, especially estrogens, are important physiological and pathological components in this sex-specific regulation. Estrogens exert their biological functions via estrogen receptors (ERs). ERα, a classic nuclear receptor, contributes to metabolic regulation and sexual behavior more than other ER subtypes. Physiological and molecular studies have identified multiple ERα-rich nuclei in the hypothalamus of the central nervous system (CNS) as sites of actions that mediate effects of estrogens. Much of our understanding of ERα regulation has been obtained using transgenic models such as ERα global or nuclei-specific knockout mice. A fundamental question concerning how ERα is regulated in wild-type animals, including humans, in response to alterations in steroid hormone levels, due to experimental manipulation (i.e., castration and hormone replacement) or physiological stages (i.e., puberty, pregnancy, and menopause), lacks consistent answers. This review discusses how different sex hormones affect ERα expression in the hypothalamus. This information will contribute to the knowledge of estrogen action in the CNS, further our understanding of discrepancies in correlation of altered sex hormone levels with metabolic disturbances when comparing both sexes, and improve health issues in postmenopausal women.

Hormone replacement therapy is associated with gastro-oesophageal reflux disease: a retrospective cohort study

PubMed Central

2012-01-01

Background Oestrogen and progestogen have the potential to influence gastro-intestinal motility; both are key components of hormone replacement therapy (HRT). Results of observational studies in women taking HRT rely on self-reporting of gastro-oesophageal symptoms and the aetiology of gastro-oesophageal reflux disease (GORD) remains unclear. This study investigated the association between HRT and GORD in menopausal women using validated general practice records. Methods 51,182 menopausal women were identified using the UK General Practice Research Database between 1995–2004. Of these, 8,831 were matched with and without hormone use. Odds ratios (ORs) were calculated for GORD and proton-pump inhibitor (PPI) use in hormone and non-hormone users, adjusting for age, co-morbidities, and co-pharmacy. Results In unadjusted analysis, all forms of hormone use (oestrogen-only, tibolone, combined HRT and progestogen) were statistically significantly associated with GORD. In adjusted models, this association remained statistically significant for oestrogen-only treatment (OR 1.49; 1.18–1.89). Unadjusted analysis showed a statistically significant association between PPI use and oestrogen-only and combined HRT treatment. When adjusted for covariates, oestrogen-only treatment was significant (OR 1.34; 95% CI 1.03–1.74). Findings from the adjusted model demonstrated the greater use of PPI by progestogen users (OR 1.50; 1.01–2.22). Conclusions This first large cohort study of the association between GORD and HRT found a statistically significant association between oestrogen-only hormone and GORD and PPI use. This should be further investigated using prospective follow-up to validate the strength of association and describe its clinical significance. PMID:22642788

Hyperthyroidism due to thyroid-stimulating hormone secretion after surgery for Cushing's syndrome: a novel cause of the syndrome of inappropriate secretion of thyroid-stimulating hormone.

PubMed

Tamada, Daisuke; Onodera, Toshiharu; Kitamura, Tetsuhiro; Yamamoto, Yuichi; Hayashi, Yoshitaka; Murata, Yoshiharu; Otsuki, Michio; Shimomura, Iichiro

2013-07-01

Hyperthyroidism with the syndrome of inappropriate secretion of TSH (SITSH) occurred by a decrease in hydrocortisone dose after surgery for Cushing's syndrome. This is a novel cause of SITSH. The aim of this study was to describe and discuss 2 cases of SITSH patients that were found after surgery for Cushing's syndrome. We also checked whether SITSH occurred in 7 consecutive patients with Cushing's syndrome after surgery. A 45-year-old Japanese woman with ACTH-independent Cushing's syndrome and a 37-year-old Japanese man with ACTH-dependent Cushing's syndrome presented SITSH caused by insufficient replacement of hydrocortisone for postoperative adrenal insufficiency. When the dose of hydrocortisone was reduced to less than 20 mg/d within 18 days after surgery, SITSH occurred in both cases. We examined whether the change of the hydrocortisone dose induced the secretion of TSH. Free T₃ and TSH were normalized by the hydrocortisone dose increase of 30 mg/d, and these were elevated by the dose decrease of 10 mg/d. We also checked TSH and thyroid hormone levels of the 7 consecutive patients with Cushing's syndrome after surgery. Six (66.6 %) of 9 patients showed SITSH. This is the first report that insufficient replacement of hydrocortisone after surgery for Cushing's syndrome caused SITSH. Hyperthyroidism by SITSH as well as adrenal insufficiency can contribute to withdrawal symptoms of hydrocortisone replacement. We need to consider the possibility of SITSH for the pathological evaluation of withdrawal syndrome of hydrocortisone replacement.

The confounding effect of the development of idiopathic orthostatic edema and thyrotoxcosis on weight fluctuation related to effects on free water clearance in a woman with long-standing surgically induced panhypopituitarism and diabetes insipidus.

PubMed

Check, J H; Weidner, J

2015-01-01

To evaluate the effect of idiopathic orthostatic edema and the effect of thyrotoxicosis on weight fluctuation and fluid retention in the presence of surgically induced panhypopituitarism and diabetes insipidus controlled with hormone replacement. Dextroamphetamine sulfate was used for weight gain when no other etiologic factor was found. Methimazole was used when weight loss occurred when serum T4 and free T4 indicated thyrotoxicosis. Sympathomimetic amine therapy very effectively controlled the weight gain and methimazole controlled the weight loss. Hypopituitarism and diabetes insipidus controlled with hormone replacement do not protect against fluid retention from idiopathic edema.

Sex hormone concentrations and the risk of breast cancer recurrence in postmenopausal women without hot flashes.

PubMed

Emond, Jennifer A; Patterson, Ruth E; Natarajan, Loki; Laughlin, Gail A; Gold, Ellen B; Pierce, John P

2011-05-01

We examined if the reduced risk of breast cancer events seen among women without baseline hot flash symptoms in the Women's Healthy Eating and Living (WHEL) dietary intervention trial was related to changes in sex hormone concentrations. Baseline and year one concentrations of total and bioavailable estradiol, and testosterone and sex hormone-binding globulin (SHBG) were compared by intervention arm among 447 postmenopausal women without hot flashes. Cox proportional hazard models tested interaction terms between study arm and baseline hormone concentrations adjusted for study site, antiestrogen use, positive nodes, tumor size, oophorectomy status, and hormone replacement therapy use. Sex hormone concentrations did not differ by study arm at baseline nor at year one. Twenty-two (9.8%) events occurred in the intervention arm versus 42 (18.9%) in the comparison arm (P = 0.009). Baseline bioavailable testosterone was significantly, positively associated with additional events (HR 1.69, 95% CI: 1.00-2.84; P = 0.049). There were significant interactions between the intervention and total (P = 0.015), and bioavailable (P = 0.050) testosterone: the intervention was more protective among participants with higher baseline total (HR 0.3, 95% CI: 0.2-0.7) or bioavailable (HR 0.4, 95% CI: 0.2-0.7) testosterone than for participants with lower baseline total (HR 0.8, 95% CI: 0.4-1.5) or bioavailable (HR 0.8, 95% CI: 0.4-1.5) testosterone. No significant effects were seen for estradiol or SHBG. The WHEL dietary intervention may have modified other risk factors of recurrence correlated with testosterone. Sex hormones should be considered as part of a larger biological system related to the risk of breast cancer recurrence. ©2011 AACR.

Synthesis and chemical reactions of the steroidal hormone 17α-methyltestosterone.

PubMed

El-Desoky, El-Sayed Ibrahim; Reyad, Mahmoud; Afsah, Elsayed Mohammed; Dawidar, Abdel-Aziz Mahmoud

2016-01-01

Structural modifications of natural products with complex structures like steroids require great synthetic effort. A review of literature is presented on the chemistry of the steroidal hormone 17α-methyltestosterone that is approved by Food and Drug Administration (FDA) in the United States as an androgen for estrogen-androgen hormone replacement therapy treatment. The analog also offers special possibilities for the prevention/treatment of hormone-sensitive cancers. The testosterone skeleton has important functionalities in the molecule that can act as a carbonyl component, an active methylene compound, α,β-unsaturated enone and tertiary hydroxyl group in various chemical reactions to access stereoisomeric steroidal compounds with potent activity. In addition, microbiological methods of synthesis and transformation of this hormone are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON MENOPAUSE-2017 UPDATE.

PubMed

Cobin, Rhoda H; Goodman, Neil F

2017-07-01

EXECUTIVE SUMMARY This American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) Position Statement is designed to update the previous menopause clinical practice guidelines published in 2011 but does not replace them. The current document reviews new clinical trials published since then as well as new information regarding possible risks and benefits of therapies available for the treatment of menopausal symptoms. AACE reinforces the recommendations made in its previous guidelines and provides additional recommendations on the basis of new data. A summary regarding this position statement is listed below: New information available from randomized clinical trials and epidemiologic studies reported after 2011 was critically reviewed. No previous recommendations from the 2011 menopause clinical practice guidelines have been reversed or changed. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, selective estrogen-receptor modulators (SERMs), and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. Newer information enhances AACE's guidance for the use of hormone therapy in different subsets of women. Newer information helps to support the use of various types of estrogens, SERMs, and progesterone, as well as the route of delivery. Newer information supports the previous recommendation against the use of bioidentical hormones. The use of nonhormonal therapies for the symptomatic relief of menopausal symptoms is supported. New recommendations in this position statement include: 1. the use of menopausal hormone therapy in symptomatic postmenopausal women should be based on consideration of all risk factors for cardiovascular disease, age, and time from menopause. 2. the use of transdermal as compared with oral estrogen preparations may be considered less likely to produce thrombotic risk and perhaps the risk of stroke and coronary artery disease. 3. when the use of progesterone is necessary, micronized progesterone is considered the safer alternative. 4. in symptomatic menopausal women who are at significant risk from the use of hormone replacement therapy, the use of selective serotonin re-uptake inhibitors and possibly other nonhormonal agents may offer significant symptom relief. 5. AACE does not recommend use of bioidentical hormone therapy. 6. AACE fully supports the recommendations of the Comité de l'Évolution des Pratiques en Oncologie regarding the management of menopause in women with breast cancer. 7. HRT is not recommended for the prevention of diabetes. 8. In women with previously diagnosed diabetes, the use of HRT should be individualized, taking in to account age, metabolic, and cardiovascular risk factors. AACE = American Association of Clinical Endocrinologists; ACE = American College of Endocrinology; BMI = body mass index; CAC = coronary artery calcification; CEE = conjugated equine estrogen; CEPO = Comité de l'Évolution des Pratiques en Oncologie; CAD = coronary artery disease; CIMT = carotid intima media thickness; CVD = cardiovascular disease; FDA = Food and Drug Administration; HDL = high-density lipoprotein; HRT = hormone replacement therapy; HT = hypertension; KEEPS = Kronos Early Estrogen Prevention Study; LDL = low-density lipoprotein; MBS = metabolic syndrome; MPA = medroxyprogesterone acetate; RR = relative risk; SERM = selective estrogen-receptor modulator; SSRI = selective serotonin re-uptake inhibitor; VTE = venous thrombo-embolism; WHI = Women's Health Initiative.

ESTROGEN REPLACEMENT THERAPY INDUCES FUNCTIONAL ASYMMETRY ON AN ODOR MEMORY/DISCRIMINATION TEST

PubMed Central

Doty, Richard L.; Kisat, Mehreen; Tourbier, Isabelle

2008-01-01

The secondary afferents of the olfactory system largely project to the ipsilateral cortex without synapsing in the thalamus, making unilateral olfactory testing a useful probe of ipsilateral hemispheric activity. In light of evidence that lateralized performance on some perceptual tasks may be influenced by estrogen, we assessed left:right nostril differences in two measures of olfactory function in 14 post-menopausal women receiving estrogen replacement therapy (ERT) and 48 post-menopausal women receiving no such therapy. Relative to women not taking ERT, those receiving ERT exhibited better performance in the left nostril and poorer performance in the right nostril on an odor memory/discrimination test. Similar laterality effects were not observed for an odor detection threshold test employing phenyl ethyl alcohol. These results suggest that estrogen influences the lateralization of an odor memory/discrimination task and that hormone replacement therapy in the menopause may be an excellent paradigm for understanding lateralizing effects of hormones on some sensory processes. PMID:18466883

Modulation of hepatic reticuloendothelial system phagocytosis by pancreatic hormones.

PubMed

Cornell, R P; McClellan, C C

1982-12-01

Experiments were conducted to determine the influence of the pancreatic hormones insulin, glucagon, and somatostatin on reticuloendothelial system (RES) phagocytosis both in vivo and in the isolated perfused livers of rats. Chronic pancreatic hormonal treatment consisted of twice daily injections SC of NPH insulin with doses ranging from 0.75 U on day 1 to 9.0 U on day 13 and unchanged doses of glucagon (200 micrograms) and somatostatin (50 micrograms). Chronic treatment with insulin significantly depressed by 48% intravascular phagocytosis of colloidal carbon administered IV at a dose of 8 mg/100 g, while glucagon and somatostatin stimulated macrophage endocytic function by 32% and 26%, respectively, compared to the control value. Acute treatment with the three pancreatic hormones at 30 min prior to carbon administration similarly produced insulin depression as well as glucagon and somatostatin stimulation of RES phagocytosis. Addition of the three hormones at near physiologic concentrations (20 ng/ml for insulin, 10 ng/ml for glucagon, and 5 ng/ml for somatostatin) to the recirculating perfusate of isolated perfused rat livers simultaneous with 24 mg of colloidal carbon likewise resulted in phagocytic reduction after insulin and enhancement after glucagon and somatostatin. Experiments involving insulin in vitro with isolated perfused livers as well as glucose replacement therapy concomitant with insulin in vivo demonstrated that hypoglycemia is not necessary for phagocytic depression by insulin while severe hypoglycemia in the perfusion medium is sufficient to depress carbon uptake by isolated perfused livers independent of insulin. Both pancreatic hormones and the level of glycemia seem to be important in modulating hepatic reticuloendothelial system phagocytosis.

Follow-up of congenital heart disease patients with subclinical hypothyroidism.

PubMed

Martínez-Quintana, Efrén; Rodríguez-González, Fayna

2015-08-01

Subclinical hypothyroidism or mild thyroid failure is a common problem in patients without known thyroid disease. Demographic and analytical data were collected in 309, of which 181 were male and 128 were female, congenital heart disease (CHD) patients. CHD patients with thyroid-stimulating hormone above 5.5 mIU/L were also followed up from an analytical point of view to determine changes in serum glucose, cholesterol, N-terminal pro b-type natriuretic peptide, and C-reactive protein concentrations. Of the CHD patients, 35 (11.3%) showed thyroid-stimulating hormone concentration above 5.5 mIU/L. Of them, 27 were followed up during 2.4±1.2 years - 10 were under thyroid hormone replacement treatment, and 17 were not. Of the 27 patients (25.9%), 7 with subclinical hypothyroidism had positive anti-thyroid peroxidase, and 3 of them (42.8%) with positive anti-thyroid peroxidase had Down syndrome. Down syndrome and hypoxaemic CHD patients showed higher thyroid-stimulating hormone concentrations than the rest of the congenital patients (p<0.001). No significant differences were observed in serum thyroxine, creatinine, uric acid, lipids, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations before and after the follow-up in those CHD patients with thyroid-stimulating hormone above 5.5 mIU/L whether or not they received levothyroxine therapy. CHD patients with subclinical hypothyroidism showed no significant changes in serum thyroxine, cholesterol, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations whether or not they were treated with thyroid hormone replacement therapy.

Sex differences in Parkinson's disease.

PubMed

Gillies, Glenda E; Pienaar, Ilse S; Vohra, Shiv; Qamhawi, Zahi

2014-08-01

Parkinson's disease (PD) displays a greater prevalence and earlier age at onset in men. This review addresses the concept that sex differences in PD are determined, largely, by biological sex differences in the NSDA system which, in turn, arise from hormonal, genetic and environmental influences. Current therapies for PD rely on dopamine replacement strategies to treat symptoms, and there is an urgent, unmet need for disease modifying agents. As a significant degree of neuroprotection against the early stages of clinical or experimental PD is seen, respectively, in human and rodent females compared with males, a better understanding of brain sex dimorphisms in the intact and injured NSDA system will shed light on mechanisms which have the potential to delay, or even halt, the progression of PD. Available evidence suggests that sex-specific, hormone-based therapeutic agents hold particular promise for developing treatments with optimal efficacy in men and women. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

[Panhypopituitarism caused by an intrasellar cystic mass in late-onset hypogonadism clinic].

PubMed

Yamamoto, Yoshiyuki; Takada, Shingo; Kinjo, Takanori; Nonomura, Daichi; Yoneda, Suguru; Nomura, Hironori; Tei, Norihide; Matsumiya, Kiyomi; Okusu, Takahiro

2013-10-01

A 74-year-old man who was referred to our late onset hypogonadism clinic presented with sweating and loss of appetite. His aging males' symptoms (AMS) and international index of erectile function (IIEF-5) scores were 59 and 2, respectively. His hormonal examination revealed extremely low free testosterone values. The patient was started on androgen replacement therapy, but his symptoms did not improve. Additional hormonal examinations revealed low values for other anterior pituitary hormones. Magnetic resonance imaging revealed an intrasellar cystic mass with suprasellar extension. We considered this mass caused hypothalamic hypopituitarism. A load test for anterior pituitary hormones revealed panhypogonadism. His symptoms improved after administration of adrenal and thyroid hormones and androgen. Five months after start of drug administration, his AMS score improved to 29, but IIEF-5 score showed little change. As a matter of course, not only androgen but all pituitary-related hormones are needed for hypopituitarism patients.

The effect of prothrombotic blood abnormalities on risk of deep vein thrombosis in users of hormone replacement therapy: a prospective case-control study.

PubMed

Douketis, Jim D; Julian, Jim A; Crowther, Mark A; Kearon, Clive; Bates, Shannon M; Barone, Marisa; Piovella, Franco; Middeldorp, Saskia; Prandoni, Paolo; Johnston, Marilyn; Costantini, Lorrie; Ginsberg, Jeffrey S

2011-01-01

Few studies have assessed the effect of prothrombotic blood abnormalities on the risk of deep vein thrombosis (DVT) with hormone replacement therapy (HRT). We studied postmenopausal women with suspected DVT in whom HRT use and prothrombotic blood abnormalities were sought. Cases had unprovoked DVT and controls had no DVT and without DVT risk factors. The risk of DVT was determined in women with and without prothrombotic abnormalities. A total of 510 postmenopausal women with suspected DVT were assessed; 57 cases and 283 controls were identified. Compared to HRT, nonusers without the factor V Leiden mutation, the risk of DVT was increased in estrogen-progestin HRT users (odds ratio [OR], 3.2; 95% confidence interval [CI]: 1.2-8.6) and in nonusers with the factor V Leiden mutation (OR, 5.3; 1.9-15.4) and appears multiplied in users of estrogen-progestin HRT with the factor V Leiden mutation (OR, 17.1; 3.7-78). Compared to HRT, nonusers with normal factor VIII, the risk of DVT was increased in estrogen-progestin HRT users with normal factor VIII (OR, 2.8; 1.0-7.9) and in HRT nonusers with the highest factor VIII quartile (OR, 6.0; 2.1-17), and appears to be multiplied in women who are users of estrogen-progestin HRT with the highest factor VIII quartile (OR, 17.0; 3.6-80). In postmenopausal women who are estrogen-progestin HRT users, the presence of the factor V Leiden mutation or an elevated factor VIII level appears to have a multiplicative effect on their overall risk of DVT, increasing it 17-fold compared to women without these blood abnormalities who are HRT nonusers.

Laparoscopic gastric bypass in patients on thyroid replacement therapy for subnormal thyroid function - prevalence and short-term outcome.

PubMed

Szomstein, Samuel; Avital, Shmuel; Brasesco, Oscar; Mehran, Amir; Cabral, Jose M; Rosenthal, Raul

2004-01-01

Hypothyroidism is associated with increased body weight. Weight gain may occur despite normal levels of serum thyroid stimulating hormone (TSH) and thyroxine (T4) achieved by replacement therapy. We evaluated the prevalence of patients on thyroid replacement for subnormal thyroid function who were operated on for morbid obesity and monitored their postoperative weight loss pattern. Data was identified from a prospectively accrued database of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) or laparoscopic adjustable gastric banding (LAGB) for morbid obesity from February 2000 to November 2001. All patients with subnormal thyroid function, diagnosed by past thyroid function tests and treated by an endocrinologist, who were on thyroid replacement therapy, were identified; 5 of these were matched for age, gender, preoperative body mass index (BMI) and surgical procedure (LRYGBP) to 5 non-hypothyroid patients. Weight loss at 3 and 9 months after surgery was compared between the 2 groups. 192 patients underwent LRYGBP (n=155) or LAGB (n=37). Of the 21 patients (10.9%) on thyroid replacement identified, 14 were primary, 4 were postablative, and 3 were post-surgical; 17 underwent LRYGBP. All patients had normal preoperative serum levels of TSH and T4. Comparison of the 2 matched groups of patients revealed no difference in weight loss at 3 and 9 months after surgery (P=1.0). The prevalence of euthyroid patients on thyroid replacement for subnormal thyroid function who undergo surgical intervention for morbid obesity is high. Short-term weight loss in these patients is comparable to normal thyroid patients. Longer follow-up may be necessary to demonstrate the weight loss pattern in this group.

Resolution of non-alcoholic steatohepatitis after growth hormone replacement in a pediatric liver transplant patient with panhypopituitarism.

PubMed

Gilliland, Thomas; Dufour, Sylvie; Shulman, Gerald I; Petersen, Kitt Falk; Emre, Sukru H

2016-12-01

NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency. Refractory NAFLD in panhypopituitarism may be amenable to GH replacement. Here, we report a pediatric case of NASH secondary to panhypopituitarism from craniopharyngioma, which recurred by 11 months after LDLT. Despite low-dose GH replacement, the patient remained GH deficient. Pubertal dosed GH therapy led to rapid and complete resolution of hepatic steatosis, which we tracked using serial 1 H MRS. Pediatric patients with NASH cirrhosis secondary to panhypopituitarism can be good candidates for liver transplantation, but hormone deficiencies predispose to recurrence after transplant. High-dose GH replacement should be considered in pediatric patients with GH deficiency and recurrent disease. A multidisciplinary team approach is essential for successful outcomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Selective estrogen receptor modulator effects of epimedium extracts on breast cancer and uterine growth in nude mice.

PubMed

Indran, Inthrani Raja; Zhang, Shi-Jun; Zhang, Zhi Wei; Sun, Feng; Gong, Yinhan; Wang, Xiaochong; Li, Jun; Erdelmeier, Clemens A J; Koch, Egon; Yong, Eu Leong

2014-01-01

Epimedium is popularly used in traditional Chinese medicine to treat sexual dysfunction, menstrual irregularity, and osteoporosis. The estrogenic effects of the prenylated flavonoids of Epimedium make it an attractive alternative for hormone replacement therapy. Here, we examined the therapeutic potential of the estrogenic herb extract of Epimedium brevicornum as an alternative to hormone replacement therapy in a breast cancer mouse model. To that end, athymic and ovariectomized female nude mice were subcutaneously injected into the mammary fat pads with MCF-7 breast cancer cells, randomly grouped and fed with soy-free feeds, alone or in combination with ethinyl estradiol or different doses of the estrogenic herb extract of E. brevicornum. Our findings demonstrate that unlike ethinyl estradiol, it did not promote the growth of breast cancer xenograft volume and weight, with the highest dose showing a significant reduction in growth and ERα protein content. Moreover, the extract increased uterine weight at the lowest dose, while higher doses had no effects. Put together, our data shows for the first time that despite the estrogenic activity of E. brevicornum, its action is largely tissue specific and dose-dependent. Our data on E. brevicornum presents in vivo evidence for its selective estrogen receptor modulator effect and warrants exploration of its use as an alternative to hormone replacement therapy in menopausal women. Georg Thieme Verlag KG Stuttgart · New York.

Daidzein–Estrogen Interaction in the Rat Uterus and Its Effect on Human Breast Cancer Cell Growth

PubMed Central

Gaete, Leonardo; Bustamante, Rodrigo; Villena, Joan; Lemus, Igor; Gidekel, Manuel; Cabrera, Gustavo; Astorga, Paola

2012-01-01

Abstract Sex hormone replacement therapy provides several advantages in the quality of life for climacteric women. However, estrogen-induced cell proliferation in the uterus and mammary gland increases the risk of cancer development in these organs. The lower incidence of mammary cancer in Asian women as compared with Western women has been attributed to high intake of soy isoflavones, including genistein. We have previously shown that genistein induces an estradiol-like hypertrophy of uterine cells, but does not induce cell proliferation, uterine eosinophilia, or endometrial edema. It also inhibits estradiol-induced mitosis in uterine cells and hormone-induced uterine eosinophilia and endometrial edema. Nevertheless, genistein stimulates growth of human breast cancer cells in culture; therefore, it is not an ideal estrogen for use in hormone replacement therapy (HRD). The present study investigated the effect of another soy isoflavone, daidzein (subcutaneous, 0.066 mg/kg body weight), in the same animal model, and its effect on responses induced by subsequent treatment (1 h later) with estradiol-17β (E2; subcutaneous, 0.33 mg/kg body weight). In addition, we investigated the effects of daidzein (1 μg/mL) or E2 on the growth of human breast cancer cells in culture. Results indicate that daidzein stimulates growth of breast cancer cells and potentiates estrogen-induced cell proliferation in the uterus. We suggest caution for the use of daidzein or formulas containing this compound in HRD. Future research strategies should be addressed in the search for new phytoestrogens that selectively inhibit cell proliferation in the uterus and breast. PMID:23216111

UGT2B17 gene deletion associated with an increase in bone mineral density similar to the effect of hormone replacement in postmenopausal women.

PubMed

Giroux, S; Bussières, J; Bureau, A; Rousseau, F

2012-03-01

UGT2B17 is one of the most important enzymes for androgen metabolism. In addition, the UGT2B17 gene is one of the most commonly deleted regions of the human genome. The deletion was previously found associated with higher femoral bone density in men and women, and we replicated this association in a sample of postmenopausal who never used hormone therapy. Deletion of the UGT2B17 gene was previously shown to be associated with a higher hip bone mineral density (BMD). Using a PCR assay, we tried to replicate the association among a large group of 2,379 women. We examined the effect of the deletion on femoral neck BMD and lumbar spine BMD according to the menopausal status and hormone replacement therapy (HRT). We used a high-throughput PCR assay to identify the gene and the deletion in a population of well-characterized women. Two additional polymorphisms, UGT2B28 deletion and UGT2B15 rs1902023 G > T were also investigated. Only UGT2B17 deletion was associated with LS and FN BMD. Furthermore, the association was seen only among postmenopausal women who had never used hormone replacement as in the first reported association. We confirmed the association between UGT2B17 deletion and a higher LS and FN BMD. In addition, we show that the association is observed among postmenopausal women who never used HRT consistent with the enzymatic function of UGT2B17. The analysis shows that those having one or two UGT2B17 alleles benefit from HRT, which is not the case for null carriers.

Massive pleural and pericardial effusion due to hypothyroidism in a patient with a surgically treated thyroid-stimulating hormone-producing pituitary adenoma.

PubMed

Lee, Ji-Hoon; Park, MinA; Park, Myung Jae; Jo, Yong Suk

2018-05-14

Hypothyroidism is relatively rare etiology of serositis with effusion, but massive pleural effusion is very unusual. This is a report of massive pleural effusion in patient taking methimazole after surgical resection of thyroid-stimulating hormone (TSH)-producing pituitary adenoma (TSHoma). The patient was clinically and biochemically hypothyroid and responded well to discontinuation of methimazole and thyroid hormone replacement therapy. When assessing patients with pleural effusion, we should not rely on laboratory test results alone, as a detailed medical history and thorough physical examination could be more useful.

Age-dependent Effects of 17β-estradiol on the Dynamics of Estrogen Receptor β (ERβ) Protein–Protein Interactions in the Ventral Hippocampus*

PubMed Central

Mott, Natasha N.; Pinceti, Elena; Rao, Yathindar S.; Przybycien-Szymanska, Magdalena M.; Prins, Sarah A.; Shults, Cody L.; Yang, Xinli; Glucksman, Marc J.; Roberts, James L.; Pak, Toni R.

2014-01-01

Recent clinical evidence suggests that the neuroprotective and beneficial effects of hormone therapy may be limited by factors related to age and reproductive status. The patient's age and length of time without circulating ovarian hormones are likely to be key factors in the specific neurological outcomes of hormone therapy. However, the mechanisms underlying age-related changes in hormone efficacy have not been determined. We hypothesized that there are intrinsic changes in estrogen receptor β (ERβ) function that determine its ability to mediate the actions of 17β-estradiol (E2) in brain regions such as the ventral hippocampus. In this study, we identified and quantified a subset of ERβ protein interactions in the ventral hippocampus that were significantly altered by E2 replacement in young and aged animals, using two-dimensional differential gel electrophoresis coupled with liquid chromatography–electrospray ionization–tandem mass spectrometry. This study demonstrates quantitative changes in ERβ protein–protein interactions with E2 replacement that are dependent upon age in the ventral hippocampus and how these changes could alter processes such as transcriptional regulation. Thus, our data provide evidence that changes in ERβ protein interactions are a potential mechanism for age-related changes in E2 responsiveness in the brain after menopause. PMID:24390426

Thyroiditis de Quervain. Are there predictive factors for long-term hormone-replacement?

PubMed

Schenke, S; Klett, R; Braun, S; Zimny, M

2013-01-01

Subacute thyroiditis is a usually self-limiting disease of the thyroid. However, approximately 0.5-15% of the patients require permanent thyroxine substitution. Aim was to determine predictive factors for the necessity of long-term hormone-replacement (LTH). We retrospectively reviewed the records of 72 patients with subacute thyroiditis. Morphological and serological parameters as well as type of therapy were tested as predictive factors of consecutive hypothyroidism. Mean age was 49 ± 11 years, f/m-ratio was 4.5 : 1. Thyroid pain and signs of hyperthyroidism were leading symptoms. Initial subclinical or overt hyperthyroidism was found in 20% and 37%, respectively. Within six months after onset 15% and 1.3% of the patients developed subclinical or overt hypothyroidism, respectively. At latest follow-up 26% were classified as liable to LTH. At onset the thyroid was enlarged in 64%, and at latest follow-up in 8.3%, with a significant reduction of the thyroid volume after three months. At the endpoint the thyroid volume was less in patients in the LTH group compared with the non-LTH group (41.7% vs. 57.2% of sex-adjusted upper norm, p = 0.041). Characteristic ultrasonographic features occurred in 74% of the patients in both lobes. Serological and morphological parameters as well as type of therapy were not related with the need of LTH. In this study the proportion of patients who received LTH was 26%. At the endpoint these patients had a lower thyroid volume compared with euthyroid patients. No predictive factors for LTH were found.

Fertility desires, choice of hormone replacement and the effect of length of time since menopause on bone density in women with premature ovarian insufficiency: a review of 223 consecutive new referrals to a tertiary centre.

PubMed

Mittal, Monica; Kreatsa, Maria; Narvekar, Nitish; Savvas, Michael; Hamoda, Haitham

2014-09-01

Premature ovarian insufficiency can have significant implications for the affected women. This review assesses the fertility desires, choice of hormone replacement, and the effect of time since menopause on the bone density of these women. This is a retrospective analysis of 223 consecutive new referrals. The average age (mean [± standard deviation]) of the women was 37.35 (± 5.88) years, with 24.1% (n = 19/79) presenting within 12 months of the onset of symptoms, most commonly, vasomotor type symptoms (n = 98/223; 43.9%). Of the women included, 58.7% (n = 131/223) took hormone replacement therapy (HRT), most commonly, an oral (n = 90/131; 68.7%) sequential preparation (n = 91/131; 69.5%), with a significant number of women >40 years of age preferring the transdermal route (n = 26/54; 48.1%; p<0.01). A total of 37.7% (n = 84/223) of the women expressed concerns regarding their future fertility, more notable in women ≤ 40 years (n = 72/142; 50.7%; p < 0.01). Of these, 41.7% (n = 35/84) took HRT, most commonly, a sequential regimen (n = 26/35; 74.3%) with oral estradiol (n = 30/35; 85.7%); 69.5% (n = 155/223) of the women had had a bone densitometry scan performed, with 66.5% (n = 103/155) showing normal bone mineral density (BMD), but a greater likelihood of having reduced BMD the greater the time delay in presentation. No difference was seen for the three broad categories of BMD when further analysed for the cause of premature ovarian insufficiency, but a significant difference was noted for the spinal Z-scores, whereby women who underwent a surgically induced menopause were noted to have lower BMD compared with the other causes (p < 0.01). These findings can be useful in counselling women and guiding clinicians in their management of women with premature ovarian insufficiency. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Coronary artery disease in women: an unsolved dilemma.

PubMed

Aziz, Fahad

2014-04-01

Cardiovascular disease (CVD) is the leading cause of death in women, as well as an important cause of disability, although many women and their physicians underestimate the risk. The pathogenesis, presentation and diagnosis of CVDs are different in women than men, which make the women prone to under-treatment for these diseases. More gender-based research regarding the management of coronary artery disease (CAD) in women needs to be done. Exercise, hypertension treatment, smoking cessation and aspirin therapy are effective measures for the primary prevention of CAD in women. The roles of hormone replacement therapy in primary prevention are not well established. Hormone replacement therapy has not been effective in lowering the risk of recurrent myocardial infarction. Cardiologists and family physicians should emphasize the use of proven treatments, with particular attention given to underserved populations.

[Pituitary insufficiency after traumatic brain injury: consequences? Screening?].

PubMed

Ciancia, S

2012-06-01

Traumatic brain injury has been considered for long as a rare cause of hypopituitarism. Recent studies have already shown a prevalence of 30% of pituitary dysfunction following moderate or severe head injury that may persist into the chronic phase of recovery, hypogonadism and GH deficiency being the most common hormonal deficiencies. Hypopituitarism may impede recovery and contribute to chronic disability in these patients. However, there are limited data available regarding the impact of hypopituitarism, and the indications of hormonal replacement (especially GH replacement and hypogonadism treatment) still remain to be defined. The screening strategy for TBI - induced hypopituitarism has recently been revised. Copyright © 2012 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Treatment of neurogenic diabetes insipidus.

PubMed

Chanson, Philippe; Salenave, Sylvie

2011-12-01

Central or neurogenic diabetes insipidus results from a deficiency in antidiuretic hormone (ADH) or arginine-vasopressin (AVP). Treatment is based on replacement therapy with the hormone analog desmopressin (d-DAVP). d-DAVP can be administered subcutaneously to infants or patients with postoperative or posttraumatic brain injury being monitored for transient diabetes insipidus. Intranasal and oral forms are also available. The recently introduced lyophilisate, which melts under the tongue, has replaced the tablet form (recently withdrawn from the market in France) and provides better bioavailability. Irrespective of the mode of administration, it is usually the patient who finds the effective minimal dose necessary for a normal life, i.e. without excessive polyuria, particularly at night. Patient education is necessary to avoid the risk of water intoxication and hyponatremia. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

NASA Astrophysics Data System (ADS)

Wiley, Teresa S.; Haraldsen, Jason T.

2012-03-01

We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

Validation of an immunoassay for canine thyroid-stimulating hormone and changes in serum concentration following induction of hypothyroidism in dogs.

PubMed

Williams, D A; Scott-Moncrieff, C; Bruner, J; Sustarsic, D; Panosian-Sahakian, N; Unver, E; el Shami, A S

1996-11-15

To validate a new immunoradiometric assay for canine thyroid-stimulating hormone (cTSH) and to document changes in serum cTSH concentration during induction of hypothyroidism in dogs. Six healthy adult male Beagles. Sensitivity, specificity, precision, and accuracy of the cTSH assay were evaluated in vitro. Hypothyroidism was induced in dogs by i.v. administration of sodium iodide I 131 solution. Subsequently, L-thyroxine was administered orally to normalize serum thyroxine concentrations. The cTSH assay appeared to be specific and was sufficiently sensitive to detect cTSH in the serum of these dogs prior to induction of hypothyroidism. There was a 35-fold increase in mean serum cTSH concentration following induction of hypothyroidism, and 35 days after initiation of thyroid replacement therapy, mean serum cTSH concentration was not significantly greater than mean baseline value. Assay of serum cTSH is likely to prove helpful in the differential diagnosis of primary, secondary, and tertiary hypothyroidism in dogs, and in monitoring response to thyroid hormone replacement treatment.

Hormone Replacement Therapy: Will it affect seizure control and AED levels?

PubMed Central

Harden, Cynthia L.

2008-01-01

Interest in the years of reproductive changes for women with epilepsy (WWE), specifically perimenopause, menopause and postmenopause has been emerging in the epilepsy community. This article discusses evidence for changes in seizure frequency during perimenopause and postmenopause. Further, a catamenial epilepsy pattern during the reproductive years may be a hallmark for the observed seizure frequency change during these years; that is, an increase at perimenopause but a decrease at menopause. This finding implies that a subset of WWE are particularly susceptible to endogenous reproductive hormonal changes. An adverse effect on seizure frequency with the use of hormone replacement therapy (HRT) during postmenopause for WWE was reported in questionnaires, and was later borne out in a clinical trial. The laboratory counterpart of this human trial, HRT in ovariectomized rodent seizure models, shows that estrogen and progesterone are neuroprotective and do not uniformly increase seizure frequency. Possible reasons for the discrepancy between “the lab and the clinic” are presented. Strategies for managing HRT in symptomatic postmenopausal WWE using estrogenic and progestogenic compounds that may be less likely to promote seizures are discussed. PMID:18187348

GnRH neurons of young and aged female rhesus monkeys co-express GPER but are unaffected by long-term hormone replacement

PubMed Central

Naugle, Michelle M.; Gore, Andrea C.

2014-01-01

Menopause is caused by changes in the function of the hypothalamic-pituitary-gonadal (HPG) axis that controls reproduction. Hypophysiotropic gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus orchestrate the activity of this axis and are regulated by hormonal feedback loops. The mechanisms by which GnRH responses to the primary regulatory sex-steroid hormone, estradiol (E2) are still poorly understood in the context of menopause. Our goal was to determine whether the G protein-coupled estrogen receptor (GPER) is co-expressed in adult primate GnRH neurons, and whether this changes with aging and/or E2 treatment. We used immunofluorescence double labeling to characterize the co-expression of GPER in GnRH perikarya and terminals in the hypothalamus. Young and aged rhesus macaques were ovariectomized and given long-term (~2 year) hormone treatments (E2, E2 + progesterone, or vehicle) selected to mimic currently prescribed hormone replacement therapies used for the alleviation of menopausal symptoms in women. We found that about half of GnRH perikarya co-expressed GPER, while only about 12% of GnRH processes and terminals in the median eminence (ME) were double labeled. Additionally, many GPER labeled processes were in direct contact with GnRH neurons, often wrapped around the perikarya and processes and in close proximity in the ME. These results extend prior work by showing robust colocalization of GPER in GnRH in a clinically relevant model, and support the possibility that GPER-mediated E2 regulation of GnRH occurs both in the soma and terminals in nonhuman primates. PMID:25428637

Subclinical Hypothyroidism after 131I-Treatment of Graves' Disease: A Risk Factor for Depression?

PubMed

Yu, Jing; Tian, Ai-Juan; Yuan, Xin; Cheng, Xiao-Xin

2016-01-01

Although it is well accepted that there is a close relationship between hypothyroidism and depression, previous studies provided inconsistent or even opposite results in whether subclinical hypothyroidism (SCH) increased the risk of depression. One possible reason is that the etiology of SCH in these studies was not clearly distinguished. We therefore investigated the relationship between SCH resulting from 131I treatment of Graves' disease and depression. The incidence of depression among 95 patients with SCH and 121 euthyroid patients following 131I treatment of Graves' disease was studied. The risk factors of depression were determined with multivariate logistic regression analysis. Thyroid hormone replacement therapy was performed in patients with thyroid-stimulating hormone (TSH) levels exceeding 10 mIU/L. Patients with SCH had significantly higher Hamilton Depression Scale scores, serum TSH and thyroid peroxidase antibody (TPOAb) levels compared with euthyroid patients. Multivariate logistic regression analysis revealed SCH, Graves' eye syndrome and high serum TPO antibody level as risk factors for depression. L-thyroxine treatment is beneficial for SCH patients with serum TSH levels exceeding 10 mIU/L. The results of the present study demonstrated that SCH is prevalent among 131I treated Graves' patients. SCH might increase the risk of developing depression. L-thyroxine replacement therapy helps to resolve depressive disorders in SCH patients with TSH > 10mIU/L. These data provide insight into the relationship between SCH and depression.

[Analysis of prescriptions associated to hormone replacement therapy in Midi-Pyrénées region].

PubMed

Gass-Jégu, Florence; Damase-Michel, Christine; Hurault-Delarue, Caroline; Bourrel, Robert; Montastruc, Jean-Louis

2012-01-01

The aim of the present study was 1- to describe hormone replacement therapy (HRT) prescription in Midi-Pyrénées region (South West France) and 2- to compare the prescriptions of associated drugs to those of women who took HRT with prescriptions to women who did not take HRT. From 2004 to 2008, HRT prescription decreased for women aged 50 to 59 years in Midi-Pyrénées: 13.95% to 10.33% estradiol/progestin association consumers. During the first 6 months of 2008, 20,161 women took the association estradiol/progestin. Transdermal/percutaneous forms of estradiol (71.21%) and natural progesterone were mainly prescribed. The number of different dispensed drugs was significantly higher in the HRT group: 5.18 versus 2.82 in the control group (p < 0.0001). All classes were concerned except antineoplastic drugs and immunomodulators, drugs for diabetes and raloxifene which were more prescribed to controls. In the period of the study, 7,035 patients took estrogen alone (25.87% of HRT consumers). The same phenomena were observed in this group. Women exposed to HRT in Midi-Pyrénées, great consumers of drugs, represent a population who require particular medical supervision, because of the risks of HRT and pathologies and/or numerous associated drugs. © 2012 Société Française de Pharmacologie et de Thérapeutique.

Dehydroepiandrosterone replacement in patients with Addison's disease has a bimodal effect on regulatory (CD4+CD25hi and CD4+FoxP3+) T cells.

PubMed

Coles, Alasdair J; Thompson, Sara; Cox, Amanda L; Curran, Suzanne; Gurnell, Elli M; Chatterjee, V Krishna

2005-12-01

Oral replacement of the near-total deficiency of dehydroepiandrosterone (DHEA) in patients with Addison's disease (adrenal insufficiency) enhances mood and well-being and reduces fatigue. We studied the immunological effects of 12 wk of oral DHEA treatment in ten patients with Addison's disease receiving their normal mineralo- and glucocorticoid hormone replacement. We found that baseline circulating regulatory T cells were reduced in Addison's disease patients compared to controls, a hitherto unrecognised defect in this disorder. Oral DHEA treatment had a bimodal effect on naturally occurring regulatory (CD4+CD25hiFoxP3+) T cells and lymphocyte FoxP3 expression. Oral DHEA replacement restored normal levels of regulatory T cells and led to increased FoxP3 expression. These effects were probably responsible for a suppression of constitutive cytokine expression following DHEA withdrawal. In contrast, oral DHEA treatment led to reduced FoxP3 expression induced by TCR engagement and so augmented the cytokine response, but without a bias towards the Th1 or Th2 phenotype. NK and NKT cell numbers fell during DHEA treatment, and homeostatic lymphocyte proliferation was increased. We conclude that DHEA replacement in Addison's disease has significant immunomodulatory properties and propose that it has a greater impact on the human immune system than would be expected from its classification as a dietary supplement.

Role of 17 beta-estradiol on type IV collagen fibers volumetric density in the basement membrane of bladder wall.

PubMed

de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues

2007-10-01

The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.

[Long-term effects of 7-year growth hormone substitution on bone metabolism, bone density, and bone quality in growth hormone-deficient adults].

PubMed

Wilhelm, Birgit; Kann, Peter Herbert

2004-10-15

Subnormal bone mineral density (BMD) and increased fracture risk are described in patients with growth hormone deficiency (GHD). Growth hormone (GH) has been reported to have beneficial effects on bone in GHD. The aim of this study was to investigate the long-term effects of GH replacement therapy on bone metabolism, BMD, and bone quality in patients with GHD. 20 adult patients with GHD (eleven male, nine female, mean age 42.5 years) were included in the study and randomized to either GH or placebo in a dose of 0.25 U/kg body weight/week. After 6 months all patients received GH. After a 1-year double-blind, placebo-controlled study the patients were followed for another 72 months in an open study. The patients were compared to 20 age- und sex-matched healthy controls. Bone turnover was determined by ICTP (type I collagen carboxyterminal cross-linked telopeptide) as parameter of bone resorption and PICP (carboxyterminal propeptide of type I procollagen) as marker of bone formation. BMD was measured at the lumbar spine by dual-photon absorptiometry (DPA) and at the forearm by single-photon absorptiometry (SPA). Apparent phalangeal ultrasound transmission velocity (APU) was assessed as parameter of bone quality independent of BMD. At the beginning of the study BMD at both measuring sites was lower in patients with GHD than in healthy controls. During the 1st year of GH replacement therapy BMD decreased, followed by a continuous increase in BMD (about 12%) up to 60 months which remained unchanged thereafter, building up a plateau. After 72 months no significant difference between the patients and the healthy controls could be detected. Concerning parameters of bone turnover, first ICTP as marker of bone resorption showed a significant increase, later on the marker of bone formation increased as well. APU decreased during the first 6 months of treatment, but had returned to its baseline value after 24 months and remained unchanged throughout the rest of the study. BMD is subnormal in adults with GHD. GH replacement therapy stimulates bone turnover in patients with GHD and in the long term such stimulation results in an increased BMD. Thereby, GH shows a triphasic action on BMD: an initial decrease in BMD during the 1st year, followed by a continuous increase in BMD with buildup of a stable plateau after 60 months. The newly formed bone seems to have normal bone elasticity.

[Clinical experiences with Climen in peri- and postmenopausal women].

PubMed

Husmann, F

1997-01-01

42 women with signs of androgenization were treated with Climen in the peri- and postmenopause for a period longer than 12 months. The effect on most typical climacteric syndromes was comparable to other free available compounds. Concerning our patients, Climen was more effective than other compounds. In no case the withdrawal of Climen due to side-effects was necessary. Surprisingly an androgenetical loss of hair was stopped in 9 out of 10 cases. Climen widens essentially the therapeutical possibilities concerning hormone replacement in peri- and postmenopausal women and should not only be used in women with signs of androgenization.

The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells

PubMed Central

Ghatge, Radhika P; Jacobsen, Britta M; Schittone, Stephanie A; Horwitz, Kathryn B

2005-01-01

Introduction Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. Method A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacking or containing progesterone receptor and/or androgen receptor. Results In progesterone receptor-positive cells, MPA was found to be an effective progestin through both progesterone receptor isoforms in transient transcription assays. Interestingly, DHT signaled through progesterone receptor type B. Expression profiling of endogenous progesterone receptor-regulated genes comparing progesterone and MPA suggested that although MPA may be a somewhat more potent progestin than progesterone, it is qualitatively similar to progesterone. To address effects of MPA through androgen receptor, expression profiling was performed comparing progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene regulatory overlap between DHT and MPA through androgen receptor and none with progesterone. Interestingly, there was no difference between pharmacological MPA and physiological MPA, suggesting that high-dose therapeutic MPA may be superfluous. Conclusion Our comparison of the gene regulatory profiles of MPA and progesterone suggests that, for physiologic hormone replacement therapy, the actions of MPA do not mimic those of endogenous progesterone alone. Clinically, the complex pharmacology of MPA not only influences its side-effect profile; but it is also possible that the increased breast cancer risk and/or the therapeutic efficacy of MPA in cancer treatment is in part mediated by androgen receptor. PMID:16457685

Turner syndrome--issues to consider for transition to adulthood.

PubMed

Lucaccioni, Laura; Wong, Sze Choong; Smyth, Arlene; Lyall, Helen; Dominiczak, Anna; Ahmed, S Faisal; Mason, Avril

2015-03-01

Turner syndrome (TS) is associated with a spectrum of health problems across the age span, which requires particular attention during the transition period in these adolescents. The majority of girls with TS require oestrogen replacement from puberty onwards, which is important for adequate feminization, uterine development and maintenance of bone health. There is a lifetime increased risk from autoimmune conditions like hypothyroidism, coeliac disease, hearing loss and aortic dilatation with the potential to lead to aortic dissection. A systematic and holistic approach to provision of health care in TS is needed. Several unanswered questions remain, including the choice of hormone replacement therapy in the young person with TS and in adulthood; the optimal mode of cardiovascular assessment; the best management and assessment prior to and during pregnancy. The optimal model of care and transition to adult services in TS requires attention. Further research is needed in relation to cardiovascular risk assessment, pregnancy management and hormone replacement therapy in TS. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Hypopituitarism: growth hormone and corticotropin deficiency.

PubMed

Capatina, Cristina; Wass, John A H

2015-03-01

This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI. The diagnosis needs dynamic testing in most cases. Treatment of AGHD is recommended in patients with documented severe deficiency, and treatment of CAI is mandatory in all cases. Despite significant progress in replacement hormonal therapy, more physiologic treatments and more reliable indicators of treatment adequacy are still needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Abrupt onset of muscle dysfunction after treatment for Grave's disease: a case report.

PubMed

Hernán Martínez, José; Sánchez, Alfredo; Torres, Oberto; Palermo, Coromoto; Santiago, Mónica; Figueroa, Carlos; Trinidad, Rafael; Mangual, Michelle; Gutierrez, Madeleine; González, Eva; Miranda, María de Lourdes

2014-01-01

Myopathy is a known complication of hypothyroidism, commonly characterized by an elevation in Creatine Kinase (CPK) due to increase capillary permeability proportional to the hypothyroid state. Thyroid hormone is important for the expression of fast myofibrillar proteins in the muscle. In hypothyroidism the expression of these proteins are deficient and there is an increase accumulation of slow myofibrillar proteins. A rapid or abrupt descend in thyroid hormones caused by radioiodine therapy after prolonged hyperthyroidism can lead to local hypothyroid state within the muscle tissue, resulting in CPK elevation and hypothyroid myopathy. Hormone replacement leads to resolution of symptoms and normalization of muscle enzymes serum levels.

Premature Craniosynostosis: A Complication of Thyroid Replacement Therapy

ERIC Educational Resources Information Center

Penfold, James L.; Simpson, Donald A.

1975-01-01

Presented are case studies of 3 children, infancy to 9-years-old, whose premature skull ossification (craniosynostosis) is traced to iatrogenic hyperthyroidism from the administration of excessive amounts of thyroid hormone. (CL)

Subclinical hypothyroidism, mood, and cognition in older adults: a review.

PubMed

Joffe, Russell T; Pearce, Elizabeth N; Hennessey, James V; Ryan, Joseph J; Stern, Robert A

2013-02-01

To perform a critical review of the literature on the mood and cognitive changes associated with subclinical hypothyroidism (SCH), with an emphasis on older adults. To evaluate these data against the Consensus Statement on the management of SCH from the American Association of Clinical Endocrinologists, the American Thyroid Association, and The Endocrine Society. A comprehensive literature review. Subclinical hypothyroidism may be associated with an increased risk of mood and cognitive dysfunction, although the strength of this association and the efficacy of replacement hormone therapy require further investigation. It remains unclear whether SCH leads to significant mood and cognitive impairments in most older patients. More research is required to determine the nature and extent of this association and whether thyroid hormone replacement therapy is appropriate and effective in treating SCH-associated neurobehavioral impairments. Copyright © 2012 John Wiley & Sons, Ltd.

Pituitary function within the first year after traumatic brain injury or subarachnoid haemorrhage.

PubMed

Tölli, A; Borg, J; Bellander, B-M; Johansson, F; Höybye, C

2017-02-01

Reports on long-term variations in pituitary function after traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) diverge. The aim of the current study was to evaluate the prevalence and changes in pituitary function during the first year after moderate and severe TBI and SAH and to explore the relation between pituitary function and injury variables. Adults with moderate and severe TBI or SAH were evaluated at 10 days, 3, 6 and 12 months post-injury/illness. Demographic, clinical, radiological, laboratory, including hormonal data were collected. A total of 91 adults, 56 (15 women/41 men) with TBI and 35 (27 women/8 men) with SAH were included. Perturbations in pituitary function were frequent early after the event but declined during the first year of follow-up. The most frequent deficiency was hypogonadotrope hypogonadism which was seen in approximately 25 % of the patients. Most of the variations were transient and without clinical significance. At 12 months, two patients were on replacement with hydrocortisone, four men on testosterone and one man on replacement with growth hormone. No relations were seen between hormonal levels and injury variables. Perturbations in pituitary function continue to occur during the first year after TBI and SAH, but only a few patients need replacement therapy. Our study could not identify a marker of increased risk of pituitary dysfunction that could guide routine screening. However, data demonstrate the need for systematic follow-up of pituitary function after moderate or severe TBI or SAH.

Sex Hormone Effects on Physical Activity Levels: Why Doesn’t Jane Run as Much as Dick?

PubMed Central

Bowen, Robert S.; Turner, Michael J.; Lightfoot, J. Timothy

2010-01-01

The relationship between physical activity levels and disease rates have become an important health related concern in the developed world. Heart disease, certain cancers, and obesity persist at epidemic rates in the United States and Western Europe. Increased physical activity levels have been shown to reduce the occurrence of many chronic diseases leading to reductions in the burden on the health care system. Activity levels in humans are affected by many cultural and environmental factors, nevertheless current research points to a strong biological input with potential genetic, neurological, and endocrinological origins. Of unique interest, the sex hormones appear to have a very strong influence on activity levels. The current animal literature suggests that females tend to be more active than males due to biological pathways of estrogenic origin. The majority of human epidemiological and anthropological data, on the contrary, suggest women are less active than men in spite of this inherent activity-increasing mechanism. The purpose of this manuscript was to review the current literature regarding the control of physical activity levels by the sex hormones in humans. Using the natural transitional phases of the aging endocrine system, natural periodicity of the menstrual cycle, and pharmacological/hormone replacement therapy as variable experimental stages, some authors have been able to provide some information regarding the existence of an inherent activity-increasing mechanism in humans. In brief, activity levels during life stages prior to and after menopause do not significantly differ, despite the vast changes in sex hormone levels and function. Activity difference throughout a regular menstrual cycle do not appear to influence activity levels in humans either—an effect that is pronounced in the female rodent. The use of hormone replacement therapies provide researchers with more systematic controls over hormone modulation in human subjects; however, this benefit comes with additional confounding variables, mostly due to disease or other states of malfunction. Despite the addition of these confounding factors, minor changes to the activity pattern have been observed in women, especially during the initial administration for the therapy. Observations are yet to be made in male subjects during replacement therapy. In general, some evidence exists suggesting that a biological mechanism—extending from the sex hormones—influences activity in humans. Unfortunately, despite a small number of investigative reports, the paucity of human research investigating how the sex hormones affect activity levels in humans prevents conclusive delineation of the mechanisms involved. Future research in this unique sub-field of endocrinology and exercise science utilizing more appropriate research protocols and effective techniques will provide definitive evidence of such mechanisms. PMID:21142285

Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review.

PubMed

Streed, Carl G; Harfouch, Omar; Marvel, Francoise; Blumenthal, Roger S; Martin, Seth S; Mukherjee, Monica

2017-08-15

Recent reports estimate that 0.6% of adults in the United States, or approximately 1.4 million persons, identify as transgender. Despite gains in rights and media attention, the reality is that transgender persons experience health disparities, and a dearth of research and evidence-based guidelines remains regarding their specific health needs. The lack of research to characterize cardiovascular disease (CVD) and CVD risk factors in transgender populations receiving cross-sex hormone therapy (CSHT) limits appropriate primary and specialty care. As with hormone therapy in cisgender persons (that is, those whose sex assigned at birth aligns with their gender identity), existing research in transgender populations suggests that CVD risk factors are altered by CSHT. Currently, systemic hormone replacement for cisgender adults requires a nuanced discussion based on baseline risk factors and age of administration of exogenous hormones because of concern regarding an increased risk for myocardial infarction and stroke. For transgender adults, CSHT has been associated with the potential for worsening CVD risk factors (such as blood pressure elevation, insulin resistance, and lipid derangements), although these changes have not been associated with increases in morbidity or mortality in transgender men receiving CSHT. For transgender women, CSHT has known thromboembolic risk, and lower-dose transdermal estrogen formulations are preferred over high-dose oral formulations. In addition, many studies of transgender adults focus predominantly on younger persons, limiting the generalizability of CSHT in older transgender adults. The lack of randomized controlled trials comparing various routes and formulations of CSHT, as well as the paucity of prospective cohort studies, limits knowledge of any associations between CSHT and CVD.

Novel AICDA mutation in a case of autosomal recessive hyper-IgM syndrome, growth hormone deficiency and autoimmunity.

PubMed

Fazel, A; Kashef, S; Aleyasin, S; Harsini, S; Karamizadeh, Z; Zoghi, S; Flores, S K; Boztug, K; Rezaei, N

The Hyper-immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders, which have been rarely reported to be associated with growth hormone deficiency (GHD). A nine-year-old girl with recurrent urinary tract infections, diarrhoea, sinopulmonary infections, and failure to thrive since the age of six months had normal CD3+, CD4+, CD8+T lymphocytes, and CD19+B lymphocytes and natural killer (NK) cells, but extremely elevated IgM and significantly decreased IgG and IgA. In view of the patient's short stature, growth hormone evaluation was carried out and growth hormone deficiency established. The patient underwent Ig replacement therapy and received growth hormone therapy in addition to antibiotics and responded well. Furthermore, the patient developed benign cervical lymphadenopathy, as well as elevated erythrocyte sedimentation rate, positive autoantibodies to SSA-Ro, and severely dry eyes, which partially responded to both the punctate occlusion and systemic corticosteroids, at the age of seven years. Sequencing analysis of the exons from activation-induced cytidine deaminase (AICDA) gene revealed that the patient was homozygous for a single T to C transversion at position 455 in exon 4, which replaces a Valine with an Alanine. To our knowledge, this is a new AICDA mutation, which has not been reported previously in HIGM. The mutation analysis could improve diagnosis of HIGM patients and also elaborating on the spectrum of AICDA mutations. Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

Ligand-independent activation of the oestrogen receptor by mutation of a conserved tyrosine.

PubMed Central

White, R; Sjöberg, M; Kalkhoven, E; Parker, M G

1997-01-01

The oestrogen receptor is a member of the nuclear receptor family of transcription factors which, on binding the steroid hormone 17beta-oestradiol, interacts with co-activator proteins and stimulates gene expression. Replacement of a single tyrosine in the hormone-binding domain generated activated forms of the receptor which stimulated transcription in the absence of hormone. This increased activation is related to a decrease in hydrophobicity and a reduction in size of the side chain of the amino acid with which the tyrosine is replaced. Ligand-independent, in common with ligand-dependent transcriptional activation, requires an amphipathic alpha-helix at the C-terminus of the ligand-binding domain which is essential for the interaction of the receptor with a number of potential co-activator proteins. In contrast to the wild-type protein, constitutively active receptors were able to bind both the receptor-interacting protein RIP-140 and the steroid receptor co-activator SRC-1 in a ligand-independent manner, although in the case of SRC-1 this was only evident when the receptors were prebound to DNA. We propose, therefore, that this tyrosine is required to maintain the receptor in a transcriptionally inactive state in the absence of hormone. Modification of this residue may generate a conformational change in the ligand-binding domain of the receptor to form an interacting surface which allows the recruitment of co-activators independent of hormone binding. This suggests that this tyrosine may be a target for a different signalling pathway which forms an alternative mechanism of activating oestrogen receptor-mediated transcription. PMID:9135157

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium

PubMed Central

Ryan, Zachary C.; Ketha, Hemamalini; McNulty, Melissa S.; McGee-Lawrence, Meghan; Craig, Theodore A.; Grande, Joseph P.; Westendorf, Jennifer J.; Singh, Ravinder J.; Kumar, Rajiv

2013-01-01

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost−/−) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion. PMID:23530237

Sclerostin alters serum vitamin D metabolite and fibroblast growth factor 23 concentrations and the urinary excretion of calcium.

PubMed

Ryan, Zachary C; Ketha, Hemamalini; McNulty, Melissa S; McGee-Lawrence, Meghan; Craig, Theodore A; Grande, Joseph P; Westendorf, Jennifer J; Singh, Ravinder J; Kumar, Rajiv

2013-04-09

Inactivating mutations of the SOST (sclerostin) gene are associated with overgrowth and sclerosis of the skeleton. To determine mechanisms by which increased amounts of calcium and phosphorus are accreted to enable enhanced bone mineralization in the absence of sclerostin, we measured concentrations of calciotropic and phosphaturic hormones, and urine and serum calcium and inorganic phosphorus in mice in which the sclerostin (sost) gene was replaced by the β-D-galactosidase (lacZ) gene in the germ line. Knockout (KO) (sost(-/-)) mice had increased bone mineral density and content, increased cortical and trabecular bone thickness, and greater net bone formation as a result of increased osteoblast and decreased osteoclast surfaces compared with wild-type (WT) mice. β-Galactosidase activity was detected in osteocytes of sost KO mice but was undetectable in WT mice. Eight-week-old, male sost KO mice had increased serum 1α,25-dihydroxyvitamin D, decreased 24,25-dihydroxyvitamin D, decreased intact fibroblast growth factor 23, and elevated inorganic phosphorus concentrations compared with age-matched WT mice. 25-Hydroxyvitamin D 1α-hydroxylase cytochrome P450 (cyp27B1) mRNA was increased in kidneys of sost KO mice compared with WT mice. Treatment of cultured proximal tubule cells with mouse recombinant sclerostin decreased cyp27B1 mRNA transcripts. Urinary calcium and renal fractional excretion of calcium were decreased in sost KO mice compared with WT mice. Sost KO and WT mice had similar serum calcium and parathyroid hormone concentrations. The data show that sclerostin not only alters bone mineralization, but also influences mineral metabolism by altering concentrations of hormones that regulate mineral accretion.

MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults.

PubMed

de Carvalho, Gisah Amaral; Paz-Filho, Gilberto; Mesa Junior, Cleo; Graf, Hans

2018-06-01

Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations. Primary hypothyroidism due to chronic autoimmune thyroiditis is largely the most common cause of thyroid hormone deficiency. Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH. The standard treatment of primary and central hypothyroidism is hormone replacement therapy with levothyroxine sodium (LT4). Treatment guidelines of hypothyroidism recommend monotherapy with LT4 due to its efficacy, long-term experience, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life and low cost. Despite being easily treatable with a daily dose of LT4, many patients remain hypothyroid due to malabsorption syndromes, autoimmune gastritis, pancreatic and liver disorders, drug interactions, polymorphisms in DIO2 (iodothyronine deiodinase 2), high fiber diet, and more frequently, non-compliance to LT4 therapy. Compliance to levothyroxine treatment in hypothyroidism is compromised by daily and fasting schedule. Many adult patients remain hypothyroid due to all the above mentioned and many attempts to improve levothyroxine therapy compliance and absorption have been made. © 2018 European Society of Endocrinology.

Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy.

PubMed

Christ, Emanuel R; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

2016-01-21

Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

Hormone replacement therapy and false positive recall in the Million Women Study: patterns of use, hormonal constituents and consistency of effect

PubMed Central

Banks, Emily; Reeves, Gillian; Beral, Valerie; Bull, Diana; Crossley, Barbara; Simmonds, Moya; Hilton, Elizabeth; Bailey, Stephen; Barrett, Nigel; Briers, Peter; English, Ruth; Jackson, Alan; Kutt, Elizabeth; Lavelle, Janet; Rockall, Linda; Wallis, Matthew G; Wilson, Mary; Patnick, Julietta

2006-01-01

Introduction Current and recent users of hormone replacement therapy (HRT) have an increased risk of being recalled to assessment at mammography without breast cancer being diagnosed ('false positive recall'), but there is limited information on the effects of different patterns of HRT use on this. The aim of this study is to investigate in detail the relationship between patterns of use of HRT and false positive recall. Methods A total of 87,967 postmenopausal women aged 50 to 64 years attending routine breast cancer screening at 10 UK National Health Service Breast Screening Units from 1996 to 1998 joined the Million Women Study by completing a questionnaire before screening and were followed for their screening outcome. Results Overall, 399 (0.5%) participants were diagnosed with breast cancer and 2,629 (3.0%) had false positive recall. Compared to never users of HRT, the adjusted relative risk (95% CI) of false positive recall was: 1.62 (1.43–1.83), 1.80 (1.62–2.01) and 0.76 (0.52–1.10) in current users of oestrogen-only HRT, oestrogen-progestagen HRT and tibolone, respectively (p (heterogeneity) < 0.0001); 1.65 (1.43–1.91), 1.49 (1.22–1.81) and 2.11 (1.45–3.07) for current HRT used orally, transdermally or via an implant, respectively (p (heterogeneity) = 0.2); and 1.84 (1.67–2.04) and 1.75 (1.49–2.06) for sequential and continuous oestrogen-progestagen HRT, respectively (p (heterogeneity) = 0.6). The relative risk of false positive recall among current users appeared to increase with increasing time since menopause, but did not vary significantly according to any other factors examined, including duration of use, hormonal constituents, dose, whether single- or two-view screening was used, or the woman's personal characteristics. Conclusion Current use of oestrogen-only and oestrogen-progestagen HRT, but not tibolone, increases the risk of false positive recall at screening. PMID:16417651

IGF-I replacement therapy in children with congenital IGF-I deficiency (Laron syndrome) maintains heart dimension and function.

PubMed

Scheinowitz, Mickey; Feinberg, Micha S; Laron, Zvi

2009-06-01

Untreated patients with congenital growth hormone deficiency (GHD) and IGF-I deficiency are characterized not only by dwarfism but also by acromicria and organomicria, such as the heart. We assessed cardiac dimensions and function in very young patients with Laron syndrome (LS) undergoing IGF-I replacement therapy. Two to seven echocardiographic measurements were performed during IGF-I replacement therapy on male (n=4) and female (n=4) LS -patients, mean+/-SD age of 7.1+/-3.6 years (range 1.6-11.6 years), weight 16.1+/-9.7 kg, and height 89.9+/-18.5 cm. As aged- and gender-matched controls served 44 healthy children, age: 8.7+/-5.5 years, weight: 36.1+/-22.4 kg, and height: 129.7+/-33.1cm. Data of LS patients were normalized to body surface area and compared to the control group as well as nomograms of normal echocardiographic parameters for this age group. Left ventricular diastolic and systolic dimensions (LVDD/ LVSD, mm) and LV mass (gr) were significantly smaller in boys and girls with IGF-I treated LS compared with controls while the shortening fraction (%) and intraventricular septum thickness (mm) were similar. When compared with standard values for this age group, all treated LS patients were within 1 standard deviation of the mean. IGF-I therapy of young patients with Laron syndrome maintain LV dimensions and function within the normal range of aged-matched controls.

Worse renal disease in postmenopausal F2[Dahl S x R]-intercross rats: detection of novel QTLs affecting hypertensive kidney disease.

PubMed

Herrera, Victoria L M; Pasion, Khristine A; Moran, Ann Marie; Ruiz-Opazo, Nelson

2013-01-01

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of ovarian hormones. Furthermore, the detection of distinct GIS-QTLs in postmenopausal intercross female rats suggests that distinct genetic mechanisms underlie hypertensive glomerulosclerosis in premenopausal and postmenopausal states.

Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

PubMed Central

Herrera, Victoria L. M.; Pasion, Khristine A.; Moran, Ann Marie; Ruiz-Opazo, Nelson

2013-01-01

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of ovarian hormones. Furthermore, the detection of distinct GIS-QTLs in postmenopausal intercross female rats suggests that distinct genetic mechanisms underlie hypertensive glomerulosclerosis in premenopausal and postmenopausal states. PMID:23393608

Childhood Thyroid Cancer Treatment (PDQ®)—Patient Version

Cancer.gov

Childhood thyroid cancer treatment usually includes surgery and may include radioactive iodine therapy, targeted therapy, and hormone replacement therapy. Learn more about the diagnosis and treatment of childhood thyroid cancer in this expert-reviewed summary.

Preliminary Hormonal Correlations in Female Patients as a Function of Somatic and Neurological Symptom Clusters: An Exploratory Development of a Multi-Hormonal Map for Bio-Identical Replacement Therapy (MHRT).

PubMed

Braverman, Eric R; Oscar-Berman, Marlene; Kreuk, Florian; Kerner, Mallory; Dushaj, Kristina; Li, Mona; Stratton, Danielle; Trudesdell, Courtney; Blum, Kenneth

2013-12-06

Females develop multiple hormonal alterations and certain genes may be involved in the intensity of subsequent symptoms including both mood and drug seeking. Seventy Four (74) females were included (mean age=60.23, SD=9.21, [43-87]). A medical evaluation was completed with hormone screening using a number of statistical analyses such as Pearson product moment; one way ANOVA and Regression analysis along with a Bonferroni significance correction p<.004. Of 120 correlations performed, significant hormone/domain correlations were as follows: DHEA/Genitourinary (r=.30, p<.05); FSH/Pulmonary (r=-.29, p<.05); Pregnenolone/Genitourinary (r=.40, p<.006) /Immunological (r=.38, p<.008); Testosterone/total endorsed symptoms (r=-0.34, p<.016); TSH/Pulmonary (r=-.33, p<.03) /Gynecological (r=.30, p<.05). Estrone/Musculoskeletal (r=-0.43, p<.012). After a Bonferroni correction (experiment-wise p<.00045) for statistical significance, no hormones remained significance. In the follow-up phase FSH/Neuropsychiatric (r=.56, p<.05) and Musculoskeletal (r=.67, p<.013); DHEA/Immunological (r=.64, p<.04); LH/ Musculoskeletal (r=.59, p<.34); Free Testosterone/Neuropsychiatric (r=.64, p<.019), Musculoskeletal (r=.68, p<.01), and Dermatologic (r=.57, p<.04); Total Testosterone/Immunological (r=.63, p<.028); TSH/Endocrinological (r=-.62, p<.031). Factor analysis of the MQ yielded two factors with eigenvalues > 1.0 (high loadings: first: Pulmonary, GI, Cardiovascular, and Immunological; second: Musculoskeletal, Gynecological, and the three Neurological domains). Both factors had significant correlations: first/pregnenolone (r=.37, p<.019); second/TSH (r=.33, p<.034). An additional factor analysis of hormone level clusters showed significant correlations with various domains. This study highlights the need to test the core biological endocrine hormones associated with females. Future research will focus on the relationship of for example Leptin and the electrophysiology of the brain. We are cautiously proposing a new paradigm shift whereby we replace the old nomenclature of HRT to MHRT.

Suicidal ideation among postmenopausal women on hormone replacement therapy: The Korean National Health and Nutrition Examination Survey (KNHANES V) from 2010 to 2012.

PubMed

Lee, Ji-Yoon; Park, Yong-Kyu; Cho, Kyung-Hwan; Kim, Seon-Mee; Choi, Youn-Seon; Kim, Do-Hoon; Nam, Ga-Eun; Han, Kyung-Do; Kim, Yang-Hyun

2016-01-01

Suicide is a major public health problem around the world. Some studies have found that hormone replacement therapy (HRT) is associated with depression in postmenopausal women. Depression is a well-known risk factor for suicide; therefore, we investigated the relationship between HRT and suicidal ideation in postmenopausal Korean women. We included 2286 postmenopausal women with or without HRT from the Korean National Health and Nutrition Examination Survey 2010-2012. The use and duration of HRT and mental health status, including stress, depressive mood, and suicidal ideation and attempts, were assessed by self-report questionnaires. The proportion of participants with depressive mood and suicidal ideation was higher in the HRT group than the non-HRT group (all p values<0.05). As the duration of HRT increased, the percentage of participants with suicidal ideation increased (p for trend=0.006). After adjusting for all covariates, the odds ratio (95% confidence intervals) for suicidal ideation was 1.742 (1.223-2.482) in the women with HRT, compared to women without HRT. HRT duration longer than 10 years was associated with suicidal ideation (odds ratio=2.089 and 95% confidence intervals=1.069-4.084). The cross-sectional design, a possibility of incorrect answer about menopausal status, and no assessment of the type of HRT are the main limitations of this study. Postmenopausal women receiving HRT, especially for more than 10 years, showed increased suicidal ideation compared with postmenopausal women without HRT. Physicians should pay attention to mood symptoms and suicidal ideation in postmenopausal women with HRT. Copyright © 2015 Elsevier B.V. All rights reserved.

Thyroid hormone is essential for pituitary somatotropes and lactotropes.

PubMed

Stahl, J H; Kendall, S K; Brinkmeier, M L; Greco, T L; Watkins-Chow, D E; Campos-Barros, A; Lloyd, R V; Camper, S A

1999-04-01

Mice homozygous for a disruption in the alpha-subunit essential for TSH, LH, and FSH activity (alphaGsu-/-) exhibit hypothyroidism and hypogonadism similar to that observed in TSH receptor-deficient hypothyroid mice (hyt) and GnRH-deficient hypogonadal mutants (hpg). Although the five major hormone-producing cells of the anterior pituitary are present in alphaGsu-/- mice, the relative proportions of each cell type are altered dramatically. Thyrotropes exhibit hypertrophy and hyperplasia, and somatotropes and lactotropes are underrepresented. The size and number of gonadotropes in alphaGsu mutants are not remarkable in contrast to the hypertrophy characteristic of gonadectomized animals. The reduction in lactotropes is more severe in alphaGsu mutants (13-fold relative to wild-type) than in hyt or hpg mutants (4.5- and 1.5-fold, respectively). In addition, T4 replacement therapy of alphaGsu mutants restores lactotropes to near-normal levels, illustrating the importance of T4, but not alpha-subunit, for lactotrope proliferation and function. T4 replacement is permissive for gonadotrope hypertrophy in alphaGsu mutants, consistent with the role for T4 in the function of gonadotropes. This study reveals the importance of thyroid hormone in developing the appropriate proportions of anterior pituitary cell types.

Is the secret for a successful aging to keep track of cancer pathways?

PubMed

Tramontano, Donatella; De Amicis, Francesca

2018-06-15

A successful aging could be gained by life satisfaction, social functioning, or psychological resources and, definitely, by increasing resistance to diverse age-related pathologies. Nowadays, cancer can be considered an age-related disease since the incidence of most cancers increases with age, rising more rapidly beginning in midlife. Although adults with extended longevity are less likely to develop cancer, it is now emerging that aging and cancer share common molecular links, and thus targeting these mechanisms may be suitable to treat multiple disorders, for the prolonging of healthy aging. At present, one of the cornerstones of antiaging is hormone-replacement therapy to treat diseases associated with a state of age-related sex-hormone deficiency in women and men; however, many studies question the relationship of hormone replacement to cancer recurrence. Here, we discuss signaling and metabolic molecular crossroad linking aging and cancer. This is useful to argue about the current knowledge of prolongevity and druggable targets and to motivate specific intervention strategies that could modify practices of the aging population, activating multiple longevity pathways but keeping track of cancer pathways, thereby potentially preserving health status. © 2018 Wiley Periodicals, Inc.

Motivational Interviewing to Increase Physical Activity in Breast Cancer Survivors

DTIC Science & Technology

2011-05-01

1 cup 9. Over the last month, how often did you eat vegetable soups? Include tomato soup, gazpacho, beef with vegetable soup, minestrone soup, and...than $ 10,000 --2 $10,000-$19,999 --3 $20,000- $ 39,999 Are you currently on hormonal therapy? 12. If YES, what do you take? 1 Tamoxifen __ 4...know 15. Have you received any hormone replacement therapy within the past week (i.e., estrogen)? __ 1 No __ 2 Yes __ 3 Don’t know 16. Have you

Stem cell therapy and its potential role in pituitary disorders.

PubMed

Lara-Velazquez, Montserrat; Akinduro, Oluwaseun O; Reimer, Ronald; Woodmansee, Whitney W; Quinones-Hinojosa, Alfredo

2017-08-01

The pituitary gland is one of the key components of the endocrine system. Congenital or acquired alterations can mediate destruction of cells in the gland leading to hormonal dysfunction. Even though pharmacological treatment for pituitary disorders is available, exogenous hormone replacement is neither curative nor sustainable. Thus, alternative therapies to optimize management and improve quality of life are desired. An alternative modality to re-establish pituitary function is to promote endocrine cell regeneration through stem cells that can be obtained from the pituitary parenchyma or pluripotent cells. Stem cell therapy has been successfully applied to a plethora of other disorders, and is a promising alternative to hormonal supplementation for resumption of normal hormone homeostasis. In this review, we describe the common causes for pituitary deficiencies and the advances in cellular therapy to restore the physiological pituitary function.

SEX DIFFERENCES AND REPRODUCTIVE HORMONE INFLUENCES ON HUMAN ODOR PERCEPTION

PubMed Central

Doty, Richard L.; Cameron, E. Leslie

2009-01-01

The question of whether men and women differ in their ability to smell has been the topic of scientific investigation for over a hundred years. Although conflicting findings abound, most studies suggest that, for at least some odorants, women outperform men on tests of odor detection, identification, discrimination, and memory. Most functional imaging and electrophysiological studies similarly imply that, when sex differences are present, they favor women. In this review we examine what is known about sex-related alterations in human smell function, including influences of the menstrual cycle, pregnancy, gonadectomy, and hormone replacement therapy on a range of olfactory measures. We conclude that the relationship between reproductive hormones and human olfactory function is complex and that simple associations between circulating levels of gonadal hormones and measures of olfactory function are rarely present. PMID:19272398

Obesity and Breast Cancer.

PubMed

Fortner, Renée T; Katzke, Verena; Kühn, Tilman; Kaaks, Rudolf

The relationship between adiposity and breast cancer risk and prognosis is complex, with associations that differ depending on when body size is assessed (e.g., pre- vs. postmenopausal obesity) and when breast cancer is diagnosed (i.e., pre- vs. postmenopausal disease). Further, the impact of obesity on risk differs by tumor hormone receptor status (e.g., estrogen (ER) and progesterone (PR) receptor) and, among postmenopausal women, use of exogenous hormones (i.e., hormone replacement therapy (HRT)). In the context of these complexities, this review focuses on associations between childhood and adolescent adiposity, general adiposity, weight changes (i.e., loss and gain), abdominal adiposity, and breast cancer risk and survival. Finally, we discuss potential mechanisms linking adiposity to breast cancer.

Effect of Ovarian Hormone Therapy on Cognition in the Aged Female Rhesus Macaque.

PubMed

Kohama, Steven G; Renner, Lauren; Landauer, Noelle; Weiss, Alison R; Urbanski, Henryk F; Park, Byung; Voytko, Mary Lou; Neuringer, Martha

2016-10-05

Studies of the effect of hormone therapy on cognitive function in menopausal women have been equivocal, in part due to differences in the type and timing of hormone treatment. Here we cognitively tested aged female rhesus macaques on (1) the delayed response task of spatial working memory, (2) a visuospatial attention task that measured spatially and temporally cued reaction times, and (3) a simple reaction time task as a control for motor speed. After task acquisition, animals were ovariectomized (OVX). Their performance was compared with intact controls for 2 months, at which time no group differences were found. The OVX animals were then assigned to treatment with either a subcutaneous sham implant (OVX), 17-β estradiol (E) implant (OVX+E) or E implant plus cyclic oral progesterone (OVX+EP). All groups were then tested repeatedly over 12 months. The OVX+E animals performed significantly better on the delayed response task than all of the other groups for much of the 12 month testing period. The OVX+EP animals also showed improved performance in the delayed response task, but only at 30 s delays and with performance levels below that of OVX+E animals. The OVX+E animals also performed significantly better in the visuospatial attention task, particularly in the most challenging invalid cue condition; this difference also was maintained across the 12 month testing period. Simple reaction time was not affected by hormonal manipulation. These data demonstrate that chronic, continuous administration of E can exert multiple beneficial cognitive effects in aged, OVX rhesus macaque females. Hormone therapy after menopause is controversial. We tested the effects of hormone replacement in aged rhesus macaques, soon after surgically-induced menopause [ovariectomy (OVX)], on tests of memory and attention. Untreated ovarian-intact and OVX animals were compared with OVX animals receiving estradiol (E) alone or E with progesterone (P). E was administered in a continuous fashion via subcutaneous implant, whereas P was administered orally in a cyclic fashion. On both tests, E-treated animals performed better than the other 3 experimental groups across 1 year of treatment. Thus, in this monkey model, chronic E administered soon after the loss of ovarian hormones had long-term benefits for cognitive function. Copyright © 2016 the authors 0270-6474/16/3610416-09$15.00/0.

How Is Hypoparathyroidism Treated?

MedlinePlus

... treatment of hypoparathyroidism. Journal of Clinical Endocrinology and Metabolism, 83 , 3480-3486. Winer, K. K., Zhang, B., Shrader, J. A., Peterson, D., Smith, M., Albert, P. S., et al. (2012). Synthetic human parathyroid hormone 1-34 replacement therapy: A randomized ...

Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

PubMed Central

Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

2013-01-01

Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID:23794460

THYROID HORMONE REPLACEMENT REDUCES THE RISK OF CARDIOVASCULAR DISEASES IN DIABETIC NEPHROPATHY PATIENTS WITH SUBCLINICAL HYPOTHYROIDISM.

PubMed

Seo, Changhwan; Kim, Seonghun; Lee, Misol; Cha, Min-Uk; Kim, Hyoungnae; Park, Seohyun; Yun, Hae-Ryong; Jhee, Jong Hyun; Kee, Youn Kyung; Han, Seung Hyeok; Yoo, Tae-Hyun; Kang, Shin-Wook; Park, Jung Tak

2018-03-01

Patients with diabetic nephropathy (DMN) have an increased risk of cardiovascular disease (CVD). However, strategies to reduce this risk are limited. Thyroid hormone replacement therapy (THRT) in patients with hypothyroidism has been shown to reduce several surrogate markers of CVD. Therefore, we performed a study to determine if THRT would reduce CVD risk in patients with subclinical hypothyroidism (SCH) and DMN. This was a retrospective, nonrandomized study of patients with type 2 diabetes, DMN, and SCH. Those with known thyroid dysfunction or taking THRT at baseline were excluded. Patients receiving THRT for at least 180 days were included in the THRT group, while the remaining patients were assigned to the non-THRT group. The primary outcome was CVD events, which included coronary syndrome, cerebrovascular events, and peripheral artery diseases. Among the 257 patients, 83 (32.3%) were in the THRT group. The mean ages were 62.7 ± 12.3 and 66.8 ± 12.4 years in the THRT and non-THRT groups, respectively. The corresponding numbers of male patients were 32 (40.0%) and 94 (53.1%). During a mean follow-up of 38.0 ± 29.2 months, 98 CVD events were observed. Acute coronary syndrome and cerebrovascular event prevalence rates were lower in the THRT group than the non-THRT group, but there was no difference for peripheral artery diseases. Multivariate Cox analysis revealed that THRT was independently associated with a decreased CVD event risk. THRT may decrease the risk of CVD in DMN patients with SCH. Randomized trials are needed to verify this finding. CV = cardiovascular DMN = diabetic nephropathy eGFR = estimated glomerular filtration rate fT4 = free thyroxine HbA1c = glycosylated hemoglobin HR = hazard ratio hs-CRP = high-sensitivity C-reactive protein LDL-C = low-density lipoprotein cholesterol SCH = subclinical hypothyroidism T2DM = type 2 diabetes THRT = thyroid hormone replacement therapy TSH = thyroid-stimulating hormone.

Trends in organ donor management: 2002 to 2012.

PubMed

Callahan, Devon S; Kim, Dennis; Bricker, Scott; Neville, Angela; Putnam, Brant; Smith, Jennifer; Bongard, Frederic; Plurad, David

2014-10-01

Refinements in donor management have resulted in increased numbers and quality of grafts after neurologic death. We hypothesize that the increased use of hormone replacement therapy (HRT) has been accompanied by improved outcomes over time. Using the Organ Procurement and Transplant Network donor database, all brain-dead donors procured from July 1, 2001 to June 30, 2012 were studied. Hormone replacement therapy was identified by an infusion of thyroid hormone. An expanded criteria donor was defined as age 60 years or older. Incidence of HRT administration and number of donors and organs recovered were calculated. Using the Organ Procurement and Transplant Network thoracic recipient database transplant list, wait times were examined. There were 74,180 brain-dead donors studied. Hormone replacement therapy use increased substantially from 25.6% to 72.3% of donors. However, mean number of organs procured per donor remained static (3.51 to 3.50; p = 0.083), and the rate of high-yield donors decreased (46.4% to 43.1%; p < 0.001). Incidence of traumatic brain injury donors decreased (42.1% to 33.9%; p < 0.001) relative to an increased number of expanded criteria donors (22.1% to 26%). Despite this, there has been an increase in the raw number of donors (20,558 to 24,308; p < 0.001) and organs (5,857 to 6,945; p < 0.001). There has been an increase in organs per traumatic brain injury donor (4.02 to 4.12; p = 0.002) and a decrease in days on the waiting list (462.2 to 170.4 days; p < 0.001) for a thoracic transplant recipient. The marked increase in the use of HRT in the management of brain-dead donors has been accompanied by increased organ availability overall. Potential mechanisms might include successful conversion of previously unacceptable donors and improved recovery in certain subsets of donors. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Hypothyroidism: challenges when treating older adults.

PubMed

Pearson, Tamera

2013-01-01

Hypothyroidism frequently affects older adults' general sense of health, their cognitive abilities, and quality of life. Management decisions regarding when to start treatment and at what dosage to begin medication are influenced by both laboratory values and patient symptoms. Although specific guidelines regarding management of hypothyroidism in older adults do not exist, general recommendations include initiating hormone replacement with levothyroxine (Levoxyl(®), Synthroid(®), and others) at 12.5 mcg to 25 mcg and titrating the dose slowly based on response at 6-week intervals. Multiple medications and certain foods can interact with levothyroxine; therefore, the best dosage time is when a person is fasting or 4 hours postprandial. Using a consistent brand-name drug for hormone replacement with levothyroxine is important due to variations in the active ingredient in generic formulations. Providers need to be aware of the prevalence of hypothyroidism and management issues when caring for older adults. Copyright 2013, SLACK Incorporated.

Interrelationship Between Alcohol Intake and Endogenous Sex-Steroid Hormones on Diabetes Risk in Postmenopausal Women.

PubMed

Rohwer, Rachelle D; Liu, Simin; You, Nai-Chieh; Buring, Julie E; Manson, JoAnn E; Song, Yiqing

2015-01-01

We examined whether circulating concentrations of sex hormones, including estradiol, testosterone, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS), were associated with alcohol intake or mediated the alcohol-type 2 diabetes (T2D) association. Among women not using hormone replacement therapy and free of baseline cardiovascular disease, cancer, and diabetes in the Women's Health Study, 359 incident cases of T2D and 359 matched controls were chosen during 10 years of follow-up. Frequent alcohol intake (≥1 drink/day) was positively and significantly associated with higher plasma estradiol concentrations in an age-adjusted model (β = 0.14, 95% confidence interval [CI], 0.03, 0.26), compared to rarely/never alcohol intake. After adjusting for additional known covariates, this alcohol-estradiol association remained significant (β = 0.19, 95% CI, 0.07, 0.30). Testosterone (β = 0.13, 95% CI, -0.05, 0.31), SHBG (β = 0.07, 95% CI, -0.07, 0.20), and DHEAS (β = 0.14, 95% CI, -0.04, 0.31) showed positive associations without statistical significance. Estradiol alone or in combination with SHBG appeared to influence the observed protective association between frequent alcohol consumption and T2D risk, with a 12%-21% reduction in odds ratio in the multivariate-adjusted models. Our cross-sectional analysis showed positive associations between alcohol intake and endogenous estradiol concentrations. Our prospective data suggested that baseline concentrations of estradiol, with or without SHBG, might influence the alcohol-T2D association in postmenopausal women.

Simulation of Post-Thyroidectomy Treatment Alternatives for Triiodothyronine or Thyroxine Replacement in Pediatric Thyroid Cancer Patients

PubMed Central

Ben-Shachar, Rotem; Huang, Stephen A.; DiStefano, Joseph J.

2012-01-01

Background As in adults, thyroidectomy in pediatric patients with differentiated thyroid cancer is often followed by 131I remnant ablation. A standard protocol is to give normalizing oral thyroxine (T4) or triiodothyronine (T3) after surgery and then withdraw it for 2 to 6 weeks. Thyroid remnants or metastases are treated most effectively when serum thyrotropin (TSH) is high, but prolonged withdrawals should be avoided to minimize hypothyroid morbidity. Methods A published feedback control system model of adult human thyroid hormone regulation was modified for children using pediatric T4 kinetic data. The child model was developed from data for patients ranging from 3 to 9 years old. We simulated a range of T4 and T3 replacement protocols for children, exploring alternative regimens for minimizing the withdrawal period, while maintaining normal or suppressed TSH during replacement. The results are presented with the intent of providing a quantitative basis to guide further studies of pediatric treatment options. Replacement was simulated for up to 3 weeks post-thyroidectomy, followed by various withdrawal periods. T4 vs. T3 replacement, remnant size, dose size, and dose frequency were tested for effects on the time for TSH to reach 25 mU/L (withdrawal period). Results For both T3 and T4 replacement, higher doses were associated with longer withdrawal periods. T3 replacement yielded shorter withdrawal periods than T4 replacement (up to 3.5 days versus 7–10 days). Higher than normal serum T3 concentrations were required to normalize or suppress TSH during T3 monotherapy, but not T4 monotherapy. Larger remnant sizes resulted in longer withdrawal periods if T4 replacement was used, but had little effect for T3 replacement. Conclusions T3 replacement yielded withdrawal periods about half those for T4 replacement. Higher than normal hormone levels under T3 monotherapy can be partially alleviated by more frequent, smaller doses (e.g., twice a day). LT4 may be the preferred option for most children, given the convenience of single daily dosing and familiarity of pediatric endocrinologists with its administration. Remnant effects on withdrawal period highlight the importance of minimizing remnant size. PMID:22578300

GCC signaling in colorectal cancer: Is colorectal cancer a paracrine deficiency syndrome?

PubMed Central

Li, P.; Lin, J.E.; Marszlowicz, G.P.; Valentino, M.A.; Chang, C.; Schulz, S.; Pitari, G.M.; Waldman, S.A.

2011-01-01

Summary Guanylyl cyclase C (GCC) is the receptor expressed by intestinal cells for the paracrine hormones guanylin and uroguanylin that coordinate mucosal homeostasis and its silencing contributes to intestinal transformation. It orchestrates proliferative and metabolic circuits by limiting the cell cycle and programming metabolic transitions central to regeneration along the crypt-villus axis. Mice deficient in GCC are more susceptible to colon cancer induced by germline mutations or carcinogens. Moreover, guanylin and uroguanylin are the most commonly lost gene products in colon cancer. The role of GCC as a tumor suppressor and the universal loss of its hormones in transformation suggest a paradigm in which colorectal cancer is a disease of paracrine hormone insufficiency. Indeed, GCC signaling reverses the tumorigenic phenotype of human colon cancer cells by regulating proliferation and metabolism. These data suggest a pathophysiological hypothesis in which GCC is a tumor suppressor coordinating proliferative homeostasis whose silencing through hormone loss initiates transformation. The correlative therapeutic hypothesis suggests that colorectal cancer is a disease of hormone insufficiency that can be prevented or treated by oral hormone replacement therapy employing GCC ligands. PMID:19771320

Sex hormones and skeletal muscle weakness.

PubMed

Sipilä, Sarianna; Narici, Marco; Kjaer, Michael; Pöllänen, Eija; Atkinson, Ross A; Hansen, Mette; Kovanen, Vuokko

2013-06-01

Human ageing is accompanied with deterioration in endocrine functions the most notable and well characterized of which being the decrease in the production of sex hormones. Current research literature suggests that low sex hormone concentration may be among the key mechanism for sarcopenia and muscle weakness. Within the European large scale MYOAGE project, the role of sex hormones, estrogens and testosterone, in causing the aging-related loss of muscle mass and function was further investigated. Hormone replacement therapy (HRT) in women is shown to diminish age-associated muscle loss, loss in fast muscle function (power), and accumulation of fat in skeletal muscle. Further HRT raises the protein synthesis rate in skeletal muscle after resistance training, and has an anabolic effect upon connective tissue in both skeletal muscle and tendon, which influences matrix structure and mechanical properties. HRT influences gene expression in e.g. cytoskeletal and cell-matrix proteins, has a stimulating effect upon IGF-I, and a role in IL-6 and adipokine regulation. Despite low circulating steroid-hormone level, postmenopausal women have a high local concentration of steroidogenic enzymes in skeletal muscle.

Association of Hormone-Related Characteristics and Breast Cancer Risk by Estrogen Receptor/Progesterone Receptor Status in the Shanghai Breast Cancer Study

PubMed Central

Bao, Ping-Ping; Shu, Xiao Ou; Gao, Yu-Tang; Zheng, Ying; Cai, Hui; Deming, Sandra L.; Ruan, Zhi-Xian; Gu, Kai; Lu, Wei; Zheng, Wei

2011-01-01

Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER−)/PR-negative (PR−) cases, 301 ER+/PR− cases, 254 ER−/PR+ cases, and 3,474 controls aged 20–70 years in Shanghai, China (phase I, 1996–1998; phase II, 2002–2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)2) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER−/PR− subtype (for parity, Pheterogeneity = 0.02; for BMI, Pheterogeneity < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR− subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR− tumors and ER−/PR+ tumors. PMID:21768404

Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer.

PubMed

Blomain, Erik S; Merlino, Dante J; Pattison, Amanda M; Snook, Adam E; Waldman, Scott A

2016-09-01

Obesity has emerged as a principal cause of mortality worldwide, reflecting comorbidities including cancer risk, particularly in colorectum. Although this relationship is established epidemiologically, molecular mechanisms linking colorectal cancer and obesity continue to be refined. Guanylyl cyclase C (GUCY2C), a membrane-bound guanylyl cyclase expressed in intestinal epithelial cells, binds the paracrine hormones guanylin and uroguanylin, inducing cGMP signaling in colorectum and small intestine, respectively. Guanylin is the most commonly lost gene product in sporadic colorectal cancer, and its universal loss early in transformation silences GUCY2C, a tumor suppressor, disrupting epithelial homeostasis underlying tumorigenesis. In small intestine, eating induces endocrine secretion of uroguanylin, the afferent limb of a novel gut-brain axis that activates hypothalamic GUCY2C-cGMP signaling mediating satiety opposing obesity. Recent studies revealed that diet-induced obesity suppressed guanylin and uroguanylin expression in mice and humans. Hormone loss reflects reversible calorie-induced endoplasmic reticulum stress and the associated unfolded protein response, rather than the endocrine, adipokine, or inflammatory milieu of obesity. Loss of intestinal uroguanylin secretion silences the hypothalamic GUCY2C endocrine axis, creating a feed-forward loop contributing to hyperphagia in obesity. Importantly, calorie-induced guanylin loss silences the GUCY2C-cGMP paracrine axis underlying obesity-induced epithelial dysfunction and colorectal tumorigenesis. Indeed, genetically enforced guanylin replacement eliminated diet-induced intestinal tumorigenesis in mice. Taken together, these observations suggest that GUCY2C hormone axes are at the intersection of obesity and colorectal cancer. Moreover, they suggest that hormone replacement that restores GUCY2C signaling may be a novel therapeutic paradigm to prevent both hyperphagia and intestinal tumorigenesis in obesity. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Guanylyl Cyclase C Hormone Axis at the Intersection of Obesity and Colorectal Cancer

PubMed Central

Blomain, Erik S.; Merlino, Dante J.; Pattison, Amanda M.; Snook, Adam E.

2016-01-01

Obesity has emerged as a principal cause of mortality worldwide, reflecting comorbidities including cancer risk, particularly in colorectum. Although this relationship is established epidemiologically, molecular mechanisms linking colorectal cancer and obesity continue to be refined. Guanylyl cyclase C (GUCY2C), a membrane-bound guanylyl cyclase expressed in intestinal epithelial cells, binds the paracrine hormones guanylin and uroguanylin, inducing cGMP signaling in colorectum and small intestine, respectively. Guanylin is the most commonly lost gene product in sporadic colorectal cancer, and its universal loss early in transformation silences GUCY2C, a tumor suppressor, disrupting epithelial homeostasis underlying tumorigenesis. In small intestine, eating induces endocrine secretion of uroguanylin, the afferent limb of a novel gut-brain axis that activates hypothalamic GUCY2C-cGMP signaling mediating satiety opposing obesity. Recent studies revealed that diet-induced obesity suppressed guanylin and uroguanylin expression in mice and humans. Hormone loss reflects reversible calorie-induced endoplasmic reticulum stress and the associated unfolded protein response, rather than the endocrine, adipokine, or inflammatory milieu of obesity. Loss of intestinal uroguanylin secretion silences the hypothalamic GUCY2C endocrine axis, creating a feed-forward loop contributing to hyperphagia in obesity. Importantly, calorie-induced guanylin loss silences the GUCY2C-cGMP paracrine axis underlying obesity-induced epithelial dysfunction and colorectal tumorigenesis. Indeed, genetically enforced guanylin replacement eliminated diet-induced intestinal tumorigenesis in mice. Taken together, these observations suggest that GUCY2C hormone axes are at the intersection of obesity and colorectal cancer. Moreover, they suggest that hormone replacement that restores GUCY2C signaling may be a novel therapeutic paradigm to prevent both hyperphagia and intestinal tumorigenesis in obesity. PMID:27251363

Bioidentical Hormones, Menopausal Women, and the Lure of the “Natural” in U.S. Anti-Aging Medicine

PubMed Central

Fishman, Jennifer R.; Flatt, Michael A.; Settersten, Richard A.

2015-01-01

In 2002, the Women’s Health Initiative, a large-scale study of the safety of hormone replacement therapy (HRT) for women conducted in the United States, released results suggesting that use of postmenopausal HRT increased women’s risks of stroke and breast cancer. In the years that followed, as rates of HRT prescription fell, another hormonal therapy rose in its wake: bioidentical hormone replacement therapy (BHRT). Anti-aging clinicians, the primary prescribers of BHRT, tout it as a safe and effective alternative to treat menopausal symptoms and, moreover, as a preventative therapy for age-related diseases and ailments. Through in-depth interviews with 31 U.S.-based anti-aging clinicians and 25 female anti-aging patients, we analyze attitudes towards BHRT. We illustrate how these attitudes reveal broader contemporary values, discourses, and discomforts with menopause, aging, and biomedicine. The attraction to and promise of BHRT is rooted in the idea that it is a “natural” therapy. BHRT is given both biomedical and embodied legitimacy by clinicians and patients because of its purported ability to become part of the body’s “natural” processes. The normative assumption that “natural” is inherently “good” not only places BHRT beyond reproach, but transforms its use into a health benefit. The clinical approach of anti-aging providers also plays a role by validating patients’ embodied experiences and offering a “holistic” solution to their symptoms, which anti-aging patients see as a striking contrast to their experiences with conventional biomedical health care. The perceived virtues of BHRT shed light on the rhetoric of anti-aging medicine and a deeply complicated relationship between conventional biomedicine, hormonal technologies, and women’s bodies. PMID:25795991

Hormone replacement therapy is not associated with an increased risk of leukemia (United States).

PubMed

Ross, Julie A; Sinner, Penny J; Blair, Cindy K; Cerhan, James R; Folsom, Aaron R

2005-06-01

Recent studies have reported an increased risk of certain cancers associated with hormone replacement therapy (HRT), possibly due to stimulation of estrogen receptors. Since estrogen receptors are expressed on certain hematopoietic cells, it is possible that HRT use may also increase the risk of leukemia. A cohort of 37,172 post-menopausal Iowa women ages 55-69 years with no history of prior cancer was linked annually to the population-based state cancer registry through 2001. In addition to other self-reported cancer risk factors, participants were asked about current and former use of HRT in 1986 and on four subsequent follow-up questionnaires. A total of 201 cases of leukemia were identified over 16 years of follow-up including 74 acute myeloid leukemias (AMLs) and 87 chronic lymphocytic leukemias (CLLs). Compared to never users of HRT at study baseline, current [multivariate relative risk (RR), 1.09; 95% confidence interval (CI) 0.70-1.71)] and former users (RR=0.82, 95% CI=0.59-1.15) were at no increased risk of developing leukemia. For AML, current users also had no increased risk (RR=0.83, 95% CI=0.37-1.84) and there was a suggestion that former users had a slightly decreased risk (RR=0.66, 95% CI=0.37-1.17). For CLL, all RRs were around unity. We conclude that HRT is unlikely to be an appreciable risk factor for leukemia.

A randomised, double-blind trial comparing raloxifene HCl and continuous combined hormone replacement therapy in postmenopausal women: effects on compliance and quality of life.

PubMed

Voss, Simon; Quail, Deborah; Dawson, Alison; Bäckström, Tjorbörn; Aguas, Fernanda; Erenus, Mithat; The, Hok Sien; Bonnar, John; De Geyter, Christian; Hunter, Myra; Nickelsen, Thomas

2002-08-01

To compare continuous combined hormone replacement therapy (ccHRT) and raloxifene with respect to compliance and quality of life, which were predefined secondary endpoints of a large, prospective study designed to investigate the uterine effects of both treatments. Double-blind, randomised controlled trial of six-month duration. One hundred and twenty-nine gynaecology hospital departments, clinics or practices specialised in women's healthcare, located in Europe, South Africa and Israel. Healthy postmenopausal women (n = 1008). Changes in quality of life using the Women's Health Questionnaire (WHQ) and compliance using a compliance questionnaire and pill count. Adverse event and early discontinuation rates and satisfaction with treatment using a visual analogue scale (VAS). Women taking raloxifene reported greater satisfaction with their treatment as assessed on the VAS (P = 0.004), and a lower proportion, as compared with ccHRT, reported being worried by the treatment (9.6% vs 20.2%, P < 0.01). Women taking ccHRT reported greater deterioration in scores from the WHQ for depressed mood and menstrual symptoms than those taking raloxifene (P < 0.01). For memory, vasomotor symptoms and sexual behaviour, the ccHRT group reported significantly greater mean improvements (P < 0.05). Over half (58.8%) of those taking raloxifene noticed no effect, 37.7% felt better and 3.4% felt worse as measured using the compliance questionnaire. Fifty percent of the women taking ccHRT felt better, 37.8% noticed no effect but over 10% felt worse. More women on raloxifene (94.6%) than on ccHRT (85.9%) reported that they were taking their double-blinded medication regularly (P < 0.01). A lower rate of adverse event-related discontinuations, the lack of negative effects on quality of life and a smaller proportion of women being worried by the drug treatment were associated with higher treatment satisfaction and better compliance in postmenopausal women taking ccHRT or raloxifene.

Excess fat in the abdomen but not general obesity is associated with poorer metabolic and cardiovascular health in premenopausal and postmenopausal Asian women.

PubMed

Goh, Victor Hng Hang; Hart, William George

2018-01-01

To examine the associations of various metabolites and hormones and hormone replacement therapy (HRT) with obesity. This is a cross-sectional study of 1326 Singaporean women. A DXA-derived percent body fat (PBF) of ≥35% and percent abdominal fat (PAbdF) of >21.8% were used, respectively, to define women with general (GOb) and abdominal (AbdOb) obesity. Higher levels of insulin and glucose, lower levels of HDL, higher levels of TC/HDL and HOMA values, and different levels of some hormones were noted only in the women with abdominal, and not general obesity. The incidence of general and abdominal obesity was higher in postmenopausal women with or without HRT, except that those who were on conjugated estradiol-only HRT had no increase in the incidence of general obesity compared with premenopausal women. Abdominal obesity is associated with insulin resistance and with higher risks of metabolic syndrome and cardiovascular diseases, whereas general obesity is not. Abdominal obesity may predispose to a higher risk of diabetes. The onset of the menopause tends to increase the incidence of general and abdominal obesity, except that postmenopausal women on conjugated estradiol HRT appear to be relatively protected from general obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

[Psycho-medical care of transsexuals in Spain in the era of depathologization of transsexualism as a mental disorder. An overall review].

PubMed

Wittich, Regina-Michaela

2013-12-01

To identify the strengths and weaknesses of Spanish healthcare protocols for transsexual persons and to compare them to current international protocols. To review the current status as regards transsexuality etiology and prevalence. To suggest measures to optimize care to achieve a significant improvement, including options for saving financial resources. A comparison of the contents of texts related to transsexualism in the ICD-10, DSM-IV, and guidelines of the Spanish gender units with international standards of care for transgender persons and the last draft version of the DSM-5. Systematic revision of the literature related to the etiology and prevalence of transsexualism. Significant discrepancies have been found as regards the minimum time period for diagnosis, access to hormone replacement therapy and to genital surgery, and the requirement of the so-called real-life experience. Impact of sex hormones on the etiology of transsexualism and underestimation of its prevalence was confirmed. The access to hormonal and surgical treatment requires a profound review, and decentralization of transsexual care is recommended, because all university hospitals haves psychiatrists, clinical psychologists, and endocrinologists available. Although gender reassignment surgery also requires plastic surgery specialists, plastic surgeons currently receive training in this field. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

A critical synopsis: Continuous growth of proximal tubular kidney epithelial cells in hormone-supplemented serum-free medium

NASA Technical Reports Server (NTRS)

Chuman, L. M.; FINE; COHEN; Saier, M. H.

1985-01-01

The kidney forms urine and reabsorbs electrolytes and water. Kidney cell lines and hormone supplemented serum free medium were used for growth. The hormones were insulin, transferrin, vasopressin, cholesterol, prostaglandins, hydrocortisone, and triidothyronine. Epithelial cell lines are polar and form hemicysts. The Madin-Darby canine kidney(MDCK) cell line used is distal tubulelike. LLC-PK sub 1 cells are derived from pig kidneys and have the properties of different kidney segments. The LLC-PK sub 1 cells with proximal tubule properties were maintained in hormone-supplemented serum free medium. Seven factors (the aforementioned homrones and selenium) were needed for growth. Hormone-defined medium supported LLC-PK sub 1 cell growth, allowed transport (as seen by hemicyst formation), and influenced cell morphology. Vasopressin (used for growth and morphology) could be partially replaced by isobutylmethylxanthine or dibutyryl cAMP. The defined medium was used to isolate rabbit proximal tubule kidney epithelial cells free of fibroblasts.

[Combined l-thyroxine and l-triiodothyronine replacement therapy in congenital hypothyroidism].

PubMed

Péter, Ferenc; Muzsnai, Agota

2013-05-12

L-thyroxine replacement therapy is the treatment of choice for hypothyroidism. Recently, several studies suggested to complete it with l-triiodothyronine in acquired hypothyroidism. To study the role of combined l-thyroxine and l-triiodothyronine therapy in special cases with congenital hypothyroidism. Data of 16 patients (age: 11.9 ± 6.3 years; mean ± SD) are presented who had high serum free thyroxine values or even above the upper limit of reference range (21.16 ± 2.5 pmol/l) together with nonsuppressed TSH levels (15.7 ± 5.7 mIU/l), and therefore received l-triiodothyronine in completion (0.18 ± 0.09 μg/kg) once a day. The combined replacement therapy resulted in a rapid improvement of the hormone parameters (TSH: 4.2 ± 3.15 mIU/l; free thyroxine: 16.55 ± 2.4 and free triiodothyronine: 7.4 ± 1.8 pmol/l). The efficiency of this combined therapy proved to be more evident (TSH: 4.33 ± 3.2 mIU/l; free thyroxine: 16.85 ± 3.1 and free triiodothyronine: 6.4 ± 0.85 pmol/l) in 10 patients treated for a longer period of time (duration of treatment: 2.9 ± 2.0 years). The dose of thyroxine substitution decreased from 2.6 ± 0.9 to 2.18 ± 0.6 μg/kg/day), the ratio of these hormones was between 5:1 and 19:1 and the quotient of free fractions was normalized (3.8 ± 0.4→2.6 ± 0.3) during the replacement therapy. According to the observation of the authors a serious disturbance of feed-back mechanism may develop in some (>5%) children with congenital hypothyroidism (increased TSH release despite elevated free thyroxine level) after normal function of the feed-back system for years. Hormone parameters of these patients improve, then become normal on combined therapy supporting the rationale for this treatment method.

Managing Depression during the Menopausal Transition

ERIC Educational Resources Information Center

Pearson, Quinn M.

2010-01-01

The menopausal transition is associated with both first onset of depression and recurrent depression. Risk factors include vasomotor symptoms, a history of premenstrual dysphoria, postpartum depression, major depression, and sleep disturbances. Hormone replacement therapy, complementary and alternative medicine approaches, and counseling…

Female Pattern Hair Loss

MedlinePlus

... susceptible women, but is most commonly seen after menopause. In female pattern hair loss some excess loss of hair is noted, but ... all. Spironolactone pills help many women, especially whose hair loss starts before menopause but takes many months. Hormone replacement pills, such ...

A national probability survey of American Medical Association gynecologists and primary care physicians concerning menopause.

PubMed

Singh, Betsy; Liu, Xiao-Dong; Der-Martirosian, Claudia; Hardy, Mary; Singh, Vijay; Shepard, Neil; Gandhi, Sonal; Khorsan, Raheleh

2005-09-01

This survey intended to clarify physicians' understanding of the issues surrounding women, menopause, alternative medicine, and drug therapy for the treatment of menopause. This study was designed as a national probability sample survey of primary care physicians and gynecologists nationwide. Its focus was to identify major concerns and issues identified by patients about menopause and perceived communication with effectiveness how to communicate with their patients. Physicians were also asked to rate their comfort level in recommending the use of herbal remedies and which herbal remedy they felt comfortable recommending to interested patients. Data indicated that a patient's complaint about menopausal symptoms was the most common factor leading to discussion of menopausal issues with physicians (91%) and that the primary concern to the patient was management of menopausal symptoms. Other factors were controversies about hormone replacement therapy, long-term health implications of menopause, and hormone replacement therapy. Eighty percent of the physician found confusing messages with regard to menopause to be the most challenging aspect in patient communication. The second most challenging issue is "inconclusive data about hormone replacement therapy" (56%). Seventy-six percent of the physicians found "showing sympathy" to be the most important factor for the physicians to communicate effectively with patients, whereas "being honest and open" was the most important patient attitude cited for the same purpose. When it comes to herbal therapy for menopause symptom control, only 4% of the physicians indicated that none of their patients take any remedies. Only 18% were not very comfortable in discussing or recommending herbal therapies, whereas the rest ranged from fairly comfortable to completely comfortable. This study has provided data with regard to physician understanding of menopause treatment options and their primary interaction with patients on this issue. More in-depth studies concerning efficacy and/or side effects of each available treatment will be the relevant next step, given the controversies about both hormone replacement therapy and alternative therapies. The relative efficacy, safety, and cost-effectiveness of different treatments should also be put into the context of both clinical diagnosis and physicians' clinical judgment. Attention to comments by physicians and patients with regard to communication may produce better information exchange and trust between patient and physician.

Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

PubMed

Limón-Morales, Ofelia; Soria-Fregozo, Cesar; Arteaga-Silva, Marcela; González, Marisela Hernández; Vázquez-Palacios, Gonzalo; Bonilla-Jaime, Herlinda

2014-11-01

Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular genetics of growth hormone deficient children: correlation with auxology and response to first year of growth hormone therapy.

PubMed

Khadilkar, Vaman; Phadke, Nikhil; Khatod, Kavita; Ekbote, Veena; Gupte, Supriya Phanse; Nadar, Ruchi; Khadilkar, Anuradha

2017-05-24

With the paucity of available literature correlating genetic mutation and response to treatment, we aimed to study the genetic makeup of children with growth hormone (GH) deficiency in Western India and correlate the mutation with auxology and response to GH treatment at end of 1 year. Fifty-three (31 boys and 22 girls) children with severe short stature (height for age z-score <-3) and failed GH stimulation test were studied. Those having concomitant thyroid hormone or cortisol deficiencies were appropriately replaced prior to starting GH treatment. A magnetic resonance imaging (MRI) brain scan was done in all. Genetic mutations were tested for in GH1, GHRH, LHX3, LHX4 and PROP1, POU1F1 and HESX1 genes. Mean age at presentation was 9.7±5.1 years. Thirty-seven children (Group A) had no genetic mutation detected. Six children (Group B) had mutations in the GH releasing hormone receptor (GHRHR) gene, while eight children (Group C) had mutation in the GH1 gene. In two children, one each had a mutation in PROP1 and LHX3. There was no statistically significant difference in baseline height, weight and BMI for age z-score and height velocity for age z-score (HVZ). HVZ was significantly lower, post 1 year GH treatment in the group with homozygous GH1 deletion than in children with no genetic defect. Response to GH at the end of 1 year was poor in children with the homozygous GH1 deletion as compared to those with GHRHR mutation or without a known mutation.

Mammographic parenchymal texture as an imaging marker of hormonal activity: a comparative study between pre- and post-menopausal women

NASA Astrophysics Data System (ADS)

Daye, Dania; Bobo, Ezra; Baumann, Bethany; Ioannou, Antonios; Conant, Emily F.; Maidment, Andrew D. A.; Kontos, Despina

2011-03-01

Mammographic parenchymal texture patterns have been shown to be related to breast cancer risk. Yet, little is known about the biological basis underlying this association. Here, we investigate the potential of mammographic parenchymal texture patterns as an inherent phenotypic imaging marker of endogenous hormonal exposure of the breast tissue. Digital mammographic (DM) images in the cranio-caudal (CC) view of the unaffected breast from 138 women diagnosed with unilateral breast cancer were retrospectively analyzed. Menopause status was used as a surrogate marker of endogenous hormonal activity. Retroareolar 2.5cm2 ROIs were segmented from the post-processed DM images using an automated algorithm. Parenchymal texture features of skewness, coarseness, contrast, energy, homogeneity, grey-level spatial correlation, and fractal dimension were computed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate feature classification performance in distinguishing between 72 pre- and 66 post-menopausal women. Logistic regression was performed to assess the independent effect of each texture feature in predicting menopause status. ROC analysis showed that texture features have inherent capacity to distinguish between pre- and post-menopausal statuses (AUC>0.5, p<0.05). Logistic regression including all texture features yielded an ROC curve with an AUC of 0.76. Addition of age at menarche, ethnicity, contraception use and hormonal replacement therapy (HRT) use lead to a modest model improvement (AUC=0.78) while texture features maintained significant contribution (p<0.05). The observed differences in parenchymal texture features between pre- and post- menopausal women suggest that mammographic texture can potentially serve as a surrogate imaging marker of endogenous hormonal activity.

Bisphenol S and F: A Systematic Review and Comparison of the Hormonal Activity of Bisphenol A Substitutes

PubMed Central

Bolden, Ashley L.

2015-01-01

Background Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled “BPA-free.” Some of the chemical replacements, however, are also bisphenols and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes. Objectives This review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA. Methods We conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol. Results We identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive end points, and enzyme expression. Conclusions Based on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects. Citation Rochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes. Environ Health Perspect 123:643–650; http://dx.doi.org/10.1289/ehp.1408989 PMID:25775505

Endocrinology Update: Hypopituitarism.

PubMed

Heidelbaugh, Joel J

2016-12-01

Hypopituitarism is defined as a deficiency of one or more pituitary hormones due to a decline in function of the pituitary gland and/or hypothalamus, which can result in higher risks of morbidity and mortality and decreased quality of life. Although hypopituitarism is a rare condition, it commonly develops after traumatic brain injury and in the setting of functioning and nonfunctioning pituitary adenomas. The diagnosis is based on detailed investigation of symptoms of target endocrine gland function relative to the corresponding pituitary hormone deficiency. The clinical manifestations of hypopituitarism result from the degree of the specific hormone deficiency. A thorough and longitudinal history and physical examination, including visual field testing, are paramount. Management consists of prompt pharmacotherapy, surgery, and/or radiotherapy to restore normal endocrine function and quality of life. In most patients with anterior and posterior pituitary hormone deficiency, corresponding hormone replacement is the mainstay of therapy. The prognosis for patients with hypopituitarism depends on the manner of and age at presentation, degree and severity of hormonal impairment, and response to medical and surgical therapies. Patients with hypopituitarism require lifelong monitoring of serum hormone levels and symptoms of hormone deficiency or excess. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Kidney growth and renal functions under the growth hormone replacement therapy in children.

PubMed

Ece, Aydın; Çetinkaya, Semra; Ekşioğlu, Seçil; Şenel, Saliha; Özkasap, Serdar; Giniş, Tayfur; Sen, Velat; Şahin, Cahit

2014-05-01

The aim of this study was to investigate the kidney growth and renal functions in children receiving recombinant human growth hormone (rhGH) treatment. A total of 37 children who received rhGH for 1.5 years before the study was started and 48 healthy controls were included at first evaluation. Hormone levels were determined and kidney sizes were measured by ultrasound. Kidney functions were assessed by serum creatinine and estimated glomerular filtration rate (eGFR). After 3 years of first evaluation, 23 patients were re-assessed. Kidney sizes were found to be lower in rhGH received children compared with controls at first evaluation (p<0.05). Significant positive correlations were found between anthropometric measurements and kidney length and kidney volume (p<0.05). Height was the most significant predictor of kidney volume in rhGH received children (p<0.001). After 3-years of follow-up significantly increases were found in kidney length and volume compared with the first measurements (p<0.05). Increase percentage of body height was similar to increasing percent of kidney length and liver long axis (14.2%, 11.7.1% and 7.7%, respectively, p>0.05). Although no abnormal renal function test results were found at first and second evaluations; rhGH received children had significantly lower eGFR, at first evaluation, compared with controls; however, renal functions significantly increased after 3 years of follow-up (p<0.05). In conclusion, effect rhGH treatment on kidney growth is parallel to growth in body height and other visceral organs. A 3-years rhGH treatment resulted in significant increases in renal functions.

Safety of hormonal replacement therapy and oral contraceptives in systemic lupus erythematosus: a systematic review and meta-analysis.

PubMed

Rojas-Villarraga, Adriana; Torres-Gonzalez, July-Vianneth; Ruiz-Sternberg, Ángela-María

2014-01-01

There is conflicting data regarding exogenous sex hormones [oral contraceptives (OC) and hormonal replacement therapy (HRT)] exposure and different outcomes on Systemic Lupus Erythematosus (SLE). The aim of this work is to determine, through a systematic review and meta-analysis the risks associated with estrogen use for women with SLE as well as the association of estrogen with developing SLE. MEDLINE, EMBASE, SciElo, BIREME and the Cochrane library (1982 to July 2012), were databases from which were selected and reviewed (PRISMA guidelines) randomized controlled trials, cross-sectional, case-control and prospective or retrospective nonrandomized, comparative studies without language restrictions. Those were evaluated by two investigators who extracted information on study characteristics, outcomes of interest, risk of bias and summarized strength of evidence. A total of 6,879 articles were identified; 20 full-text articles were included. Thirty-two meta-analyses were developed. A significant association between HRT exposure (Random model) and an increased risk of developing SLE was found (Rate Ratio: 1.96; 95%-CI: 1.51-2.56; P-value<0.001). One of eleven meta-analyses evaluating the risk for SLE associated with OC exposure had a marginally significant result. There were no associations between HRT or OC exposure and specific outcomes of SLE. It was not always possible to Meta-analyze all the available data. There was a wide heterogeneity of SLE outcome measurements and estrogen therapy administration. An association between HRT exposure and SLE causality was observed. No association was found when analyzing the risk for SLE among OC users, however since women with high disease activity/Thromboses or antiphospholipid-antibodies were excluded from most of the studies, caution should be exercised in interpreting the present results. To identify risk factors that predispose healthy individuals to the development of SLE who are planning to start HRT or OC is suggested.

Partial hypopituitarism and Langerhans cell histiocytosis

PubMed Central

Balaguruswamy, S; Chattington, P D

2011-01-01

A case of multisystem Langerhans cell histiocytosis with pituitary involvement nearly 20 years after initial presentation. A 48-year-old man had histiocytosis X 22 years ago initially involving the groin; subsequently his external auditory meatus, scalp, gum, mandibular bone, perineum and axilla were involved and treated. The pituitary gland was involved 4 years ago. A thyrotropin-releasing hormone test showed delayed response suggestive of hypothalamic disease. Prolactin levels were normal. A gonadotropin-releasing hormone test showed impaired testosterone and gonadotrophin response in keeping with pituitary disease. A glucagon stimulation test showed an impaired growth hormone response but a normal cortisol increase. MRI pituitary showed an empty sella. There was no evidence of diabetes insipidus. Bone mineral densitometry was normal. He has partial hypopituitarism needing thyroxine and testosterone replacement. He also developed type 2 diabetes mellitus 9 years ago. He is closely monitored for any development of diabetes insipidus and the need for growth hormone supplementation. PMID:22715201

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men

PubMed Central

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Meschi, Tiziana; Ticinesi, Andrea; Dominguez, Ligia J.; Barbagallo, Mario; Dall'Aglio, Elisabetta; Ceda, Gian Paolo

2014-01-01

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly. PMID:24723948

The Interplay between Magnesium and Testosterone in Modulating Physical Function in Men.

PubMed

Maggio, Marcello; De Vita, Francesca; Lauretani, Fulvio; Nouvenne, Antonio; Meschi, Tiziana; Ticinesi, Andrea; Dominguez, Ligia J; Barbagallo, Mario; Dall'aglio, Elisabetta; Ceda, Gian Paolo

2014-01-01

The role of nutritional status as key factor of successful aging is very well recognized. Among the different mechanisms by which nutrients may exert their beneficial effects is the modulation of the hormonal anabolic milieu, which is significantly reduced with aging. Undernutrition and anabolic hormonal deficiency frequently coexist in older individuals determining an increased risk of mobility impairment and other adverse outcomes. Mineral assessment has received attention as an important determinant of physical performance. In particular, there is evidence that magnesium exerts a positive influence on anabolic hormonal status, including Testosterone, in men. In this review we summarize data from observational and intervention studies about the role of magnesium in Testosterone bioactivity and the potential underlying mechanisms of this relationship in male subjects. If larger studies will confirm these pivotal data, the combination of hormonal and mineral replacements might be adopted to prevent or delay the onset of disability in the elderly.

Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid hormone: A case report.

PubMed

Li, Qianrui; Liu, Yuping; Zhang, Qianying; Tian, Haoming; Li, Jianwei; Li, Sheyu

2017-07-01

Myalgia and elevated creatine kinase (CK) are occasionally observed during the treatment of hyperthyroid patients. Relative hypothyroidism resulted from rapid thyroid hormone reduction had been promoted as a plausible cause of these myopathic changes, however rarely reported. We hereby presented a 20-year-old female with Grave's disease, who developed myopathy and elevated CK during rapid correction of thyroid hormone. Relative hypothyroidism-induced myopathy. Antithyroid drug (ATD) dosage was reduced without levothyroxine replacement. The muscular symptoms were recovered with CK level returned to normal after adoption of the euthyroid status. Differentiation of relative hypothyroidism from other causes of myopathy, especially with the effect of ATD, is important for clinical practice, although difficult in many cases.

Plasma steroids, body composition, and fat distribution: effects of age, sex, and exercise training.

PubMed

He, Zihong; Rankinen, Tuomo; Leon, Arthur S; Skinner, James S; Tchernof, André; Bouchard, Claude

2018-03-05

Plasma steroid hormone levels vary between men and women, but their associations with BMI and adiposity are controversial. Furthermore, little is known about the role of exercise programs on the relationship between steroid hormones and adiposity. This report evaluates these relationships for plasma levels of adrenal, gonadal, and conjugated steroids with body composition and fat distribution in sedentary men and women, aged 17-65 years, and their responses to an exercise program. In the sedentary state, 270 men (29% Blacks) and 304 women (34% Blacks) from the HERITAGE Family Study were available. Among them, 242 men and 238 women completed a 20-week fully standardized exercise program. Fourteen steroid hormones and SHBG concentrations were assayed in a fasted state and were compared for their associations with adiposity in men and women and in response to the exercise program. Covariates adjusted for in partial correlation analysis were age, ancestry, menopause status (women), and oral contraceptives/hormone replacement treatment status (women) at baseline, as well as baseline value of the trait for the training response. Differences among normal weight, overweight, and obese subjects were also considered. Statistical significance was set at P < 0.0001. Baseline levels of dihydrotesterone (DHT), 17 hydroxy progesterone (OHPROG), sex hormone-binding globulin (SHBG), and testosterone (TESTO) were negatively associated with fat mass and abdominal fat (P < 0.0001) in men and for SHBG in women (P < 0.0001). TESTO was not correlated with fat-free mass in men or women, but was significantly associated with % fat-free mass in men. No association was detected between baseline steroid hormone levels and changes in adiposity traits in response to 20 weeks of exercise. In men, low DHT, OHPROG, SHBG, and TESTO were associated with higher adiposity and abdominal and visceral fat. A similar adiposity profile was observed in women with low SHBG.

[The new concept of osteoporosis. Early diagnosis, prevention and therapy are possible today].

PubMed

Hesch, R D; Harms, H; Rittinghaus, E F; Brabant, G

1990-04-15

A paradigma of osteoporosis pathology is discussed, at the center of which is the hormone-related disturbance of the osteoblast/osteoclast functional unit. A liberal replacement of estrogen-gestagen in post-menopausal women is advocated. Early diagnosis with the aid of quantitative computed tomography makes it possible to establish the indication for timely hormonal treatment in the future, which can result in a measureable increase in bone mass. Late therapy, that is, treatment initiated after the occurrence of fractures, has proven largely ineffective.

Hypothyroidism During Tyrosine Kinase Inhibitor Therapy Is Associated with Longer Survival in Patients with Advanced Nonthyroidal Cancers.

PubMed

Lechner, Melissa G; Vyas, Chirag M; Hamnvik, Ole-Petter R; Alexander, Erik K; Larsen, P Reed; Choueiri, Toni K; Angell, Trevor E

2018-04-01

Tyrosine kinase inhibitor (TKI)-induced thyroid dysfunction is recognized as a common adverse effect of treatment, but the importance of incident hypothyroidism during TKI therapy remains unclear. This study analyzed the prognostic significance of hypothyroidism during TKI therapy in cancer patients. This was a retrospective cohort study of adult patients with advanced nonthyroidal cancer treated with TKI and available thyroid function testing at three affiliated academic hospitals from 2000 to 2017. Patients with preexisting thyroid disease were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid status with TKI treatment was determined from thyroid function testing and initiation of thyroid medication, and classified as euthyroid (thyrotropin [TSH] normal), subclinical hypothyroidism (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement). Multivariate models were used to evaluate the effect of TKI-related hypothyroidism on overall survival (OS). Of 1120 initial patients, 538 remained after exclusion criteria. SCH occurred in 72 (13%) and OH in 144 (27%) patients with TKI therapy. Patients with hypothyroidism had significantly longer OS, with median OS in euthyroid patients of 685 days [confidence interval (CI) 523-851] compared to 1005 days [CI 634-1528] in SCH and 1643 days [CI 1215-1991] in OH patients (p < 0.0001). After adjustment for age, sex, race/ethnicity, cancer type, cancer stage, ECOG performance status, and checkpoint inhibitor therapy, OH remained significantly associated with OS (hazard ratio = 0.561; p < 0.0001), whereas SCH did not (hazard ratio = 0.796; p = 0.165). Analysis of hypothyroid patients (SCH and OH) with TSH >5 and <10 mIU/L stratified by hormone replacement status showed improved survival associated with hormone replacement. New hypothyroidism in cancer patients treated with TKI is associated with significantly improved OS, should not necessitate TKI dose reduction or discontinuation, and may provide independent prognostic information.

Estrogenic phytochemicals reduce bone adiposity and improves bone quality following ovariectomy.

EPA Science Inventory

Menopause causes increased adiposity and the risk of osteoporosis. Partly as a result of the carcinogenic concerns of hormone replacement therapy, increasing numbers of post-menopausal women are taking botanical and dietary supplements to manage these adverse body composition cha...

Growth hormone deficiency after mild combat-related traumatic brain injury.

PubMed

Ioachimescu, Adriana G; Hampstead, Benjamin M; Moore, Anna; Burgess, Elizabeth; Phillips, Lawrence S

2015-08-01

Traumatic brain injury (TBI) has been recognized as a cause of growth hormone deficiency (GHD) in civilians. However, comparable data are sparse in veterans who incurred TBI during combat. Our objective was to determine the prevalence of GHD in veterans with a history of combat-related TBI, and its association with cognitive and psychosocial dysfunction. Single center prospective study. Twenty male veterans with mild TBI incurred during combat 8-72 months prior to enrollment. GHD was defined by a GH peak <3 μg/L during glucagon stimulation test. Differences in neuropsychological, emotional, and quality of life of the GHD Veterans were described using Cohen's d. Large effect sizes were considered meaningful. Mean age was 33.7 years (SD 7.8) and all subjects had normal thyroid hormone and cortisol levels. Five (25%) exhibited a subnormal response to glucagon. Sixteen participants (80%) provided sufficient effort for valid neuropsychological assessment (12 GH-sufficient, 4 GHD). There were large effect size differences in self-monitoring during memory testing (d = 1.46) and inhibitory control (d = 0.92), with worse performances in the GHD group. While fatigue and post-traumatic stress disorder were comparable, the GHD group reported more depression (d = 0.80) and lower quality of life (d = 0.64). Our study found a 25% prevalence of GHD in veterans with mild TBI as shown by glucagon stimulation. The neuropsychological findings raise the possibility that GHD has adverse effects on executive abilities and mood. Further studies are needed to determine whether GH replacement is an effective treatment in these patients.

Microstructure alterations in the hypothalamus in cranially radiated childhood leukaemia survivors but not in craniopharyngioma patients unaffected by hypothalamic damage.

PubMed

Follin, Cecilia; Fjalldal, Sigridur; Svärd, Daniel; van Westen, Danielle; Gabery, Sanaz; Petersén, Åsa; Lätt, Jimmy; Rylander, Lars; Erfurth, Eva Marie

2017-10-01

Metabolic complications are frequent in childhood leukaemia (ALL) survivors treated with cranial radiotherapy (CRT). These complications are potentially mediated by damage to the hypothalamus (HT), as childhood onset (CO) craniopharyngioma (CP) survivors without HT involvement are spared overt obesity. Diffusion tensor imaging (DTI) shows brain tissue microstructure alterations, by fractional anisotrophy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). We used DTI to determine the integrity of the microstructure of the HT in ALL survivors. Case-control study. Three groups were included: (i) 27 CRT treated ALL survivors on hormone supplementation, (ii) 17 CO-CP survivors on hormone supplementation but without HT involvement and (iii) 27 matched controls. DTI parameters of the HT were measured and body composition. Microstructural alterations in the HT were more severe in ALL survivors with a BMI ≥25 than with BMI <25. Compared to controls, ALL survivors had reduced FA (P=.04), increased MD (P<.001), AD (P<.001) and RD (P<.001) in the right and left HT. In the right HT, ALL survivors with a BMI ≥25 showed elevated MD (P=.03) and AD (P=.02) compared to ALL survivors with BMI <25. In contrast, DTI parameters did not differ between CP survivors and controls. Long-term follow-up after CRT for ALL DTI measures were affected in the HT despite complete hormone replacement. The present data suggest that ALL survivors have demyelination and axonal loss in the HT. © 2017 John Wiley & Sons Ltd.

Putative Gonadotropin Releasing Hormone Agonist Therapy and Dementia: An Application of Medicare Hospitalization Claims Data.

PubMed

Smith, Mark A; Bowen, Richard L; Nguyen, Richard Q; Perry, George; Atwood, Craig S; Rimm, Alfred A

2018-05-16

Estrogen and hormone replacement therapies to reduce Alzheimer's disease (AD) have yielded conflicting results. However, this study proposes that the well-characterized increase in serum gonadotropins following menopause or andropause are accountable for the increased risk of developing AD among the elderly population. To determine the role of gonadotropins in the development of AD and investigate gonadotropin-releasing hormone (GnRH) agonist therapy as a potential preventative and/or disease-modifying approach to AD management. Male Medicare beneficiaries aged 67 to 75 and hospitalized with prostate cancer (n = 115,789) were compared to three control groups: men of the same demographics undergoing a cholecystectomy (n = 97,267), herniorrhaphy (n = 68,778), or transurethral prostatectomy (n = 267,691). A proportion of the patients hospitalized with prostate cancer were assumed to have low concentrations of serum gonadotropins and sex steroids as a result of GnRH agonist therapy, while those in the control groups were assumed to have elevated gonadotropin but lowered sex steroid levels that are associated with andropause in this age group. The rates of development of select diagnoses of dementia, including AD, over a twelve-year follow-up period following surgery. When compared to control patients, men hospitalized with prostate cancer have a protection against dementia after twelve years of follow-up, with relative risks ranging from 0.48 to 0.83. Patients with prostate cancer are treated with the GnRH analogue leuprolide acetate, our data suggest that leuprolide acetate may be therapeutic for AD via its downregulation of serum gonadotropins.

Effects of ovariectomy and estrogen replacement therapy on laryngeal tissue: a histopathological experimental animal study.

PubMed

Tatlipinar, Arzu; Günes, Pembegül; Ozbeyli, Dilek; Cimen, Burak; Gökçeer, Tanju

2011-12-01

To determine the histopathological effect of estrogen deficiency and hormone replacement treatment on laryngeal tissue in ovariectomized rats. Animal study. The study was conducted at the animal experiment laboratory of Marmara University School of Medicine, Istanbul, Turkey. Six-month-old female Wistar albino rats were divided into the following 3 groups (n = 8 per group): sham-operated control, ovariectomized, and ovariectomized with estrogen replacement. Rats in the ovariectomized with estrogen replacement group received 17 β-estradiol valerate (200 µg/kg, subcutaneously) once a week. Animals were killed after 8 weeks of intervention. Significant changes were observed in the ovariectomized group when edema in lamina propria, inflammation in squamous, respiratory epithelia and lamina propria, pseudostratification, and cilia loss were assessed. Except cilia loss, there were no significant differences in the assessments between the sham-operated control and ovariectomized with estrogen replacement groups. On the basis of histopathological evaluations, it was shown that estrogen replacement helped to improve laryngeal changes due to experimentally induced menopause.

[Hypothyroidism-when and how to treat?

PubMed

Koehler, V F; Reincke, M; Spitzweg, C

2018-06-05

The diagnosis of hypothyroidism is primarily based on clinical signs and symptoms as well as measurement of thyroid-stimulating hormone (TSH) concentration. Subclinical hypothyroidism is characterized by elevated TSH with normal serum free thyroxine (fT 4 ) and triiodothyronine (fT 3 ) levels, while in manifest hypothyroidism serum fT 4 and fT 3 levels are reduced. Common causes of primary hypothyroidism are autoimmune thyroiditis as well as therapeutic interventions, such as thyroid surgery or radioiodine therapy. Signs and symptoms of hypothyroidism include fatigue, bradycardia, constipation and cold intolerance. In subclinical hypothyroidism, symptoms may be absent. Initiation of levothyroxine (T 4 ) therapy not only depends on the level of TSH elevation, but also on other factors, such as patient age, presence of pregnancy or comorbidities. Treatment of patients with subclinical hypothyroidism is still a controversial topic. In general, thyroid hormone replacement therapy in non-pregnant adults ≤ 70 years is clearly indicated if the TSH concentration is >10 mU/l. Standard of care for treatment of hypothyroidism is T 4 monotherapy. The biochemical treatment goal for T 4 replacement in primary hypothyroidism is a TSH level within the reference range (0.4-4.0 mU/l). In contrast, in secondary hypothyroidism, serum fT 4 levels are the basis for adjusting thyroid hormone dosage. Inadequate replacement of T 4 resulting in subclinical or even manifest hyperthyroidism should urgently be avoided. T 4 /liothyronine (T3) combination therapy is still a matter of debate and not recommended as standard therapy, but may be considered in patients with persistence of symptoms, despite optimal T 4 treatment, based on expert opinion.

Circulating adrenal hormones are not necessary for the development of sensitization to the psychomotor activating effects of amphetamine.

PubMed

Badiani, A; Morano, M I; Akil, H; Robinson, T E

1995-02-27

We reported previously that when amphetamine is given in NOVEL test cages both its acute psychomotor activating effects (rotational behaviour and locomotor activity) and the degree of sensitization are greater than when amphetamine is given in HOME cages that are physically identical to the NOVEL test cages. Since exposure to the NOVEL environment increases plasma corticosterone levels (Experiment 1) it is possible that the enhancement in the effects of amphetamine in the NOVEL condition is mediated by corticosterone. If this hypothesis is correct adrenalectomy (ADX) should abolish the difference between the HOME and NOVEL groups. This was tested in three independent experiments, in which the response (rotational behavior in Experiments 2 and 3; locomotor activity and rearing behavior in Experiment 4) to repeated injections of amphetamine was assessed in rats that underwent adrenalectomy (ADX) or a sham operation (SHAM). ADX animals received either no corticosterone replacement or one of two corticosterone replacement treatments. Adrenalectomy, with or without corticosterone replacement treatment, had no significant effect on the development of amphetamine sensitization, either in the HOME or the NOVEL environment. By contrast, the effects of adrenalectomy on the acute response to amphetamine varied depending on the behavioral measure and possibly on the dose of amphetamine (2.0 mg/kg, 3.0 mg/kg and 1.5 mg/kg IP, in Experiments 2, 3 and 4, respectively). We conclude that: (i) a stress-induced secretion of adrenal hormones is not responsible for the enhancement in sensitization to amphetamine seen in animals tested in a NOVEL environment; (ii) circulating adrenal hormones are not necessary for development of sensitization to the psychomotor activating effects of amphetamine.

Soy foods and soybean isoflavones and menopausal health.

PubMed

Messina, Mark J

2002-01-01

Soybeans are a natural dietary source of isoflavones, which have estrogen-like properties. Therefore, it is worthwhile to consider the implications for soy of the recently published findings of the Heart and Estrogen/Progestin Replacement Study (HERS) I/II and the Women's Health Initiative (WHI). The WHI found coronary heart disease (CHD) risk to be increased in women receiving hormone replacement therapy, and both studies found increases in venous thromboembolic disease in such women. Additionally, stroke and breast cancer risk were increased in the WHI, although risk of colorectal cancer and fracture was decreased. Because research suggests that it is the combination of estrogen plus progestin, and not estrogen alone, that increases breast cancer risk, soy seems unlikely to increase risk because it has no progestin activity. Similarly, there is no evidence to suggest that soy will increase venous thromboembolic disease or stroke; however, only limited data are available in this area. There are promising data suggesting that soy may decrease CHD risk, although studies conducted thus far have examined only markers of risk and not actual CHD events. Similarly, short-term studies generally suggest that soy reduces bone loss in postmenopausal women; however, such effects have been noted primarily only at the spine, and longer-term studies are needed. Finally, very limited human research suggests that soy may decrease colon cancer risk, but this is highly speculative. The results of HERS I/II and WHI suggest that soy may have some of the advantages, but not the disadvantages, of combined hormone replacement therapy (at least with respect to the specific hormones and doses used in the HERS I/II and WHI), but that large, long-term intervention studies examining disease outcome are needed before definitive conclusions can be drawn. Nevertheless, the evidence warrants recommendations that menopausal women include soy in their diets.

Effects of testosterone replacement therapy on bone metabolism in male post-surgical hypogonadotropic hypogonadism: focus on the role of androgen receptor CAG polymorphism.

PubMed

Tirabassi, G; delli Muti, N; Gioia, A; Biagioli, A; Lenzi, A; Balercia, G

2014-04-01

The relationship between androgen receptor (AR) CAG polymorphism and bone metabolism is highly controversial. We, therefore, aimed to evaluate the independent role of AR CAG repeat polymorphism on bone metabolism improvement induced by testosterone replacement therapy (TRT) in male post-surgical hypogonadotropic hypogonadism, a condition frequently associated with hypopituitarism and in which the effects of TRT have to be distinguished from those resulting from concomitant administration of pituitary function replacing hormones. 12 men affected by post-surgical hypogonadotropic hypogonadism [mean duration of hypogonadism 8.3 ± 2.05 (SD) months] were retrospectively assessed before and after TRT (from 74 to 84 weeks after the beginning of therapy). The following measures were studied: parameters of bone metabolism [serum markers and bone mineral density (BMD)], pituitary dependent hormones and genetic analysis (AR CAG repeat number). Total testosterone, estradiol, free T4 (FT4) and insulin-like growth factor-1 (IGF-1) increased between the two phases, while follicle stimulating hormone (FSH) decreased. While serum markers did not vary significantly between the two phases, BMD improved slightly but significantly in all the studied sites. The number of CAG triplets correlated negatively and significantly with all the variations (Δ-) of BMDs. Conversely, Δ-testosterone correlated positively and significantly with all studied Δ-BMDs, while Δ-FSH, Δ-estradiol, Δ-FT4, and Δ-IGF-1 did not correlate significantly with any of the Δ-BMDs. Multiple linear regression analysis, after correction for Δ-testosterone, showed that CAG repeat length was negatively and significantly associated with ∆-BMD of all measured sites. Our data suggest that, in post-surgical male hypogonadotropic hypogonadism, shorter AR CAG tract is independently associated with greater TRT-induced improvement of BMD.

CARDIAC STRUCTURAL AND FUNCTIONAL ABNORMALITIES IN FEMALES WITH UNTREATED HYPOPITUITARISM DUE TO SHEEHAN SYNDROME: RESPONSE TO HORMONE REPLACEMENT THERAPY.

PubMed

Laway, Bashir Ahmad; Ramzan, Mahroosa; Allai, Mohd Sultan; Wani, Arshad Iqbal; Misgar, Raiz Ahmad

2016-09-01

Data on cardiac abnormalities in females with untreated hypopituitarism are limited. We investigated echocardiographic abnormalities in females with untreated hypopituitarism and their response to treatment. Twenty-three females with treatment-naïve hypopituitarism and 30 matched healthy controls were evaluated for cardiac structure and function. Echocardiographic evaluation was done at presentation and after achieving a euthyroid and eucortisol state. Fourteen (61%) patients had mitral regurgitation, and 11 (48%) had pericardial effusion as against none among controls. Indices of left ventricular (LV) size like LV end diastolic dimension (LVEDD; 44.5 ± 3.5 mm in cases vs. 47.6 ± 3.8 mm in controls, P = .004), and LV diastolic volume (LVEDV; 91.8 ± 18.0 mL versus 106.5 ± 20.4 mL, P = .009) were significantly lower in the SS group compared with controls. LV mass (LVM) was 70.8 ± 19.2 g in cases and 108.0 ± 33.2 g in controls (P = .02). Similarly, indices of LV systolic function like stroke volume (SV; 59.1 ± 12.0 mL in cases and 74.4 ± 15.8 mL in controls; P = .000), ejection fraction (EF; 64.3 ± 6.2 % in cases against 69.9 ± 9.2 % in controls; P = .03), and fractional shortening (FS; 34.9 ± 4.7% versus 40.1 ± 4.4%, P = .000) were significantly decreased in patients compared with controls. Cardiac abnormalities normalized with restoration of a euthyroid and eucortisol state. Pericardial effusion, mitral regurgitation, and diminished LVM are common in females with untreated hypopituitarism. ACTH = adrenocorticotrophic hormone BMI = body mass index DT = deceleration time EDV = end-diastolic volume EF = ejection fraction FS = fractional shortening GH = growth hormone IGF-1 = insulin growth factor-1 ITT = insulin tolerance test IVSd = interventricular septal diameter LH = luteinizing hormone LV = left ventricular LVEDD = LV end diastolic dimension LVEDV = LV end diastolic volume LVM = LV mass MRI = magnetic resonance imaging MVP = mitral value prolapse PPH = postpartum hemorrhage PWd = posterior wall diameter SS = Sheehan syndrome SV = stroke volume T3 = triiodothyronine T4 = thyroxine TSH = thyroid-stimulating hormone.

MANAGEMENT OF ENDOCRINE DISEASE: Risk of overtreatment in patients with adrenal insufficiency: current and emerging aspects.

PubMed

Mazziotti, G; Formenti, A M; Frara, S; Roca, E; Mortini, P; Berruti, A; Giustina, A

2017-11-01

The effects of long-term replacement therapy of adrenal insufficiency (AI) are still a matter of controversy. In fact, the established glucocorticoid replacement regimens do not completely reproduce the endogenous hormonal production and the monitoring of AI treatment may be a challenge for the lack of reliable clinical and biochemical markers. Consequently, several AI patients are frequently exposed to relative glucocorticoid excess potentially leading to develop chronic complications, such as diabetes mellitus, dyslipidemia, hypertension and fragility fractures with consequent impaired QoL and increased mortality risk. This review deals with the pathophysiological and clinical aspects concerning the over-replacement therapy of primary and secondary AI. © 2017 European Society of Endocrinology.

Effects of type of diet on pharmacokinetics of levothyroxine sodium oral solution.

PubMed

Iemura, Ryuji; Toyota, Masanori; Micallef, Mark J

2013-06-01

The pharmacokinetics of serum total thyroxine concentration (TT4) in euthyroid dogs was studied after concomitant administration of a levothyroxine oral solution with different types of dry diet. Mixing levothyroxine with different types of dry diet did not have any effect on TT4 pharmacokinetics in the dogs (Cmax 50.6 nmol/L, tmax 4.0 h and AUC 517 nmol h/L). This finding indicates that changing from one diet to another during levothyroxine-replacement therapy should not impact therapeutic effectiveness, and should be helpful for improvement of compliance with thyroid hormone replacement therapy in dogs treated for life with this replacement therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Hypogonadism and Sex Steroid Replacement Therapy in Girls with Turner Syndrome.

PubMed

Gawlik, Aneta; Hankus, Magdalena; Such, Kamila; Drosdzol-Cop, Agnieszka; Madej, Paweł; Borkowska, Marzena; Zachurzok, Agnieszka; Malecka-Tendera, Ewa

2016-12-01

Turner syndrome is the most common example of hypergonadotropic hypogonadism resulting from gonadal dysgenesis. Most patients present delayed, or even absent, puberty. Premature ovarian failure can be expected even if spontaneous menarche occurs. Laboratory markers of gonadal dysgenesis are well known. The choice of optimal hormone replacement therapy in children and adolescents remains controversial, particularly regarding the age at which therapy should be initiated, and the dose and route of estrogen administration. On the basis of a review of the literature, we present the most acceptable schedule of sex steroid replacement therapy in younger patients with Turner syndrome. Copyright © 2016 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Kinetics of removal of intravenous testosterone pulses in normal men.

PubMed

Veldhuis, Johannes D; Keenan, Daniel M; Liu, Peter Y; Takahashi, Paul Y

2010-04-01

Testosterone is secreted into the bloodstream episodically, putatively distributing into total, bioavailable (bio) nonsex hormone-binding globulin (nonSHBG-bound), and free testosterone moieties. The kinetics of total, bio, and free testosterone pulses are unknown. Design Adrenal and gonadal steroidogenesis was blocked pharmacologically, glucocorticoid was replaced, and testosterone was infused in pulses in four distinct doses in 14 healthy men under two different paradigms (a total of 220 testosterone pulses). Testosterone kinetics were assessed by deconvolution analysis of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone concentration-time profiles. Independently of testosterone dose or paradigm, rapid-phase half-lives (min) of total, free, bioavailable, SHBG-bound, and albumin-bound testosterone were comparable at 1.4+/-0.22 min (grand mean+/-S.E.M. of geometric means). Slow-phase testosterone half-lives were highest for SHBG-bound testosterone (32 min) and total testosterone (27 min) with the former exceeding that of free testosterone (18 min), bioavailable testosterone (14 min), and albumin-bound testosterone (18 min; P<0.001). Collective outcomes indicate that i) the rapid phase of testosterone disappearance from point sampling in the circulation is not explained by testosterone dose; ii) SHBG-bound testosterone and total testosterone kinetics are prolonged; and iii) the half-lives of bioavailable, albumin-bound, and free testosterone are short. A frequent-sampling strategy comprising an experimental hormone clamp, estimation of hormone concentrations as bound and free moieties, mimicry of physiological pulses, and deconvolution analysis may have utility in estimating the in vivo kinetics of other hormones, substrates, and metabolites.

Association between asthma and female sex hormones.

PubMed

Baldaçara, Raquel Prudente de Carvalho; Silva, Ivaldo

2017-01-01

The relationship between sex hormones and asthma has been evaluated in several studies. The aim of this review article was to investigate the association between asthma and female sex hormones, under different conditions (premenstrual asthma, use of oral contraceptives, menopause, hormone replacement therapy and pregnancy). Narrative review of the medical literature, Universidade Federal do Tocantins (UFT) and Universidade Federal de São Paulo (Unifesp). We searched the CAPES journal portal, a Brazilian platform that provides access to articles in the MEDLINE, PubMed, SciELO, and LILACS databases. The following keywords were used based on Medical Subject Headings: asthma, sex hormones, women and use of oral contraceptives. The associations between sex hormones and asthma remain obscure. In adults, asthma is more common in women than in men. In addition, mortality due to asthma is significantly higher among females. The immune system is influenced by sex hormones: either because progesterone stimulates progesterone-induced blocking factor and Th2 cytokines or because contraceptives derived from progesterone and estrogen stimulate the transcription factor GATA-3. The associations between asthma and female sex hormones remain obscure. We speculate that estrogen fluctuations are responsible for asthma exacerbations that occur in women. Because of the anti-inflammatory action of estrogen, it decreases TNF-α production, interferon-γ expression and NK cell activity. We suggest that further studies that highlight the underlying physiopathological mechanisms contributing towards these interactions should be conducted.

Thyroid-stimulating hormone pituitary adenomas.

PubMed

Clarke, Michelle J; Erickson, Dana; Castro, M Regina; Atkinson, John L D

2008-07-01

Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare, representing < 2% of all pituitary adenomas. The authors conducted a retrospective analysis of patients with TSH-secreting or clinically silent TSH-immunostaining pituitary tumors among all pituitary adenomas followed at their institution between 1987 and 2003. Patient records, including clinical, imaging, and pathological and surgical characteristics were reviewed. Twenty-one patients (6 women and 15 men; mean age 46 years, range 26-73 years) were identified. Of these, 10 patients had a history of clinical hyperthyroidism, of whom 7 had undergone ablative thyroid procedures (thyroid surgery/(131)I ablation) prior to the diagnosis of pituitary adenoma. Ten patients had elevated TSH preoperatively. Seven patients presented with headache, and 8 presented with visual field defects. All patients underwent imaging, of which 19 were available for imaging review. Sixteen patients had macroadenomas. Of the 21 patients, 18 underwent transsphenoidal surgery at the authors' institution, 2 patients underwent transsphenoidal surgery at another facility, and 1 was treated medically. Patients with TSH-secreting tumors were defined as in remission after surgery if they had no residual adenoma on imaging and had biochemical evidence of hypo-or euthyroidism. Patients with TSH-immunostaining tumors were considered in remission if they had no residual tumor. Of these 18 patients, 9 (50%) were in remission following surgery. Seven patients had residual tumor; 2 of these patients underwent further transsphenoidal resection, 1 underwent a craniotomy, and 4 underwent postoperative radiation therapy (2 conventional radiation therapy, 1 Gamma Knife surgery, and 1 had both types of radiation treatment). Two patients had persistently elevated TSH levels despite the lack of evidence of residual tumor. On pathological analysis and immunostaining of the surgical specimen, 17 patients had samples that stained positively for TSH, 8 for alpha-subunit, 10 for growth hormone, 7 for prolactin, 2 for adrenocorticotrophic hormone, and 1 for follicle-stimulating hormone/luteinizing hormone. Eleven patients (61%) ultimately required thyroid hormone replacement therapy, and 5 (24%) required additional pituitary hormone replacement. Of these, 2 patients required treatment for new anterior pituitary dysfunction as a complication of surgery, and 2 patients with preoperative partial anterior pituitary dysfunction developed complete panhypopituitarism. One patient had transient diabetes insipidus. The remainder had no change in pituitary function from their preoperative state. Thyroid-stimulating hormone-secreting pituitary lesions are often delayed in diagnosis, are frequently macroadenomas and plurihormonal in terms of their pathological characteristics, have a heterogeneous clinical picture, and are difficult to treat. An experienced team approach will optimize results in the management of these uncommon lesions.

Gonadal and Sexual Dysfunction in Childhood Cancer Survivors.

PubMed

Yoon, Ju Young; Park, Hyeon Jin; Ju, Hee Young; Yoon, Jong Hyung; Chung, Jin Soo; Hwang, Sang Hyun; Lee, Dong Ock; Shim, Hye Young; Park, Byung-Kiu

2017-10-01

Few studies have addressed gonadal and sexual dysfunctions in childhood cancer survivors. We evaluated the prevalence rates and risk factors for gonadal failure among adolescent/young adult childhood cancer survivors and their sexual function. Subjects were childhood cancer survivors aged 15-29 years who had completed therapy more than 2 years ago. Demographic and medical characteristics were obtained from the patients' medical records. In addition, hormonal evaluation and semen analysis were performed and sexual function was evaluated via questionnaire. The study included 105 survivors (57 males, 48 females), of which 61 were adults (age > 19 years) and 44 were adolescents. In both males and females, the proportion of survivors with low sex hormone levels did not differ among age groups or follow-up period. Thirteen female subjects (27.1%) needed sex hormone replacement, while five males subjects (8.8%) were suspected of having hypogonadism, but none were receiving sex hormone replacement. Of 27 semen samples, 14 showed azospermia or oligospermia. The proportion of normospermia was lower in the high cyclophosphamide equivalent dose (CED) group (CED ≥ 8,000 mg/m2) than the low CED group (27.3% vs. 62.5%, p=0.047). Among adults, none were married and only 10 men (35.7%) and eight women (34.3%) were in a romantic relationship. Though a significant proportion (12.0% of males and 5.3% of females) of adolescent survivors had experienced sexual activity, 13.6% had not experienced sex education. The childhood cancer survivors in this study showed a high prevalence of gonadal/sexual dysfunction; accordingly, proper strategies are needed to manage these complications.

Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

PubMed Central

Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

2015-01-01

Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

Involvement of Luteinizing Hormone in Alzheimer Disease Development in Elderly Women.

PubMed

Rao, C V

2017-03-01

Alzheimer disease (AD) is a slow progressive neurodegenerative disease that affects more elderly women than elderly men. It impairs memory, typically progresses into multidomain cognitive decline that destroys the quality of life, and ultimately leads to death. About 5.3 million older Americans are now living with this disease, and this number is projected to rise to 14 million by 2050. Annual health-care costs in the United States alone are projected to increase to about US$1.1 trillion by 2050. The initial theory that decreasing estrogen levels leads to AD development in postmenopausal women has been proven inconclusive. For example, Women's Health Research Initiative Memory Study and the population-based nested case-control study have failed to demonstrate that estrogen/progesterone (hormone replacement therapy [HRT]) or estrogen replacement therapy could prevent the cognitive decline or reduce the risk of AD. This led to the realization that AD development could be due to a progressive increase in luteinizing hormone (LH) levels in postmenopausal women. Accordingly, a large number of studies have demonstrated that an increase in LH levels is positively correlated with neuropathological, behavioral, and cognitive changes in AD. In addition, LH has been shown to promote amyloidogenic pathway of precursor protein metabolism and deposition of amyloid β plaques in the hippocampus, a region involved in AD. Cognate receptors that mediate LH effects are abundantly expressed in the hippocampus. Reducing the LH levels by treatment with gonadotropin-releasing hormone agonists could provide therapeutic benefits. Despite these advances, many questions remain and require further research.

Sphenoid mucocele with unusual panhypopituitarism.

PubMed

Devi, Saranya; Ganger, Anita; Sharma, Sanjay; Saxena, Rohit

2016-04-05

A 13-year-old boy presented with bilateral progressive proptosis, abduction deficit, optic atrophy and features suggestive of hypopituitarism secondary to a sphenoid sinus mucocele. Drainage of the mucocele along with hormone replacement therapy resulted in improvement in visual acuity and abduction. 2016 BMJ Publishing Group Ltd.

Dietary and Environmental Exposure to Cadmium and the Risk of Breast Cancer

DTIC Science & Technology

2011-10-01

feeding history, oral contraceptive use or hormone replacement therapy. There was little difference between urinary Cd concentrations based on...Flemish adolescents and adults: associations and dose- response relationships. Environ Int, 2010, 36:330-7. Ikeda, M. , Moriguchi, J. , Ezaki, T

STRATEGIES TO REDUCE OR REPLACE THE USE OF ANIMALS IN THE ENDOCRINE SCREENING AND TESTING PROGRAM.

EPA Science Inventory

Abstract: The US Environmental Protection Agency (EPA) is developing a screening and testing program for endocrine disrupting chemicals (EDCs) to detect alterations of hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen and thyroid hormone synthesis and androgen (AR...

Cardiogenic Pulmonary Edema in a Dog Following Initiation of Therapy for Concurrent Hypoadrenocorticism and Hypothyroidism.

PubMed

Paik, Jooyae; Kang, Ji-Houn; Chang, Dongwoo; Yang, Mhan-Pyo

A 5 yr old intact female cocker spaniel dog weighing 7.8 kg was referred with anorexia, vomiting, and depression. At referral, the dog was diagnosed initially with typical hypoadrenocorticism, and 2 d later, concurrent primary hypothyroidism was detected. Hormonal replacement therapies, including fludrocortisone, prednisolone, and levothyroxine, were initiated, but a few days later the dog became abruptly tachypneic, and thoracic radiographs indicated the development of pulmonary edema. Echocardiography showed that there were abnormalities indicating impaired left ventricular function, although the heart valves were normal. Following treatment with pimobendan and furosemide, the pulmonary edema resolved. The dog had no recurrence of the clinical signs after 10 mo of follow-up, despite being off all cardiac medications; consequently, the cardiac failure was transient or reversible in this dog. The case report describes the stepwise diagnosis and successful treatment of cardiogenic pulmonary edema after initiation of hormonal replacement therapy for concurrent hypoadrenocorticism and hypothyroidism in a dog.

Assessing the effect of self instructional module on knowledge of menopause & hormone replacement therapy for menopausal women in Moradabad (UP).

PubMed

Khalid, Mehvish; Chhuggani, Manju

2014-01-01

Objectives of the study were to identify the problems faced by menopausal women and to find out the remedial measures adopted by them, to assess the knowledge of menopausal women regarding menopause & hormone replacement therapy (HRT) before and after administration of self-instructional module (SIM) and to find out the acceptability and utility of the SIM. An evaluative research approach, with pre-experimental one group pre-test post-test design was adopted. Purposive sampling technique was used to obtain an adequate size of the sample. The sample comprised of 100 menopausal women living in selected community of Moradabad (UP). A knowledge questionnaire and opinionnaire were administered, and SIM on menopause and HRT administered. It was found that there was deficit in knowledge of menopausal women regarding menopause and HRT. Mean post-test knowledge scores were significantly higher than mean pre-test knowledge scores. SIM was found highly acceptable and useful by menopausal women.

Effect of Growth Hormone on Endometrial Thickness and Fertility Outcome in the Treatment of Women with Panhypopituitarism: A Case Report.

PubMed

Drakopoulos, Panagiotis; Pluchino, Nicola; Bischof, Paul; Cantero, Pablo; Meyer, Patrick; Chardonnens, Didier

2016-01-01

The role of growth hormone (GH) in female reproduction has become a topic of increasing interest over the last decade. The replacement of GH for ovulation induction in women with hypopituitarism remains controversial. The role of GH in the human endometrium is still largely unknown. To the best of our knowledge, this study represents the first case report showing evidence that GH might play a role not only for ovulation induction, but also for the development of endometrial thickness in women with hypopituitarism. A 32-year-old hypophysectomized. woman, known for primary infertility, experienced multiple IVF/embryo transfer failures with inadequate endometrial development. The use of GH replacement therapy followed by conventional controlled ovarian hyperstimulation enabled endometrial development and better ovarian response to gonadotropins, leading to a successful ongoing pregnancy. The substitution with GH resulted in fewer days of ovarian stimulation, an acceptable endometrium, and a twin pregnancy delivered at 38 weeks' gestation.

Manufacturing heterosexuality: hormone replacement therapy and menopause in urban Oaxaca.

PubMed

Ramirez, Michelle

2006-01-01

For several decades, hormone replacement therapies have been prescribed to women, not only to prevent disease but to improve the sexual functioning of menopausal women. The medical promotion of continued sexual activity in a woman's post-reproductive years is exported to locations outside of North America and Europe, which provides an opportunity to critically examine the cultural roots that have informed expert biomedical representations. This ethnographic study examined menopause and social class in Oaxaca de Juarez, Mexico using interviews, questionnaires, and textual analysis. The research found that biomedicine in conjunction with the pharmaceutical industry promoted culturally constructed gender hierarchies under the guise of optimal menopausal health. However, women's actual experience of gender and sexuality in mid-life diverged significantly from these expert representations. Themes that emerged in interviews and questionnaires included the importance of motherhood in old age, diminished sexual desire as not problematic, and greater sexual freedom at a post-reproductive age. Ultimately, biomedical discourse was not the sole arbiter of appropriate menopausal womanhood and femininity.

Should a doctor prescribe hormone replacement therapy which has been manufactured from mare's urine?

PubMed

Cox, D

1996-08-01

Many clinicians are experiencing consumer resistance to the prescription of equine HRT (that is hormone replacement therapy which has been manufactured from mare's urine). In this paper I consider the ethical implications of prescribing these preparations. I decide that patients should have a right to refuse such treatment but also ask whether a prescribing doctor should choose one preparation over another on moral grounds. I determine that there is prima facie evidence to suggest that mares may suffer and that prescription of equine HRT (instead of synthetic oestrogen-oestriol) would therefore have to be justified in terms of either offering greater benefits to the women or offering greater value for money to the health service. I find that there is no substantial evidence to suggest that equine HRT offers unique advantages over and above oestriol. I conclude that it would be preferable for a doctor to recommend the synthetic oestrogen to women who want relief from the symptoms of the menopause and protection from osteoporosis and cardiovascular disease.

Hormones and the bone marrow: panhypopituitarism and pancytopenia in a man with a pituitary adenoma.

PubMed

Lang, Dianna; Mead, Jennifer S; Sykes, David B

2015-05-01

In rare cases, pancytopenia results from hormonal deficiencies that arise in the setting of panhypopituitarism. Here we describe the unusual case of a 60-year-old man who presented with progressive fatigue and polyuria, and whose laboratory workup revealed a deficiency of the five hormones associated with the action of the anterior pituitary (thyroid hormone, testosterone, cortisol, prolactin, and insulin-like growth factor-1). Imaging of the pituitary demonstrated a cystic mass consistent with a pituitary adenoma replacing much of the normal pituitary tissue. His symptoms and hematologic abnormalities rapidly resolved with prednisone and levothyroxine supplementation. While the majority of reported cases of panhypopituitarism with bone marrow suppression are the result of peripartum sepsis or hemorrhage leading to pituitary gland necrosis (Sheehan's syndrome), it is also important to consider the diagnosis of hypopituitarism in patients with hypothyroidism, low cortisol levels, and pancytopenia. The causal relationship between pancytopenia and panhypopituitarism is not well understood, though it does reinforce the important influence of these endocrine hormones on the health of the bone marrow.

Effects of growth hormone treatment on growth in children with juvenile idiopathic arthritis.

PubMed

Simon, D; Bechtold, S

2009-11-01

Several therapeutic trials have been conducted over the past decade to evaluate the role of exogenous growth hormone (GH) as a means of correcting the growth deficiency seen in children with juvenile idiopathic arthritis (JIA). Early studies showed the benefit of GH treatment with respect to final height in patients with JIA. Of 13 patients receiving GH, 84% (11 patients) achieved a final height within their target range compared with only 22% (4 of 18 patients) of untreated patients. There are, however, factors that may limit the statural gains achieved with GH therapy including severe inflammation, severe statural deficiency at GH therapy initiation, long disease duration and delayed puberty. Data on the efficacy of GH replacement therapy in children with JIA and factors that influence the statural growth response will be reviewed. Results from therapeutic trials show that treatment with GH can decrease the statural deficit that occurs during the active phase of JIA, producing an adult height that is close to the genetically determined target height. Copyright 2009 S. Karger AG, Basel.

Salivary cortisol and cortisone in the clinical setting.

PubMed

Blair, Joanne; Adaway, Jo; Keevil, Brian; Ross, Richard

2017-06-01

A resurgence of interest in salivary biomarkers has generated evidence for their value in assessing adrenal function. The advantages of salivary measurements include only free hormone is detected, samples can be collected during normal daily routines and stress-induced cortisol release is less likely to occur than during venepuncture. We review the use of salivary biomarkers to diagnose and monitor patients for conditions of cortisol excess and deficiency and discuss the value of measuring salivary cortisone versus salivary cortisol. Developments in laboratory techniques have enabled the measurement of salivary hormones with a high level of sensitivity and specificity. In states of altered cortisol binding, salivary biomarkers are more accurate measures of adrenal reserve than serum cortisol. Salivary cortisone is a superior marker of serum cortisol compared with salivary cortisol, specifically when serum cortisol is low and during hydrocortisone therapy when contamination of saliva may result in misleading salivary cortisol concentrations. Salivary cortisol and cortisone can be used to assess cortisol excess, deficiency and hydrocortisone replacement, with salivary cortisone having the advantage of detection when serum cortisol levels are low and there is no interference from oral hydrocortisone.

[Relation between parathyroid hormone and cardiovascular risk in patients with vitamin D deficiency].

PubMed

Casado Cerrada, Jesús; Parra Caballero, Pedro; Vega Piris, Lorena; Suárez Fernández, Carmen

2013-10-05

Vitamin D deficiency and parathyroid hormone (PTH) are associated with an increased cardiovascular risk and arterial stiffness. The aim of our study is to compare the cardiovascular risk in subjects with low vitamin D, attending to the PTH concentration, as well as evaluating the response after administration of vitamin D. Prospective study of patients with a concentration of 25(OH)-vitamin D below 30nmol/l. We evaluated vascular risk parameters as blood pressure, arterial stiffness, lipid profile and glucose metabolism. Patients received vitamin D supplements for 3 months, after which the previous parameters were reassessed. A total of 32 patients were included. Those with PTH over 65pg/ml were older, had worse renal function, higher systolic blood pressure, pulse pressure and arterial stiffness. Treatment with vitamin D showed a statistically significant trend to lower blood pressure and pulse wave velocity. The increase in PTH in patients with low vitamin D involves poor control of blood pressure and increased vascular stiffness. Vitamin D replacement shows a tendency to reduce these parameters. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Effects of Music Listening on Cortisol Levels and Propofol Consumption during Spinal Anesthesia

PubMed Central

Koelsch, Stefan; Fuermetz, Julian; Sack, Ulrich; Bauer, Katrin; Hohenadel, Maximilian; Wiegel, Martin; Kaisers, Udo X.; Heinke, Wolfgang

2011-01-01

Background: This study explores effects of instrumental music on the hormonal system (as indicated by serum cortisol and adrenocorticotropic hormone), the immune system (as indicated by immunoglobulin A) and sedative drug requirements during surgery (elective total hip joint replacement under spinal anesthesia with light sedation). This is the first study investigating this issue with a double-blind design using instrumental music. Methodology/Principal Findings: Patients (n = 40) were randomly assigned either to a music group (listening to instrumental music), or to a control group (listening to a non-musical placebo stimulus). Both groups listened to the auditory stimulus about 2 h before, and during the entire intra-operative period (during the intra-operative light sedation, subjects were able to respond lethargically to verbal commands). Results indicate that, during surgery, patients of the music group had a lower propofol consumption, and lower cortisol levels, compared to the control group. Conclusion/Significance: Our data show that listening to music during surgery under regional anesthesia has effects on cortisol levels (reflecting stress-reducing effects) and reduces sedative requirements to reach light sedation. PMID:21716581

Possible effects of an early diagnosis and treatment in patients with growth hormone deficiency: the state of art.

PubMed

Stagi, Stefano; Scalini, Perla; Farello, Giovanni; Verrotti, Alberto

2017-09-16

Growth hormone deficiency (GHD) is a relatively uncommon and heterogeneous endocrine disorder presenting in childhood with short stature. However, during the neonatal period, the metabolic effects of GHD may to require prompt replacement therapy to avoid possible life-threatening complications. An increasing amount of data suggests the importance of an early diagnosis and treatment of GHD because of its auxological, metabolic, and neurodevelopmental features with respect to the patients diagnosed and treated later in life.The available results show favourable auxological outcomes for patients with GHD diagnosed and treated with r-hGH early in life compared with those from patients with GHD who do not receive this early diagnosis and treatment. Because delayed referral for GHD diagnosis and treatment is still frequent, these results highlight the need for more attention in the diagnosis and treatment of GHD.Despite these very encouraging data regarding metabolic and neurodevelopmental features, further studies are needed to better characterize these findings. Overall, the importance of early diagnosis and treatment of GHD needs to be addressed.

Clinical outcomes of patients with hypothyroidism undergoing percutaneous coronary intervention

PubMed Central

Zhang, Ming; Sara, Jaskanwal D.S.; Matsuzawa, Yasushi; Gharib, Hossein; Bell, Malcolm R.; Gulati, Rajiv; Lerman, Lilach O.

2016-01-01

Abstract Aims The aim of this study was to investigate the association between hypothyroidism and major adverse cardiovascular and cerebral events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). Methods and results Two thousand four hundred and thirty patients who underwent PCI were included. Subjects were divided into two groups: hypothyroidism ( n = 686) defined either as a history of hypothyroidism or thyroid-stimulating hormone (TSH) ≥5.0 mU/mL, and euthyroidism ( n = 1744) defined as no history of hypothyroidism and/or 0.3 mU/mL ≤ TSH < 5.0 mU/mL. Patients with hypothyroidism were further categorized as untreated ( n = 193), or those taking thyroid replacement therapy (TRT) with adequate replacement (0.3 mU/mL ≤ TSH < 5.0 mU/mL, n = 175) or inadequate replacement (TSH ≥ 5.0 mU/mL, n = 318). Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. Median follow-up was 3.0 years (interquartile range, 0.5–7.0). After adjustment for covariates, the risk of MACCE and its constituent parts was higher in patients with hypothyroidism compared with those with euthyroidism (MACCE: HR: 1.28, P = 0.0001; myocardial infarction (MI): HR: 1.25, P = 0.037; heart failure: HR: 1.46, P = 0.004; revascularization: HR: 1.26, P = 0.0008; stroke: HR: 1.62, P = 0.04). Compared with untreated patients or those with inadequate replacement, adequately treated hypothyroid patients had a lower risk of MACCE (HR: 0.69, P = 0.005; HR: 0.78, P = 0.045), cardiac death (HR: 0.43, P = 0.008), MI (HR: 0.50, P = 0.0004; HR: 0.60, P = 0.02), and heart failure (HR: 0.50, P = 0.02; HR: 0.52, P = 0.017). Conclusion Hypothyroidism is associated with a higher incidence of MACCE compared with euthyroidism in patients undergoing PCI. Maintaining adequate control on TRT is beneficial in preventing MACCE. PMID:26757789

Short-term effects on bone turnover of replacing milk with cola beverages: a 10-day interventional study in young men.

PubMed

Kristensen, Mette; Jensen, Marlene; Kudsk, Jane; Henriksen, Marianne; Mølgaard, Christian

2005-12-01

In the Western world, increased consumption of carbonated soft drinks combined with a decreasing intake of milk may increase the risk of osteoporosis. This study was designed to reflect the trend of replacing milk with carbonated beverages in a group of young men on a low-calcium diet and studies the effects of this replacement on calcium homeostasis and bone turnover. This controlled crossover intervention study included 11 healthy men (22-29 years) who were given a low-calcium basic diet in two 10-day intervention periods with an intervening 10-day washout. During one period, they drank 2.5 l of Coca Cola per day and during the other period 2.5 l of semi-skimmed milk. Serum concentrations of calcium, phosphate, 25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol (1,25(OH)2D), osteocalcin, bone-specific alkaline phosphatase (B-ALP) and cross-linked C-telopeptides (CTX), plasma intact parathyroid hormone (PTH) and urinary cross-linked N-telopeptides (NTX) were determined at baseline and endpoint of each intervention period. An increase in serum phosphate (P<0.001), 1,25(OH)2D (P<0.001), PTH (P=0.046) and osteocalcin (P<0.001) was observed in the cola period compared to the milk period. Also, bone resorption was significantly increased following the cola period, seen as increased serum CTX (P<0.001) and urinary NTX (P<0.001) compared to the milk period. No changes were observed in serum concentrations of calcium or B-ALP. This study demonstrates that over a 10-day period high intake of cola with a low-calcium diet induces increased bone turnover compared to a high intake of milk with a low-calcium diet. Thus, the trend towards a replacement of milk with cola and other soft drinks, which results in a low calcium intake, may negatively affect bone health as indicated by this short-term study.

Effects of growth hormone therapy on bone density and fracture risk in age-related osteoporosis in the absence of growth hormone deficiency: a systematic review and meta-analysis.

PubMed

Barake, Maya; Arabi, Asma; Nakhoul, Nancy; El-Hajj Fuleihan, Ghada; El Ghandour, Sarah; Klibanski, Anne; Tritos, Nicholas A

2018-01-01

In adults, growth hormone deficiency (GHD) has been associated with low bone mineral density (BMD), an effect counteracted by growth hormone (GH) replacement. Whether GH is beneficial in adults with age-related bone loss and without hypopituitarism is unclear. We conducted a systematic literature search using Medline, Embase and the Cochrane Register of Controlled Trials. We extracted and analyzed data according to the bone outcome included [bone mineral content (BMC), BMD, and bone biomarker, fracture risk]. We performed a meta-analysis when possible. We included eight studies. Seven randomized 272 post-menopausal women, 61-69 years, to GH or control, for 6-24 months, and the eighth was an extension trial. Except for one study, all women received concurrent osteoporosis therapies. There was no significant effect of GH, as compared to control, on BMD at the lumbar spine (Weighted mean difference WMD = -0.01 [-0.04, 0.02]), total hip (WMD = 0 [-0.05, 0.06]) or femoral neck (WMD = 0 [-0.03, 0.04]). Similarly, no effect was seen on BMC. GH significantly increased the bone formation marker procollagen type-I carboxy-terminal propeptide (PICP) (WMD = 14.03 [2.68, 25.38]). GH resulted in a trend for increase in osteocalcin and in bone resorption markers. Patients who received GH had a significant decrease in fracture risk as compared to control (RR = 0.63 [0.46, 0.87]). Reported adverse events were not major, mostly related to fluid retention. GH may not improve bone density in women with age-related bone loss but may decrease fracture risk. Larger studies of longer duration are needed to further explore these findings in both genders, and to investigate the effect of GH on bone quality.

A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement.

PubMed

Asghar, Ali; Ikram, Mubasher; Islam, Najmul

2012-07-28

Parathyroid adenoma with cystic degeneration is a rare cause of primary hyperparathyroidism. The clinical and biochemical presentation may mimic parathyroid carcinoma. We report the case of a 55 year old lady, who had longstanding history of depression and acid peptic disease. Serum calcium eight months prior to presentation was slightly high, but she was never worked up. She was found to be Vitamin D deficient while being investigated for generalized body aches. A month after she was replaced with Vitamin D, she presented to us with parathyroid crisis. Her corrected serum calcium was 23.0 mg/dL. She had severe gastrointestinal symptoms and acute kidney injury. She had unexplained consistent hypokalemia until surgery. Neck ultrasound and CT scan revealed giant parathyroid cyst extending into the mediastinum. After initial medical management for parathyroid crisis, parathyroid cystic adenoma was surgically excised. Her serum calcium, intact parathyroid hormone, creatinine and potassium levels normalized after surgery. This case of parathyroid crisis, with very high serum calcium and parathyroid hormone levels, is a rare presentation of parathyroid adenoma with cystic degeneration. This case also highlights that Vitamin D replacement may unmask subclinical hyperparathyroidism. Consistent hypokalemia until surgery merits research into its association with hypercalcemia.

Myopathy in hyperthyroidism as a consequence of rapid reduction of thyroid hormone

PubMed Central

Li, Qianrui; Liu, Yuping; Zhang, Qianying; Tian, Haoming; Li, Jianwei; Li, Sheyu

2017-01-01

Abstract Rationale: Myalgia and elevated creatine kinase (CK) are occasionally observed during the treatment of hyperthyroid patients. Relative hypothyroidism resulted from rapid thyroid hormone reduction had been promoted as a plausible cause of these myopathic changes, however rarely reported. Patient concerns: We hereby presented a 20-year-old female with Grave's disease, who developed myopathy and elevated CK during rapid correction of thyroid hormone. Diagnoses: Relative hypothyroidism-induced myopathy. Interventions: Antithyroid drug (ATD) dosage was reduced without levothyroxine replacement. Outcomes: The muscular symptoms were recovered with CK level returned to normal after adoption of the euthyroid status. Lessons: Differentiation of relative hypothyroidism from other causes of myopathy, especially with the effect of ATD, is important for clinical practice, although difficult in many cases. PMID:28746208

The influence of conformational restriction in the C-terminus of growth hormone secretagogues on their potency.

PubMed

Peschke, Bernd; Ankersen, Michael; Bauer, Michael; Hansen, Thomas Kruse; Hansen, Birgit Sehested; Nielsen, Karin Kramer; Raun, Kirsten; Richter, Lutz; Westergaard, Lisbet

2002-06-01

In order to obtain more potent growth hormone secretagogues, a comparison of ipamorelin and NN703 suggested the addition of a polar group at the C-terminus of NN703. A study was conducted using constrained amines for this purpose. Here, substituted 4-piperidinylamino- and 4-dimethylaminopiperidino-substituents were found to give the most active compounds. A replacement of the 4-dimethylaminopiperidino-substituent with 4-hydroxypiperidino resulted in a series of compounds, which showed in vitro activity with EC(50) values in the low nanomolar range, and favourable kinetic properties, such as 40% oral bioavailability. The most promising compound was also tested in a swine in vivo model, resulting in a growth hormone level with a C(max) of over 40 ng mL(-1).

Menopause and the vaginal microbiome.

PubMed

Muhleisen, Alicia L; Herbst-Kralovetz, Melissa M

2016-09-01

For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identifying target regions for vigilance improvement under hormone replacement therapy in postmenopausal syndrome patients by means of electroencephalographic tomography (LORETA).

PubMed

Saletu, B; Anderer, P; Saletu-Zyhlarz, G M; Gruber, D; Metka, M; Huber, J

2005-04-01

Daytime fatigue, which at the neurophysiological level is due to vigilance decrements, is a frequent complaint in postmenopausal women. In a three-arm, 2-month, parallel group-design study, vigilance-promoting effects of a novel continuous combination (=Climodien 2/3) of estradiol valerate (EV; 2 mg) and dienogest (DNG; 3 mg) were compared with the effects of both EV alone and placebo in 55 insomniac, postmenopausal syndrome patients. Low-resolution brain electromagnetic tomography (LORETA) was undertaken to identify the cerebral target regions of hormone replacement therapy. An omnibus significance test revealed Climodien to increase activity in 882 of 2,394 voxels in the alpha-2 band, followed by 733, 706, and 664 voxels in the beta-2, beta-1, and beta-3 bands, and 509 voxels in the delta band, whereas 2 mg EV alone did not produce a significant suprathreshold activity. Current density increased predominantly in the right hemisphere, which had already been described in the literature as the center of the vigilance system. In the fast alpha range, which plays a major role in the context of vigilance, increased activity was found in the right prefrontal, temporal, and superior parietal cortices, i.e., those brain areas of the right-sided fronto-parietal neuronal network that are responsible for sustained attention. A further activity increase was seen in the anterior cingulate gyrus associated with attentional control and conflict monitoring. The right temporal lobe showed increased current density in all frequency bands. Electroencephalographic tomography (LORETA) identified the right-hemispheric vigilance system as the target region of Climodien.

The effects of hormone replacement therapy on dry eye syndromes evaluated by Schirmer test depend on patient age.

PubMed

Feng, Yanhong; Feng, Gang; Peng, Shuli; Li, Hui

2016-04-01

This study was performed to explore the effects of hormone replacement therapy (HRT) on aqueous tear production and tear quality in dry eye syndrome (DES) patients of different ages. Eighty-eight women with DES at least one year after spontaneous menopause were randomly divided into the HRT group that were treated with orally estrogen and medroxyprogesterone acetate or a control group that did not receive any treatment. The aqueous tear production and tear quality were measured by Schirmer test and tear film break up time (TBUT) before and after one month of treatment. The subjects were subdivided according to age; the HRT group was divided into groups A (age range: 44-49 years) and B (age range: 50-57 years), and the controls were divided into groups C (age range: 46-49 years) and D (age range: 50-55 years). The changes in results of Schirmer test and TBUT before and after treatment were compared within each group and were correlated with the age of the participants. After one-month follow-up, HRT use improved the Schirmer test but the effect was significant only for participants less than 50 years old. The improvement in Schirmer test result was negatively correlated with the age of the participants. The TBUT did not change significantly within each group after HRT use. HRT use may improve aqueous tear production but not the quality of tears in DES, and the effect on tear production is dependent on age. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cutaneous estradiol permeation, penetration and metabolism in pig and man.

PubMed

Mahmoud, A; Haberland, A; Dürrfeld, M; Heydeck, D; Wagner, S; Schafer-Korting, M

2005-01-01

Drug development in dermatotherapy and also development of transdermal therapeutic systems (TTS) demand high-predictive in vitro models to estimate drug levels in skin and systemic uptake. Here we compare three ready-to-use models, reconstructed human epidermis, split porcine skin and the perfused porcine forelimb. 17beta-Estradiol (E(2)), which is highly metabolized by skin cells, serves as model drug since E(2) application is of high relevance in hormone replacement therapy while topical E(2) may promote wound healing. E(2) TTS, gel and an ethanolic solution were investigated for cutaneous penetration, permeation and metabolism. E(2) TTS enabled an E(2) uptake of 42.9% of the applied dose accompanied by a high percentage of E(2) metabolism (30% of the penetrated dose) in the perfused porcine forelimb. In Franz cell experiments with reconstructed human epidermis and split porcine skin, the gel allowed an E(2) uptake of 41.7 and 22.9% of the applied dose accompanied by a high E(2) metabolism (42.6 and 28.6% of the penetrated dose). Due to toxic effects of the vehicle, this was not true with an ethanolic solution, then E(2) permeation and metabolism were clearly diminished. Most importantly, the in vitro models proved to be predictive with respect to the E(2)/estrone ratio in female plasma under transdermal hormone replacement therapy. In vitro tests should reduce the need for both animal and human studies for cutaneous uptake and metabolism in the future. Copyright 2005 S. Karger AG, Basel.

Dietary Boron and Hormone Replacement Therapy as Risk Factors for Lung Cancer in Women

PubMed Central

Mahabir, S.; Spitz, M. R.; Barrera, S. L.; Dong, Y. Q.; Eastham, C.; Forman, M. R.

2012-01-01

Hormone replacement therapy (HRT) may reduce lung cancer risk. Dietary boron may have actions similar to those of HRT; however, no previous study has reported the associations between dietary boron intake and lung cancer risk or the joint effects of boron intake and HRT use on lung cancer risk. The authors examined the associations between boron intake and the joint effects of boron intake and HRT on lung cancer risk in women. In an ongoing case-control study in Houston, Texas (July 1995 through April 2005, end date for this analysis), 763 women were diagnosed with lung cancer, and 838 were matched healthy controls with data on both diet and HRT. Multiple logistic regression analyses were conducted to assess the associations between dietary boron and HRT with lung cancer risk. After adjustment for potential confounders, the odds ratios for lung cancer with decreasing quartiles of dietary boron intake were 1.0, 1.39 (95% confidence interval (CI): 1.02, 1.90), 1.64 (95% CI: 1.20, 2.24), and 1.95 (95% CI: 1.42, 2.68) mg/day, respectively, for all women (ptrend < 0.0001). In joint-effects analyses, compared with women with high dietary boron intake who used HRT, the odds ratio for lung cancer for low dietary boron intake and no HRT use was 2.07 (95% CI: 1.53, 2.81). Boron intake was inversely associated with lung cancer in women, whereas women who consumed low boron and did not use HRT were at substantial increased odds. PMID:18343880

CHARACTERIZATION OF SPONTANEOUS AND INDUCED PUBERTY IN GIRLS WITH TURNER SYNDROME.

PubMed

Folsom, Lisal J; Slaven, James E; Nabhan, Zeina M; Eugster, Erica A

2017-07-01

To characterize puberty in girls with Turner syndrome (TS) and determine whether specific patient characteristics are associated with the timing of menarche. We also sought to compare spontaneous versus induced puberty in these patients. Medical records of girls followed in our Pediatric Endocrine clinic for TS from 2007 to 2015 were reviewed. Fifty-three girls were included, of whom 10 (19%) achieved menarche spontaneously and 43 (81%) received hormone replacement therapy (HRT). Of girls receiving HRT, a younger age at estrogen initiation correlated with a longer time to menarche (P = .02), and a mosaic karyotype was associated with a shorter time to menarche (P = .02), whereas no relationship was seen for body mass index, estrogen regimen, or maternal age at menarche. Nineteen girls (44%) receiving HRT had bleeding on estrogen alone at a wide dose range and were more likely to be on transdermal than oral preparations (P = .01). Girls with spontaneous puberty achieved menarche at a younger age (P<.01) and were more likely to have mosaic TS (P = .02). Significant variability in the timing of menarche exists among girls with TS. However, age at pubertal induction and karyotype were significantly correlated with age at menarche in our patients. A wide range of estrogen doses is seen in girls who bleed prior to progesterone, suggesting extreme variability in estrogen sensitivity among patients with TS. Girls achieving spontaneous menarche are younger and more likely to have a mosaic karyotype than those with induced menarche. Large-scale prospective studies are needed to confirm these results. BMI = body mass index; HRT = hormone replacement therapy; TS = Turner syndrome.

Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4.

PubMed

Filges, Isabel; Bischof-Renner, Andrea; Röthlisberger, Benno; Potthoff, Christian; Glanzmann, René; Günthard, Joëlle; Schneider, Jacques; Huber, Andreas R; Zumsteg, Urs; Miny, Peter; Szinnai, Gabor

2012-02-01

Clinical presentation of hypopituitarism in the neonate may be variable, ranging from absent to severe nonspecific symptoms and may be life-threatening in patients with adrenocorticotropic hormone deficiency. The LIM homeobox gene 4 (LHX4) transcription factor regulates early embryonic development of the anterior pituitary gland. Autosomal dominant mutations in LHX4 cause congenital hypopituitarism with variable combined pituitary hormone deficiency (CPHD). We report on a neonate with unexplained heart failure and minor physical anomalies, suggesting a midline defect. She was diagnosed with complete CPHD. Cardiac function was rescued by replacement with hydrocortisone and thyroxine; hypoglycaemia stopped under growth hormone therapy. Magnetic resonance imaging revealed a dysgenetic pituitary gland suggesting an early developmental defect. Array comparative genomic hybridization showed a maternally inherited 1.5-megabase microdeletion in 1q25.2q25.3, including the LHX4 gene. Haploinsufficiency of LHX4 likely explains the predominant pituitary phenotype in the proposita and we suggest variable intrafamilial penetrance of the inherited microdeletion. To the best of our knowledge, we are the first to report on heart failure as a rare nonspecific symptom of treatable CPHD in the newborn. Variably penetrant pituitary insufficiency, including this severe and atypical presentation, can be correlated with LHX4 insufficiency and highlights the role of LHX4 for pituitary development.

Identification of genes mediating thyroid hormone action in the developing mouse cerebellum.

PubMed

Takahashi, Masaki; Negishi, Takayuki; Tashiro, Tomoko

2008-02-01

Despite the indispensable role thyroid hormone (TH) plays in brain development, only a small number of genes have been identified to be directly regulated by TH and its precise mechanism of action remains largely unknown, partly because most of the previous studies have been carried out at postnatal day 15 or later. In the present study, we screened for TH-responsive genes in the developing mouse cerebellum at postnatal day 4 when morphological alterations because of TH status are not apparent. Among the new candidate genes selected by comparing gene expression profiles of experimentally hypothyroid, hypothyroid with postnatal thyroxine replacement, and control animals using oligoDNA microarrays, six genes were confirmed by real-time PCR to be positively (orc1l, galr3, sort1, nlgn3, cdk5r2, and zfp367) regulated by TH. Among these, sort1, cdk5r2, and zfp367 were up-regulated already at 1 h after a single injection of thyroxine to the hypothyroid or control animal, suggesting them to be possible primary targets of the hormone. Cell proliferation and apoptosis examined by BrdU incorporation and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling assay revealed that hypothyroidism by itself did not enhance apoptosis at this stage, but rather increased cell survival, possibly through regulation of these newly identified genes.

Proteomic comparison by iTRAQ combined with mass spectrometry of egg white proteins in laying hens (Gallus gallus) fed with soybean meal and cottonseed meal

PubMed Central

He, Tao; Zhang, Haijun; Wang, Jing; Wu, Shugeng; Yue, Hongyuan; Qi, Guanghai

2017-01-01

Cottonseed meal (CSM) is commonly used in hens’ diets to replace soybean meal (SBM). However, the molecular consequences of this substitution remains unclear. To investigate the impact of this substitution at the molecular level, iTRAQ combined with biochemical analysis was performed in Hy-Line W-36 hens supplemented with a mixed diet of CSM and SBM. Egg weight, albumen height, and Haugh unit were significantly reduced in the CSM100 group (100% crude protein of SBM replaced by CSM) compared with the SBM group (P<0.05). A total of 15 proteins, accounting for 75% of egg white proteins with various biological functions of egg whites, were found to be reduced. This finding may relate to the decrease of albumen quality in the CSM100 group. Oviduct magnum morphology and hormone analysis indicated that a reduced level of plasma progesterone caused reduced growth of the tubular gland and epithelial cells in the magnum, further decreasing egg white protein synthesis in the magnum. These findings help demonstrate the molecular mechanisms of a CSM diet that cause adverse effects on albumen quality, while also showing that SBM should not be totally replaced with CSM in a hen diet. PMID:28813468

Soy isoflavone supplementation and breast density in postmenopausal women

USDA-ARS?s Scientific Manuscript database

Soy isoflavones may protect against breast cancer. Breast density, a marker for breast cancer risk, increases as a result of hormone replacement therapy. We examined the relation between isoflavone supplementation and breast density using the mammograms from 358 women who participated in the multi-s...

Burn-induced Myxedema Crisis

PubMed Central

Batista, Ann S.; Zane, Laura L.; Smith, Lane M.

2017-01-01

Myxedema crisis (MC) is a rare but life-threatening illness characterized by multi-system organ impairment from thyroid hormone deficiency that is often brought on by an eliciting event. We present the case of MC with a rapid progression of hypothermia, altered mental status, and respiratory failure that was instigated by a flash burn to the face. The patient’s condition was refractory to rewarming and supportive efforts until thyroid hormone was replaced. This case illustrates the need for a high index of suspicion for patients with a rapid onset of metabolic encephalopathy immediately after an injury or burn. PMID:29849399

Resection of a Retrochiasmatic Craniopharyngioma by Combined Modified Orbital Craniotomy and Transnasal Endoscopic Techniques.

PubMed

Patel, Nirav J; Dunn, Ian

2018-04-01

A 20-year-old patient presented with hydrocephalus but intact vision and hormone function. The MRI showed a large seller, suprasellar and third ventricular mass. We chose a combined approach utilizing the translyvian, lamina terminals route, with a possible interhemispheric approach. But, we also utilized a transnasal endoscopic approach for the tumor that remained below the diaphragma sellae. The patient did well, with complete tumor resection via a staged approach, but did require hormone replacement. The link to the video can be found at: https://youtu.be/yzpfOxzI4cQ .

Multihormonal regulation of thyroglobulin production by the OVNIS 6H thyroid cell line.

PubMed

Aouani, A; Hovsépian, S; Fayet, G

1988-02-01

The hormonal regulation of thyroglobulin production has been studied using a clone of the ovine thyroid cell line: OVNIS 6H. 3 among the 6 hormones proposed for serum replacement are required for an optimal thyroglobulin production; insulin, hydrocortisone and thyrotropin. Insulin alone stimulates thyroglobulin production. The presence of insulin is also required to observe hydrocortisone and TSH stimulations. Newborn calf serum inhibits thyroglobulin production. The best conditions for optimal thyroglobulin expression and TSH responsiveness are obtained in serum-free medium supplemented with 5 micrograms/ml insulin, 100 nM hydrocortisone and 1 mU/ml TSH.

Dermatosis associated with menopause

PubMed Central

Nair, Pragya A.

2014-01-01

Menopause is defined as permanent irreversible cessation of menses brought by decline in ovarian follicular activity. Hormonal alteration results in various physical, psychological, and sexual changes in menopausal women. Associated dermatological problems can be classified as physiological changes, age-related changes, changes due to estrogen deficiency and due to hormone replacement therapy. Dermatosis seen due to estrogen deficiency includes Atrophic Vulvovaginitis, Vulvar Lichen Sclerosus, Dyaesthetic Vulvodynia, Hirsutism, Alopecia, Menopausal Flushing, Keratoderma Climactericum, Vulvovaginal Candidiasis. Dermatologists and gynecologists need to be familiar with the problems of menopausal women, as with increase in life expectancy, women passing through this phase is rising. PMID:25540566

Lack of normal MR enhancement of the pituitary gland: findings in three siblings with combined pituitary hormone deficiency.

PubMed

Falcone, S; Sanchez, J; Quencer, R M

1998-02-01

We present the MR appearance of the sella turcica in three sibling dwarfs with combined pituitary hormone deficiency in which MR images revealed a peripheral curvilinear band of enhancement about the pituitary gland in all three patients, a normal-size pituitary gland in two siblings, a mildly enlarged pituitary gland in one sibling, and a thin infundibulum and a normal posterior pituitary bright spot in all three siblings. Possible antecedents include an abnormal vascular supply, pituitary gland replacement by a nonfunctioning adenoma, a proteinaceous cyst, or a hamartoma.

Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement

PubMed Central

Bianco, Antonio C.; Bauer, Andrew J.; Burman, Kenneth D.; Cappola, Anne R.; Celi, Francesco S.; Cooper, David S.; Kim, Brian W.; Peeters, Robin P.; Rosenthal, M. Sara; Sawka, Anna M.

2014-01-01

Background: A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Methods: Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. Results: We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non–levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. Conclusions: We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine–liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile. PMID:25266247

Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.

PubMed

Jonklaas, Jacqueline; Bianco, Antonio C; Bauer, Andrew J; Burman, Kenneth D; Cappola, Anne R; Celi, Francesco S; Cooper, David S; Kim, Brian W; Peeters, Robin P; Rosenthal, M Sara; Sawka, Anna M

2014-12-01

A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non-levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine-liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile.

Central hypothyroidism in adults: better understanding for better care.

PubMed

Grunenwald, Solange; Caron, Philippe

2015-02-01

Central hypothyroidism (CH) is a rare cause of hypothyroidism generally related to a hypothalamic-pituitary disorder or arising as an iatrogenic complication. In adults, CH may be secondary to quantitative and/or qualitative alterations in thyroid-stimulating hormone (TSH) secretion. The disease is difficult to diagnose clinically because it lacks specific clinical signs and these may be masked by other anterior pituitary hormone secretion deficiencies. In patients with long-standing and marked CH, a diagnosis may be made based on low free T4 levels and normal, low or moderately increased TSH levels. In patients with early-stage or moderate CH, exploration of the circadian TSH cycle, determination of TSH response after a TRH test or recombinant TSH injection, estimation of TSH index, or evaluation of peripheral indexes of thyroid hormone metabolism may be required to establish a diagnosis. Regarding treatment, patients should receive levothyroxine replacement therapy, but hormone objectives during follow-up need to be precisely determined in order to reduce cardiovascular risks and to improve the quality of life of patients.

Dry Eye Syndrome in Menopause and Perimenopausal Age Group.

PubMed

Peck, Travis; Olsakovsky, Leslie; Aggarwal, Shruti

2017-01-01

Dry eye disease (DED) is a multifactorial ocular surface disease that causes symptoms of ocular pain, discomfort, and decreased visual acuity. It significantly affects quality of life of patients. It is more prevalent in the females and is being specifically in the menopausal and postmenopausal age group. This is believed to be due to the changes in balance of sex hormones. Sex hormones - estrogens and androgens - influence production of all components of the tear film including aqueous layer, lipid, and mucin. Various mechanisms such as decrease in hormonal levels, shift in feedback mechanisms, and changes in receptor receptivity interplay to alter the ocular surface homeostasis and subsequently result in DED. Several studies have suggested potential role of hormone replacement therapy in menopause-associated dry eye symptoms. The purpose of this review is to help the non ophthalmic physicians about DED encountered commonly in menopausal age group. It is important for primary care physicians to understand DED due to its high prevalence, often debilitating symptoms and the potentially preventable and treatable nature of the condition.

Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity.

PubMed

Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

2016-05-23

The uroguanylin-GUCY2C gut-brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ER(T2)-Rosa-STOP(loxP/loxP)-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms regulating food consumption through loss of anorexigenic endocrine signaling. The correlative therapeutic paradigm suggests that, in the context of hormone insufficiency with preservation of receptor sensitivity, obesity may be prevented or treated by GUCY2C hormone replacement.

Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study.

PubMed

Francomano, D; Bruzziches, R; Barbaro, G; Lenzi, A; Aversa, A

2014-04-01

Modifications of cardiovascular and metabolic parameters during testosterone (T) replacement and withdrawal have never been investigated in severely obese hypogonadal men. Twenty-four severely obese (mean BMI 42; mean age 54.5) hypogonadal men (mean T = 245 ± 52 ng/dL) were enrolled in an observational, parallel-arm, open-label, 54-week study of hypocaloric diet plus physical activity (DPE; n = 12) or DPE plus T injections (DPE + T; n = 12), followed by 24 weeks of DPE alone. Primary endpoints were variations from baseline of cardiovascular (cardiac performance, blood pressure, endothelial function, carotid intima-media thickness, CIMT; epicardial fat thickness, EF) and body composition (fat/lean mass) parameters. Secondary endpoints were variations from baseline of hormonal (T and GH) and metabolic (oral glucose tolerance test, lipids, fibrinogen) parameters. At 54 weeks, DPE + T showed improvements in EF, ejection fraction, diastolic function, CIMT and endothelial function (p < 0.01 vs. controls). Also, hormonal (T, p < 0.0001; GH, p < 0.01), metabolic (HOMA, p < 0.01; microalbuminuria, p < 0.01), lipid (total cholesterol, p < 0.05) and inflammatory (fibrinogen, p < 0.05) parameters improved. After 24 weeks from T withdrawal, all cardiac and hormonal parameters returned to baseline, while fat but not lean mass and blood pressure ameliorations were maintained. An inverse relationship either between EF vs. endothelial function and EF vs. T levels was found (r (2) = -0.46, p < 0.001 and r (2) = -0.56, p < 0.0005, respectively) while direct relationship between T vs. endothelial function occurred (r (2) = 0.43, p < 0.005) in DPE + T. A 33 % dropout rate was reported in DPE without serious adverse events. In middle-aged hypogonadal obese men, 1-year T treatment was safe and improved cardio-metabolic and hormonal parameters. We firstly demonstrated that T withdrawal determines a return back to hypogonadism within 6 months, with loss of cardiovascular and some body composition improvements attained.

Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity

PubMed Central

Kim, G W; Lin, J E; Snook, A E; Aing, A S; Merlino, D J; Li, P; Waldman, S A

2016-01-01

Background/Objectives: The uroguanylin-GUCY2C gut–brain axis has emerged as one component regulating feeding, energy homeostasis, body mass and metabolism. Here, we explore a role for this axis in mechanisms underlying diet-induced obesity (DIO). Subjects/Methods: Intestinal uroguanylin expression and secretion, and hypothalamic GUCY2C expression and anorexigenic signaling, were quantified in mice on high-calorie diets for 14 weeks. The role of endoplasmic reticulum (ER) stress in suppressing uroguanylin in DIO was explored using tunicamycin, an inducer of ER stress, and tauroursodeoxycholic acid (TUDCA), a chemical chaperone that inhibits ER stress. The impact of consumed calories on uroguanylin expression was explored by dietary manipulation. The role of uroguanylin in mechanisms underlying obesity was examined using Camk2a-Cre-ERT2-Rosa-STOPloxP/loxP-Guca2b mice in which tamoxifen induces transgenic hormone expression in brain. Results: DIO suppressed intestinal uroguanylin expression and eliminated its postprandial secretion into the circulation. DIO suppressed uroguanylin through ER stress, an effect mimicked by tunicamycin and blocked by TUDCA. Hormone suppression by DIO reflected consumed calories, rather than the pathophysiological milieu of obesity, as a diet high in calories from carbohydrates suppressed uroguanylin in lean mice, whereas calorie restriction restored uroguanylin in obese mice. However, hypothalamic GUCY2C, enriched in the arcuate nucleus, produced anorexigenic signals mediating satiety upon exogenous agonist administration, and DIO did not impair these responses. Uroguanylin replacement by transgenic expression in brain repaired the hormone insufficiency and reconstituted satiety responses opposing DIO and its associated comorbidities, including visceral adiposity, glucose intolerance and hepatic steatosis. Conclusions: These studies reveal a novel pathophysiological mechanism contributing to obesity in which calorie-induced suppression of intestinal uroguanylin impairs hypothalamic mechanisms regulating food consumption through loss of anorexigenic endocrine signaling. The correlative therapeutic paradigm suggests that, in the context of hormone insufficiency with preservation of receptor sensitivity, obesity may be prevented or treated by GUCY2C hormone replacement. PMID:27214655

Hypopituitarism following envenoming by Russell's vipers (Daboia siamensis and D. russelii) resembling Sheehan's syndrome: first case report from Sri Lanka, a review of the literature and recommendations for endocrine management.

PubMed

Antonypillai, C N; Wass, J A H; Warrell, D A; Rajaratnam, H N

2011-02-01

Russell's vipers (Daboia russelii and D. siamensis) inhabit 10 South and South East Asian countries. People envenomed by these snakes suffer coagulopathy, bleeding, shock, neurotoxicity, acute kidney injury and local tissue damage leading to severe morbidity and mortality. An unusual complication of Russell's viper bite envenoming in Burma (D. siamensis) and southern India (D. russelii) is hypopituitarism but until now it has not been reported elsewhere. Here, we describe the first case of hypopituitarism following Russell's viper bite in Sri Lanka, review the literature on this subject and make recommendations for endocrine investigation and management. A 49-year-old man was bitten and seriously envenomed by D. russelii in 2005. He was treated with antivenom but although he recovered from the acute effects he remained feeling unwell. Hypopituitarism, with deficiencies of gonadal, steroid and thyroid axes, was diagnosed 3 years later. He showed marked improvement after replacement of anterior pituitary hormones. We attribute his hypopituitarism to D. russelii envenoming. Russell's viper bite is known to cause acute and chronic hypopituitarism and diabetes insipidus, perhaps through deposition of fibrin microthrombi and haemorrhage in the pituitary gland resulting from the action of venom procoagulant enzymes and haemorrhagins. Forty nine cases of hypopituitarism following Russell's viper bite have been described in the English language literature. Patients with acute hypopituitarism may present with hypoglycaemia and hypotension during the acute phase of envenoming. Those with chronic hypopituitarism seem to have recovered from envenoming but present later with features of hypopituitarism. Over 85% of these patients had suffered acute kidney injury immediately after the bite. Steroid replacement in acute hypopituitarism is life saving. All 11 patients with chronic hypopituitarism in whom the outcome of treatment was reported, showed marked improvement with hormone replacement. Unrecognized acute hypopituitarism is potentially fatal while chronic hypopituitarism can be debilitating. Physicians should therefore be aware of this complication of severe envenoming by Russell's vipers, especially in Burma and South India, so that the diagnosis may be made without delay and replacement started with essential hormones such as hydrocortisone and thyroxine.

Physiologic Growth Hormone-Replacement Therapy and Craniopharyngioma Recurrence in Pediatric Patients: A Meta-Analysis.

PubMed

Alotaibi, Nawaf M; Noormohamed, Nadia; Cote, David J; Alharthi, Salman; Doucette, Joanne; Zaidi, Hasan A; Mekary, Rania A; Smith, Timothy R

2018-01-01

A systematic review and meta-analysis were conducted to examine the effect of growth hormone-replacement therapy (GHRT) on the recurrence of craniopharyngioma in children. PubMed, Embase, and Cochrane databases were searched through April 2017 for studies that evaluated the effect of GHRT on the recurrence of pediatric craniopharyngioma. Pooled effect estimates were calculated with fixed- and random-effects models. Ten studies (n = 3487 patients) met all inclusion criteria, including 2 retrospective cohorts and 8 case series. Overall, 3436 pediatric patients were treated with GHRT after surgery and 51 were not. Using the fixed effect model, we found that the overall craniopharyngioma recurrence rate was lower among children who were treated by GHRT (10.9%; 95% confidence interval 9.80%-12.1%; I 2  = 89.1%; P for heterogeneity <0.01; n = 10 groups) compared with those who were not (35.2%; 95% confidence interval 23.1%-49.6%; I 2  = 61.7%; P for heterogeneity = 0.11; n = 3); the P value comparing the 2 groups was <0.01. Among patients who were treated with GHRT, subgroup analysis revealed that there was a greater prevalence of craniopharyngioma recurrence among studies conducted outside the United States (P < 0.01), single-center studies (P < 0.01), lower impact factor studies (P = 0.03), or studies with a lower quality rating (P = 0.01). Using the random-effects model, we found that the results were not materially different except for when stratifying by GHRT, impact factor, or study quality; this led to nonsignificant differences. Both Begg's rank correlation test (P = 0.7) and Egger's linear regression test (P = 0.06) indicated no publication bias. This meta-analysis demonstrated a lower recurrence rate of craniopharyngioma among children treated with GHRT than those who were not. Copyright © 2017 Elsevier Inc. All rights reserved.

Cross-sectional analyses of participation in cancer screening and use of hormone replacement therapy and medications in meat eaters and vegetarians: the EPIC-Oxford study

PubMed Central

Appleby, Paul N; Bradbury, Kathryn E; Key, Timothy J

2017-01-01

Objectives To examine differences in health-related behaviours such as screening or testing for cancer, use of hormone replacement therapy (HRT) and use of other medications in different diet groups. Design We studied 31 260 participants across four diet groups (18 155 meat eaters, 5012 fish eaters, 7179 vegetarians, 914 vegans) in the UK EPIC-Oxford cohort. Information was collected in 5-year (around 2000–2003) or 10-year (around 2007) follow-up questionnaires regarding participation in breast screening, cervical screening, prostate-specific antigen (PSA) testing, use of HRT and use of medications for the past 4 weeks. Using Poisson regression, we estimated the prevalence ratios (PR) for each behaviour across people of different diet groups, using meat eaters as the reference group. Results Compared with meat eaters, vegetarian (PR: 0.94, 95% CI 0.89 to 0.98) and vegan (PR: 0.82, 95% CI 0.71 to 0.95) women reported lower participation in breast screening, and vegetarian men were less likely to report PSA testing (PR: 0.82, 95% CI 0.71 to 0.96). No differences were observed among women for cervical screening. In women, all non-meat-eating groups reported lower use of HRT compared with meat eaters (P heterogeneity <0.0001). Lower reported use of any medication was observed for participants in all non-meat-eating groups with no (P<0.0001) or one (P=0.0002) self-reported illness. No heterogeneity was observed across the diet groups for the reported use of specific medication for high blood pressure, high blood cholesterol, asthma, diabetes and thyroid disease. Conclusions Differences in self-reported breast screening, PSA testing, HRT use and overall medication use were observed across the diet groups. Whether such differences contribute to differential long-term disease risks requires further study. PMID:29284719

The Impact of Menopause: Implications for Mental Health Counselors.

ERIC Educational Resources Information Center

Baldo, Tracy D.; Schneider, Mercedes K.; Slyter, Marty

2003-01-01

The purpose of this article is to present a brief, informative view of the impact of menopause along with implications for mental health counselors. Menopause and associated stages are defined; symptoms associated with these stages are discussed; the benefits, risks, and consequences of hormone replacement therapy are considered; and…

Stromal-Epithelial Interactions and Tamoxifen-Sensitivity: A Bench-to-Beside Model of Chemoprevention

DTIC Science & Technology

2007-05-01

uniformity of the cohort. Women were considered to be peri- menopausal, as defined by < 6 menstrual periods/year in the absence of pregnancy, polycystic ...surgical removal of both ovaries , respectively. Socio-demographic variables (age, race), hormone- replacement (HRT)-use, and family history of breast

Vasodilating effect of norethisterone and its 5 alpha metabolites: a novel nongenomic action.

PubMed

Perusquía, Mercedes; Villalón, Carlos M; Navarrete, Erika; García, Gustavo A; Pérez-Palacios, Gregorio; Lemus, Ana E

2003-08-15

Estrogens are generally administered in hormone replacement therapy in combination with synthetic progestins. Studies of cardiovascular risk factors in postmenopausal women have shown a variety of responses according to the molecular structure of the progestin used in hormone replacement therapy schemes. The present study sets out to determine the vasoactive effects of norethisterone and its 5alpha-dihydro (5alpha-norethisterone) and -tetrahydro (3alpha,5alpha-norethisterone and 3beta,5alpha-norethisterone) metabolites in isolated precontracted rat thoracic aorta. The addition of norethisterone and 3alpha,5alpha-norethisterone in rat aorta exhibited a potent, concentration-response inhibition of noradrenaline-induced contraction, while 5alpha- and 3beta,5alpha-norethisterone had very little, if any, vasorelaxing effect. Relaxation to norethisterone and 3alpha,5alpha-norethisterone had very rapid time-courses and it was neither affected by the absence of endothelium nor by the inhibitor of nitric oxide synthase, Nomega-nitro-L-arginine methyl ester (L-NAME). The addition of specific anti-androgen, anti-progestin and anti-estrogen compounds and protein synthesis inhibitors did not preclude the vasorelaxing effect of norethisterone and its 3alpha,5alpha-reduced metabolite. The results strongly suggest that these effects are not mediated by nuclear sex steroid hormone receptors. The overall data document a novel nongenomic endothelium-independent vasorelaxing action of a 19-nor synthetic progestin and one of its A-ring-reduced derivatives.

Update on the effect of exogenous hormone use on glioma risk in women: a meta-analysis of case-control and cohort studies.

PubMed

Lan, Yu-Long; Wang, Xun; Lou, Jia-Cheng; Ma, Bin-Bin; Xing, Jin-Shan; Zou, Shuang; Zhang, Bo

2018-04-01

Various studies have confirmed the important roles of endogenous hormones in the development of gliomas, while the roles of exogenous hormones remain controversial. Based on case-control studies and cohort studies, a meta-analysis was exerted to explore the effect of two exogenous hormones use (HRT: hormone replacement therapy; OC: oral contraceptives) on glioma risk. 16 eligible studies, including 11 case-control studies and 5 cohort studies, containing 8055027 women, were included in our study. All included studies have reported the relative risks (RRs) or odds ratios (ORs), and 95% confidence intervals (CIs). We use the fixed-effects model to calculate the estimated overall risk. In case-control studies, the risk of glioma was lower in women who had ever been treated with an exogenous hormone than in the control group (HRT: OR 0.91, 95% CI 0.84-0.99; OC: OR 0.99, 95% CI 0.91-1.07). In research of cohort studies, similar results have been obtained (HRT: RR 0.95, 95% CI 0.83-1.08; OC: RR 0.75, 95% CI 0.66-0.84). Our study further confirmed that the use of exogenous hormones has an important impact on the risk of glioma in women. However, more prospective studies are needed to further confirm this conclusion.

Predicting the probability of abnormal stimulated growth hormone response in children after radiotherapy for brain tumors.

PubMed

Hua, Chiaho; Wu, Shengjie; Chemaitilly, Wassim; Lukose, Renin C; Merchant, Thomas E

2012-11-15

To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n=72), low-grade glioma (n=28) or craniopharyngioma (n=6), who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test≥7 ng/mL. Independent predictor variables identified by multivariate logistic regression with high statistical significance (p<0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency. Copyright © 2012 Elsevier Inc. All rights reserved.

Lifetime cumulative number of menstrual cycles and serum sex hormone levels in postmenopausal women.

PubMed

Chavez-MacGregor, Mariana; van Gils, Carla H; van der Schouw, Yvonne T; Monninkhof, Evelyn; van Noord, Paulus A H; Peeters, Petra H M

2008-03-01

Lifetime cumulative number of menstrual cycles is related to breast cancer risk. The aim of this study is to investigate the relation between this index and serum sex hormone levels in postmenopausal women. Cross-sectional study including 860 naturally postmenopausal Dutch participants of the European Prospective Investigation into Cancer and Nutrition. Lifetime cumulative number of menstrual cycles was computed using questionnaire data on ages at menarche and menopause, number of pregnancies, breastfeeding, oral contraceptive use (OC) and regularity pattern. Measurements of hormones included estrone (E1), estradiol (E2), andostrenedione, testosterone, sex-hormone binding globulin (SHBG) and dehydroepiandrostenedione sulfate (DHEAS). The relation between the lifetime cumulative number of menstrual cycles and hormone levels was assessed using analysis of covariance. Relations between reproductive characteristics and hormone levels were also studied. Adjustments for characteristics at blood collection included age, years since menopause, BMI, hormone replacement therapy use, OC use, smoking habits, alcohol intake and physical activity were done. Lifetime cumulative number of cycles was related with SHBG; participants in the lowest category had higher SHBG levels. For the separate characteristics, DHEAS and androstenedione increased significantly with increasing age at menarche, while androstenedione and testosterone decreased with increasing age at menopause. For the parity characteristics, SHBG levels increased according to the number of live births. Lifetime cumulative number menstrual cycles was related only to SHBG. Therefore, free levels of estrogens or androgens may be related to this number of menstrual cycles estimate, reflecting lifetime exposure to ovarian hormones.

Promotional Tone in Reviews of Menopausal Hormone Therapy After the Women's Health Initiative: An Analysis of Published Articles

PubMed Central

Fugh-Berman, Adriane; McDonald, Christina Pike; Bell, Alicia M.; Bethards, Emily Catherine; Scialli, Anthony R.

2011-01-01

Background Even after the Women's Health Initiative (WHI) found that the risks of menopausal hormone therapy (hormone therapy) outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. Methods and Findings We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1) Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2) acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement for scientific accuracy (κ = 0.57) and substantial agreement for promotional tone (κ = 0.65). After discussion, readers found 86% of the articles to be scientifically accurate and 64% to be promotional in tone. Themes that were common in articles considered promotional included attacks on the methodology of the WHI, arguments that clinical trial results should not guide treatment for individuals, and arguments that observational studies are as good as or better than randomized clinical trials for guiding clinical decisions. The promotional articles we identified also implied that the risks associated with hormone therapy have been exaggerated and that the benefits of hormone therapy have been or will be proven. Of the ten authors studied, eight were found to have declared payment for speaking or consulting on behalf of menopausal hormone manufacturers or for research support (seven of these eight were speakers or consultants). Thirty of 32 articles (90%) evaluated as promoting hormone therapy were authored by those with potential financial conflicts of interest, compared to 11 of 18 articles (61%) by those without such conflicts (p = 0.0025). Articles promoting the use of menopausal hormone therapy were 2.41 times (95% confidence interval 1.49–4.93) as likely to have been authored by authors with conflicts of interest as by authors without conflicts of interest. In articles from three authors with conflicts of interest some of the same text was repeated word-for-word in different articles. Conclusion There may be a connection between receiving industry funding for speaking, consulting, or research and the publication of promotional opinion pieces on menopausal hormone therapy. Please see later in the article for the Editors' Summary PMID:21423581

Promotional tone in reviews of menopausal hormone therapy after the Women's Health Initiative: an analysis of published articles.

PubMed

Fugh-Berman, Adriane; McDonald, Christina Pike; Bell, Alicia M; Bethards, Emily Catherine; Scialli, Anthony R

2011-03-01

Even after the Women's Health Initiative (WHI) found that the risks of menopausal hormone therapy (hormone therapy) outweighed benefit for asymptomatic women, about half of gynecologists in the United States continued to believe that hormones benefited women's health. The pharmaceutical industry has supported publication of articles in medical journals for marketing purposes. It is unknown whether author relationships with industry affect promotional tone in articles on hormone therapy. The goal of this study was to determine whether promotional tone could be identified in narrative review articles regarding menopausal hormone therapy and whether articles identified as promotional were more likely to have been authored by those with conflicts of interest with manufacturers of menopausal hormone therapy. We analyzed tone in opinion pieces on hormone therapy published in the four years after the estrogen-progestin arm of the WHI was stopped. First, we identified the ten authors with four or more MEDLINE-indexed reviews, editorials, comments, or letters on hormone replacement therapy or menopausal hormone therapy published between July 2002 and June 2006. Next, we conducted an additional search using the names of these authors to identify other relevant articles. Finally, after author names and affiliations were removed, 50 articles were evaluated by three readers for scientific accuracy and for tone. Scientific accuracy was assessed based on whether or not the findings of the WHI were accurately reported using two criteria: (1) Acknowledgment or lack of denial of the risk of breast cancer diagnosis associated with hormone therapy, and (2) acknowledgment that hormone therapy did not benefit cardiovascular disease endpoints. Determination of promotional tone was based on the assessment by each reader of whether the article appeared to promote hormone therapy. Analysis of inter-rater consistency found moderate agreement for scientific accuracy (κ=0.57) and substantial agreement for promotional tone (κ=0.65). After discussion, readers found 86% of the articles to be scientifically accurate and 64% to be promotional in tone. Themes that were common in articles considered promotional included attacks on the methodology of the WHI, arguments that clinical trial results should not guide treatment for individuals, and arguments that observational studies are as good as or better than randomized clinical trials for guiding clinical decisions. The promotional articles we identified also implied that the risks associated with hormone therapy have been exaggerated and that the benefits of hormone therapy have been or will be proven. Of the ten authors studied, eight were found to have declared payment for speaking or consulting on behalf of menopausal hormone manufacturers or for research support (seven of these eight were speakers or consultants). Thirty of 32 articles (90%) evaluated as promoting hormone therapy were authored by those with potential financial conflicts of interest, compared to 11 of 18 articles (61%) by those without such conflicts (p=0.0025). Articles promoting the use of menopausal hormone therapy were 2.41 times (95% confidence interval 1.49-4.93) as likely to have been authored by authors with conflicts of interest as by authors without conflicts of interest. In articles from three authors with conflicts of interest some of the same text was repeated word-for-word in different articles. There may be a connection between receiving industry funding for speaking, consulting, or research and the publication of promotional opinion pieces on menopausal hormone therapy. © 2011 Fugh-Berman et al.

From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

NASA Astrophysics Data System (ADS)

Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

2005-05-01

Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

L-carnitine supplementation for the management of fatigue in patients with hypothyroidism on levothyroxine treatment: a randomized, double-blind, placebo-controlled trial.

PubMed

An, Jee Hyun; Kim, Yoon Jung; Kim, Kyeong Jin; Kim, Sun Hwa; Kim, Nam Hoon; Kim, Hee Young; Kim, Nan Hee; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop; Kim, Sin Gon

2016-10-29

Hypothyroid patients experience fatigue-related symptoms despite adequate thyroid hormone replacement. Thyroid hormone plays an essential role in carnitine-dependent fatty acid import and oxidation. We investigated the effects of L-carnitine supplementation on fatigue in patients with hypothyroidism. In total, 60 patients (age 50.0 ± 9.2 years, 3 males, 57 females) who still experienced fatigue (fatigue severity scale [FSS] score ≥ 36) were given L-carnitine (n = 30, 990 mg L-carnitine twice daily) or placebo (n = 30) for 12 weeks. After 12 weeks, although neither the FSS score nor the physical fatigue score (PFS) changed significantly, the mental fatigue score (MFS) was significantly decreased by treatment with L-carnitine compared with placebo (from 4.5 ± 1.9 to 3.9 ± 1.5 vs. from 4.2 ± 1.8 to 4.6 ± 1.6, respectively; P < 0.01). In the L-carnitine group, 75.0%, 53.6%, and 50.0% of patients showed improvement in the FSS score, PFS, and MFS, respectively, but only 20.0%, 24.0%, and 24.0%, respectively, did so in the placebo group (all P < 0.05). Both the PFS and MFS were significantly improved in patients younger than 50 years and those with free T3 ≥ 4.0 pg/mL by treatment with L-carnitine compared with placebo. Additionally, the MFS was significantly improved in patients taking thyroid hormone after thyroid cancer surgery. These results suggest that L-carnitine supplementation may be useful in alleviating fatigue symptoms in hypothyroid patients, especially in those younger than 50 years and those who have hypothyroidism after thyroidectomy for thyroid cancer (ClinicalTrials.gov: NCT01769157).

Regulation of renal NaPi-2 expression and tubular phosphate reabsorption by growth hormone in the juvenile rat.

PubMed

Woda, Craig B; Halaihel, Nabil; Wilson, Paul V; Haramati, Aviad; Levi, Moshe; Mulroney, Susan E

2004-07-01

Growth hormone (GH) is an important factor in the developmental adaptation to enhance P(i) reabsorption; however, the nephron sites and mechanisms by which GH regulates renal P(i) uptake remain unclear and are the focus of the present study. Micropuncture experiments were performed after acute thyroparathyroidectomy in the presence and absence of parathyroid hormone (PTH) in adult (14- to 17-wk old), juvenile (4-wk old), and GH-suppressed juvenile male rats. While the phosphaturic effect of PTH was blunted in the juvenile rat compared with the adult, suppression of GH in the juvenile restored fractional P(i) excretion to adult levels. In the presence or absence of PTH, GH suppression in the juvenile rat caused a significant increase in the fractional P(i) delivery to the late proximal convoluted (PCT) and early distal tubule, so that delivery was not different from that in adults. These data were confirmed by P(i) uptake studies into brush-border membrane (BBM) vesicles. Immunofluorescence studies indicate increased BBM type IIa NaP(i) cotransporter (NaPi-2) expression in the juvenile compared with adult rat, and GH suppression reduced NaPi-2 expression to levels observed in the adult. GH replacement in the [N-acetyl-Tyr(1)-d-Arg(2)]-GRF-(1-29)-NH(2)-treated juveniles restored high NaPi-2 expression and P(i) uptake. Together, these novel results demonstrate that the presence of GH in the juvenile animal is crucial for the early developmental upregulation of BBM NaPi-2 and, most importantly, describe the enhanced P(i) reabsorption along the PCT and proximal straight nephron segments in the juvenile rat.

Increased endometrial thickness in women with hypertension.

PubMed

Bornstein, J; Auslender, R; Goldstein, S; Kohan, R; Stolar, Z; Abramovici, H

2000-09-01

We noticed an increase in endometrial thickness in women with hypertension who were treated with a combination of medications, including beta-blockers. The purpose of this study was to examine whether the endometrium of hypertensive women is thicker than that of healthy women and to determine whether endometrial thickening in hypertensive women is directly related to the antihypertensive beta-blocker treatment. We compared 3 groups of postmenopausal patients as follows: (1) women with a history of essential hypertension treated with a combination of medications, including beta-blockers; (2) women with a history of hypertension treated with a combination of medications that did not include beta-blockers; and (3) healthy women without hypertension. All patients were interviewed and examined, blood tests were performed, and endometrial thickness in the anterior-posterior diameter was measured by vaginal ultrasonography. Among the exclusion criteria were diabetes or an abnormal fasting blood glucose level, obesity, hormonal medication or replacement hormonal therapy during the previous 6 months, and a history of hormonal disturbances, infertility, or polycystic ovary syndrome. Of 45 hypertensive women enrolled in the study, 22 were treated with a beta-blocker combination medication and 23 were treated with other antihypertensive medications. They were compared with 25 healthy women. There was no statistically significant difference in endometrial thickness between women treated with medications, including beta-blockers, and those who were treated with other hypotensive agents. Twenty percent of women with hypertension and none of the healthy women had endometrium >5 mm thick (P <.017; odds ratio, 8.22; 95% confidence interval, 1.22-infinity). Twenty percent of hypertensive postmenopausal women were found to have increased endometrial thickness. However, we were unable to substantiate an association between the type of treatment administered, whether beta-blockers were included, and the increase in endometrial thickness.

Prevalence of migraine and Raynaud phenomenon in women with apical ballooning syndrome (Takotsubo or stress cardiomyopathy).

PubMed

Scantlebury, Dawn C; Prasad, Abhiram; Rabinstein, Alejandro A; Best, Patricia J M

2013-05-01

Apical ballooning syndrome (ABS), migraine, and Raynaud phenomenon are characterized by female predominance, identifiable triggers, and, likely, vascular dysfunction. Estrogen deficiency, such as in menopause, is considered to be a predisposing factor for ABS. We investigated the association of ABS with migraine, Raynaud phenomenon, and hormonal factors. We compared 25 consecutive residents (all women) of Olmsted County, Minnesota, presenting with ABS, to 2 age-matched control groups from the same community: 25 women presenting with ST-segment elevation myocardial infarction (STEMI), matched for the index ABS event date, and 50 women with neither diagnosis. The patients with ABS were more likely to have a migraine history (11 [44%] vs 4 [16%] STEMI controls, p = 0.031, and vs 6 [12%] population controls, p = 0.003), and "possible migraine" (including other headache syndromes suggestive of migraine; 15 [60%] vs 6 [24%] STEMI controls, p = 0.012; and vs 12 [24%] population controls, p = 0.003). Of the patients with ABS, 4 (16%) had Raynaud phenomenon compared to no STEMI controls and 1 (2%) population control (p = 0.038). No differences were present in parity, menopausal status, years since the onset of menopause, and frequency of oophorectomy. Current hormonal replacement therapy use was greater in those with ABS than in the population controls: 4 (16%) versus none (p = 0.002). In conclusion, the association of ABS with migraine and Raynaud phenomenon supports a role of vasomotor dysfunction in the pathogenesis of ABS. The absence of an association with reproductive characteristics and the finding that ABS occurred despite exogenous hormonal use in some patients suggests that estrogen deficiency per se is not the primary factor in the pathophysiology. Copyright © 2013 Elsevier Inc. All rights reserved.

The influence of sex hormones on functional cerebral asymmetries in postmenopausal women.

PubMed

Bayer, Ulrike; Erdmann, Gisela

2008-07-01

Studies investigating changes in functional cerebral asymmetries (FCAs) with hormonal fluctuations during the menstrual cycle in young women have led to controversial hypotheses about an influence of estrogen (E) and/or progesterone (P) on FCAs. Based on methodical, but also on principal problems in deriving conclusions about hormone effects from correlational designs, the present study investigated hemispheric asymmetries in postmenopausal women, who received hormone replacement either with E alone (E group, n=32), an E-P combination (E-P group, n=29) or no hormone substitution (control group, n=31). Speed and accuracy of responses to a word- and a face decision task, both presented laterally by means of the visual half field technique, were assessed. The control group showed the typical pattern of hemispheric asymmetry with more correct responses to verbal stimuli presented in the right visual field (RVF) and to face stimuli presented in the left visual field (LVF). A hormone-effect was demonstrable only for the verbal task, in which the E group showed an enhanced performance of the right hemisphere (LVF). The E-P group showed no significant differences to the control group or the E group. The results suggest a role of E in the modulation of FCAs at least with regard to verbal processing.

[LED LIGHTING AS A FACTOR FOR THE STIMULATION OF THE HORMONE SYSTEM].

PubMed

Deynego, V N; Kaptsov, V A

2015-01-01

There are considered questions of non-visual effects of blue LED light sources on hormonal systems (cortisol, glucose, insulin) providing the high human performance. In modern conditions hygiene strategy for child and adolescent health strategy was shown to be replaced by a strategy of light stimulation of the hormonal profile. There was performed a systematic analysis of the axis "light stimulus-hypothalamus-pituitary-adrenals-cortisol-glucose-insulin". The elevation of the content of cortisol leads to the increase of the glucose level in the blood and the stimulation of the production of insulin, which can, like excessive consumption of food, give rise to irreversible decline in the number of insulin receptors on the cell surface, and thus--to a steady reduction in the ability of cells to utilize glucose, i.e. to type 2 diabetes or its aggravation.

Management of hypogonadism in adolescent girls and adult women with Prader-Willi syndrome.

PubMed

Eldar-Geva, Talia; Hirsch, Harry J; Pollak, Yehuda; Benarroch, Fortu; Gross-Tsur, Varda

2013-12-01

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by an insatiable appetite, dysmorphic features, cognitive and behavioral difficulties, and hypogonadism. The heterogeneous reproductive hormone profiles indicate that some PWS women may have symptoms of hypoestrogenism, while others may potentially be fertile. We describe our experience in the assessment and treatment of hypogonadism in adolescents and adult females with PWS. The study population consisted of 20 PWS females, age ≥16 years (27.3 ± 7.9 years), followed in our clinic (12 deletion, 7 uniparental disomy, 1 imprinting-center defect). General physical examination, pubertal assessment, body mass index (BMI), gynecological examination, ultrasonography, bone densitometry, and hormonal profiles [FSH, LH, inhibin B, estradiol, prolactin, and TSH] were performed. The relevant assessed factors were: FSH and inhibin B, menstrual cycles (oligo/amenorrhea or irregular bleeding), ultrasound findings (endometrial thickness, uterine/ovarian abnormalities), BMI, bone densitometry, and patient/caregivers attitude. We classified seven women with inhibin B >20 ng/ml as potentially fertile. Following the assessment of the above factors, we recommended the individual-specific treatment; contraceptive pills, intra-uterine device, estrogen/progesterone replacement, and cyclic progesterone, in 3, 1, 4, and 1 patients, respectively. Four patients did not follow our recommendations due to poor compliance or family refusal. We recommended contraception pills for one 26-year-old woman with inhibin B and FSH levels 53 ng/ml and 6.4 IU/L; however, she refused treatment, conceived spontaneously and had an abortion. Guidelines for hormonal replacement therapy in PWS need to be tailored individually depending on physical development, hormonal profiles, bone density, and emotional and social needs of each PWS adolescent and adult. © 2013 Wiley Periodicals, Inc.

A polymorphism in the leptin receptor gene at position 223 is associated with growth hormone replacement therapy responsiveness in idiopathic short stature and growth hormone deficiency patients.

PubMed

Su, Pen-Hua; Yang, Shun-Fa; Yu, Ju-Shan; Chen, Suh-Jen; Chen, Jia-Yuh

2012-12-01

We hypothesized that responses to growth hormone (GH) therapy by idiopathic short stature (ISS) and growth hormone deficiency (GHD) patients were associated with single nucleotide polymorphisms (SNPs) in the leptin (LEP) and leptin receptor (LEPR) genes. We retrospectively enrolled ISS (n = 32) and GHD (n = 38) patients and forty healthy age-and gender-matched children. They were genotyped for the LEP promoter at nt.-2548, and LEPR K109R and LEPR Q223R polymorphisms. Clinical and laboratory variables were determined before and after 2 years of GH treatment. ISS patients with G/A or A/A genotypes of the LEPR Q223R SNP had a significantly higher height velocity (cm/y) than ISS patients with the G/G genotype at 2 years after GH treatment. For GHD patients, G/A or A/A genotype of the LEPR K109R SNP was associated with higher body weight, higher BMI, and higher weight velocity than patients with the G/G genotype before GH treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher body weight, higher height velocity before treatment, but not after GH treatment. G/A or A/A genotype of the LEPR Q223R SNP was associated with a significantly higher weight velocity before treatment, but a significantly lower weight velocity was found at 2 years after GH treatment. These results suggest LEPR Q223R SNP (rs1137101) is associated with outcomes of GH replacement therapy in ISS and GHD patients. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Reproductive cancer risk factors among Alaska Native women: the Alaska Education and Research Towards Health (EARTH) Study.

PubMed

Redwood, Diana G; Lanier, Anne P; Johnston, Janet M; Murphy, Neil; Murtaugh, Maureen A

2012-01-01

The purpose of this study was to provide estimates for the prevalence of reproductive cancer risk factors among Alaska Native (AN) women who enrolled in the Alaska Education and Research Towards Health (EARTH) Study from 2004 to 2006. A total of 2,315 AN women 18 years or older completed reproductive health questions as part of a comprehensive health history questionnaire. The reproductive health section included menstrual status (age at menarche and menopause), pregnancy and live birth history, use of hormonal contraception, hormone replacement therapy, and history of hysterectomy and/or oophorectomy. A total of 463 (20%) of women experienced menarche before age 12 with a decline in mean age at menarche by age cohort. More than 86% had been pregnant (mean number of pregnancies, 3.8; mean number of live births, 2.9). More than one half of women (58%) had their first live birth between the ages of 18 and 24. Almost 28% of participants had completed menopause, of whom 24% completed menopause after age 52. Fewer than half (43%) reported ever using hormone replacement therapy. Almost two thirds (62%) reported ever using oral contraceptives, and fewer reported ever using birth control shots (30%) or implants (10%). This study is unique in reporting reproductive health factors among a large group of AN women. These data show that AN women have selective protective factors for reproductive cancers, including low nulliparity rates, low use of menopausal estrogens, and common use of contraceptive hormones. However, analysis by age cohorts indicates decreasing age at menarche that might increase the risk for reproductive cancers among AN women in the future. Copyright © 2012 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Influence of hormonal status on substrate utilization at rest and during exercise in the female population.

PubMed

Isacco, Laurie; Duché, Pascale; Boisseau, Nathalie

2012-04-01

During exercise, substrate utilization plays a major role in performance and disease prevention. The contribution of fat and carbohydrates to energy expenditure during exercise is modulated by several factors, including intensity and duration of exercise, age, training and diet, but also gender. Because sex hormone levels change throughout a woman's lifetime (in connection with puberty, the menstrual cycle, use of oral contraceptives and menopause), the female population has to be considered specifically in terms of substrate utilization, and metabolic and hormonal responses to exercise. Before puberty, there is no difference between males and females when it comes to substrate oxidation during exercise. This is not the case during adulthood, since women are known to rely more on fat than men for the same relative intensity of exercise. Among adult women, the menstrual cycle and use of oral contraceptives may influence substrate oxidation. While some authors have noted that the luteal phase of the menstrual cycle is connected with greater lipid oxidation, compared with the follicular stage, other authors have found no difference. Among oral contraceptive users, fat oxidation is sometimes increased during prolonged exercise with a concomitant rise in lipolytic hormones, as well as growth hormone. If this result is not always observed, the type of oral contraceptive (monophasic vs triphasic) and hormone doses may be implicated. Menopause represents a hormonal transition in a woman's life, leading to a decline in ovarian hormone production. A decrease in fat oxidation is consequently observed, and some studies have demonstrated a similar respiratory exchange ratio during prolonged exercise in postmenopausal women and in men. As is the case during puberty, no sex difference should thus appear after menopause in the absence of hormonal replacement therapy (HRT). Results concerning women who take HRT remain conflicting. HRT may act on fat loss by increasing lipid metabolism, but this depends on how the treatment is administered (orally vs transdermally). To better understand the role of ovarian hormones in substrate oxidation, studies have made use of animal protocols to investigate cellular mechanisms. Estradiol and progesterone seem to have opposite effects, with greater lipid oxidation when estradiol is used alone. However, the concentrations used (physiological levels or pharmacological doses) may considerably modify fuel selection. In cases where conflicting data are observed in studies of substrate utilization and prolonged exercise in women, methodological reasons must be called into question. Too many parameters, which oftentimes are not specified, may modulate substrate utilization and metabolic and hormonal responses to prolonged exercise. Although information is generally provided about the type of exercise, its duration and the subjects' training level, detailed information is not always given about the subjects' nutritional state and, more specifically, the hormonal status of female subjects. The primary purpose of this review was to identify the impact of hormonal status on substrate oxidation among female subjects at rest and during exercise. A second aim was to describe gender differences in substrate utilization during exercise.

Do differences in female sex hormone levels contribute to gastro-oesophageal reflux disease?

PubMed

Menon, Shyam; Prew, Sandra; Parkes, Gill; Evans, Stephanie; Smith, Lynne; Nightingale, Peter; Trudgill, Nigel

2013-07-01

Hormone replacement therapy is associated with both reflux symptoms and oesophagitis. During pregnancy, elevated sex hormones are thought to contribute to the high prevalence of reflux symptoms. Increased female sex hormone levels may thus contribute to the aetiology of gastro-oesophageal reflux disease (GORD). To determine if female sex hormone levels are associated with symptomatic acid reflux. Women with GORD symptoms undergoing oesophageal pH monitoring were prospectively recruited. 'Cases' and 'controls' were defined by normal and excess total acid exposure on pH monitoring and were age-matched and BMI-matched. Case and control groups were further stratified into premenopausal and postmenopausal groups. Demographic data were collected, body morphological parameters were measured and oestradiol, oestrone, progesterone and sex hormone-binding globulin were measured. One hundred and twenty-one women [mean age 52 (SD 11.6) years] were recruited and 104 [mean age 51 (SD 11.6) years] were matched for age and BMI. Increasing BMI, as expected, correlated with increasing acid exposure [premenopausal (r=0.404, P=0.02), postmenopausal (r=0.401, P=0.01)]. Increasing BMI also correlated with sex hormone levels [premenopausal oestradiol (r=0.52, P=0.004), postmenopausal oestrone (r=0.364, P=0.01)]. In premenopausal women, sex hormone binding globulin (r=-0.27, P=0.05) and testosterone (r=0.29, P=0.05) correlated with increasing acid exposure, but oestradiol fell just short of significance (r=0.26, P=0.06). However, on matching for BMI, no association between sex hormones and increased acid exposure on pH monitoring was found on multivariate logistic regression analysis. Female sex hormone levels do not appear to contribute to GORD, once adjustment is made for the influence of increasing BMI.

Trends in hip fracture epidemiology in Australia: possible impact of bisphosphonates and hormone replacement therapy.

PubMed

Fisher, A A; O'Brien, E D; Davis, M W

2009-08-01

The purposes of this study were to analyse trends in hip fracture (HF) epidemiology over a 13-year period (1994-2007) in the Australian Capital Territory (ACT), to assess the potential impact of concurrent changes in hormone replacement therapy (HRT) and bisphosphonate use and to present a new prediction of HFs in Australia up to 2021. Annual sex- and age-specific incidence rates (per 100,000 population) were determined and standardized using the Australian 2006 population. The projected number of HFs was estimated by two models applying age- and sex-specific HF rates averaged for 2002-2006 (model 1) or continuously changing as observed in this period (model 2, Poisson regression) to the projected population. In 2006 compared to 2001, the population > or = 60 years in the ACT increased by 19.7%. Over the last 5 years the average annual incidence HF rate compared to the previous 3-year period decreased in females > or = 60 years of age by 28.3%. Between 2001 and 2006 the number of prescriptions for HRT dispensed in the ACT declined by 54.6, while the number of prescriptions for bisphosphonate increased by 245%, accompanied by a decline in standardized incidence of HF rates of 36.4%, mainly in women (42.1%). This represents an annual cost for bisphosphonates per one prevented HF, of $A45,250 or $A576 person/year. Compared to 2006 the total number of HFs in Australia according to model 1 will increase in 2011 by 20.1% and in 2021 by 58.8%, but according to model 2 will decrease by 15.5% in 2011 and 27.5% in 2021. Our data suggest that the previously predicted rising trend in HFs in elderly women reversed, but did not so for men. This was coincident with a significant fall in HRT use and increased prescribing of bisphosphonates, which is cost-effective. However caution should be used in attributing causation as this is an ecological study. If trends in HF observed in 2002-2006 continue, the absolute number of HFs in Australia in 2011-2021 will stabilise or decline (which is more likely), despite the rapid ageing of the population.

Metabolic and cardiovascular outcomes in patients with Cushing's syndrome of different aetiologies during active disease and 1 year after remission.

PubMed

Giordano, Roberta; Picu, Andreea; Marinazzo, Elisa; D'Angelo, Valentina; Berardelli, Rita; Karamouzis, Ioannis; Forno, Daniela; Zinnà, Domenico; Maccario, Mauro; Ghigo, Ezio; Arvat, Emanuela

2011-09-01

Cushing's syndrome is associated with several comorbidities responsible for the increased cardiovascular risk, not only during the active phase but also after disease remission. In 29 patients with Cushing's syndrome (14 Cushing's diseases and 15 adrenal adenomas), waist circumference, fasting and 2-h glucose after oral glucose tolerance test (OGTT), lipid profile and blood pressure were evaluated during the active disease and 1 year after remission and compared with those in 29 sex-, age- and BMI-matched controls. During the active disease, waist circumference, 2-h glucose after OGTT, total and LDL cholesterol were higher in patients with Cushing's syndrome than in controls (P < 0·001) but similar in Cushing's disease and adrenal adenomas. The prevalence of impaired glucose tolerance (IGT), diabetes mellitus, dyslipidaemia and hypertension was higher (P < 0·001) in patients with Cushing's syndrome (27%, 24%, 59% and 72%) than in controls (10%, 0%, 21% and 10%), with no significant difference between Cushing's disease and adrenal adenomas. One year following hormonal remission, waist circumference persisted higher than in controls (P < 0·05) in both Cushing's disease and adrenal adenomas. Metabolic and cardiovascular abnormalities were still present in both groups, although with a lower prevalence, as well as with a more marked decrease in adrenal adenomas (P < 0·05 vs active disease for IGT, dyslipidaemia and hypertension). These results show that chronic hypercortisolism, independently of its aetiology, contributes to metabolic impairment and increased cardiovascular risk, while these abnormalities mostly persist in patients with previous Cushing's disease after hormonal remission. Pituitary hormonal deficiencies, hormonal replacement treatments and/or incomplete cure from Cushing's disease may account for these findings. © 2011 Blackwell Publishing Ltd.

Heat shock proteins: the missing link between hormonal and reproductive factors and rheumatoid arthritis?

PubMed

da Silva, J A

1991-10-01

Epidemiologic data suggest a strong link between hormonal and reproductive factors and the incidence of rheumatoid arthritis. Of interest is a possible protective effect of oral contraceptives or estrogen replacement therapy against the development of rheumatoid arthritis. At least 1 pregnancy also appears to reduce the risk of this disease. It has been hypothesized that hormonal contraceptive use and pregnancy elicit the production of higher amounts of endogenous heat shock proteins, which, in turn, induce immunotolerance to subsequent exposure to the actual triggering agent of rheumatoid arthritis. A related possibility is that pregnant women are exposed to specific types of heat shock proteins produced by the fetus in high concentrations. Heat shock proteins are known to be the predominant antigens related to the induction of reactive arthritis. The production of some such proteins is dependent on sex hormones in a tissue-specific way and their concentrations are raised dramatically by stimulation with estrogen and progesterone. A possible mechanism for heat protein-induced immunotolerance would be the predominant stimulation of a suppressor T cell clone. More research on the pathogenesis of rheumatic diseases and the activity of sex hormones could result in the development of a vaccine against rheumatoid arthritis.

Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study

PubMed Central

Banks, Emily; Reeves, Gillian; Beral, Valerie; Bull, Diana; Crossley, Barbara; Simmonds, Moya; Hilton, Elizabeth; Bailey, Stephen; Barrett, Nigel; Briers, Peter; English, Ruth; Jackson, Alan; Kutt, Elizabeth; Lavelle, Janet; Rockall, Linda; Wallis, Matthew G; Wilson, Mary; Patnick, Julietta

2004-01-01

Objectives To examine how lifestyle, hormonal, and other factors influence the sensitivity and specificity of mammography. Methods Women recruited into the Million Women Study completed a questionnaire about various personal factors before routine mammographic screening. A sample of 122 355 women aged 50-64 years were followed for outcome of screening and incident breast cancer in the next 12 months. Sensitivity and specificity were calculated by using standard definitions, with adjustment for potential confounding factors. Results Breast cancer was diagnosed in 726 (0.6%) women, 629 in screen positive and 97 in screen negative women; 3885 (3.2%) were screen positive but had no subsequent diagnosis of breast cancer. Overall sensitivity was 86.6% and specificity was 96.8%. Three factors had an adverse effect on both measures: use of hormone replacement therapy (sensitivity: 83.0% (95% confidence interval 77.4% to 87.6%), 84.7% (73.9% to 91.6%), and 92.1% (87.6% to 95.0%); specificity: 96.8% (96.6% to 97.0%), 97.8% (97.5% to 98.0%), and 98.1% (98.0% to 98.2%), respectively, for current, past, and never use); previous breast surgery v no previous breast surgery (sensitivity: 83.5% (75.7% to 89.1%) v 89.4% (86.5% to 91.8%); specificity: 96.2% (95.8% to 96.5%) v 97.4% (97.3% to 97.5%), respectively); and body mass index < 25 v ≥ 25 (sensitivity: 85.7% (81.2% to 89.3%) v 91.0% (87.5% to 93.6%); specificity: 97.2% (97.0% to 97.3%) v 97.4% (97.3% to 97.6%), respectively). Neither sensitivity nor specificity varied significantly according to age, family history of breast cancer, parity, past oral contraceptive use, tubal ligation, physical activity, smoking, or alcohol consumption. Conclusions The efficiency, and possibly the effectiveness, of mammographic screening is lower in users of hormone replacement therapy, in women with previous breast surgery, and in thin women compared with other women. PMID:15331472

Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism.

PubMed

Tirabassi, G; delli Muti, N; Buldreghini, E; Lenzi, A; Balercia, G

2014-08-01

Little is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism. Fourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed. In male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT. Copyright © 2014 Elsevier B.V. All rights reserved.

Impact of Sex Hormone Metabolism on the Vascular Effects of Menopausal Hormone Therapy in Cardiovascular Disease

PubMed Central

Masood, Durr-e-Nayab; Roach, Emir C.; Beauregard, Katie G.; Khalil, Raouf A.

2010-01-01

Epidemiological studies have shown that cardiovascular disease (CVD) is less common in pre-menopausal women (Pre-MW) compared to men of the same age or post-menopausal women (Post-MW), suggesting cardiovascular benefits of estrogen. Estrogen receptors (ERs) have been identified in the vasculature, and experimental studies have demonstrated vasodilator effects of estrogen/ER on the endothelium, vascular smooth muscle (VSM) and extracellular matrix. Several natural and synthetic estrogenic preparations have been developed for relief of menopausal vasomotor symptoms. However, whether menopausal hormone therapy (MHT) is beneficial in postmenopausal CVD remains controversial. Despite reports of vascular benefits of MHT from observational and experimental studies, randomized clinical trials (RCTs), such as the Heart and Estrogen/progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI), have suggested that, contrary to expectations, MHT may increase the risk of CVD. These discrepancies could be due to age-related changes in sex hormone synthesis and metabolism, which would influence the effective dose of MHT and the sex hormone environment in Post-MW. Age-related changes in the vascular ER subtype, structure, expression, distribution, and post-ER signaling pathways in the endothelium and VSM, along with factors related to the design of RCTs, preexisting CVD condition, and structural changes in the blood vessels architecture have also been suggested as possible causes of MHT failure in CVD. Careful examination of these factors should help in identifying the causes of the changes in the vascular effects of estrogen with age. The sex hormone metabolic pathways, the active versus inactive estrogen metabolites, and their effects on vascular function, the mitochondria, the inflammatory process and angiogenesis should be further examined. Also, the genomic and non-genomic effects of estrogenic compounds should be viewed as integrated rather than discrete responses. The complex interactions between these factors highlight the importance of careful design of MHT RCTs, and the need of a more customized approach for each individual patient in order to enhance the vascular benefits of MHT in postmenopausal CVD. PMID:21189141

Phytoestrogens: a viable option?

PubMed

Russell, Lori; Hicks, G Swink; Low, Annette K; Shepherd, Jinna M; Brown, C Andrew

2002-10-01

Estrogen replacement therapy is one of the most commonly prescribed medicines in the United States by traditional medical professionals. Over the past decade, the market for complementary/ alternative therapies for hormone replacement has dramatically increased. Women are seeking more "natural" alternatives to treat menopausal symptoms. Well-designed randomized clinical trials are often lacking, as is the information on efficacy and safety. This article will review several popular herbal therapies for menopausal symptoms including phytoestrogens, black cohosh (Cimicifuga racemosa), dong quai (Angelica sinensis), chast tree (Vitex agnus-castus), and wild Mexican yam. Their use, mechanism of action, and adverse effects are outlined.

The endocrine pharmacology of testosterone therapy in men

NASA Astrophysics Data System (ADS)

Oettel, Michael

The review starts off by outlining the history of the discovery of the male sex hormone testosterone and the historical background to the various, often dubious, approaches to the treatment of age-related endocrine disorders in older men. A discussion of congenital androgen deficiency in young men is followed by methods of diagnosing hypogonadism in older men. Among therapeutic options, the alternatives to direct testosterone replacement are discussed, although none of them have proved to be particularly successful in clinical practice. For testosterone replacement itself, various routes of administration and pharmaceutical formulations are now available, facilitating good monitoring and individualized therapy.

Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle.

PubMed

Bowles, D K; Maddali, K K; Ganjam, V K; Rubin, L J; Tharp, D L; Turk, J R; Heaps, C L

2004-11-01

Evidence indicates that gender and sex hormonal status influence cardiovascular physiology and pathophysiology. We recently demonstrated increased L-type voltage-gated Ca2+ current (ICa,L) in coronary arterial smooth muscle (CASM) of male compared with female swine. The promoter region of the L-type voltage-gated Ca2+ channel (VGCC) (Cav1.2) gene contains a hormone response element that is activated by testosterone. Thus the purpose of the present study was to determine whether endogenous testosterone regulates CASM ICa,L through regulation of VGCC expression and activity. Sexually mature male and female Yucatan swine (7-8 mo; 35-45 kg) were obtained from the breeder. Males were left intact (IM, n=8), castrated (CM, n=8), or castrated with testosterone replacement (CMT, n=8; 10 mg/day Androgel). Females remained gonad intact (n=8). In right coronary arteries, both Cav1.2 mRNA and protein were greater in IM compared with intact females. Cav1.2 mRNA and protein were reduced in CM compared with IM and restored in CMT. In isolated CASM, both peak and steady-state ICa were reduced in CM compared with IM and restored in CMT. In males, a linear relationship was found between serum testosterone levels and ICa. In vitro, both testosterone and the nonaromatizable androgen, dihydrotestosterone, increased Cav1.2 expression. Furthermore, this effect was blocked by the androgen receptor antagonist cyproterone. We conclude that endogenous testosterone is a primary regulator of Cav1.2 expression and activity in coronary arteries of males.

Late-onset hypogonadism: the advantages of treatment with human chorionic gonadotropin rather than testosterone.

PubMed

La Vignera, Sandro; Condorelli, Rosita Angela; Cimino, Laura; Russo, Giorgio Ivan; Morgia, Giuseppe; Calogero, Aldo E

2016-01-01

The traditional pharmacological treatment of patients with late onset hypogonadism (LOH) is represented by different formulations of testosterone (T) or alternatively by the extractive human chorionic gonadotropin (HCG). The hormone replacement treatment (HRT) is associated with the potential increase of hematocrit, serum concentrations of prostate-specific antigen (PSA) and prostate volume. Moreover, the gynecomastia represent a condition frequently associated with HRT. Recent evidences showed the role of leydig cells in the 25-hydroxylation of vitamin D and the elevated frequency of hypovitaminosis D among LOH patients. Finally, another important aspect of LOH is represented by the frequency of secondary infertility due to age or to traditional HRT. This study evaluated 40 LOH patients treated for 6 months with extractive HCG (n = 10 patients) and three different formulations of T: transdermal (n = 10 patients), undecaonate (n = 10 patients) and enantate (n = 10 patients). Hormonal, anthropometric, metabolic and sperm parameters were evaluated and compared. Moreover, the main safety parameters and the results of the main questionnaires were evaluated. After treatment, HCG group showed serum concentrations of 25-OH-vitamin D significantly higher (p < 0.05) and serum concentrations of oestrogens significantly lower (p < 0.05) compared with other groups. Moreover, they showed a mean value of hematocrit, PSA and prostate volume significantly lower (p < 0.05) compared with other groups. Finally, all the groups treated with T showed a significant reduction (p < 0.05) of sperm density and of percentage of spermatozoa with progressive motility compared with HCG group.

An Epidemiologic Study of Genetic Variation in Hormonal Pathways in Relation to the Effect of Hormone Replacement Therapy on Breast Cancer Risk

DTIC Science & Technology

2008-10-01

pathway. Within single gene analyses we observed breast cancer risk to be modestly associated with one SNPs in each GSTP1 (rs1695: OR = 1.4 [95% CI...CYP1B1*2 and GSTP1 ), breast cancer risk was 1.6 (95% CI: 1.03-2.4) times higher for carriers of 1 high risk genotype and 2.8 (95% CI: 1.5-5.3) times...breast cancer risk. We observed a that the risk of breast cancer increased as the number of high risk alleles in the combined CYP1B1- GSTP1 increased

Estrogen Abolishes Latent Inhibition in Ovariectomized Female Rats

ERIC Educational Resources Information Center

Nofrey, Barbara S.; Ben-Shahar, Osnat M.; Brake, Wayne G.

2008-01-01

Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or…

Exercise and Osteoporosis: A Dose-Response Meta-Analysis

DTIC Science & Technology

2011-05-01

411 (384) Hundrup YA, Thoning H, Rasmussen NK, Obel EB, Philip J. Use of hormone replacement therapy among Danish nurses at increased risk of...February;22(1):21-33. Ref ID: 678 (729) Schambelan M, Mulligan K, Grunfeld C, Daar ES, LaMarca A, Kotler DP, Wang J, Bozzette SA, Breitmeyer JB

Effects of adolescence-onset hypogonadism on metabolism, bone mineral density and quality of life in adulthood.

PubMed

Tam, Friederike I W; Huebner, Angela; Hofbauer, Lorenz C; Rohayem, Julia

2015-09-01

In a cross-sectional study of 54 patients with adolescence-onset hypogonadism (33 females, 21 males; age range: 19-40 years), medical care, quality of life, and health status were assessed. Most patients had received adequate medical care with short cumulative periods of interruption of hormone replacement. The prevalence of the metabolic syndrome was 27% in females and 19% in males. In comparison to the general population, females had both a lower bone mineral density (dual-energy X-ray absorptiometry, Z-score=-0.8, p<0.001) and a higher prevalence of obesity (age 19-29 years: study population 35%, general population 4%). The body fat percentage (dual-energy X-ray absorptiometry) was significantly elevated (age 19-29 years: females Z-score=+1.8, p<0.001, males Z-score=+2.4, p=0.001). Quality of life (SF-36) was normal. Despite adequate treatment, patients with early-onset hypogonadism are prone to develop signs and symptoms consistent with inadequate hormone replacement. A successful transition from pediatric to adult medicine seems important to optimize treatment outcomes.

Should a doctor prescribe hormone replacement therapy which has been manufactured from mare's urine?

PubMed Central

Cox, D

1996-01-01

Many clinicians are experiencing consumer resistance to the prescription of equine HRT (that is hormone replacement therapy which has been manufactured from mare's urine). In this paper I consider the ethical implications of prescribing these preparations. I decide that patients should have a right to refuse such treatment but also ask whether a prescribing doctor should choose one preparation over another on moral grounds. I determine that there is prima facie evidence to suggest that mares may suffer and that prescription of equine HRT (instead of synthetic oestrogen-oestriol) would therefore have to be justified in terms of either offering greater benefits to the women or offering greater value for money to the health service. I find that there is no substantial evidence to suggest that equine HRT offers unique advantages over and above oestriol. I conclude that it would be preferable for a doctor to recommend the synthetic oestrogen to women who want relief from the symptoms of the menopause and protection from osteoporosis and cardiovascular disease. PMID:8863143

Association of the Joint Effect of Menopause and Hormone Replacement Therapy and Cancer in African American Women: The Jackson Heart Study

PubMed Central

Campbell Jenkins, Brenda W.; Addison, Clifton; Wilson, Gregory; Liu, Jiankang; Fortune, Melody; Robinson, Kiana; White, Monique; Sarpong, Daniel

2011-01-01

Cancer is the second leading cause of death in the US and in Mississippi. Breast cancer (BC) is the most common cancer among women, and the underlying pathophysiology remains unknown, especially among African American (AA) women. The study purpose was to examine the joint effect of menopause status (MS) and hormone replacement therapy (HRT) on the association with cancers, particularly BC using data from the Jackson Heart Study. The analytic sample consisted of 3202 women between 35 and 84 years of which 73.7% and 22.6% were postmenopausal and on HRT, respectively. There were a total of 190 prevalent cancer cases (5.9%) in the sample with 22.6% breast cancer cases. Menopause (p < 0.0001), but not HRT (p = 0.6402), was independently associated with cancer. Similar results were obtained for BC. BC, cancer, hypertension, type 2 diabetes, prevalent cardiovascular disease, physical activity and certain dietary practices were all significantly associated with the joint effect of menopause and HRT in the unadjusted analyses. The family history of cancer was the only covariate that was significantly associated with cancer in the age-adjusted models. In examining the association of cancer and the joint effect of menopause and HRT, AA women who were menopausal and were not on HRT had a 1.97 (95% CI: 1.15, 3.38) times odds of having cancer compared to pre-menopausal women after adjusting for age; which was attenuated after further adjusting for family history of cancer. Given that the cancer and BC cases were small and key significant associations were attenuated after adjusting for the above mentioned covariates, these findings warrant further investigation in studies with larger sample sizes of cancer (and BC) cases. PMID:21776241

Effects of long-term, low-dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes.

PubMed

Yue, Yun; Hu, Ling; Tian, Qin-jie; Jiang, Jing-mei; Dong, Yi-long; Jin, Zheng-yu; Cheng, Yu-hang; Hong, Xia; Ge, Qin-sheng; Zuo, Ping-ping

2007-08-01

To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmenopausal women carrying apolipoprotein E (apoE) gene epsilon3 or epsilon4. Eighty-three postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE epsilon4 and epsilon3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. Analysis with the apoE epsilon4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group. The biochemical analysis showed that there was an increase of N-acetylaspartate (NAA)/total creatine (tCr) and a decrease of myoinositol (mI)/tCr in the hippocampus of apoE epsilon4 carriers in the HRT group, compared with the control group. For the apoE epsilon3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group. This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE epsilon3 carriers.

Stopping hormone replacement therapy: were women ill advised?

PubMed

Cumming, Grant P; Currie, Heather D; Panay, Nick; Moncur, Rik; Lee, Amanda J

2011-09-01

To survey women who stopped hormone replacement therapy (HRT) after 2002, including those who later restarted. A questionnaire on the UK-based menopause website www.menopausematters.co.uk evaluating how women are influenced by HRT advice. Main outcome measures Answers to questions regarding stopping/restarting HRT in response to the advice in the early 2000s and advice given today. A total of 1100 responses were obtained. Of those who made the decision to stop HRT themselves, 56.4% (n = 425/754) said that they were influenced by the media. In those who would potentially most benefit from HRT, 72.8% (n = 220/302) stopped without medical advice. Overall, women aged under 50 years were significantly more likely to stop HRT themselves than women over 50 (P < 0.001). In women in whom symptoms returned, 37.5% (n = 362/966) said these affected their ability to work, 45.1% (n = 436) had problems with decision-making, 53.6% (n = 518) admitted to relationships being negatively affected and 29.2% (n = 286) said that symptoms affected their social relationships. Overall 46.5% of women (n = 485/1044) would not have stopped HRT given the current understanding of risk. Compared with women over 50, significantly more women under the age of 50 said that they would not have previously stopped their HRT based on their current understanding of risk (P < 0.001). The negative impact of published research and its reporting from the early 2000s are being mitigated by current press coverage. Media reports appear to influence the younger woman more than the older woman. Health professionals and media must learn the lessons from the past.

Hormone replacement therapy in women with epilepsy: a randomized, double-blind, placebo-controlled study.

PubMed

Harden, Cynthia L; Herzog, Andrew G; Nikolov, Blagovest G; Koppel, Barbara S; Christos, Paul J; Fowler, Kristen; Labar, Douglas R; Hauser, W Allen

2006-09-01

Previous reports have suggested that hormone replacement therapy (HRT) could increase seizure activity in women with epilepsy. We sought to determine whether adding HRT to the medication regimen of postmenopausal women with epilepsy was associated with an increase in seizure frequency. This was a randomized, double-blind, placebo-controlled trial of the effect of HRT on seizure frequency in postmenopausal women with epilepsy, taking stable doses of antiepileptic drugs (AEDs), and within 10 years of their last menses. After a 3-month prospective baseline, subjects were randomized to placebo, Prempro (0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate or CEE/MPA) daily, or double-dose CEE/MPA daily for a 3-month treatment period. Twenty-one subjects were randomized after completing baseline. The subjects' ages ranged from 45 to 62 years (mean, 53 years; SD, +/-5), and the number of AEDs used ranged from none to three (median, one). Five (71%) of seven subjects taking double-dose CEE/MPA had a worsening seizure frequency of at least one seizure type, compared with four (50%) of eight taking single-dose CEE/MPA and one (17%) of six taking placebo (p = 0.05). An increase in seizure frequency of the subject's most severe seizure type was associated with increasing CEE/MPA dose (p = 0.008). An increase in complex partial seizure frequency also was associated with increasing CEE/MPA dose (p = 0.05). Two subjects taking lamotrigine had a decrease in lamotrigine levels of 25-30% while taking CEE/MPA. CEE/MPA is associated with a dose-related increase in seizure frequency in postmenopausal women with epilepsy. CEE/MPA may decrease lamotrigine levels.

First delivery and ovariectomy affect biomechanical and structural properties of the vagina in the ovine model.

PubMed

Urbankova, Iva; Callewaert, Geertje; Blacher, Silvia; Deprest, Dries; Hympanova, Lucie; Feola, Andrew; De Landsheere, Laurent; Deprest, Jan

2018-01-08

Animal models are useful for investigating the genesis of pelvic floor dysfunction and for developing novel therapies for its treatment. There is a need for an alternative large-animal model to the nonhuman primate. Therefore we studied the effects of the first vaginal delivery, ovariectomy and systemic hormonal replacement therapy (HRT) on the biomechanical and structural properties of the ovine vagina. We examined the gross anatomical properties of nulliparous, primiparous, ovariectomized multiparous, and ovariectomized hormone-replaced multiparous sheep (six animals per group). We also harvested mid-vaginal and distal vaginal tissue to determine smooth muscle contractility and passive biomechanical properties, for morphometric assessment of the vaginal wall layers, to determine collagen and elastin content, and for immunostaining for α-smooth muscle actin and estrogen receptor-α. There were no regional differences in the nulliparous vagina. One year after the first vaginal delivery, stiffness and contractility of the distal vagina were decreased, whereas the elastin content increased. The mid-vagina of ovariectomized sheep was stiff, and its epithelium was thin and lacked glycogen. HRT decreased the stiffness of the mid-vagina by 45% but had no measurable effect on contractility or elastin content, and increased epithelial thickness and glycogen content. HRT also increased the epithelial thickness and glycogen content of the distal vagina. At this location, there were no changes in morphology or stiffness. In sheep, life events including delivery and ovariectomy affect the biomechanical properties of the vagina in a region-specific way. Vaginal delivery mainly affects the distal region by decreasing stiffness and contractility. HRT can reverse the increase in stiffness of the mid-vagina observed after surgical induction of menopause. These observations are in line with scanty biomechanical measurements in comparable clinical specimens.

Reversal of idiopathic hypogonadotropic hypogonadism: a cohort study in Chinese patients

PubMed Central

Mao, Jiang-Feng; Xu, Hong-Li; Duan, Jin; Chen, Rong-Rong; Li, Li; Li, Bin; Nie, Min; Min, Le; Zhang, Hong-Bing; Wu, Xue-Yan

2015-01-01

Although idiopathic hypogonadotropic hypogonadism (IHH) has traditionally been viewed as a life-long disease caused by a deficiency of gonadotropin-releasing hormone neurons, a portion of patients may gradually regain normal reproductive axis function during hormonal replacement therapy. The predictive factors for potential IHH reversal are largely unknown. The aim of our study was to investigate the incidence and clinical features of IHH male patients who had reversed reproductive axis function. In this retrospective cohort study, male IHH patients were classified into a reversal group (n = 18) and a nonreversal group (n = 336). Concentration of gonadotropins and testosterone, as well as testicle sizes and sperm counts, were determined. Of 354 IHH patients, 18 (5.1%) acquired normal reproductive function during treatment. The median age for reversal was 24 years old (range 21–34 years). Compared with the nonreversal group, the reversible group had higher basal luteinizing hormone (LH) (1.0 ± 0.7 IU l-1 vs 0.4 ± 0.4 IU l−1, P < 0.05) and stimulated LH (28.3 ± 22.6 IU l−1 vs 1.9 ± 1.1 IU l−1, P < 0.01) levels, as well as larger testicle size (5.1 ± 2.6 ml vs 1.5 ± 0.3 ml, P < 0.01), at the initial visit. In summary, larger testicle size and higher stimulated LH concentrations are favorite parameters for reversal. Our finding suggests that reversible patients may retain partially active reproductive axis function at initial diagnosis. PMID:25578938

Fatigue and fatigue-related symptoms in patients treated for different causes of hypothyroidism.

PubMed

Louwerens, Marloes; Appelhof, Bente C; Verloop, Herman; Medici, Marco; Peeters, Robin P; Visser, Theo J; Boelen, Anita; Fliers, Eric; Smit, Johannes W A; Dekkers, Olaf M

2012-12-01

Research on determinants of well-being in patients on thyroid hormone replacement therapy is warranted, as persistent fatigue-related complaints are common in this population. In this study, we evaluated the impact of different states of hypothyroidism on fatigue and fatigue-related symptoms. Furthermore, the relationship between fatigue and the TSH receptor (TSHR)-Asp727Glu polymorphism, a common genetic variant of the TSHR, was analyzed. A cross-sectional study was performed in 278 patients (140 patients treated for differentiated thyroid carcinoma (DTC) and 138 with autoimmune hypothyroidism (AIH)) genotyped for the TSHR-Asp727Glu polymorphism. The multidimensional fatigue inventory (MFI-20) was used to assess fatigue, with higher MFI-20 scores indicating more fatigue-related complaints. MFI-20 scores were related to disease status and Asp727Glu polymorphism status. AIH patients scored significantly higher than DTC patients on all five MFI-20 subscales (P<0.001), independent of clinical and thyroid hormone parameters. The frequency of the TSHR-Glu727 allele was 7.2%. Heterozygous DTC patients had more favorable MFI-20 scores than wild-type DTC patients on four of five subscales. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue was found in DTC patients only. AIH patients had significantly higher levels of fatigue compared with DTC patients, which could not be attributed to clinical or thyroid hormone parameters. The modest effect of the TSHR-Asp727Glu polymorphism on fatigue in DTC patients should be confirmed in other cohorts.

Predicting the Probability of Abnormal Stimulated Growth Hormone Response in Children After Radiotherapy for Brain Tumors

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

Hua Chiaho, E-mail: Chia-Ho.Hua@stjude.org; Wu Shengjie; Chemaitilly, Wassim

Purpose: To develop a mathematical model utilizing more readily available measures than stimulation tests that identifies brain tumor survivors with high likelihood of abnormal growth hormone secretion after radiotherapy (RT), to avoid late recognition and a consequent delay in growth hormone replacement therapy. Methods and Materials: We analyzed 191 prospectively collected post-RT evaluations of peak growth hormone level (arginine tolerance/levodopa stimulation test), serum insulin-like growth factor 1 (IGF-1), IGF-binding protein 3, height, weight, growth velocity, and body mass index in 106 children and adolescents treated for ependymoma (n = 72), low-grade glioma (n = 28) or craniopharyngioma (n = 6),more » who had normal growth hormone levels before RT. Normal level in this study was defined as the peak growth hormone response to the stimulation test {>=}7 ng/mL. Results: Independent predictor variables identified by multivariate logistic regression with high statistical significance (p < 0.0001) included IGF-1 z score, weight z score, and hypothalamic dose. The developed predictive model demonstrated a strong discriminatory power with an area under the receiver operating characteristic curve of 0.883. At a potential cutoff point of probability of 0.3 the sensitivity was 80% and specificity 78%. Conclusions: Without unpleasant and expensive frequent stimulation tests, our model provides a quantitative approach to closely follow the growth hormone secretory capacity of brain tumor survivors. It allows identification of high-risk children for subsequent confirmatory tests and in-depth workup for diagnosis of growth hormone deficiency.« less

Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life.

PubMed

Miranda, Benjamin H; Charlesworth, Matthew R; Tobin, Desmond J; Sharpe, David T; Randall, Valerie A

2018-02-01

Male sex hormones-androgens-regulate male physique development. Without androgen signaling, genetic males appear female. During puberty, increasing androgens harness the hair follicle's unique regenerative ability to replace many tiny vellus hairs with larger, darker terminal hairs ( e.g., beard). Follicle response is epigenetically varied: some remain unaffected ( e.g., eyelashes) or are inhibited, causing balding. How sex steroid hormones alter such developmental processes is unclear, despite high incidences of hormone-driven cancer, hirsutism, and alopecia. Unfortunately, existing development models are not androgen sensitive. Here, we use hair follicles to establish an androgen-responsive human organ culture model. We show that women's intermediate facial follicles respond to men's higher androgen levels by synthesizing more hair over several days, unlike donor-matched, androgen-insensitive, terminal follicles. We demonstrate that androgen receptors-androgen-activated gene transcription regulators-are required and are present in vivo within these follicles. This is the first human organ that involves multiple cell types that responds appropriately to hormones in prolonged culture, in a way which mirrors its natural behavior. Thus, intermediate hair follicles offer a hormone-switchable human model with exceptional, unique availability of genetically identical, but epigenetically hormone-insensitive, terminal follicles. This should enable advances in understanding sex steroid hormone signaling, gene regulation, and developmental and regenerative systems and facilitate better therapies for hormone-dependent disorders.-Miranda, B. H., Charlesworth, M. R., Tobin, D. J., Sharpe, D. T., Randall, V. A. Androgens trigger different growth responses in genetically identical human hair follicles in organ culture that reflect their epigenetic diversity in life.

Congenital hypothyroidism of dogs and cats: a review.

PubMed

Bojanic, K; Acke, E; Jones, B R

2011-05-01

Congenital hypothyroidism is a rare and underdiagnosed congenital endocrine disorder in dogs and cats and the true incidence is unknown. The disorder may cause a range of clinical signs depending on the primary defect, which affect production of thyroid hormones; some cases present when adult. Hallmark clinical signs of congenital hypothyroidism are mental impairment and skeletal developmental abnormalities, resulting in disproportionate dwarfism; goitre may or may not be present. Documented causes of congenital hypothyroidism in dogs include deficiency of, or unresponsiveness to, thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH), thyroid dysgenesis, dyshormonogenesis and iodine deficiency. In cats, TSH unresponsiveness, thyroid dysgenesis, dyshormonogenesis and iodine deficiency have been confirmed. Adequate replacement therapy results in a successful outcome in the majority of cases, especially when started early in life, as permanent developmental abnormalities can be prevented. This review describes reported cases in dogs and cats, diagnostic investigation, and recommendations for treatment.

De morseir syndrome presenting as ambiguous genitalia.

PubMed

Thukral, Anubhav; Chitra, S; Chakraborty, Partho P; Roy, Ajitesh; Goswami, Soumik; Bhattacharjee, Rana; Dutta, Deep; Maisnam, Indira; Ghosh, Sujoy; Mukherjee, Satinath; Chowdhury, Subhankar

2012-12-01

A 10-year-old boy presented with genital ambiguity, poor linear growth, and delayed milestones. The aim and to highlight that although rare but congenital, hypogonadotropic hypogonadism may rarely present as ambiguity. The patient was found to have bilateral cryptorchidism with proximal penile hypospadias, microphallus with a proportionate dwarfism with mildly delayed bone age, and karyotype 46XY. Euthyroid with normal steroid axis, growth hormone insufficient as suggested by auxology, low IGF1, and poor response to clonidine stimulation. MRI brain shows hypoplastic corpus callosum, hypoplastic anterior pituitary, and ectopic posterior pituitary bright spot. The patient underwent laparoscopic removal of right intrabdominal testis and orchidoplexy was performed on the left one. Testicular biopsy revealed no malignancy and growth hormone replacement was initiated. The patient awaits definitive repair of hypospadias. As a provisional diagnosis of combined growth hormone and gonadotropin deficiency, most probable diagnosis is septo-optic dysplasia or de moseir syndrome leading to genital ambiguity.

Empty sella syndrome secondary to intrasellar cyst in adolescence.

PubMed

Raiti, S; Albrink, M J; Maclaren, N K; Chadduck, W M; Gabriele, O F; Chou, S M

1976-09-01

A 15-year-old boy had growth failure and failure of sexual development. The probable onset was at age 10. Endocrine studies showed hypopituitarism with deficiency of growth hormone and follicle-stimulating hormone, an abnormal response to metyrapone, and deficiency of thyroid function. Luteinizing hormone level was in the low-normal range. Posterior pituitary function was normal. Roentgenogram showed a large sella with some destruction of the posterior clinoids. Transsphenoidal exploration was carried out. The sella was empty except for a whitish membrane; no pituitary tissue was seen. The sella was packed with muscle. Recovery was uneventful, and the patient was given replacement therapy. On histologic examination,the cyst wall showed low pseudostratified cuboidal epithelium and occasional squamous metaplasia. Hemosiderin-filled phagocytes and acinar structures were also seen. The diagnosis was probable rupture of an intrasellar epithelial cyst, leading to empty sella syndrome.

Predilection for frailty remedial strategies among black and white seniors.

PubMed

Miller, D K; Morrison, M J; Blair, S D; Miller, J P; Morley, J E

1998-04-01

Frailty prevention and remedial programs based on exercise, hormone replacement, and vitamin supplementation are becoming available for use with older patients, but success of these programs depends largely on seniors' willingness to participate. We evaluated preferences for specific aspects of these programs using a sample of 359 older persons recruited from potential delivery sites. Main effects and subgroup analyses were done. Subjects preferred stretching, chair-based, walking, and dynamic balance exercises over lifting weights, dancing, hormone and vitamin therapy; exercising alone in their own homes over exercising in groups; and vitamins over hormones. Preferences were affected to some extent by sex, race, recruitment site, and functional status. However, subjects' willingness even to consider exercise was rarely as high as the desired levels of participation set forth in Healthy People 2000. Physicians and public health authorities need to educate older persons about effective methods to prevent or treat frailty.

Associations of blood lead levels with reproductive hormone levels in men and postmenopausal women: Results from the SPECT-China Study

NASA Astrophysics Data System (ADS)

Chen, Chi; Wang, Ningjian; Zhai, Hualing; Nie, Xiaomin; Sun, Honglin; Han, Bing; Li, Qin; Chen, Yi; Cheng, Jing; Xia, Fangzhen; Zhao, Li; Zheng, Yanjun; Shen, Zhoujun; Lu, Yingli

2016-11-01

We examined whether blood lead levels (BLLs) were associated with reproductive hormone levels in a cross-sectional study using data from the SPECT-China study. We selected 2286 men and 1571 postmenopausal women without hormone replacement therapy. BLLs, blood cadmium, total testosterone (TT), oestradiol (E2), luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin(SHBG) levels were measured. The results showed that median values (interquartile range) of BLLs were 44.00 μg/L (29.00-62.30) for men and 41.00 μg/L (27.00-59.81) for postmenopausal women. In linear regression, after adjusting for age, current smoking status, body mass index, systolic blood pressure, diabetes and blood cadmium level, TT (P for trend = 0.001) and SHBG (P for trend < 0.001) levels were still positively associated with BLLs in men. Meanwhile, significant positive associations were found for BLLs with SHBG (P for trend = 0.002), FSH (P for trend = 0.001) and LH (P for trend = 0.026) levels in postmenopausal women. Additionally, the association between BLL and SHBG was modified by dysglycaemia (P for interaction = 0.03) in postmenopausal women. In conclusion, BLLs were associated with reproductive hormone levels in the general population of Chinese men and postmenopausal women, which may have important implications for human health. Concerted efforts to reduce adult lead exposure are warranted.

Monoamines and neurosteroids in sexual function during induced hypogonadism in healthy men.

PubMed

Bloch, Miki; Rubinow, David R; Berlin, Kate; Kevala, Karl R; Kim, Hee-Yong; Schmidt, Peter J

2006-04-01

Although the behavioral effects of high-dose androgen administration may involve alterations in serotonergic activity, few studies have investigated the impact of androgen withdrawal on the central nervous system in humans. To examine the effects of pharmacologically induced hypogonadism on several cerebrospinal fluid (CSF) systems that could mediate the behavioral concomitants of hypogonadism. Double-blind assessment of the effects of the short-term induction of hypogonadism and subsequent replacement with testosterone and placebo in a crossover design. National Institutes of Health, Bethesda, Md. Twelve healthy male volunteers. We administered the gonadotropin-releasing hormone agonist leuprolide acetate (7.5 mg intramuscularly every 4 weeks) to the healthy male volunteers, creating a hypogonadal state, and then either replaced testosterone (200 mg intramuscularly) or administered a placebo every 2 weeks for 1 month. Mood and behavioral symptoms were monitored with daily self-ratings, and lumbar punctures were performed during both hypogonadal (placebo) and testosterone-replaced conditions for CSF levels of steroids and monoamine metabolites. The CSF testosterone, dihydrotestosterone, and androsterone levels were significantly lower during hypogonadism (P=.002, .04, and .046, respectively), but no significant changes were observed in CSF measures of 5-hydroxyindoleacetic acid, homovanillic acid, dehydroepiandrosterone, or pregnenolone. Decreased sexual interest was observed during the hypogonadal state compared with both baseline and testosterone replacement (P=.009) and correlated significantly with CSF measures of androsterone during both hypogonadism and testosterone replacement (r = -0.76 and -0.81, respectively; P<.01). Moreover, the change in severity of decreased sexual interest correlated significantly with the change in CSF androsterone levels between testosterone replacement and hypogonadism (r = -0.68; P<.05). The CSF 5-hydroxyindoleacetic acid and homovanillic acid levels did not correlate significantly with any behavioral or CSF measure. These data suggest that the neurosteroid androsterone contributes to the regulation of sexual function in men.

Clinical, behavioural and pharmacogenomic factors influencing the response to levothyroxine therapy in patients with primary hypothyroidism-protocol for a systematic review.

PubMed

Dew, Rosie; Okosieme, Onyebuchi; Dayan, Colin; Eligar, Vinay; Khan, Ishrat; Razvi, Salman; Pearce, Simon; Wilkes, Scott

2017-03-21

Suboptimal thyroid hormone therapy including under-replacement and over-replacement is common amongst patients with hypothyroidism. This is a significant health concern as affected patients are at risk of adverse cardiovascular or metabolic consequences. Despite a growing body of evidence on the effects of various factors on thyroid hormone replacement, a systematic appraisal of the evidence is lacking. This review aims to appraise and quantify the extent to which clinical, behavioural and pharmacogenomic factors affect levothyroxine therapy in patients with primary hypothyroidism. The databases Web of Science, Cochrane Library, EMBASE and PubMed will be searched. Patients must be adults over the age of 18 years, suffering from primary hypothyroidism including overt and subclinical hypothyroidism and receiving levothyroxine treatment. Studies in children, pregnant women and patients with secondary or tertiary hypothyroidism will not be included. We will also exclude studies focused on forms of thyroid hormone replacement therapy other than levothyroxine. The primary outcome is to quantify the effect of clinical, behavioural and pharmacogenomic factors on thyroid stimulating hormone (TSH) levels. Secondary outcomes are the effect these factors have on thyroxine (T4) and triiodothyronine (T3) levels, mortality, morbidity, quality of life, treatment complications, adverse effects, physical and social functioning. Studies will be screened through reading the title, abstract and then full text. Two reviewers will independently extract the data and select articles, and a third reviewer will be consulted if there is any disagreement. We will undertake a meta-analysis of studies in which there is a defined intervention or exposure, patients are receiving levothyroxine for hypothyroidism, there is an appropriate control group of levothyroxine treated patients that are not exposed to the intervention, and the primary outcome is determined by serum TSH levels. Studies will comprise of randomised controlled trials as well as observational data. Eligible studies will be assessed for bias using the risk of bias tool available in the Cochrane handbook 2011, and the quality of evidence will be judged according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. A flow diagram describing the data search will be created according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis: The PRISMA statement. A narrative synthesis will be undertaken in the description of the data, and summary tables will be created of the results. This review will be the first systematic review of this nature. The evidence synthesised will be useful to general practitioners in their management of hypothyroidism. Findings will be disseminated at conferences and in professional and peer-reviewed journals. PROSPERO CRD42015027211.

The Preoptic Area and the RFamide-Related Peptide Neuronal System Gate Seasonal Changes in Chemosensory Processing.

PubMed

Jennings, Kimberly J; Chasles, Manon; Cho, Hweyryoung; Mikkelsen, Jens; Bentley, George; Keller, Matthieu; Kriegsfeld, Lance J

2017-11-01

Males of many species rely on chemosensory information for social communication. In male Syrian hamsters (Mesocricetus auratus), as in many species, female chemosignals potently stimulate sexual behavior and a concurrent, rapid increase in circulating luteinizing hormone (LH) and testosterone (T). However, under winter-like, short-day (SD) photoperiods, when Syrian hamsters are reproductively quiescent, these same female chemosignals fail to elicit behavioral or hormonal responses, even after T replacement. It is currently unknown where in the brain chemosensory processing is gated in a seasonally dependent manner such that reproductive responses are only displayed during the appropriate breeding season. The goal of the present study was to determine where this gating occurred by identifying neural loci that respond differentially to female chemosignals across photoperiods, independent of circulating T concentrations. Adult male Syrian hamsters were housed under either long-day (LD) (reproductively active) or SD (reproductively inactive) photoperiods with half of the SD animals receiving T replacement. Animals were exposed to either female hamster vaginal secretions (FHVSs) diluted in mineral oil or to vehicle, and the activational state of chemosensory processing centers and elements of the neuroendocrine reproductive axis were examined. Components of the chemosensory pathway upstream of hypothalamic centers increased expression of FOS, an indirect marker of neuronal activation, similarly across photoperiods. In contrast, the preoptic area (POA) of the hypothalamus responded to FHVS only in LD animals, consistent with its role in promoting expression of male sexual behavior. Within the neuroendocrine axis, the RF-amide related peptide (RFRP), but not the kisspeptin neuronal system responded to FHVS only in LD animals. Neither response within the POA or the RFRP neuronal system was rescued by T replacement in SD animals, mirroring photoperiodic regulation of reproductive responses. Considering the POA and the RFRP neuronal system promote reproductive behavior and function in male Syrian hamsters, differential activation of these systems represents a potential means by which photoperiod limits expression of reproduction to the appropriate environmental context. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

Sex Hormones Coordinate Neutrophil Immunity in the Vagina by Controlling Chemokine Gradients.

PubMed

Lasarte, Sandra; Samaniego, Rafael; Salinas-Muñoz, Laura; Guia-Gonzalez, Mauriel A; Weiss, Linnea A; Mercader, Enrique; Ceballos-García, Elena; Navarro-González, Teresa; Moreno-Ochoa, Laura; Perez-Millan, Federico; Pion, Marjorie; Sanchez-Mateos, Paloma; Hidalgo, Andres; Muñoz-Fernandez, Maria A; Relloso, Miguel

2016-02-01

Estradiol-based contraceptives and hormonal replacement therapy predispose women to Candida albicans infections. Moreover, during the ovulatory phase (high estradiol), neutrophil numbers decrease in the vaginal lumen and increase during the luteal phase (high progesterone). Vaginal secretions contain chemokines that drive neutrophil migration into the lumen. However, their expression during the ovarian cycle or in response to hormonal treatments are controversial and their role in vaginal defense remains unknown.To investigate the transepithelial migration of neutrophils, we used adoptive transfer of Cxcr2(-/-) neutrophils and chemokine immunofluorescence quantitative analysis in response to C. albicans vaginal infection in the presence of hormones.Our data show that the Cxcl1/Cxcr2 axis drives neutrophil transepithelial migration into the vagina. Progesterone promotes the Cxcl1 gradient to favor neutrophil migration. Estradiol disrupts the Cxcl1 gradient and favors neutrophil arrest in the vaginal stroma; as a result, the vagina becomes more vulnerable to pathogens. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

PROP1 gene mutations in a 36-year-old female presenting with psychosis

PubMed Central

Rijal, Tshristi; Jha, Kunal Kishor; Saluja, Harpreet

2017-01-01

Summary Combined pituitary hormonal deficiency (CPHD) is a rare disease that results from mutations in genes coding for transcription factors that regulate the differentiation of pituitary cells. PROP1 gene mutations are one of the etiological diagnoses of congenital panhypopituitarism, however symptoms vary depending on phenotypic expression. We present a case of psychosis in a 36-year-old female with congenital panhypopituitarism who presented with paranoia, flat affect and ideas of reference without a delirious mental state, which resolved with hormone replacement and antipsychotics. Further evaluation revealed that she had a homozygous mutation of PROP1 gene. In summary, compliance with hormonal therapy for patients with hypopituitarism appears to be effective for the prevention and treatment of acute psychosis symptoms. Learning points: Patients with PROP1 gene mutation may present with psychosis with no impairment in orientation and memory. There is currently inadequate literature on this topic, and further study on the possible mechanisms of psychosis as a result of endocrine disturbance is required. Compliance with hormonal therapy for patients with hypopituitarism appears to be effective for prevention and treatment of acute psychosis symptoms. PMID:28458894

Sex Hormones and Cardiometabolic Health: Role of Estrogen and Estrogen Receptors.

PubMed

Clegg, Deborah; Hevener, Andrea L; Moreau, Kerrie L; Morselli, Eugenia; Criollo, Alfredo; Van Pelt, Rachael E; Vieira-Potter, Victoria J

2017-05-01

With increased life expectancy, women will spend over three decades of life postmenopause. The menopausal transition increases susceptibility to metabolic diseases such as obesity, diabetes, cardiovascular disease, and cancer. Thus, it is more important than ever to develop effective hormonal treatment strategies to protect aging women. Understanding the role of estrogens, and their biological actions mediated by estrogen receptors (ERs), in the regulation of cardiometabolic health is of paramount importance to discover novel targeted therapeutics. In this brief review, we provide a detailed overview of the literature, from basic science findings to human clinical trial evidence, supporting a protective role of estrogens and their receptors, specifically ERα, in maintenance of cardiometabolic health. In so doing, we provide a concise mechanistic discussion of some of the major tissue-specific roles of estrogens signaling through ERα. Taken together, evidence suggests that targeted, perhaps receptor-specific, hormonal therapies can and should be used to optimize the health of women as they transition through menopause, while reducing the undesired complications that have limited the efficacy and use of traditional hormone replacement interventions. Copyright © 2017 Endocrine Society.

Association of perceived tinnitus with duration of hormone replacement therapy in Korean postmenopausal women: a cross-sectional study.

PubMed

Lee, Seong-Su; Han, Kyung-do; Joo, Young-Hoon

2017-07-10

The purpose of this study was to determine the relationship between hormone replacement therapy (HRT) and tinnitus in South Korea using data from the Korea National Health and Nutrition Examination Surveys (KNHANES) (2010-2012). Cross-sectional analysis of a nationwide health survey. KNHANES is a nationally representative cross-sectional survey of South Korea population. Only postmenopausal women aged 19-65 years were included in the study (n=2736). Auditory function was evaluated using pure-tone audiometric testing according to established KNHANES protocols. Subjects were questioned about their experience with tinnitus. Exogenous hormone-related factors included the starting age and duration of HRT. The overall prevalence of tinnitus was 22.2% among postmenopausal women. (1) Tinnitus severity was significantly higher in women using HRT (p=0.0024) and (2) significantly lower in women who breast fed their children (p=0.0386). (3) According to logistic regression models, the longer duration of HRT was significantly associated with increasing tinnitus (OR=1.323, 95% CI 1.007 to 1.737, p=0.0441). A longer duration of HRT was associated with developing tinnitus in Korean postmenopausal women. Further experimental and epidemiological researches are needed to elucidate the causal relationship between HRT and tinnitus. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Leptin as a Modulator of Neuroendocrine Function in Humans

PubMed Central

Khan, Sami M.; Hamnvik, Ole-Petter R.; Brinkoetter, Mary

2012-01-01

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

[Hormone replacement therapy and cognitive function].

PubMed

Huang, Chun-Ping; Hong, Chi-Tzong; Huang, I-Tsan

2006-12-01

Observational studies have suggested that postmenopausal hormone replacement therapy (HRT) may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The effects of HRT on dementia and mild cognitive impairment were assessed in a subgroup of participants in the Women's Health Initiative Memory Study (WHIMS) (a multicenter, randomized, double-blind, placebo-controlled clinical trial). There were two study arms, one involved 4,532 postmenopausal women who received continuous combined estrogen (conjugated equine estrogens [CEE] plus medroxyprogesterone acetate [MPA]) or placebo, and the other involved 2,947 hysterectomized women randomized to continuous unopposed CEE or placebo. All participants were aged 65 years or older. CEE with or without MPA did not protect against (but substantially increased the risk of) dementia of any cause or cognitive decline. Incidence of probable dementia in the estrogen-alone trial was statistically similar to that in the estrogen plus progestin trial. When data from both trials were pooled, the overall risk for probable dementia was increased by 76% (HR, 1.76; 95% CI, 1.19 to 2.60; P = 0.005). A second report from WHIMS suggested that cognitive decline in women aged 65 years and older was greater in those receiving hormone therapy than in those receiving placebo (HR, 1.25; 95% CI, 0.97-1.60). The WHIMS results clearly indicate that CEE with or without MPA should not be used to prevent dementia or enhance cognition in women older than 65 years.

Administration of arginine plus growth hormone releasing hormone to evaluate growth hormone (GH) secretory status in children with GH deficiency.

PubMed

Keller, A; Donaubauer, J; Kratzsch, J; Pfaeffle, R; Hirsch, W; Kiess, W; Keller, E

2007-12-01

Diagnosis of growth hormone deficiency (GHD) in childhood is usually based on growth hormone (GH) response to at least two provocative stimuli. The aim of this study was to determine whether sequential administration of arginine (Arg) plus GH releasing hormone (GHRH) could be a useful tool in evaluating GHD in children. Thirty patients with short stature (mean age 9.0 years) with decreased growth rate were tested for GHD with Arg and the insulin tolerance test (ITT). Patients with confirmed GHD (peak GH <8 ng/ml) were subsequently tested with Arg + GHRH. Maximum GH stimulation for Arg and ITT was 6.3 (1.0-7.8) and 6.7 (0.5-7.7) ng/ml, respectively. Peak GH for the Arg + GHRH test was 36.3 (4.3-84.5) ng/ml and significantly different from the other provocative tests. Peak GH values for the three tests were not significantly correlated between tests or with clinical parameters. There were no significant differences in Arg + GHRH results between children with or without abnormal hypothalamic-pituitary MRI scans. Arg + GHRH gave higher GH levels than insulin or Arg alone. Because of the different causes of childhood GHD (hypothalamic and/or pituitary dysfunction), the Arg + GHRH test is unsuitable .for evaluating GHD and deciding whether GH replacement therapy is indicated.

Hot issues in female and male hormonal contraception.

PubMed

Gava, Giulia; Lantadilla, Claudia; Martelli, Valentina; Fattorini, Anna; Seracchioli, Renato; Meriggiola, Maria C

2016-02-01

In recent years a number of significant developments in the field of female hormonal contraception have been made which have produced new formulations and delivery systems providing high efficacy, safety and important non-contraceptive benefits. In particular long-acting reversible contraception (LARC) formulations have been demonstrated to ensure extremely high efficacy in typical use, minimal contraindications, optimal safety in all women thereby representing the best option for most women of all ages. Their effectiveness is not reliant upon user adherence and their ability to reduce unintended pregnancies and abortions has been proven. Unfortunately the same considerations cannot be made for male hormonal contraception. Although a large number of men are interested and would welcome the opportunity to use male contraceptive methods, no safe, effective and reversible methods are available on the market. Current methods available for men are limited to condoms and vasectomy. Highly effective prototype regimens have been developed but the pharmaceutical industry is unwilling to pursue further development and market these products. Of all new approaches to male contraception, hormonal methods are the closest to clinical application. These are based on the reversible suppression of luteinizing hormone and follicle stimulating hormone with subsequent reversible inhibition of spermatogenesis and consequent replacement to maintain androgen dependent physiological functions. Most approaches tested combination regimens such as testosterone and a progestin or testosterone and a GnRH analog.

Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1.

PubMed

Meyer Zu Schwabedissen, Henriette E; Ferreira, Celio; Schaefer, Anima M; Oufir, Mouhssin; Seibert, Isabell; Hamburger, Matthias; Tirona, Rommel G

2018-07-01

Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α -mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Low-dose hydrocortisone replacement is associated with improved arterial stiffness index and blood pressure dynamics in severely adrenocorticotrophin-deficient hypopituitary male patients.

PubMed

Behan, Lucy-Ann; Carmody, David; Rogers, Bairbre; Hannon, Mark J; Davenport, Colin; Tormey, William; Smith, Diarmuid; Thompson, Christopher J; Stanton, Alice; Agha, Amar

2016-06-01

Increased cardiovascular and cerebrovascular morbidity and mortality in hypopituitary subjects may be linked to inappropriate glucocorticoid exposure; however, the pathophysiology remains unclear. We aimed to examine the effect of three commonly prescribed hydrocortisone (HC) regimens on vascular risk factors. An open crossover study randomising ten hypopituitary men with severe adrenocorticotrophic hormone deficiency to three HC dose regimens: dose A (20mg mane and 10mg tarde), dose B (10mg mane and 10mg tarde) and dose C (10mg mane and 5mg tarde). Following 6 weeks on each regimen, participants underwent 24-h serum cortisol sampling, 24-h ambulatory blood pressure (BP) measurements, calculation of the Ambulatory Arterial Stiffness Index (AASI), oral glucose tolerance testing and fasting serum osteoprotegerin (OPG) sampling. There were no differences in 24-h BP between dose regimens and controls; however, low-dose HC replacement (dose C) was associated with the lowest AASI, indicating a less stiff arterial tree (P<0.05) compared with the other dose regimens. Loss of the physiologic nocturnal BP dip was more common in higher HC replacement regimens, although only significant for dose B compared with dose C (P=0.03). Twenty per cent of patients had abnormal glucose tolerance, but this was unrelated to dose regimen. OPG correlated strongly with 24-h BP in those on dose A only (r=0.65, P=0.04). Currently prescribed HC replacement doses do not result in significant differences in absolute BP levels or improvements in insulin sensitivity. However, lower HC doses may result in lower arterial stiffness and a more physiological nocturnal BP dip. Long-term studies are required to confirm these findings and evaluate their impact on vascular morbidity in this patient group. © 2016 European Society of Endocrinology.

Effects of growth hormone and low dose estrogen on bone growth and turnover in long bones of hypophysectomized rats

NASA Technical Reports Server (NTRS)

Kidder, L. S.; Schmidt, I. U.; Evans, G. L.; Turner, R. T.

1997-01-01

Pituitary hormones are recognized as critical to longitudinal growth, but their role in the radial growth of bone and in maintaining cancellous bone balance are less clear. This investigation examines the histomorphometric effects of hypophysectomy (Hx) and ovariectomy (OVX) and the subsequent replacement of growth hormone (GH) and estrogen (E), in order to determine the effects and possible interactions between these two hormones on cortical and cancellous bone growth and turnover. The replacement of estrogen is of interest since Hx results in both pituitary and gonadal hormone insufficiencies, with the latter being caused by the Hx-associated reduction in follicle stimulating hormone (FSH). All hypophysectomized animals received daily supplements of hydrocortisone (500 microg/kg) and L-thyroxine (10 microg/kg), whereas intact animals received daily saline injections. One week following surgery, hypophysectomized animals received either daily injections of low-dose 17 beta-estradiol (4.8 microg/kg s.c.), 3 X/d recombinant human GH (2 U/kg s.c.), both, or saline for a period of two weeks. Flurochromes were administered at weekly intervals to label bone matrix undergoing mineralization. Whereas Hx resulted in reductions in body weight, uterine weight, and tibial length, OVX significantly increased body weight and tibial length, while reducing uterine weight. The combination of OVX and Hx resulted in values similar to Hx alone. Treatment with GH normalized body weight and bone length, while not affecting uterine weight in hypophysectomized animals. Estrogen increased uterine weight, while not impacting longitudinal bone growth and reduced body weight. Hypophysectomy diminished tibial cortical bone area through reductions in both mineral appositional rate (MAR) and bone formation rate (BFR). While E had no effect, GH increased both MAR and BFR, though not to sham-operated (control) levels. Hypophysectomy reduced proximal tibial trabecular number and cancellous bone area, and increased trabecular separation. Both GH and E reduced cancellous osteopenia, although employing different mechanisms. GH reduced the decrease in trabecular thickness, whereas E reduced the decrease in trabecular number and the increase in trabecular separation. Hypophysectomy reduced both Tb.MAR and Tb.BFR while treatment with GH enhanced them. This investigation has shown that Hx and GH have a dramatic impact on selected static and dynamic indices of rat cortical and cancellous histomorphometry. Furthermore, the mechanisms of action of GH and E differ, and suggest that some of the skeletal changes associated with Hx are caused by deficiencies in estrogen as well as deficiencies in growth hormone.

Sex hormones and the female voice.

PubMed

Abitbol, J; Abitbol, P; Abitbol, B

1999-09-01

In the following, the authors examine the relationship between hormonal climate and the female voice through discussion of hormonal biochemistry and physiology and informal reporting on a study of 197 women with either premenstrual or menopausal voice syndrome. These facts are placed in a larger historical and cultural context, which is inextricably bound to the understanding of the female voice. The female voice evolves from childhood to menopause, under the varied influences of estrogens, progesterone, and testosterone. These hormones are the dominant factor in determining voice changes throughout life. For example, a woman's voice always develops masculine characteristics after an injection of testosterone. Such a change is irreversible. Conversely, male castrati had feminine voices because they lacked the physiologic changes associated with testosterone. The vocal instrument is comprised of the vibratory body, the respiratory power source and the oropharyngeal resonating chambers. Voice is characterized by its intensity, frequency, and harmonics. The harmonics are hormonally dependent. This is illustrated by the changes that occur during male and female puberty: In the female, the impact of estrogens at puberty, in concert with progesterone, produces the characteristics of the female voice, with a fundamental frequency one third lower than that of a child. In the male, androgens released at puberty are responsible for the male vocal frequency, an octave lower than that of a child. Premenstrual vocal syndrome is characterized by vocal fatigue, decreased range, a loss of power and loss of certain harmonics. The syndrome usually starts some 4-5 days before menstruation in some 33% of women. Vocal professionals are particularly affected. Dynamic vocal exploration by televideoendoscopy shows congestion, microvarices, edema of the posterior third of the vocal folds and a loss of its vibratory amplitude. The authors studied 97 premenstrual women who were prescribed a treatment of multivitamins, venous tone stimulants (phlebotonics), and anti-edematous drugs. We obtained symptomatic improvement in 84 patients. The menopausal vocal syndrome is characterized by lowered vocal intensity, vocal fatigue, a decreased range with loss of the high tones and a loss of vocal quality. In a study of 100 menopausal women, 17 presented with a menopausal vocal syndrome. To rehabilitate their voices, and thus their professional lives, patients were prescribed hormone replacement therapy and multi-vitamins. All 97 women showed signs of vocal muscle atrophy, reduction in the thickness of the mucosa and reduced mobility in the cricoarytenoid joint. Multi-factorial therapy (hormone replacement therapy and multi-vitamins) has to be individually adjusted to each case depending on body type, vocal needs, and other factors.

Influence of growth hormone therapy on selected dental and skeletal system parameters.

PubMed

Partyka, Małgorzata; Chałas, Renata; Dunin-Wilczyńska, Izabella; Drohomyretska, Myroslava; Klatka, Maria

2018-03-14

Growth hormone deficiency (GHD) is one of the main indications for growth hormone therapy. One characteristic of this disease is bone age delay in relation to the chronological age. Pituitary dysfunction negatively affects the growth and development of the jaws and teeth of the child. The secretion of endocrine glands regulates growth, development, and gender differentiation. It also controls the growth of bones and teeth, regulates metabolism of calcium and phosphate, proteins, lipids and carbohydrates. The primary role in the endocrine system is played by the pituitary gland which is responsible for the production of somatotropin [1]. Dysfunction of the pituitary gland has a negative effect on the growth and development of long bones in the body, and may have an adverse effect on the development of maxilla, mandible and dentition of a child. There is some information in the literature that dental age is delayed in short stature children; the replacement of deciduous teeth by permanent teeth is also delayed, and newly erupted permanent teeth often require orthodontic treatment. Applying hormonal therapy positively affects the process of replacement of dentition [2, 3, 4, 5, 6]. The aim of the study was to assess bone and dental age, as well as analyze the state of dentition in children diagnosed with GH deficiency treated with growth hormone, depending on the duration of treatment. The study material consisted of 110 children (27 males, 83 females), hospitalized for somatotropin hypopituitarism in the Department of Paediatric Endocrinology and Diabetology at the Medical University of Lublin, Poland. The mean birth age was 13 years (156 months) with a standard deviation of 2 years and 6 months (30 months). 47 children (43%) started treatment with the growth hormone (group starting treatment) and 63 children (57%) whose treatment was started 2-3 years previously (group in the course of treatment). The control group consisted of 41 generally healthy children (15males, 25 females) with ENT problems, such as hypoacusis and a condition after nasal injury, hospitalized in the Department of Paediatric Otolaryngology at the Medical University of Lublin, Poland. The mean age was 11 years and 5 months (137 months) with standard deviation of 2 years and 5 months (29 months). Informed consent was obtained from the parents. The study was approved by the Bioethical Committee at the Medical University of Lublin (Resolution No. KE-0254 /216 /2012).

Carcinoma of the endometrium.

PubMed

Southcott, B M

2001-01-01

The incidence of endometrial cancer is highest among relatively affluent Caucasians. Although it has a comparatively low mortality rate compared with other gynaecological cancers, it is capable of aggressive behaviour. Endometrial cancer is uncommon in premenopausal women. The incidence rises with age and is significantly increased when there is exposure to unopposed estrogen, including hormone replacement therapy (HRT). Even when HRT is given in the form of estrogen and cyclical progesterone there is probably some increased risk. The long term use of tamoxifen for breast cancer is also associated with an increased incidence of endometrial cancer. Transvaginal ultrasound and pipelle or hysteroscopy endometrial biopsies are tending to replace the traditional dilation and curettage in establishing a diagnosis. 90% of endometrial tumours are surgically resectable on presentation. This remains the first line management--minimally, a total abdominal hysterectomy and bi-lateral salpingo oophorectomy. Prognostic factors include the histological grade, the depth of invasion of the myometrium, the presence or absence of lymph-vascular space invasion and involved regional nodes, tumour volume, and the presence or absence of involvement of the cervix. The pelvis is a major anatomical site at risk of recurrence, and since cytotoxic chemotherapy and hormone therapies have limited effectiveness, radiotherapy is the adjuvant therapy of choice where adverse prognostic factors are present. A move towards more radical surgery--the addition of lymphadenectomy with a total abdominal hysterectomy and bi-lateral salpingo oophorectomy, may modify the value of adjuvant therapy and has highlighted the need to demonstrate the exact place of post operative radiotherapy in the management of endometrial cancer. The ASTEC trial in the UK, run by the Medical Research Council, has the dual aims of determining the benefit of lymphadenectomy and of post operative adjuvant radiotherapy in patients with endometrial cancer confined to the corpus. Patients who are not medically fit for surgery or who have inoperable disease are managed with radical radiotherapy but the results in both these groups are inferior to those obtained with radical surgery. Spread outside the pelvis to para-aortic nodes may still be salvaged with local irradiation, but systemic disease is incurable and treatment is largely palliative including consideration of local irradiation, hormone therapy or chemotherapy for symptomatic relief. As reliable techniques for diagnosis are refined an even larger proportion of patients will be diagnosed with early disease. This, together with the development of new cytotoxic agents and sophisticated radiotherapy techniques to reduce normal tissue morbidity, will require the establishment of further clinical trials to refine optimal management.

Clinical outcomes of patients with hypothyroidism undergoing percutaneous coronary intervention.

PubMed

Zhang, Ming; Sara, Jaskanwal D S; Matsuzawa, Yasushi; Gharib, Hossein; Bell, Malcolm R; Gulati, Rajiv; Lerman, Lilach O; Lerman, Amir

2016-07-07

The aim of this study was to investigate the association between hypothyroidism and major adverse cardiovascular and cerebral events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). Two thousand four hundred and thirty patients who underwent PCI were included. Subjects were divided into two groups: hypothyroidism (n = 686) defined either as a history of hypothyroidism or thyroid-stimulating hormone (TSH) ≥5.0 mU/mL, and euthyroidism (n = 1744) defined as no history of hypothyroidism and/or 0.3 mU/mL ≤ TSH < 5.0 mU/mL. Patients with hypothyroidism were further categorized as untreated (n = 193), or those taking thyroid replacement therapy (TRT) with adequate replacement (0.3 mU/mL ≤ TSH < 5.0 mU/mL, n = 175) or inadequate replacement (TSH ≥ 5.0 mU/mL, n = 318). Adjusted hazard ratios (HRs) were calculated using Cox proportional hazards models. Median follow-up was 3.0 years (interquartile range, 0.5-7.0). After adjustment for covariates, the risk of MACCE and its constituent parts was higher in patients with hypothyroidism compared with those with euthyroidism (MACCE: HR: 1.28, P = 0.0001; myocardial infarction (MI): HR: 1.25, P = 0.037; heart failure: HR: 1.46, P = 0.004; revascularization: HR: 1.26, P = 0.0008; stroke: HR: 1.62, P = 0.04). Compared with untreated patients or those with inadequate replacement, adequately treated hypothyroid patients had a lower risk of MACCE (HR: 0.69, P = 0.005; HR: 0.78, P = 0.045), cardiac death (HR: 0.43, P = 0.008), MI (HR: 0.50, P = 0.0004; HR: 0.60, P = 0.02), and heart failure (HR: 0.50, P = 0.02; HR: 0.52, P = 0.017). Hypothyroidism is associated with a higher incidence of MACCE compared with euthyroidism in patients undergoing PCI. Maintaining adequate control on TRT is beneficial in preventing MACCE. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

A rare cause of respiratory distress and edema in neonate: Panhypopituitarism.

PubMed

Dursun, Fatma; Kirmizibekmez, Heves; Metin, Fazilet

2017-01-01

Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine.

Mutations in the F-box gene SNEEZY result in decreased arabidopsis GA signaling

USDA-ARS?s Scientific Manuscript database

We previously reported that the SLEEPY1 (SLY1) homolog, F-box gene SNEEZY/SLEEPY2 (SNE/SLY2), can partly replace SLY1 in gibberellin (GA) hormone signaling through interaction with DELLAs RGA and GAI. To determine whether SNE normally functions in GA signaling, we characterized the phenotypes of tw...

Frequency and management of breakthrough bleeding with continuous use of the transvaginal contraceptive ring: a randomized controlled trial.

PubMed

Sulak, Patricia J; Smith, Virginia; Coffee, Andrea; Witt, Iris; Kuehl, Alicia L; Kuehl, Thomas J

2008-09-01

To assess bleeding patterns with continuous use of the transvaginal contraceptive ring. We did a prospective analysis of daily menstrual flow during a 21/7 cycle followed by 6 months of continuous use and institution of a randomized protocol to manage breakthrough bleeding/spotting. Seventy-four women completed the baseline 21/7 phase and were randomized equally into two groups during the continuous phase. Group 1 was instructed to replace the ring monthly on the same calendar day with no ring-free days. Group 2 was instructed to use the same process, but if breakthrough bleeding/spotting occurred for 5 days or more, they were to remove the ring for 4 days, store it, and then reinsert that ring. Sixty-five women completed the continuous phase with reduced average flow scores in the continuous phase compared with the 21/7 phase (P<.02). Most patients had no to minimal bleeding during continuous use, with group 2 experiencing a statistically greater percentage of days without breakthrough bleeding or spotting (95%) compared with group 1 (89%) (P=.016). Instituting a 4-day hormone-free interval was more (P<.001) effective in resolving breakthrough bleeding/spotting than continuing ring use. A reduction in bleeding occurred during continuous use with replacement of the transvaginal ring compared with baseline 21/7 use. Continuous vaginal ring use resulted in an acceptable bleeding profile in most patients, reduction in flow, reduction in pelvic pain, and a high continuation rate.

Effect of Transient Hypothyroidism During Infancy on the Postnatal Ontogeny of Luteinising Hormone Release in the Agonadal Male Rhesus Monkey (Macaca mulatta): Implications for the Timing of Puberty in Higher Primates

PubMed Central

Plant, T. M.; Ramaswamy, S.; Bhat, G. K.; Stah, C. D.; Pohl, C. R.; Mann, D. R.

2010-01-01

The present study examined whether a transient thyroid hormone (T4) deficit during infancy in male monkeys would compromise the arrest of luteinising hormone (LH) secretion during the infant–juvenile transition, and/or interfere with the pubertal resurgence of LH. Animals were orchidectomised and thyroidectomised (n = 3; Tx) or sham Tx (n = 3) within 5 days of birth. T4 replacement was initiated in two Tx monkeys at age 19 weeks to reestablish a euthyroid condition. Blood samples were drawn weekly for hormone assay. Body weight, crown–rump length, and bone age were assessed throughout the study. Within a week of Tx, plasma T4 declined to undetectable levels and, by 6–8 weeks of age, signs of hypothyroidism were evident. Transient hypothyroidism during infancy failed to prevent either arrest of LH secretion during the infant–juvenile transition or the pubertal resurgence of LH secretion, both of which occurred at similar ages to sham Tx animals. Although body weight exhibited complete catch-up with T4 replacement, crown–rump length and bone age did not. Thus, bone age at the time of the pubertal LH resurgence in Tx animals was less advanced than that in shams. Although Tx did not influence qualitatively the pattern of gonadotrophin secretion, LH levels during infancy and after pubertal LH resurgence were elevated in Tx monkeys. This was not associated with changes in LH pulse frequency and amplitude, but half-life (53 versus 65 min) of the slow second phase of LH clearance was greater in Tx animals. These results indicate that hypothalamic mechanisms dictating the pattern of gonadotrophin-releasing hormone release from birth to puberty are not dependent on T4 action during infancy, and fail to support the notion that onset of puberty is causally coupled to skeletal maturation. They also indicate that LH renal clearance mechanisms may be programmed in a T4 dependent manner during infancy. PMID:18673410

[Diagnosis of congenital endocrinological disease in newborns with prolonged jaundice and hypoglycaemia].

PubMed

Braslavsky, D; Keselman, A; Chiesa, A; Bergadá, I

2012-03-01

The association of prolonged neonatal jaundice and hypoglycaemia may be secondary to an endocrinological disease. Pituitary insufficiency and primary adrenal insufficiency are the most likely endocrine diseases that need to be ruled out. We retrospectively analysed the clinical and laboratory characteristics of thirteen patients referred to the Hospital de Niños Ricardo Gutiérrez between years 2003 and 2008 due to prolonged neonatal jaundice and hypoglycaemia secondary to pituitary insufficiency in twelve patients, and in one secondary to primary adrenal insufficiency. All patients had a history of neonatal hypoglycaemia. Ten patients had conjugated hyperbilirubinaemia and six also had elevated transaminases. Combined pituitary hormone deficiency was observed in the twelve hypopituitarism patients. Hormonal replacement normalised liver function and resolved the prolonged jaundice in all the patients. None of them underwent liver biopsy. Hypoglycaemia also remitted after hormonal therapy. Prolonged or cholestatic jaundice associated with neonatal hypoglycaemia is highly likely to be due to pituitary hormone deficiency or primary adrenal insufficiency. Early diagnosis and treatment of these children reverts the prolonged jaundice and prevents morbidity and mortality due to recurrent hypoglycaemia and hormone deficiencies. Copyright © 2011 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Molecular cloning and structural characterization of Ecdysis Triggering Hormone from Choristoneura fumiferana.

PubMed

P, Bhagath Kumar; K, Kasi Viswanath; S, Tuleshwori Devi; R, Sampath Kumar; Doucet, Daniel; Retnakaran, Arthur; Krell, Peter J; Feng, Qili; Ampasala, Dinakara Rao

2016-07-01

At the end of each stadium, insects undergo a precisely orchestrated process known as ecdysis which results in the replacement of the old cuticle with a new one. This physiological event is necessary to accommodate growth in arthropods since they have a rigid chitinous exoskeleton. Ecdysis is initiated by the direct action of Ecdysis Triggering Hormones on the central nervous system. Choristoneura fumiferana is a major defoliator of coniferous forests in Eastern North America. It is assumed that, studies on the ecdysis behavior of this pest might lead to the development of novel pest management strategies. Hence in this study, the cDNA of CfETH was cloned. The open reading frame of the cDNA sequence was found to encode three putative peptides viz., Pre-Ecdysis Triggering Hormone (PETH), Ecdysis Triggering Hormone (ETH), and Ecdysis Triggering Hormone Associated Peptide (ETH-AP). The CfETH transcript was detected in the epidermal tissue of larval and pupal stages, but not in eggs and adults. In order to explore the structural conformation of ETH, ab initio modelling and Molecular Dynamics (MD) Simulations were performed. Further, a library of insecticides was generated and virtual screening was performed to identify the compounds displaying high binding capacity to ETH. Copyright © 2016 Elsevier B.V. All rights reserved.

Hormonal control of angiotensinogen production.

PubMed

Dzau, V J; Herrmann, H C

The renin-angiotensin-aldosterone system appears to be under neural and hormonal control. Plasma angiotensinogen concentration is elevated in Cushing's disease, during pregnancy and in women taking oral contraceptives. An in vitro liver slice system was used to study the hormonal control of angiotensinogen synthesis and release in the rat. Dexamethasone administration in vivo resulted in increase in the in vitro rate of release of angiotensinogen by liver slices into the incubation media. This increase was inhibited by actinomycin D, an inhibitor of protein synthesis and vincristine which blocks secretion. Similarly, ethinyl estradiol treatment resulted in a 50% increase in angiotensinogen production. Hyperthyroid state was achieved by injecting rats with L-thyroxine daily for seven days. Hepatic production rate of angiotensinogen rose 21/2-fold above control and was accompanied by increases in plasma angiotensinogen concentration and plasma renin activity. In contrast, plasma angiotensinogen concentration and plasma renin activity were reduced in thyroidectomized rats. The rate of angiotensinogen production by liver slices of these rats decreased by five-fold below that of intact animals. These changes were largely corrected when thyroidectomized rats were treated with replacement doses of L-thyroxine. We conclude that hepatic angiotensinogen biosynthesis is under hormonal control. Glucocorticoid, estrogen and thyroid hormones all stimulate angiotensinogen production. These results may in part explain the pathogenesis of hypertension associated with certain disease states.

Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis.

PubMed

Yang, Ju Dong; Abdelmalek, Manal F; Guy, Cynthia D; Gill, Ryan M; Lavine, Joel E; Yates, Katherine; Klair, Jagpal; Terrault, Norah A; Clark, Jeanne M; Unalp-Arida, Aynur; Diehl, Anna Mae; Suzuki, Ayako

2017-01-01

Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. We collected data from 3 large U.S. studies of patients with NAFLD (between October 2004 and June 2013) to assess the association between histologic severity and sex, menopause status, synthetic hormone use, and menstrual abnormalities in 1112 patients with a histologic diagnosis of NAFLD. We performed logistic or ordinal logistic regression models, adjusting for covariates relevant to an increase of hepatic metabolic stress. Premenopausal women were at an increased risk of lobular inflammation, hepatocyte ballooning, and Mallory-Denk bodies than men and also at an increased risk of lobular inflammation and Mallory-Denk bodies than postmenopausal women (P < .01). Use of oral contraceptives was associated with an increased risk of lobular inflammation and Mallory-Denk bodies in premenopausal women, whereas hormone replacement therapy was associated with an increased risk of lobular inflammation in postmenopausal women (P < .05). Being a premenopausal woman or a female user of synthetic hormones is associated with increased histologic severity of hepatocyte injury and inflammation among patients with NAFLD at given levels of hepatic metabolic stress. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Consequences of not treating children with laron syndrome (primary growth hormone insensitivity).

PubMed

Laron, Z

2001-01-01

The follow-up of a large cohort of patients with Laron syndrome (LS) from infancy to adult age has enabled us to determine the effects of long-term insulin-like growth factor-I (IGF-I) deficiency on auxological, biochemical, physiological and psychological parameters. We found that early and continuous IGF-I deficiency (the anabolic effector of growth hormone) causes dwarfism, acromicria, organomicria, marked obesity, insulin resistance, retardation of skeletal maturation and osteoporosis, as well as muscular and central nervous tissue underdevelopment, and a series of biochemical changes including hypercholesterolemia. These multiple pathologies impair the quality of life of these patients. It is concluded that patients with LS need IGF-I replacement treatment throughout life.

Autoimmune Addison's disease - An update on pathogenesis.

PubMed

Hellesen, Alexander; Bratland, Eirik; Husebye, Eystein S

2018-06-01

Autoimmunity against the adrenal cortex is the leading cause of Addison's disease in industrialized countries, with prevalence estimates ranging from 93-220 per million in Europe. The immune-mediated attack on adrenocortical cells cripples their ability to synthesize vital steroid hormones and necessitates life-long hormone replacement therapy. The autoimmune disease etiology is multifactorial involving variants in immune genes and environmental factors. Recently, we have come to appreciate that the adrenocortical cell itself is an active player in the autoimmune process. Here we summarize the complex interplay between the immune system and the adrenal cortex and highlight unanswered questions and gaps in our current understanding of the disease. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Is complementary and alternative therapy effective for women in the climacteric period?

PubMed

Kim, Mi Young; Choi, Seung Do; Ryu, Aeli

2015-04-01

Vasomotor symptoms start about 2 years prior to menopause in women who are approaching menopause, and early menopause symptoms appear including emotional disturbance and anxiety, followed by physical changes such as vaginal dryness, urinary incontinence and skin wrinkles. As time progresses, osteoporosis, cardiovascular diseases, and dementia occur consecutively. Hormone therapy is primarily considered for the relief of menopause symptoms in postmenopausal women. However, as hormone replacement has emerged as a therapy that increases the potential risk of thrombosis, cerebral infarction and breast cancer, complementary and alternative medicine has drawn much attention. This study aimed to examine the types and effects of evidence-based complementary and alternative therapies that are currently used.

Resolution of Autoimmune Oophoritis after Thymectomy in a Myasthenia Gravis Patient

PubMed Central

Özdemir, Özlem; Eren, Erdal; Sağlam, Halil; Okan, Mehmet; Tarım, Ömer Faruk

2011-01-01

Myasthenia gravis (MG) is an autoimmune disorder characterized by autoantibodies against acetylcholine receptors. MG is generally an isolated disorder but may occur concomitantly with other autoimmune diseases. We describe an eighteen-year-old girl with MG who was admitted to our clinic with secondary amenorrhea and diagnosed as autoimmune oophoritis. Since her myasthenic symptoms did not resolve with anticholinesterase therapy, thymectomy was performed. After thymectomy, her menses have been regular without any hormonal replacement therapy. To our knowledge, this is the first report on a patient with autoimmune ovarian insufficiency and MG in whom premature ovarian insufficiency resolved after thymectomy, without hormonal therapy. Conflict of interest:None declared. PMID:22155465

[Thyroid status peculiarities of elderly patients 5 years after operation depending on the volume of surgical intervention].

PubMed

Aristarhov, V G; Danilov, N V; Aristarkhov, R V; Puzin, D A; Birykov, C V

2016-01-01

Long-term results of treatment of 180 patients operated 5 years ago for benign thyroid nodular pathology have been analyzed in the present paper, the results being analyzed depending on the volume of surgical intervention. The rate of postoperative hypothyrodism is lower in patients who had undergone limited thyroid resection, recurrent cases are more frequent, but they are not clinically significant and seldom require reoperation. It should also be noted that those patients have fewer cardiac complaints as the dose of hormone replacement therapy preparations is small. Elder patients who had undergone functionally significant thyroidectomy and need to take great doses of Thyroxin (107-150 mcg/day) have cardiac complaints more often (43 %) comparing to those who had undergone limited resections (35 %).

A Cross-Sectional Cohort Study of Cerebrovascular Disease and Late Effects After Radiation Therapy for Craniopharyngioma.

PubMed

Lo, Andrea C; Howard, A Fuchsia; Nichol, Alan; Hasan, Haroon; Martin, Monty; Heran, Manraj; Goddard, Karen

2016-05-01

The study objective was to describe radiation-induced vascular abnormalities, stroke prevalence, and stroke risk factors in survivors of childhood craniopharyngioma. Twenty survivors of childhood craniopharyngioma who received radiotherapy (RT) were included in the study. A clinical history, quality of life assessment, cognitive functioning assessment, magnetic resonance angiogram or computed tomography angiogram, fasting lipid profile, and fasting glucose or hemoglobin A1c test were obtained. Median age at diagnosis was 10.3 years and median age at time of study was 29.0 years. Vascular abnormalities were detected in six (32%) of 19 patients' angiograms (vascular stenosis, decreased artery size, aneurysm, cavernoma, and small vessel disease). Five (25%) of 20 patients experienced a stroke after RT. Median time since RT was 27.8 versus 9.1 years in patients with versus without vascular abnormalities (P = 0.02). A low level of high-density lipoproteiin (HDL) was present in 100% (5/5) of patients who had a post-RT stroke as compared with 13% (2/15) of patients who did not have any post-RT stroke (P = 0.02). Previous stroke had occurred in 0% (0/5) of patients receiving growth hormone (GH) replacement at the time of study, compared to 40% (6/15) of patients who were not receiving GH replacement (P = 0.09). Patients with craniopharyngioma treated with RT have a high prevalence of stroke and vascular abnormalities, particularly those with low HDL and longer duration of time since RT. There is a trend to suggest that continual GH replacement may reduce the risk of stroke. These patients should undergo careful monitoring and aggressive modification of stroke risk factors. © 2016 Wiley Periodicals, Inc.

Gonadal Hormone Modulation of Mu, Kappa, and Delta Opioid Antinociception in Male and Female Rats

PubMed Central

Stoffel, Erin C.; Ulibarri, Catherine M.; Folk, John E.; Rice, Kenner C.

2005-01-01

Previous studies suggest that sex differences in morphine antinociception in rodents might be attributed to the activational effects of gonadal hormones. The present study determined whether hormonal modulation of opioid antinociception in adult rats extends to opioids other than the prototypic mu agonist morphine. Male and female rats were sham-gonadectomized (sham-GDX) or gonadectomized (GDX) and replaced with no hormone, estradiol (E2, females), progesterone (P4, females), E2+P4 (females), or testosterone (males). Approximately 28 days later, nociception was evaluated on the 50°C hot plate and warm water tail withdrawal tests before and after subcutaneous administration of hydromorphone, buprenorphine, U50,488, or SNC 80. In sham-GDX (gonadally intact) rats, the mu agonists and U50,488 were less effective in females than in males in at least one nociceptive test, and the delta agonist SNC 80 was less effective in males than in females. In males, gonadectomy tended to decrease, and testosterone tended to increase antinociception produced by 3 of the 4 agonists. In females, gonadectomy and hormone treatment had more variable effects, although E2 tended to decrease mu opioid antinociception. The present results suggest that activational effects of gonadal hormones are relatively modest and somewhat inconsistent on antinociception produced by various opioid agonists in the adult rat. Perspective: This study demonstrates that reproductive hormones such as testosterone in males and estradiol in females do not consistently modulate sensitivity to the analgesic effects of opioids in the adult organism. PMID:15820914

Cross-sex testosterone therapy in ovariectomized mice: addition of low-dose estrogen preserves bone architecture.

PubMed

Goetz, Laura G; Mamillapalli, Ramanaiah; Devlin, Maureen J; Robbins, Amy E; Majidi-Zolbin, Masoumeh; Taylor, Hugh S

2017-11-01

Cross-sex hormone therapy (XHT) is widely used by transgender people to alter secondary sex characteristics to match their desired gender presentation. Here, we investigate the long-term effects of XHT on bone health using a murine model. Female mice underwent ovariectomy at either 6 or 10 wk and began weekly testosterone or vehicle injections. Dual-energy X-ray absorptiometry (DXA) was performed (20 wk) to measure bone mineral density (BMD), and microcomputed tomography was performed to compare femoral cortical and trabecular bone architecture. The 6-wk testosterone group had comparable BMD with controls by DXA but reduced bone volume fraction, trabecular number, and cortical area fraction and increased trabecular separation by microcomputed tomography. Ten-week ovariectomy/XHT maintained microarchitecture, suggesting that estrogen is critical for bone acquisition during adolescence and that late, but not early, estrogen loss can be sufficiently replaced by testosterone alone. Given these findings, we then compared effects of testosterone with effects of weekly estrogen or combined testosterone/low-dose estrogen treatment after a 6-wk ovariectomy. Estrogen treatment increased spine BMD and microarchitecture, including bone volume fraction, trabecular number, trabecular thickness, and connectivity density, and decreased trabecular separation. Combined testosterone-estrogen therapy caused similar increases in femur and spine BMD and improved architecture (increased bone volume fraction, trabecular number, trabecular thickness, and connectivity density) to estrogen therapy and were superior compared with mice treated with testosterone only. These results demonstrate estradiol is critical for bone acquisition and suggest a new cross-sex hormone therapy adding estrogens to testosterone treatments with potential future clinical implications for treating transgender youth or men with estrogen deficiency. Copyright © 2017 the American Physiological Society.

Growth Hormone and Aging

DTIC Science & Technology

2000-08-01

hypopituitarism on Life Expectancy treatment is capable of increasing bone mass in J. Clin. Endocrinol Metab. 81: 1169 - 1172 patients with GH...performance and mass in adults with Nueroendocrinolgy 43 (suppl): 111 (1986). hypopituitarism : Effects of one year of GH treatment. 30. Osterziel KJ...disease The effect of low dose recombinant hGH in hypopituitarism . replacement on regional fat distribution, insulin Lancet, 336:285-288 (1990

A rare cause of respiratory distress and edema in neonate: Panhypopituitarism

PubMed Central

Dursun, Fatma; Kirmizibekmez, Heves; Metin, Fazilet

2017-01-01

Clinical presentation of hypopituitarism may be variable in the neonate. Symptoms are generally nonspecific, ranging from absent to severe, and even life-threatening, due to adrenocorticotrophic hormone deficiency. Presently described is a case of unexplained respiratory distress and edema in a neonate. Initial screening revealed panhypopituitarism. Respiratory distress improved after replacement treatment with hydrocortisone and thyroxine. PMID:28971179

76 FR 38214 - Report to Congress on Abnormal Occurrences; Fiscal Year 2010; Dissemination of Information

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-29

... without a thyroid. The child was immediately placed on replacement hormone therapy and continues such... NRC for a final determination. On July 1, 2010, after the NRC Medical Radiation Safety Team (MSRT) had...--Mohamed Megahy MD, Ltd (the licensee) indicated that on May 1, 2007, a patient was given 3,807 MBq (102.9...

Vestigialization of an Allosteric Switch: Genetic and Structural Mechanisms for the Evolution of Constitutive Activity in a Steroid Hormone Receptor

PubMed Central

Bridgham, Jamie T.; Keay, June; Ortlund, Eric A.; Thornton, Joseph W.

2014-01-01

An important goal in molecular evolution is to understand the genetic and physical mechanisms by which protein functions evolve and, in turn, to characterize how a protein's physical architecture influences its evolution. Here we dissect the mechanisms for an evolutionary shift in function in the mollusk ortholog of the steroid hormone receptors (SRs), a family of biologically essential transcription factors. In vertebrates, the activity of SRs allosterically depends on binding a hormonal ligand; in mollusks, however, the SR ortholog (called ER, because of high sequence similarity to vertebrate estrogen receptors) activates transcription in the absence of ligand and does not respond to steroid hormones. To understand how this shift in regulation evolved, we combined evolutionary, structural, and functional analyses. We first determined the X-ray crystal structure of the ER of the Pacific oyster Crassostrea gigas (CgER), and found that its ligand pocket is filled with bulky residues that prevent ligand occupancy. To understand the genetic basis for the evolution of mollusk ERs' unique functions, we resurrected an ancient SR progenitor and characterized the effect of historical amino acid replacements on its functions. We found that reintroducing just two ancient replacements from the lineage leading to mollusk ERs recapitulates the evolution of full constitutive activity and the loss of ligand activation. These substitutions stabilize interactions among key helices, causing the allosteric switch to become “stuck” in the active conformation and making activation independent of ligand binding. Subsequent changes filled the ligand pocket without further affecting activity; by degrading the allosteric switch, these substitutions vestigialized elements of the protein's architecture required for ligand regulation and made reversal to the ancestral function more complex. These findings show how the physical architecture of allostery enabled a few large-effect mutations to trigger a profound evolutionary change in the protein's function and shaped the genetics of evolutionary reversibility. PMID:24415950

Female reproductive and hormonal factors and incidence of primary total knee arthroplasty due to osteoarthritis.

PubMed

Hussain, Sultana Monira; Wang, Yuanyuan; Giles, Graham G; Graves, Stephen; Wluka, Anita E; Cicuttini, Flavia M

2018-03-07

To examine the associations of female reproductive and hormonal factors with incidence of total knee arthroplasty (TKA) for osteoarthritis, and whether the associations differ according to overweight/obesity status. This study included 22,289 women in the Melbourne Collaborative Cohort Study. Data on age at menarche, pregnancy, parity, years of menstruation, oral contraceptive pill (OCP), menopausal status and hormone replacement therapy (HRT) were collected in 1990-1994. Incidence of TKA during 2001-2013 was determined by linking cohort records to the National Joint Replacement Registry. All analyses were adjusted for age, BMI at midlife, change in BMI (early reproductive age to midlife), country of birth, physical activity, smoking, and education. Over 12.7 years, 1,208 TKAs for osteoarthritis were identified. Ever pregnancy was associated with increased TKA risk (HR=1.32, 95%CI 1.06-1.63). Parity was positively associated with TKA risk (p for trend=0.003). OCP users had increased TKA risk than non-users (OCP<5 years, HR=1.25, 95%CI 1.08-1.45; OCP≥5 years, HR=1.17, 95%CI 1.00-1.37). One year increase in menstruation was associated with 1% decreased TKA risk (HR=0.99, 95%CI 0.97-0.99). These associations remained significant only in normal weight women at early reproductive age. Current HRT users had increased TKA risk than non-users (HR=1.33, 95%CI 1.11-1.60); the association was significant only in non-obese women at midlife. Reproductive and hormonal factors were associated with knee osteoarthritis risk. These associations remained significant in normal weight women at early reproductive age and non-obese women at midlife. Further work is needed to understand the complex effect of these factors on knee osteoarthritis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

SHBG, sex hormones, and inflammatory markers in older women.

PubMed

Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Corsi, Anna Maria; Giallauria, Francesco; Guralnik, Jack M; Zuliani, Giovanni; Cattabiani, Chiara; Parrino, Stefano; Ablondi, Fabrizio; Dall'aglio, Elisabetta; Ceresini, Graziano; Basaria, Shehzad; Ferrucci, Luigi

2011-04-01

In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state.

SHBG, Sex Hormones, and Inflammatory Markers in Older Women

PubMed Central

Ceda, Gian Paolo; Lauretani, Fulvio; Bandinelli, Stefania; Corsi, Anna Maria; Giallauria, Francesco; Guralnik, Jack M.; Zuliani, Giovanni; Cattabiani, Chiara; Parrino, Stefano; Ablondi, Fabrizio; Dall'Aglio, Elisabetta; Ceresini, Graziano; Basaria, Shehzad; Ferrucci, Luigi

2011-01-01

Context: In premenopausal and older women, high testosterone and estradiol (E2) and low SHBG levels are associated with insulin resistance and diabetes, conditions characterized by low-grade inflammation. Objective: The aim of the study was to examine the relationship between SHBG, total testosterone, total E2, and inflammatory markers in older women. Design and Patients: We conducted a retrospective cross-sectional study of 433 women at least 65 yr old from the InCHIANTI Study, Italy, who were not on hormone replacement therapy or recently hospitalized and who had complete data on SHBG, testosterone, E2, C-reactive protein (CRP), IL-6, soluble IL-6 receptor (sIL-6r), and TNF-α. Relationships between sex hormones and inflammatory markers were examined by multivariate linear regression analyses adjusted for age, body mass index, smoking, insulin, physical activity, and chronic disease. Results: In fully adjusted analyses, SHBG was negatively associated with CRP (P = 0.007), IL-6 (P = 0.008), and sIL-6r (P = 0.02). In addition, testosterone was positively associated with CRP (P = 0.006), IL-6 (P = 0.001), and TNF-α (P = 0.0002). The negative relationship between testosterone and sIL-6r in an age-adjusted model (P = 0.02) was no longer significant in a fully adjusted model (P = 0.12). E2 was positively associated with CRP (P = 0.002) but not with IL-6 in fully adjusted models. In a final model including E2, testosterone, and SHBG, and all the confounders previously considered, SHBG (0.23 ± 0.08; P = 0.006) and E2 (0.21 ± 0.08; P = 0.007), but not testosterone (P = 0.21), were still significantly associated with CRP. Conclusion: In late postmenopausal women not on hormone replacement therapy, SHBG and E2 are, respectively, negative and positive, independent and significant correlates of a proinflammatory state. PMID:21239514

Building Muscles, Keeping Muscles: Protein Turnover During Space Flight

NASA Technical Reports Server (NTRS)

Ferrando, Arny; Bloomberg, Jacob; Lee, Angie (Technical Monitor)

2002-01-01

As we age we lose muscle mass and strength. The problem is a matter of use it or lose it and more - a fact to which any active senior can attest. An imbalance in the natural cycle of protein turnover may be a contributing factor to decreased muscle mass. But the answer is not so simple, since aging is associated with changes in hormones, activity levels, nutrition, and often, disease. The human body constantly uses amino acids to build muscle protein, which then breaks down and must be replaced. When protein turnover gets out of balance, so that more protein breaks down than the body can replace, the result is muscle loss. This is not just the bane of aging, however. Severely burned people may have difficulty building new muscle long after the burned skin has been repaired. Answers to why we lose muscle mass and strength - and how doctors can fix it - may come from space. Astronauts usually eat a well-balanced diet and maintain an exercise routine to stay in top health. During long-duration flight, they exercise regularly to reduce the muscle loss that results from being in a near-weightless environment. Despite these precautions, astronauts lose muscle mass and strength during most missions. They quickly recover after returning to Earth - this is a temporary condition in an otherwise healthy population. Members of the STS-107 crew are participating in a study of the effects of space flight, hormone levels, and stress on protein turnover. When we are under stress, the body responds with a change in hormone levels. Researchers hypothesize that this stress-induced change in hormones along with the near-weightlessness might result in the body synthesizing less muscle protein, causing muscles to lose their strength and size. Astronauts, who must perform numerous duties in a confined and unusual environment, experience some stress during their flight, making them excellent candidates for testing the researchers' hypothesis.

CLOMIPHENE CITRATE IN THE TREATMENT OF IDIOPATHIC OR FUNCTIONAL HYPOGONADOTROPIC HYPOGONADISM IN MEN: A CASE SERIES AND REVIEW OF THE LITERATURE.

PubMed

Liel, Yair

2017-03-01

Late-onset hypogonadotropic hypogonadism (LOH) is a complex, heterogeneous entity. Whenever treatment is indicated, the endocrine literature has recommend testosterone replacement. We present our experience with clomiphene citrate treatment in patients with LOH and a review of the literature. This retrospective case series included 18 male patients with hypogonadotropic hypogonadism, roughly according to the European Male Aging Study criteria for LOH, attended at an academic hospital outpatient clinic. Data were retrieved from the patients' electronic medical records. The patients' mean age (±SD) was 44.3 ± 6.3 years (range 21-67 years) referred for evaluation of low testosterone together with decreased libido, erectile dysfunction, fatigue or tiredness, anxiety, and osteoporosis. Clomiphene was initially prescribed at doses between 25 mg 3 times a week and 50 mg/day. At 6 to 8 weeks following initiation of treatment, mean basal total-testosterone increased from 7.6 ± 2.6 to 19.3 ± 5.2 nmol/L (P<.0001). Mean basal luteinizing hormone (LH) increased from 2.7 ± 2.1 to 8.3 ± 3.5 nmol/L (P<.0001). Mean basal follicle-stimulating hormone (FSH) increased from 4.2 ± 3.6 to 8.6 ± 6.2 nmol/L (P = .007). Testosterone and LH responses were invariably observed, including 2 patients with history of nonpituitary cranial pathologies, 2 with somewhat elevated FSH, and 1 with an eating disorder. Twelve (67%) patients reported improvement in symptoms. Side effects included transient nipple tenderness in 1 patient. Available data suggest that clomiphene is an efficient and convenient alternative to testosterone replacement therapy in a substantial subset of patients with LOH. Additional long-term controlled studies should further establish the role of clomiphene in LOH. FSH = follicle-stimulating hormone LH = luteinizing hormone LOH = late-onset hypogonadotropic hypogonadism.

Adjunct therapy for type 1 diabetes mellitus.

PubMed

Lebovitz, Harold E

2010-06-01

Insulin replacement therapy in type 1 diabetes mellitus (T1DM) is nonphysiologic. Hyperinsulinemia is generated in the periphery to achieve normal insulin concentrations in the liver. This mismatch results in increased hypoglycemia, increased food intake with weight gain, and insufficient regulation of postprandial glucose excursions. Islet amyloid polypeptide is a hormone synthesized in pancreatic beta cells and cosecreted with insulin. Circulating islet amyloid polypeptide binds to receptors located in the hindbrain and increases satiety, delays gastric emptying and suppresses glucagon secretion. Thus, islet amyloid polypeptide complements the effects of insulin. T1DM is a state of both islet amyloid polypeptide and insulin deficiency. Pramlintide, a synthetic analog of islet amyloid polypeptide, can replace this hormone in patients with T1DM. When administered as adjunctive therapy to such patients treated with insulin, pramlintide decreases food intake and causes weight loss. Pramlintide therapy is also associated with suppression of glucagon secretion and delayed gastric emptying, both of which decrease postprandial plasma glucose excursions. Pramlintide therapy improves glycemic control and lessens weight gain. Agents that decrease intestinal carbohydrate digestion (alpha-glucosidase inhibitors) or decrease insulin resistance (metformin) might be alternative adjunctive therapies in T1DM, though its benefits are marginally supported by clinical data.

Risk Factors for Breast Cancer, Including Occupational Exposures

PubMed Central

Meo, Margrethe; Vainio, Harri

2011-01-01

The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women. PMID:22953181

Association between hormone replacement therapy and dementia: is it time to forget?

PubMed

Almeida, Osvaldo P; Flicker, Leon

2005-06-01

The results of in vitro and animal studies provide a strong rationale for the use of hormone replacement therapy (HRT) to prevent dementia and Alzheimer's disease (AD). In humans, the results of 16 observational studies are consistent with the hypothesis that estrogen use reduces the risk of AD by 10 to 60%. However, women who are prescribed HRT are less likely to have hypertension, diabetes and history of stroke than nonusers. As all of these factors have been associated with increased risk of dementia (including AD), this "prescription bias" may have a significant impact on the results of observational studies. Randomized trials are designed with the aim of avoiding many of the potential biases and confounding (measured or unmeasured) of observational studies. The results of the Women's Health Initiative Memory Study (WHIMS) indicate that HRT (estrogen plus progestin or estrogen alone) increases the risk of dementia (hazard ratio, HR = 1.8, 95% CI = 1.2-2.6). Taking into account the results of the WHIMS and the adverse health events associated with the use of estrogen plus progestin or estrogen alone, we conclude that HRT cannot be recommended as a safe and effective strategy to prevent dementia.

Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

PubMed Central

de Souza, Patrícia Reis; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda

2016-01-01

The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-γ and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome. PMID:27403034

The epidemiology of serum sex hormones in postmenopausal women

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

Cauley, J.A.; Kuller, L.H.; LeDonne, D.

1989-06-01

Serum sex hormones may be related to the risk of several diseases including osteoporosis, heart disease, and breast and endometrial cancer in postmenopausal women. In the current report, the authors examined the epidemiology of serum sex hormones in 176 healthy, white postmenopausal women (mean age 58 years) recruited from the metropolitan Pittsburgh, Pennsylvania, area. The data were collected during 1982-1983; none of the women were on estrogen replacement therapy. Serum concentrations of estrone, estradiol, testosterone, and androstenedione were measured by a combination of extraction, column chromatography, and radioimmunoassay. Neither age nor time since menopause was a significant predictor of sexmore » hormones. The degree of obesity was a major determinant of estrone and estradiol. The estrone levels of obese women were about 40% higher than the levels of nonobese women. There was a weak relation between obesity and the androgens. Cigarette smokers had significantly higher levels of androstenedione than nonsmokers, with little difference in serum estrogens between smokers and nonsmokers. Both estrone and estradiol levels tended to decline with increasing alcohol consumption. Physical activity was an independent predictor of serum estrone. More active women had lower levels of estrone. There was a positive relation of muscle strength with estrogen levels. The data suggest interesting relations between environmental and lifestyle factors and serum sex hormones. These environmental and lifestyle factors are potentially modifiable and, hence, if associations between sex hormones and disease exist, modification of these factors could affect disease risks.« less

Subclinical Hyperthyroidism: When to Consider Treatment.

PubMed

Donangelo, Ines; Suh, Se Young

2017-06-01

Subclinical hyperthyroidism is defined by a low or undetectable serum thyroid-stimulating hormone level, with normal free thyroxine and total or free triiodothyronine levels. It can be caused by increased endogenous production of thyroid hormone (e.g., in Graves disease, toxic nodular goiter, or transient thyroiditis), by administration of thyroid hormone to treat malignant thyroid disease, or by unintentional excessive replacement therapy. The prevalence of subclinical hyperthyroidism in the general population is about 1% to 2%; however, it may be higher in iodinedeficient areas. The rate of progression to overt hyperthyroidism is higher in persons with thyroid-stimulating hormone levels less than 0.1 mIU per L than in persons with low but detectable thyroid-stimulating hormone levels. Subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation and heart failure in older adults, increased cardiovascular and all-cause mortality, and decreased bone mineral density and increased bone fracture risk in postmenopausal women. However, the effectiveness of treatment in preventing these conditions is unclear. A possible association between subclinical hyperthyroidism and quality-of-life parameters and cognition is controversial. The U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for thyroid dysfunction in asymptomatic persons. The American Thyroid Association and the American Association of Clinical Endocrinologists recommend treating patients with thyroid-stimulating hormone levels less than 0.1 mIU per L if they are older than 65 years or have comorbidities such as heart disease or osteoporosis.

Associations between cadmium exposure and circulating levels of sex hormones in postmenopausal women

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

Ali, Imran; Engström, Annette; Vahter, Marie

Recent epidemiological as well as in vivo and in vitro studies collectively suggest that the metalloestrogen cadmium (Cd) could be a potential risk factor for hormone-related cancers in particularly breast cancer. Assessment of the association between Cd exposure and levels of endogenous sex hormones is of pivotal importance, as increased levels of such have been associated with a higher risk of breast cancer in postmenopausal women. The present study investigated the perceived relationship (multivariable-adjusted linear regression analyses) between Cd exposure [blood Cd (B-Cd) and urinary Cd (U-Cd)], and serum levels of androstenedione, testosterone, estradiol, and sex-hormone binding globulin (SHBG), inmore » 438 postmenopausal Swedish women without hormone replacement therapy (HRT). A significant positive association between B-Cd (median 3.4 nmol/L) and serum testosterone levels, as well as a significant inverse association between B-Cd and serum estradiol levels and with the estradiol/testosterone ratio were encountered. However, U-Cd (median 0.69 nmol/mmol creatinine) was inversely associated with serum estradiol levels only. Our data may suggest that Cd interferes with the levels of testosterone and estradiol in postmenopausal women, which might have implications for breast cancer risk. - Highlights: • Low level cadmium exposure may interfere with the levels of steroid hormones. • Cadmium exposure was associated with increased serum testosterone concentrations. • Cadmium exposure was associated with decreased estradiol/testosterone ratio. • Cadmium exposure may have implications for breast-cancer promotion.« less

Progestogens’ effects and mechanisms for object recognition memory across the lifespan

PubMed Central

Walf, Alicia A.; Koonce, Carolyn J.; Frye, Cheryl A.

2016-01-01

This review explores the effects of female reproductive hormones, estrogens and progestogens, with a focus on progesterone and allopregnanolone, on object memory. Progesterone and its metabolites, in particular allopregnanolone, exert various effects on both cognitive and non-mnemonic functions in females. The well-known object recognition task is a valuable experimental paradigm that can be used to determine the effects and mechanisms of progestogens for mnemonic effects across the lifespan, which will be discussed herein. In this task there is little test-decay when different objects are used as targets and baseline valance for objects is controlled. This allows repeated testing, within-subjects designs, and longitudinal assessments, which aid understanding of changes in hormonal milieu. Objects are not aversive or food-based, which are hormone-sensitive factors. This review focuses on published data from our laboratory, and others, using the object recognition task in rodents to assess the role and mechanisms of progestogens throughout the lifespan. Improvements in object recognition performance of rodents are often associated with higher hormone levels in the hippocampus and prefrontal cortex during natural cycles, with hormone replacement following ovariectomy in young animals, or with aging. The capacity for reversal of age- and reproductive senescence-related decline in cognitive performance, and changes in neural plasticity that may be dissociated from peripheral effects with such decline, are discussed. The focus here will be on the effects of brain-derived factors, such as the neurosteroid, allopregnanolone, and other hormones, for enhancing object recognition across the lifespan. PMID:26235328

Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications

PubMed Central

Lee, Jung Eun

2017-01-01

Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs) are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life. PMID:28443254

Obesity-associated Breast Cancer: Analysis of risk factors.

PubMed

Engin, Atilla

2017-01-01

Several studies show that a significantly stronger association is obvious between increased body mass index (BMI) and higher breast cancer incidence. Furthermore, obese women are at higher risk of all-cause and breast cancer specific mortality when compared to non-obese women with breast cancer. In this context, increased levels of estrogens due to excessive aromatization activity of the adipose tissue, overexpression of pro-inflammatory cytokines, insulin resistance, hyperactivation of insulin-like growth factors (IGFs) pathways, adipocyte-derived adipokines, hypercholesterolemia and excessive oxidative stress contribute to the development of breast cancer in obese women. While higher breast cancer risk with hormone replacement therapy is particularly evident among lean women, in postmenopausal women who are not taking exogenous hormones, general obesity is a significant predictor for breast cancer. Moreover, increased plasma cholesterol leads to accelerated tumor formation and exacerbates their aggressiveness. In contrast to postmenopausal women, premenopausal women with high BMI are inversely associated with breast cancer risk. Nevertheless, life-style of women for breast cancer risk is regulated by avoiding the overweight and a high-fat diet. Estrogen-plus-progestin hormone therapy users for more than 5 years have elevated risks of both invasive ductal and lobular breast cancer. Additionally, these cases are more commonly node-positive and have a higher cancer-related mortality. Collectively, in this chapter, the impacts of obesity-related estrogen, cholesterol, saturated fatty acid, leptin and adiponectin concentrations, aromatase activity, leptin and insulin resistance on breast cancer patients are evaluated. Obesity-related prognostic factors of breast cancer also are discussed at molecular basis.

Insulin resistance, metabolic syndrome and chronic low grade inflammation in Sheehan's syndrome on standard replacement therapy: a case control study.

PubMed

Bhat, Manzoor Ahmad; Laway, Bashir Ahmad; Shah, Zaffar Amin; Wani, Arshad Iqbal; Mubarik, Idrees

2015-06-01

Increased clustering of metabolic risk factors has been demonstrated in patients with hypopituitarism on standard replacement therapy. This usually has been attributed to persistent growth hormone deficiency, though contribution from underlying etiology of hypopituitarism cannot be underestimated. We, therefore, studied conventional metabolic risk factors and pro inflammatory markers in a cohort of hypopituitary patients in whom the etiology was Sheehan's syndrome. We studied 30 GH naive patients with Sheehan's syndrome (SS) on standard replacement therapy and compared with healthy age, BMI and parity matched controls. All subjects were normotensive, non-diabetic, non-smokers and none had history of any acute or chronic illness. We recorded height, weight, BMI, waist circumference and waist hip ratio, besides measuring biochemical parameters like lipid profile, fasting plasma glucose and insulin, sVCAM-1, ICAM-1 and hsCRP. Metabolic syndrome and impaired glucose tolerance were more common with SS patients. Similarly total cholesterol (mean ± SD, 5.21 ± 0.98 vs 4.57 ± 0.88, P = 0.00), LDL-cholesterol (3.15 ± 0.90 vs 2.67 ± 0.75, P = 0.02), triglycerides (2.14 ± 1.00 vs 1.43 ± 0.45, P = 0.00) and pro-inflammatory markers i.e. hsCRP (3.95 ± 2.58 vs 1.45 ± 2.77, P = 0.00) were significantly higher in patients with SS. hsCRP positively correlated with fasting insulin (r = 0.40, P = 0.02), HOMA-IR (r = 0.38, P = 0.03) and negatively with HDL (r = - 0.33, P = 0.05). GH naïve SS patients on standard replacement therapy have increased clustering of metabolic and pro-inflammatory risk factors.

Effects of additional milk replacer feeding on calf health, growth, and selected blood metabolites in calves.

PubMed

Quigley, J D; Wolfe, T A; Elsasser, T H

2006-01-01

The objective of the experiment was to evaluate effects of increased milk replacer feeding on growth, intake, feed efficiency, and health parameters in stressed calves. Holstein bull calves (n = 120; approximately 3 to 8 d of age) were purchased from sale barns and dairy farms and housed in fiberglass hutches. In addition, wood shavings contaminated with coronavirus were mixed with clean shavings and added to each hutch before the start of the experiment. Calves were fed either a fixed amount (454 g/d) of a 20% crude protein (CP), 20% fat milk replacer to weaning at 28 d or a variable amount (454, 681, 908, and 454 g/d on d 0 to 7, 8 to 14, 15 to 31, and 32 to 41, respectively) of a milk replacer containing 28% CP and 17% fat without or with added dietary supplement containing bovine serum. Calves were also fed commercial calf starter and water ad libitum. Plasma IgG concentration in most calves on arrival at the facility was < 10 g/L. Intake, change in body weight, feed efficiency, morbidity and mortality, and selected plasma metabolites were determined. Body weight at 28 d, 56 d, daily body weight gain, intake of milk replacer, fecal scores, days with diarrhea, and days treated with antibiotics were increased with feeding variable amount of milk replacer over the 56-d study. Starter intake from d 1 to 56 was reduced from 919 to 717 g/d in calves fed fixed and variable amounts of milk replacer, respectively. Morbidity, measured as the number of days that calves had diarrhea, was increased by 53% when a variable amount of milk replacer was fed. Calves fed variable milk replacer were treated with antibiotics for 3.1 d compared with 1.9 d for calves fed 454 g of milk replacer/d. Concentrations of plasma glucose, urea N, and insulin-like growth factor-I were increased when calves were fed variable amount of milk replacer. Dietary supplement containing bovine serum had no effect on any parameter measured. There was no effect of milk replacer feeding on concentrations of nonesterified fatty acids, total protein, or growth hormone concentrations. Plasma tumor necrosis factor-alpha was highest in calves with the highest plasma IgG concentrations on the day of arrival and might be related to the calf's ability to identify pathogens in the environment. Under conditions of this study, calves fed variable amount of milk replacer and exposed to immunological challenge before weaning had greater BW gain, but also increased incidence of diarrhea that required added veterinary treatments.

Hormone replacement therapy improves contractile function and myonuclear organization of single muscle fibres from postmenopausal monozygotic female twin pairs.

PubMed

Qaisar, Rizwan; Renaud, Guillaume; Hedstrom, Yvette; Pöllänen, Eija; Ronkainen, Paula; Kaprio, Jaakko; Alen, Markku; Sipilä, Sarianna; Artemenko, Konstantin; Bergquist, Jonas; Kovanen, Vuokko; Larsson, Lars

2013-05-01

Ageing is associated with a decline in muscle mass and strength leading to increased physical dependency in old age. Postmenopausal women experience a greater decline than men of similar age in parallel with the decrease in female sex steroid hormone production. We recruited six monozygous female twin pairs (55-59 years old) where only one twin pair was on hormone replacement therapy (HRT use = 7.8 ± 4.3 years) to investigate the association of HRT with the cytoplasmic volume supported by individual myonuclei (myonuclear domain (MND) size,) together with specific force at the single fibre level. HRT use was associated with a significantly smaller (∼27%; P < 0.05) mean MND size in muscle fibres expressing the type I but not the IIa myosin heavy chain (MyHC) isoform. In comparison to non-users, higher specific force was recorded in HRT users both in muscle fibres expressing type I (∼27%; P < 0.05) and type IIa (∼23%; P < 0.05) MyHC isoforms. These differences were fibre-type dependent, i.e. the higher specific force in fast-twitch muscle fibres was primarily caused by higher force per cross-bridge while slow-twitch fibres relied on both a higher number and force per cross-bridge. HRT use had no effect on fibre cross-sectional area (CSA), velocity of unloaded shortening (V0) and relative proportion of MyHC isoforms. In conclusion, HRT appears to have significant positive effects on both regulation of muscle contraction and myonuclei organization in postmenopausal women.

The History and Future of Treatment of Hypothyroidism

PubMed Central

McAninch, Elizabeth A.; Bianco, Antonio C.

2016-01-01

Thyroid hormone replacement has been used for more than a century to treat hypothyroidism. Natural thyroid preparations (thyroid extract, desiccated thyroid, or thyroglobulin), which contain both thyroxine (T4) and triiodothyronine (T3), were the first pharmacologic treatments available and dominated the market for the better part of the 20th century. Dosages were adjusted to resolve symptoms and to normalize the basal metabolic rate and/or serum protein-bound iodine level, but thyrotoxic adverse effects were not uncommon. Two major developments in the 1970s led to a transition in clinical practice: 1) The development of the serum thyroid-stimulating hormone (TSH) radioimmunoassay led to the discovery that many patients were overtreated, resulting in a dramatic reduction in thyroid hormone replacement dosage, and 2) the identification of peripheral deiodinase-mediated T4-to-T3 conversion provided a physiologic means to justify l-thyroxine monotherapy, obviating concerns about inconsistencies with desiccated thyroid. Thereafter, l-thyroxine mono-therapy at doses to normalize the serum TSH became the standard of care. Since then, a subgroup of thyroid hormone–treated patients with residual symptoms of hypothyroidism despite normalization of the serum TSH has been identified. This has brought into question the inability of l-thyroxine monotherapy to universally normalize serum T3 levels. New research suggests mechanisms for the inadequacies of l-thyroxine monotherapy and highlights the possible role for personalized medicine based on deiodinase polymorphisms. Understanding the historical events that affected clinical practice trends provides invaluable insight into formulation of an approach to help all patients achieve clinical and biochemical euthyroidism. PMID:26747302

Resumption of menstruation and pituitary response to gonadotropin-releasing hormone in functional hypothalamic amenorrhea subjects undertaking estrogen replacement therapy.

PubMed

Shen, Z Q; Xu, J J; Lin, J F

2013-11-01

Functional hypothalamic amenorrhea (FHA) refers to a functional menstrual disorder with various causes and presentations. Recovery of menstrual cyclicity is common in long-term follow-up but the affecting factors remain unknown. To explore factors affecting the menstrual resumption and to evaluate the pituitary response to gonadotropin-releasing hormone (GnRH) in FHA. Thirty cases with FHA were recruited. All subjects were put on continuous 1 mg/day estradiol valerate orally and followed up monthly. Recovery was defined as the occurrence of at least three consecutive regular cycles. Responder referred to those who recovered within two years of therapy. Gonadotropin response to the 50 μg GnRH challenge was tested every three months. Nineteen (63.3%) subjects recovered with a mean time to recovery of 26.8 months. Time to recovery was negatively correlated with body mass index (BMI) before and by amenorrhea. Twentyone cases had undertaken therapy for more than two years and 10 of them recovered. BMI before and by amenorrhea were negatively correlated with the recovery. Significant increase of serum luteinizing hormone (LH) and LH response to GnRH were noted after recovery. Menstrual resumption was common in FHA undertaking estrogen replacement therapy (ERT). The likelihood of recovery was affected by their BMI before and by amenorrhea but not by the weight gain during therapy. Low serum LH and attenuated LH response to GnRH were the main features of pituitary deficiency in FHA. The menstrual resumption in FHA was accompanied by the recovery of serum LH and the LH response to GnRH.

An increase in estradiol facilitates the onset of paternal behavior in the dwarf hamster (Phodopus campbelli).

PubMed

Romero-Morales, Luis; Martínez-Torres, Martín; Cárdenas, Mario; Álvarez, Carmen; Carmona, Agustín; Cedillo, Benita; Loya-Zurita, Eduardo; Luis, Juana

2018-03-01

In the dwarf hamster (Phodopus campbelli), activational effects of testosterone (T) and estradiol (E 2 ) in the regulation of paternal behavior have been repeatedly rejected because peripheral concentrations of E 2 do not change across the reproductive cycle of males. Further, castration no affected paternal behavior despite that both T and E 2 concentrations decreased significantly. However, the role of these hormones has not been evaluated in models of castration and hormonal replacement in virgin males. Here, we analysed the effects of E 2 and T in paternal behavior in virgin male dwarf hamster (Phodopus campbelli). Thirty paternal (PAT) males were bilaterally castrated; of them, 10 were implanted with T, 10 with E 2 and 10 males received no treatment. Other 10 PAT males underwent sham-castration. Seventeen aggressive (AGG) males were also bilaterally castrated; of these, 10 AGG received E 2 replacement, 7 were not treated. Other 7 AGG males were submitted to sham-castration. Following treatments, paternal behavior tests were conducted again. T and E 2 levels in plasma were quantified by radioimmunoassay (RIA). The results showed that the treatments did not affect the paternal behavior of males that were initially paternal. Neither castration nor sham-castration surgery affected the behavior of AGG males. However, when these males were treated with E 2 and the concentrations of this hormone increase significantly they became paternal. Our data suggest that an increase in E 2 levels shifted infanticidal behavior to paternal behavior in dwarf hamster. Copyright © 2018 Elsevier Inc. All rights reserved.

Music facilitate the neurogenesis, regeneration and repair of neurons.

PubMed

Fukui, Hajime; Toyoshima, Kumiko

2008-11-01

Experience has shown that therapy using music for therapeutic purposes has certain effects on neuropsychiatric disorders (both functional and organic disorders). However, the mechanisms of action underlying music therapy remain unknown, and scientific clarification has not advanced. While that study disproved the Mozart effect, the effects of music on the human body and mind were not disproved. In fact, more scientific studies on music have been conducted in recent years, mainly in the field of neuroscience, and the level of interest among researchers is increasing. The results of past studies have clarified that music influences and affects cranial nerves in humans from fetus to adult. The effects of music at a cellular level have not been clarified, and the mechanisms of action for the effects of music on the brain have not been elucidated. We propose that listening to music facilitates the neurogenesis, the regeneration and repair of cerebral nerves by adjusting the secretion of steroid hormones, ultimately leading to cerebral plasticity. Music affects levels of such steroids as cortisol (C), testosterone (T) and estrogen (E), and we believe that music also affects the receptor genes related to these substances, and related proteins. In the prevention of Alzheimer's disease and dementia, hormone replacement therapy has been shown to be effective, but at the same time, side effects have been documented, and the clinical application of hormone replacement therapy is facing a serious challenge. Conversely, music is noninvasive, and its existence is universal and mundane. Thus, if music can be used in medical care, the application of such a safe and inexpensive therapeutic option is limitless.

The menopause 'It's somewhere between a taboo and a joke'. A focus group study.

PubMed

Duffy, O; Iversen, L; Hannaford, P C

2011-08-01

To explore the menopause from the perspective of women in the community, with specific emphasis on their experience of menopausal symptoms, management strategies and support post the Women's Health Initiative trial. Four focus groups were conducted with 14 middle-aged women living in the Grampian region of Scotland. The groups lasted up to 2 hours and were analyzed using the framework approach. Symptom experience was multifaceted and varied, depending on factors such as embarrassment from symptoms, loss of identity, expectations, social support and effectiveness of management strategies. Lack of support was highlighted as a reason why some participants felt confused about the symptoms that they could attribute to the menopause and the management strategies available to them. A variety of management strategies had been used including hormone replacement therapy, herbal remedies and lifestyle changes, with varying levels of success. Some women who chose not to use hormone replacement therapy (HRT) preferred to use lifestyle changes or felt that their symptoms did not warrant hormonal therapy. Some women felt that they had to persuade their family doctor to prescribe HRT and felt that their doctors were too restrictive in prescribing this treatment. Although having good social support in general, some respondents felt less supported about the menopause and felt that improved support networks would diminish some of the confusion about symptoms experienced and management strategies available. In spite of the negative publicity surrounding HRT in recent years, a number of women perceived their family doctor as too restrictive when prescribing HRT.

Variation in the biochemical response to l-thyroxine therapy and relationship with peripheral thyroid hormone conversion efficiency

PubMed Central

Midgley, John E M; Larisch, Rolf; Dietrich, Johannes W; Hoermann, Rudolf

2015-01-01

Several influences modulate biochemical responses to a weight-adjusted levothyroxine (l-T4) replacement dose. We conducted a secondary analysis of the relationship of l-T4 dose to TSH and free T3 (FT3), using a prospective observational study examining the interacting equilibria between thyroid parameters. We studied 353 patients on steady-state l-T4 replacement for autoimmune thyroiditis or after surgery for malignant or benign thyroid disease. Peripheral deiodinase activity was calculated as a measure of T4–T3 conversion efficiency. In euthyroid subjects, the median l-T4 dose was 1.3 μg/kg per day (interquartile range (IQR) 0.94,1.60). The dose was independently associated with gender, age, aetiology and deiodinase activity (all P<0.001). Comparable FT3 levels required higher l-T4 doses in the carcinoma group (n=143), even after adjusting for different TSH levels. Euthyroid athyreotic thyroid carcinoma patients (n=50) received 1.57 μg/kg per day l-T4 (IQR 1.40, 1.69), compared to 1.19 μg/kg per day (0.85,1.47) in autoimmune thyroiditis (P<0.01, n=76) and 1.08 μg/kg per day (0.82, 1.44) in patients operated on for benign disease (P< 0.01, n=80). Stratifying patients by deiodinase activity categories of <23, 23–29 and >29 nmol/s revealed an increasing FT3–FT4 dissociation; the poorest converters showed the lowest FT3 levels in spite of the highest dose and circulating FT4 (P<0.001). An l-T4-related FT3–TSH disjoint was also apparent; some patients with fully suppressed TSH failed to raise FT3 above the median level. These findings imply that thyroid hormone conversion efficiency is an important modulator of the biochemical response to l-T4; FT3 measurement may be an additional treatment target; and l-T4 dose escalation may have limited success to raise FT3 appropriately in some cases. PMID:26335522

Thickening of the epicardial adipose tissue can be alleviated by thyroid hormone replacement therapy in patients with subclinical hypothyroidism.

PubMed

Sayin, Irmak; Erkan, Aycan Fahri; Ekici, Berkay; Kutuk, Utku; Corakci, Ahmet; Tore, Hasan Fehmi

2016-01-01

Subclinical hypothyroidism (SCH) is a common disorder which has adverse cardiovascular effects. Epicardial adipose tissue (EAT), a novel marker of cardiovascular risk, is increased in SCH. We aimed to investigate whether L-thyroxine treatment can reverse the thickening of EAT in SCH. Forty-four patients with SCH and 42 euthyroid control subjects were included. EAT thickness was measured using transthoracic echocardiography at baseline and after restoration of the euthyroid status with 3 months of L-thyroxine treatment. At baseline, mean EAT thickness was significantly greater in the SCH group when compared to the control group (6.3 ± 1.7 mm vs. 4.1 ± 0.9 mm, respectively, p < 0.001). There was a significant positive correlation between baseline serum thyroid stimulating hormone (TSH) level and EAT thickness in the SCH group. There was a significant reduction in mean EAT thickness in response to L-thyroxine treatment (6.3 ± 1.7 mm vs. 5.1 ± 1.4 mm, p < 0.001). The decrease in EAT thickness after L-thyroxine treatment when compared to baseline (DEAT) significantly correlated to the difference in TSH levels before and after treatment (DTSH; r = 0.323; p = 0.032). Epicardial adipose tissue thickness is increased in patients with SCH. This thickening was alleviated with restoration of the euthyroid status with L-thyroxine treatment in our study population of predominantly male, relatively old subjects with greater baseline EAT thickness.

Occurrence of pituitary dysfunction following traumatic brain injury.

PubMed

Bondanelli, Marta; De Marinis, Laura; Ambrosio, Maria Rosaria; Monesi, Marcello; Valle, Domenico; Zatelli, Maria Chiara; Fusco, Alessandra; Bianchi, Antonio; Farneti, Marco; degli Uberti, Ettore C I

2004-06-01

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.

Thyrotoxicosis presenting as hypogonadism: a case of central hyperthyroidism.

PubMed

Childress, R Dale; Qureshi, M Nauman; Kasparova, Meri; Oktaei, Hooman; Williams-Cleaves, Beverly; Solomon, Solomon S

2004-11-01

Herein, we present a case of central thyrotoxicosis with well-documented serial therapeutic interventions. Thyroid-stimulating hormone (TSH)-secreting pituitary tumors represent a rare cause of hyperthyroidism. It is being diagnosed more frequently with the third-generation TSH assay. Many conditions can produce normal or elevated TSH levels in combination with elevated thyroid hormone levels. The differential diagnosis includes resistance to thyroid hormone (RTH, Refetoff's syndrome), assay interference from anti-T4/T3 and heterophile antibodies, elevated or altered binding proteins, drugs affecting peripheral metabolism, and noncompliance with thyroid replacement therapy. In contrast to RTH, our patient presented had high alpha-subunit-to-TSH molar ratio, failed TSH response to thyrotropin-releasing hormone stimulation, and a large pituitary mass. Normal or high TSH in the presence of elevated T4 or T3 is a fairly common clinical scenario with many etiologic possibilities. This TSH-producing adenoma represents an unusual initial clinical presentation, as hypogonadism appeared before features of thyrotoxicosis were appreciated. This case represents the most modern therapeutic approach to the management of this rare disease. Our patient has done well on octreotide with control of thyrotoxicosis and an additional 30% shrinkage of his tumor mass.

Therapeutic approach to malnutrition and sarcopenia.

PubMed

Burgos Peláez, Rosa

2012-01-01

Sarcopenia is a syndrome characterized by the progressive loss of muscle mass and strength with a risk of undesirable effects such as physical disability, poor quality of life and death, and it is a major contributing factor of disability and loss of independence in the elderly. Its etiopathogenics include different mechanisms that are both intrinsic to the muscle itself and related to changes in the central nervous system, as well as hormonal and lifestyle factors. Several hormones and cytokines affect muscle function and mass. The reduction in testosterone and estrogens associated with ageing speeds up the loss of muscle mass. Growth hormone is also involved in the loss of lean body mass. Although sarcopenia does not completely revert with exercise, the absence of physical activity accelerates muscle mass loss. Diagnosing sarcopenia is hindered by a lack of reliable methods for measuring muscle mass. Different strategies have been tested for its treatment: testosterone replacement therapy/other anabolic androgens, estrogens in women, growth hormone, nutritional treatment and exercise. Of all the therapeutic options available, only resistance training with or without nutritional supplementation has shown its efficacy in increasing skeletal muscle mass. Copyright © 2012 S. Karger AG, Basel.

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system.

PubMed

Gutch, Manish; Philip, Rajeev; Philip, Renjit; Toms, Ajit; Saran, Sanjay; Gupta, K K

2013-10-01

Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

A case of hypopituitarism accompanying Kearns-Sayre syndrome treated with human chorionic gonadotropin: A case report and literature review.

PubMed

Kang, Y-X; Wang, Y-J; Zhang, Q; Pang, X-H; Gu, W

2017-10-01

Kearns-Sayre syndrome (KSS) is a disorder caused by mutations in mitochondrial DNA. Here, we report an unusual case of Kearns-Sayre syndrome accompanied by hypopituitarism (deficiencies in reproductive and growth hormones). A 20-year-old male presented with growth retardation for the last 8 years, as well as the following findings: short stature, delayed puberty, myasthenia, an extraocular movement deficit, drooping eyelids, pectus carinatum and scoliosis. Cerebral enhanced magnetic resonance imaging revealed dysplasias of the pituitary, white matter and cerebellum. Laboratory work-up showed subnormal testosterone and growth hormone levels, a subnormal testicular volume, sensorineural deafness, pigmentary retinopathy, complete right bundle branch block and left anterior bundle branch block. Pathological examination revealed ragged red muscle fibres. Thus, this rare case involved the coexistence of Kearns-Sayre syndrome and hypopituitarism in a patient. Administration of coenzyme Q10 for the KSS and hormone replacement therapy for the endocrinopathies were performed for treatment of this patient. © 2016 Blackwell Verlag GmbH.

Sex differences and hormonal effects on gut microbiota composition in mice.

PubMed

Org, Elin; Mehrabian, Margarete; Parks, Brian W; Shipkova, Petia; Liu, Xiaoqin; Drake, Thomas A; Lusis, Aldons J

2016-07-03

We previously reported quantitation of gut microbiota in a panel of 89 different inbred strains of mice, and we now examine the question of sex differences in microbiota composition. When the total population of 689 mice was examined together, several taxa exhibited significant differences in abundance between sexes but a larger number of differences were observed at the single strain level, suggesting that sex differences can be obscured by host genetics and environmental factors. We also examined a subset of mice on chow and high fat diets and observed sex-by-diet interactions. We further investigated the sex differences using gonadectomized and hormone treated mice from 3 different inbred strains. Principal coordinate analysis with unweighted UniFrac distances revealed very clear effects of gonadectomy and hormone replacement on microbiota composition in all 3 strains. Moreover, bile acid analyses showed gender-specific differences as well as effects of gonodectomy, providing one possible mechanism mediating sex differences in microbiota composition.

Hypothyroidism and Nephrotic Syndrome: Why, When and How to Treat.

PubMed

Mario, F Di; Pofi, R; Gigante, A; Rivoli, L; Rosato, E; Isidori, A M; Cianci, R; Barbano, B

2017-01-01

Hypothyroidism, characterised by low/normal free thyroxine (FT4) and free triiodothyronine (FT3) with elevated thyroid-stimulating hormone (TSH), is a well-known complication of nephrotic syndrome (NS). This is a common feature of primary and secondary glomerular diseases and comprises loss of protein in the urine and increased urinary excretion of thyroid hormones and thyroxine- binding globulin. With a normal thyroid reserve, this scenario is associated with the development of subclinical hypothyroidism, with a slight increase in TSH and normal free fractions. However, with a low thyroid reserve the transition toward overt hypothyroidism is almost inevitable, affecting morbidity and mortality. As T4 replacement is a cheap and well-established treatment to achieve a stable hormone status in different types of thyroid deficiency, it is essential to recognise and appropriately treat this condition. In this article we summarise the evidence on this nephro-endocrine disorder in humans and focus on diagnostic and therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study.

PubMed

Zandi, Peter P; Carlson, Michelle C; Plassman, Brenda L; Welsh-Bohmer, Kathleen A; Mayer, Lawrence S; Steffens, David C; Breitner, John C S

2002-11-06

Previous studies have shown a sex-specific increased risk of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience findings suggest that hormone replacement therapy (HRT) could reduce a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed. To examine the relationship between use of HRT and risk of AD among elderly women. Prospective study of incident dementia among 1357 men (mean age, 73.2 years) and 1889 women (mean age, 74.5 years) residing in a single county in Utah. Participants were first assessed in 1995-1997, with follow-up conducted in 1998-2000. History of women's current and former use of HRT, as well as of calcium and multivitamin supplements, was ascertained at the initial contact. Diagnosis of incident AD. Thirty-five men (2.6%) and 88 women (4.7%) developed AD between the initial interview and time of the follow-up (3 years). Incidence among women increased after age 80 years and exceeded the risk among men of similar age (adjusted hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1066 women) compared with non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95% CI, 0.36-0.96). Risk varied with duration of HRT use, so that a woman's sex-specific increase in risk disappeared entirely with more than 10 years of treatment (7 cases among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT users compared with nonusers and 0.77 (95% CI, 0.31-1.67) compared with men. No similar effect was seen with calcium or multivitamin use. Almost all of the HRT-related reduction in incidence reflected former use of HRT (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% CI, 0.21-1.23]). Prior HRT use is associated with reduced risk of AD, but there is no apparent benefit with current HRT use unless such use has exceeded 10 years.

Exaggerated gonadotropin response to luteinizing hormone-releasing hormone in amenorrheic runners.

PubMed

Yahiro, J; Glass, A R; Fears, W B; Ferguson, E W; Vigersky, R A

1987-03-01

Most studies of exercise-induced amenorrhea have compared amenorrheic athletes (usually runners) with sedentary control subjects. Such comparisons will identify hormonal changes that develop as a result of exercise training but cannot determine which of these changes play a role in causing amenorrhea. To obviate this problem, we assessed reproductive hormone status in a group of five amenorrheic runners and compared them to a group of six eumenorrheic runners matched for body fatness, training intensity, and exercise performance. Compared to the eumenorrheic runners, the amenorrheic runners had lower serum estradiol concentrations, similar basal serum luteinizing hormone and follicle-stimulating hormone concentrations, and exaggerated responses of serum gonadotropins after administration of luteinizing hormone-releasing hormone (100 micrograms intravenous bolus). Serum prolactin levels, both basally and after thyrotropin-releasing hormone administration (500 micrograms intravenous bolus) or treadmill exercise, was similar in the two groups, as were serum thyroid function tests (including thyrotropin response to thyrotropin-releasing hormone). Changes in serum cortisol levels after short-term treadmill exercise were similar in both groups, and serum testosterone levels increased after exercise only in the eumenorrheic group. In neither group did such exercise change serum luteinizing hormone, follicle-stimulating hormone, or thyrotropin levels. We concluded that exercise-induced amenorrhea is not solely related to the development of increased prolactin output after exercise training. The exaggerated gonadotropin response to luteinizing hormone-releasing hormone seen in amenorrheic runners in comparison with matched eumenorrheic runners is consistent with a hypothalamic etiology for the menstrual dysfunction, analogous to that previously described in "stress-induced" or "psychogenic" amenorrhea.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

PubMed Central

Peroni, Cibele N.; Hayashida, Cesar Y.; Nascimento, Nancy; Longuini, Viviane C.; Toledo, Rodrigo A.; Bartolini, Paolo; Bowers, Cyril Y.; Toledo, Sergio P.A.

2012-01-01

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormone-releasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/lit mice, which represent a model of GH deficiency arising from mutated growth hormone-releasing hormone-receptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a. PMID:22473409

Central obesity increases risk of breast cancer irrespective of menopausal and hormonal receptor status in women of South Asian Ethnicity.

PubMed

Nagrani, R; Mhatre, S; Rajaraman, P; Soerjomataram, I; Boffetta, P; Gupta, S; Parmar, V; Badwe, R; Dikshit, R

2016-10-01

Current evidence suggests that the relationship between obesity and breast cancer (BC) risk may vary between ethnic groups. A total of 1633 BC cases and 1504 controls were enrolled in hospital-based case-control study in Mumbai, India, from 2009 to 2013. Along with detailed questionnaire, we collected anthropometric measurements on all participants. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence interval (CI) for BC risk associated with anthropometry measurements, stratified on tumour subtype and menopausal status. Waist-to-hip ratio (WHR) of ≥0.95 was strongly associated with risk of BC compared to WHR ≤0.84 in both premenopausal (OR = 4.3; 95% CI: 2.9-6.3) and postmenopausal women (OR = 3.4; 95% CI: 2.4-4.8) after adjustment for body mass index (BMI). Premenopausal women with a BMI ≥30 were at lower risk compared to women with normal BMI (OR = 0.5; 95% CI: 0.4-0.8). A similar protective effect was observed in women who were postmenopausal for <10 years (OR = 0.6; 95% CI: 0.4-0.9) but not in women who were postmenopausal for ≥10 years (OR = 1.8; 95% CI: 1.1-3.3). Overweight and obese women (BMI: 25-29.9 and ≥ 30 kg/m(2), respectively) were at increased BC risk irrespective of menopausal status if their WHR ≥0.95. Central obesity (measured in terms of WC and WHR) increased the risk of both premenopausal and postmenopausal BCs irrespective of hormone receptor (HR) status. Central obesity appears to be a key risk factor for BC irrespective of menopausal or HR status in Indian women with no history of hormone replacement therapy. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Analytical verification and method comparison of the ADVIA Centaur® Intact Parathyroid Hormone assay.

PubMed

Fernández-Galán, Esther; Bedini, Josep Lluís; Filella, Xavier

2017-12-01

This study is the first verification of the novel iPTH Siemens ADVIA Centaur® Intact Parathyroid Hormone (iPTHm) chemiluminescence immunoassay based on monoclonal antibodies. We also compared the iPTH results obtained using this assay with the previous ADVIA Centaur® Parathyroid Hormone assay (iPTHp) based on polyclonal antibodies. The analytical performance study of iPTHm assay included LoD, LoQ, intra- and inter-assay reproducibility, and linearity. A comparison study was performed on 369 routine plasma samples. The results were analyzed independently for patients with normal and abnormal GFR, as well as patients on hemodialysis. In addition, clinical concordance between assays was assessed. Finally, we studied PTH stability of plasma samples at 4°C. For the iPTHm assay LoD and LoQ were 0.03pmol/L and 0.10pmol/L, respectively. Intra- and inter-assay CV were between 2.3% and 6.2%. Linearity was correct in the range from 3.82 to 203.08pmol/L. Correlation studies showed a good correlation (r=0.99) between iPTHm and iPTHp, with bias of -2.55% (IC -3.48% to -1.62%) in the range from 0.32 to 117.07pmol/L. Clinical concordance, assessed by Kappa Index, was 0.874. The stability study showed that differences compared to basal iPTH concentration did not exceed 20% in any of the samples analyzed. The iPTHm assay demonstrated acceptable performance and a very good clinical concordance with iPTHp assay, currently used in our laboratory. Thus, the novel iPTHm assay can replace the previous iPTHp assay, since results provided by both assays are very similar. In our study, the stability of iPTH is not affected by storage up to 14days. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The rise and fall of the British Drug Houses, Ltd.

PubMed

Petrow, V; Hartley, F

1996-08-01

Steroid research at BDH began in earnest in 1946-1948, when Hartley and Petrow joined the company. With the need to find new progestational agents to replace ethisterone and progesterone, the company began work. They were the first to discover the vital importance of 6-methylation in enhancing the hormonal effects of steroid hormones. Their progestational studies led them to work on antifertility agents and the development of ovulation inhibitors, the mini-pill, and preliminary studies on the postcoital pill. Their search for new steroids additionally resulted in synthesis for biological evaluation of new corticoids, anabolic agents, estrogens, and mineralocorticoids. In 1968 the company, then known as The BDH Group Ltd., was incorporated into the Glaxo Group and company research terminated.

Aging of the endocrine system and its potential impact on sarcopenia.

PubMed

Vitale, Giovanni; Cesari, Matteo; Mari, Daniela

2016-11-01

Sarcopenia, occurring as a primary consequence of aging, is a progressive generalized decline of skeletal muscle mass, strength and function. The pathophysiology of sarcopenia is complex and multifactorial. One major cause of muscle mass and strength loss with aging appears to be the alteration in hormonal networks involved in the inflammatory processes, muscle regeneration and protein synthesis. This review describes the recent findings concerning the role of the aging on the endocrine system in the development of sarcopenia. We also report the benefits and safety of hormone replacement therapy in elderly subjects and discuss future perspectives in the therapy and prevention of skeletal muscle aging. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Hormonal and reproductive risk factors associated with breast cancer in Isfahan patients

PubMed Central

Tazhibi, Mehdi; Dehghani, Mohsen; Babazadeh, Shadi; Makkarian, Fariborz; Tabatabaeian, Maryam; Sadeghi, Masoumeh; Rezaei, Parisa; Faghihi, Mehri

2014-01-01

Background: Breast cancer is the most prevalent type of cancer among Iranian females; it is noteworthy that the condition of this type of cancer among Iranian women does not significantly differ from what has been reported from other countries. Considering the importance of this issue, identification of the backgrounds factors and risk factors of the breast cancer risk are highly needed. Therefore, the present study is aimed to compare the risk factors of resident patients of Isfahan province, Iran, with accredited risk factors by other countries and also identify the importance of each factor in the incidence of cancer. Materials and Methods: The present work is a case-control study, which was conducted in 2011. In order to conduct the study, 216 women who had been clinically identified with breast cancer were selected from Seiedo-Shohada Hospital, Isfahan, Iran, as the case group. Moreover, 41 healthy women who were the relatives of the selected patients (i.e., sisters and aunts) were selected as the control group. The data and information of the patients from 1999 to 2010 were collected from either assessing the database system of the center for breast cancer research or interviewing the patients through phone. To analyze the data, multiple logistic regression method was applied. Results: The range of age among selected individuals in this study was from 20-75 years old. The determinant factors for odds of breast cancer included in the applied multiple logistic regression model were the use of oral contraceptive pills (OCPs) (odds ratio [OR] =0.18, 95% confidence interval [CI] = 0.04-0.75) as the protective factor, hormone replacement therapy (OR = 10.2, 95% CI = 1.18-88.89) and menopause at old age (OR = 1.26, 95% CI = 1.11-2.12) as the risk factors. Furthermore, there was not seen any significant relationship between age, vocation, and marital status with odds of breast cancer in multiple model. Conclusion: Based on the results, use of OCPs as protective factor, hormone replacement therapy, and menopause at old age are identified as the risk factors in developing breast cancer among women. Influencing and modifiable factors should be considered very important in society based interventions and preventive interventions planning. PMID:25077162

An assessment of Manasika Bhavas in menopausal syndrome and its management

PubMed Central

Santwani, Khyati; Shukla, V. D.; Santwani, M. A.; Thaker, Gayatri

2010-01-01

The present clinical trial was conducted to evaluate the efficacy of Shirodhara and Saraswatarishta as compared to hormone replacement therapy (HRT) in the management of menopausal syndrome, along with the assessment of Manasika Bhavas. The subjects were randomly divided into three groups. A total 48 patients were selected for the study, out of which 43 patients completed the study. Specialized Ayurvedic rating scales like Manasa Pariksha Bhavas as well as the Hamilton Anxiety Rating Scale, Hamilton Depression Rating scale, and Menopause Rating Scale were adopted to assess the effect of therapy. The effects were examined on the chief complaints as well as the associated complaints. Patients undergoing Shirodhara had better relief of the disturbances of Manasa Bhavas and psychic symptoms of menopause as compared to the other two groups. Saraswatarishta also showed encouraging results in managing the associated somatic symptoms and the psychic symptoms. Hence, we conclude that it can be used as an alternative therapy to HRT. PMID:22131732

An assessment of Manasika Bhavas in menopausal syndrome and its management.

PubMed

Santwani, Khyati; Shukla, V D; Santwani, M A; Thaker, Gayatri

2010-07-01

The present clinical trial was conducted to evaluate the efficacy of Shirodhara and Saraswatarishta as compared to hormone replacement therapy (HRT) in the management of menopausal syndrome, along with the assessment of Manasika Bhavas. The subjects were randomly divided into three groups. A total 48 patients were selected for the study, out of which 43 patients completed the study. Specialized Ayurvedic rating scales like Manasa Pariksha Bhavas as well as the Hamilton Anxiety Rating Scale, Hamilton Depression Rating scale, and Menopause Rating Scale were adopted to assess the effect of therapy. The effects were examined on the chief complaints as well as the associated complaints. Patients undergoing Shirodhara had better relief of the disturbances of Manasa Bhavas and psychic symptoms of menopause as compared to the other two groups. Saraswatarishta also showed encouraging results in managing the associated somatic symptoms and the psychic symptoms. Hence, we conclude that it can be used as an alternative therapy to HRT.

No association between alcohol supplementation and autoantibodies to DNA damage in postmenopausal women in a controlled feeding study.

PubMed

Mahabir, S; Baer, D J; Johnson, L L; Frenkel, K; Dorgan, J F; Cambell, W; Hartman, T J; Clevidence, B; Albanes, D; Judd, J T; Taylor, P R

2005-08-01

Alcohol consumption is linked to increased breast cancer risk. Since oestrogens increase breast cancer risk, possibly through oxidative damage, and we have shown that alcohol consumption increases serum oestrogens, we tested whether moderate alcohol supplementation increased oxidative DNA damage among healthy postmenopausal women not on hormone replacement therapy in a randomized controlled crossover study. We used serum 5-hydroxymethyl-2-deoxyuridine (5-HMdU) autoantibodies (aAbs) as a marker of oxidative DNA damage. The results showed no evidence for increased or decreased levels of oxidative DNA damage among women who consumed 15 g or 30 g alcohol per day for 8 weeks compared with women in the 0 g alcohol group. We conclude that among healthy women, it is possible that an 8-week trial of moderate alcohol supplementation might be too short to make enough 5-HMdU aAbs to compare differences by alcohol dose. In future studies, a panel of biomarkers for DNA damage should be used.

Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction.

PubMed

Curtò, L; Trimarchi, F

2016-10-01

Hypopituitarism is an uncommon and under-investigated endocrine disorder in old age since signs and symptoms are unspecific and, at least in part, can be attributed to the physiological effects of aging and related co-morbidities. Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. In these circumstances, hypopituitarism is a rarely life-threatening condition, but evolution may be more dramatic as a result of pituitary apoplexy, or when a serious condition of adrenal insufficiency suddenly occurs. Clinical presentation depends on the effects that each pituitary deficit can cause, and on their mutual relationship, but also, inevitably, it depends on the severity and duration of the deficit itself, as well as on the general condition of the patient. Indeed, indications and methods of hormone replacement therapy must include the need to normalize the endocrine profile without contributing to the worsening of intercurrent diseases, such as those of glucose and bone metabolism, and the cardiovascular system, or to the increasing cancer risk. Hormonal requirements of elderly patients are reduced compared to young adults, but a prompt diagnosis and appropriate treatment of pituitary deficiencies are strongly recommended, also in this age range.

Association between depressive symptoms and reproductive variables in a group of perimenopausal women attending a menopause clinic in México City.

PubMed

Flores-Ramos, Mónica; Heinze, Gerhard; Silvestri-Tomassoni, Roberto

2010-02-01

The aim of this study was to explore the association between depressive symptoms and some variables related to the reproductive life, such as history of premenstrual dysphoric disorder, antecedent of postpartum depression, previous use of hormonal contraceptives, and current hot flushes, in a group of perimenopausal women attending a menopause clinic. Perimenopausal women, 45 to 55 years old, who had not received hormonal replacement therapy and/or psychotropic medication, were invited to participate in this study. 141 perimenopausal women were included; we obtained their psychiatric and gynecological data, and we evaluated their depressive symptomatology using the CES-D scale. There were a significantly higher number of cases of previous depressive episodes, PMDD and PPD history in depressed patients compared with non-depressed women; current hot flushes prevalence was similar between depressed and non-depressed women. Patients with a PMDD history were more likely to have experienced previous depressive episodes, a PPD history and high levels of depression. Variables associated with the level of depression were a previous history of PMDD, current hot flushes, and previous depressive episodes. The occurrence of perimenopausal depression is related to a previous history of PMDD, PPD, and depressive episodes; hot flushes only increase the severity of the depressive episode.

Growth impairment after TBI of leukemia survivors children: a model- based investigation.

PubMed

Galletto, Chiara; Gliozzi, Antonio; Nucera, Daniele; Bertorello, Nicoletta; Biasin, Eleonora; Corrias, Andrea; Chiabotto, Patrizia; Fagioli, Franca; Guiot, Caterina

2014-10-13

Children receiving Total Body Irradiation (TBI) in preparation for Hematopoietic Stem Cell Transplantation (HSCT) are at risk for Growth Hormone Deficiency (GHD), which sometimes severely compromises their Final Height (FH). To better represent the impact of such therapies on growth we apply a mathematical model, which accounts both for the gompertzian-like growth trend and the hormone-related 'spurts', and evaluate how the parameter values estimated on the children undergoing TBI differ from those of the matched normal population. 25 patients long-term childhood lymphoblastic and myeloid acute leukaemia survivors followed at Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children's Hospital (Turin, Italy) were retrospectively analysed for assessing the influence of TBI on their longitudinal growth and for validating a new method to estimate the GH therapy effects. Six were treated with GH therapy after a GHD diagnosis. We show that when TBI was performed before puberty overall growth and pubertal duration were significantly impaired, but such growth limitations were completely reverted in the small sample (6 over 25) of children who underwent GH replacement therapies. Since in principle the model could account for any additional growth 'spurt' induced by therapy, it may become a useful 'simulation' tool for paediatricians for comparing the predicted therapy effectiveness depending on its timing and dosage.

Computational modeling of the amphibian thyroid axis ...

EPA Pesticide Factsheets

In vitro screening of chemicals for bioactivity together with computational modeling are beginning to replace animal toxicity testing in support of chemical risk assessment. To facilitate this transition, an amphibian thyroid axis model has been developed to describe thyroid homeostasis during Xenopus laevis pro-metamorphosis. The model simulates the dynamic relationships of normal thyroid biology throughout this critical period of amphibian development and includes molecular initiating events (MIEs) for thyroid axis disruption to allow in silico simulations of hormone levels following chemical perturbations. One MIE that has been formally described using the adverse outcome pathway (AOP) framework is thyroperoxidase (TPO) inhibition. The goal of this study was to refine the model parameters and validate model predictions by generating dose-response and time-course biochemical data following exposure to three TPO inhibitors, methimazole, 6-propylthiouracil and 2-mercaptobenzothiazole. Key model variables including gland and blood thyroid hormone (TH) levels were compared to empirical values measured in biological samples at 2, 4, 7 and 10 days following initiation of exposure at Nieuwkoop and Faber (NF) stage 54 (onset of pro-metamorphosis). The secondary objective of these studies was to relate depleted blood TH levels to delayed metamorphosis, the adverse apical outcome. Delayed metamorphosis was evaluated by continuing exposure with a subset of larvae until a

Changes in biomarkers of bone turnover in an aripiprazole add-on or switching study.

PubMed

Lodhi, Rohit J; Masand, Salaj; Malik, Amna; Shivakumar, Kuppuswami; McAllister, Victoria D M; O'Keane, Veronica; Young, Leah C; Heald, Adrian H; Sherwood, Roy A; Aitchison, Katherine J

2016-02-01

The association between mental illness and osteoporosis and fractures is particularly pronounced in psychotic disorders. Antipsychotic use has previously been described to affect bone density. A 52-week follow-up of patients switched to aripiprazole or with aripiprazole added on, conducting a specific analysis of markers of bone turnover: urinary NTX (a biomarker of bone resorption) and serum BSAP (a biomarker of bone formation). Baseline and serial measurements of bone markers NTX, BSAP and of hormones prolactin, oestrogen and testosterone were done at weeks 0 and 1, 2, 6, 12, 26 and 52, respectively. NTX concentration reduced over time but this did not reach significance in the whole group (log-NTX: β=-0.0012, p=0.142). For BSAP the addition of or replacement with aripiprazole produced a significant reduction (log-BSAP: β=-0.00039, p=0.002). Analysis with prolactin similarly showed a significant reduction (log-prolactin: β=-0.0024, p<0.001); other hormones did not change significantly. Sensitivity analysis to compare the switchers to aripiprazole versus the "add-on" showed that the former group had a significant reduction in NTX. We found that switching to aripiprazole was associated with changes in molecular biomarkers of bone resorption, indicating a more favourable profile for bone health. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of timing and dose of thyroid hormone replacement on mental, psychomotor, and behavioral development in children with congenital hypothyroidism.

PubMed

Bongers-Schokking, Jacoba J; de Muinck Keizer-Schrama, Sabine M P F

2005-12-01

To evaluate the influence of initial and postinitial treatment factors on cognitive, psychomotor, and psychological outcome in schoolchildren with congenital hypothyroidism (CH). We studied 45 patients (19 with severe CH and 26 with mild CH) and 37 control children by correlating initial and postinitial treatment factors (free thyroxine and thyroid-stimulating hormone [TSH] concentrations, and the percentage of overtreatment and undertreatment periods) with the results of neuropsychological tests and behavior (as reported on the Teacher Report Form [TRF]). The global IQ of the children with CH was comparable to that of the controls; visuomotor and verbal scores were lower, and total TRF scores were higher. Ethnic group, previous development, and overtreatment predicted IQ and verbal scores, with higher scores seen for the overtreated patients than for the control children and those patients who had not been overtreated. As initial treatment was less satisfactory, total TRF scores were higher. Our study suggests that initial and postinitial suboptimal treatment of CH leads to abnormalities in IQ and specific fields. Overtreatment may advance cognitive development in 5-1/2- to 7-year-olds. Suboptimal initial treatment may lead to behavioral problems. We recommend that TSH concentrations be maintained within the normal range in patients with CH.

Musculo-skeletal pain, psychological distress, and hormones during the menopausal transition.

PubMed

Finset, Arnstein; Øverlie, Inger; Holte, Arne

2004-01-01

To investigate the relationship between sex hormones (estradiol, testosterone, androstendione, DHEA-S) and prolactin on one hand and musculo-skeletal pain and psychological distress on the other during the menopausal transition. Fifty-seven regularly menstruating women, who were studied over five consecutive years, who reached menopause before the fifth assessment, and did not use hormone replacement therapy were included in the study. Hormones were sampled and a questionnaire including questions on psychological distress and musculo-skeletal pain were administered at the five points of assessment. Data on last year before menopause (T1), first (T2) and second (T3) year after menopause are reported. DHEA-S, but neither testosterone nor androstendione, was inversely related to distress and pain. Pain contributed to the variance of DHEA-S over the menopausal transition, whereas DHEA-S levels did not predict pain or distress when baseline levels were controlled for. Prolactin was at T1 and T2 positively associated with distress and at T2 positively associated with musculo-skeletal pain. Musculo-skeletal pain pre-menopause was significantly related to estradiol. DHEA-S was negatively associated, and prolactin positively associated with musculo-skeletal pain and psychological distress. Whereas post-menopause DHEA-S levels were influenced by pain scores, no significant effect of pre-menopause hormones on post-menopause pain and distress was found.