Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy.

PubMed

Going, Scott; Lohman, Timothy; Houtkooper, Linda; Metcalfe, Lauve; Flint-Wagner, Hilary; Blew, Robert; Stanford, Vanessa; Cussler, Ellen; Martin, Jane; Teixeira, Pedro; Harris, Margaret; Milliken, Laura; Figueroa-Galvez, Arturo; Weber, Judith

2003-08-01

Osteoporosis is a major public health concern. The combination of exercise, hormone replacement therapy, and calcium supplementation may have added benefits for improving bone mineral density compared to a single intervention. To test this notion, 320 healthy, non-smoking postmenopausal women, who did or did not use hormone replacement therapy (HRT), were randomized within groups to exercise or no exercise and followed for 12 months. All women received 800 mg calcium citrate supplements daily. Women who exercised performed supervised aerobic, weight-bearing and weight-lifting exercise, three times per week in community-based exercise facilities. Regional bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry. Women who used HRT, calcium, and exercised increased femoral neck, trochanteric and lumbar spine bone mineral density by approximately 1-2%. Trochanteric BMD was also significantly increased by approximately 1.0% in women who exercised and used calcium without HRT compared to a negligible change in women who used HRT and did not exercise. The results demonstrate that regional BMD can be improved with aerobic, weight-bearing activity combined with weight lifting at clinically relevant sites in postmenopausal women. The response was significant at more sites in women who used HRT, suggesting a greater benefit with hormone replacement and exercise compared to HRT alone.

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.

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

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

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.

Hormone replacement therapy may reduce the return of endogenous lead from bone to the circulation.

PubMed Central

Webber, C E; Chettle, D R; Bowins, R J; Beaumont, L F; Gordon, C L; Song, X; Blake, J M; McNutt, R H

1995-01-01

Hormone replacement therapy (HRT) in postmenopausal women suppresses the increase in bone resorption expected as circulating levels of endogenous estrogen decline. We tested the hypothesis that bone lead content might remain elevated in women on HRT. Fifty six women who at recruitment were on average 35 years postmenopausal were placed on calcium supplementation. Six months later 33 of these women were prescribed either low dose or moderate dose hormone replacement in addition to the calcium supplementation. After approximately 4 years of hormone replacement, lead content was measured at the tibia and calcaneus by in vivo fluorescence excitation, and lead concentrations were measured in serum, whole blood, and urine. Women not taking hormones had significantly lower lead concentrations in cortical bone compared to all women on HRT (p = 0.007). Tibia lead content (mean +/- SD) for women on calcium only was 11.13 +/- 6.22 microgram/g bone mineral. For women on HRT, tibia bone lead was 19.37 +/- 8.62 micrograms/g bone mineral on low-dose HRT and 16.87 +/- 11.68 micrograms/g bone mineral on moderate-dose HRT. There were no differences between groups for lead concentrations measured in trabecular bone, whole blood, serum or urine. Hormone replacement maintains cortical bone lead content. In women not on HRT, there will be a perimenopausal release of lead from bone. Images Figure 1. PMID:8747022

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.

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…

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.

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.

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

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.

Clinical monograph: hormone replacement therapy.

PubMed

Deady, Joan

2004-01-01

For decades, hormone replacement therapy (HRT), which includes both estrogen and progestin, has been administered to postmenopausal women to mainly treat the symptoms of menopause and help prevent osteoporosis, with the added benefit of preventing coronary heart disease (CHD). Recently released study results have left clinicians wondering if HRT should be used at all, and, if so, with whom and under what circumstances. To provide readers with an example of the real-world operation of a pharmacy and therapeutics (P&T) committee in its use of a concise clinical monograph to guide its formulary decisions. The most relevant information for this committee, interested in evidence, was an analysis of the most current pivotal trials and observational studies that help define the place in therapy of HRT and provide information on product efficacy and safety. These included the Heart and Estrogen/progestin Replacement Study (HERS) and its extension trial, HERS II, in postmenopausal women with CHD and an average age of 67 years. The Women's Health Initiative (WHI) study, where the mean age of postmenopausal women was 63 years was also reviewed. The U.S. Food and Drug Administration (FDA) statements through January 8, 2003, on the appropriate use of these agents were also included in this clinical monograph for P&T committee review. HERS and HERS II provided evidence that HRT does not provide secondary prevention in women with CHD. Data from the WHI study concluded that HRT promotes CHD and breast cancer in this age group. The Women's Health, Osteoporosis, Progestin, Estrogen study concluded that lower doses of conjugated estrogens (0.3 mg) are just as effective in treating postmenopausal symptoms as higher doses (0.625 mg) and result in fewer side effects. The risk of breast cancer outweighs the benefits of osteoporosis prevention from HRT. According to labeling changes recommended by the FDA, HRT (or estrogen replacement therapy) should be limited to the shortest possible

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.

[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.

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

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.

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.

Hormone replacement therapy diminishes hearing in peri-menopausal mice.

PubMed

Price, Katharine; Zhu, Xiaoxia; Guimaraes, Patricia F; Vasilyeva, Olga N; Frisina, Robert D

2009-06-01

We recently discovered that progestin in hormone replacement therapy (HRT) for post-menopausal women has detrimental effects on the ear and central auditory system [Guimaraes, P., Frisina, S.T., Mapes, F., Tadros, S.F., Frisina, D.R., Frisina, R.D., 2006. Progestin negatively affects hearing in aged women. Proc. Natl. Acad. Sci. - PNAS 103, 14246-14249]. To start determining the generality and neural bases of these human findings, the present study examined the effects of combination HRT (estrogen+progestin) and estrogen alone on hearing in peri-menopausal mice. Specifically, auditory brainstem responses (ABRs-sensitivity of the auditory system) and distortion-product otoacoustic emissions (DPOAEs-cochlear outer hair cell system) were employed. Middle age female CBA mice received either a time-release, subcutaneous implanted pellet of estrogen+progestin, estrogen alone, or placebo. Longitudinal comparisons of ABR threshold data obtained at 4 months of treatment revealed statistically significant declines in auditory sensitivity over time for the combined estrogen+progestin treatment group, with the estrogen only group revealing milder changes at 3, 6 and 32 kHz. DPOAE testing revealed statistically significant differences for the estrogen+progestin treatment group in the high and middle frequency ranges (15-29 and 30-45 kHz) after as early as 2 months of treatment (p<0.01 and p<0.001, respectively). Statistically significant changes were also seen at 4 months of treatment across all frequencies for the combined HRT group. These data suggest that estrogen+progestin HRT therapy of 4 months duration impairs outer hair cell functioning and overall auditory sensitivity. These findings indicate that estrogen+progestin HRT may actually accelerate age-related hearing loss, relative to estrogen monotherapy; findings that are consistent with the clinical hearing loss observed in aging women that have taken combination HRT.

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.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

PubMed

Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

2017-05-01

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

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

Quantification of the adverse effect of ethinylestradiol containing oral contraceptive pills when used in conjunction with growth hormone replacement in routine practice.

PubMed

Phelan, Niamh; Conway, Sophy H; Llahana, Sofia; Conway, Gerard S

2012-05-01

Oestrogen antagonizes the action of growth hormone (GH). For women with combined GH and oestrogen deficiency, transdermal oestradiol is more favourable in this regard compared to oral oestradiol. Oral contraceptive pills containing ethinylestradiol (EE) are commonly used in young women with GHD and there is little information on the impact of this form of oestrogen. A case note review of women with growth hormone deficiency (GHD) attending a tertiary endocrine clinic comparing the dose of GH and serum insulin-like growth factor 1 concentrations and the type of exogenous oestrogen. All women with GHD between the ages of 18 and 47 attending University College London Hospitals (UCLH) were included and grouped according to type of oestrogen replacement. Weight, GH dose and serum IGF-I concentrations were recorded at 121 visits in 88 women. The daily dose of GH was significantly higher and the GH responsivity was significantly lower in the EE group compared to those taking no oestrogen and transdermal oestrogen. The additional cost of GH for women using EE compared to transdermal oestradiol was £6016 per patient per year. Effectiveness of GH improved in all women changing from EE to another form of oestrogen. Use of oral contraceptive pills containing EE should be avoided in women receiving treatment with GH. Alternative options include oral or transdermal hormone replacement therapy (HRT) preparations for those that require oestrogen replacement or a progesterone-based regimen for contraceptive purposes. © 2012 Blackwell Publishing Ltd.

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.

The effect of growth hormone replacement in patients with hypopituitarism on pituitary tumor recurrence, secondary cancer, and stroke.

PubMed

Jasim, Sina; Alahdab, Fares; Ahmed, Ahmed T; Tamhane, Shrikant U; Sharma, Anu; Donegan, Diane; Nippoldt, Todd B; Murad, M Hassan

2017-05-01

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995-2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53-1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70-1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51-2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.

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.

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.

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

Multiple cutaneous hemangiomas in a patient with combined pituitary hormone deficiency.

PubMed

Aykut, Ayca; Ozen, Samim; Sımsek, Damla Gokşen; Onay, Huseyin; Cogulu, Ozgur; Darcan, Sukran; Ozkinay, Ferda

2014-01-01

Combined pituitary hormone deficiency (CPHD) refers to a rare heterogeneous group of conditions in which there is a deficiency in at least two anterior pituitary hormones. Patients with POU1F1 mutations show a combined pituitary deficiency with low or absent levels of growth hormone, prolactin, and thyroid-stimulating hormone. In this study, a 7-month-old girl with a CPHD is presented. She had facial dysmorphologic features, hypertrichosis, and hypotonia. Additionally, she also presented with multiple cutaneous hemangioma that until now has not been reported in association with this disorder.

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

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.

Hormone Replacement Therapy and Colorectal Cancer Incidence and Mortality in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

PubMed

Symer, Matthew M; Wong, Natalie Z; Abelson, Jonathan S; Milsom, Jeffrey W; Yeo, Heather L

2018-06-01

Hormone replacement therapy has been shown to reduce colorectal cancer incidence, but its effect on colorectal cancer mortality is controversial. The objective of this study was to determine the effect of hormone replacement therapy on survival from colorectal cancer. We performed a secondary analysis of data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a large multicenter randomized trial run from 1993 to 2001, with follow-up data recently becoming mature. Participants were women aged 55 to 74 years, without recent colonoscopy. Data from the trial were analyzed to evaluate colorectal cancer incidence, disease-specific mortality, and all-cause mortality based on subjects' use of hormone replacement therapy at the time of randomization: never, current, or former users. A total of 75,587 women with 912 (1.21%) incident colorectal cancers and 239 associated deaths were analyzed, with median follow-up of 11.9 years. Overall, 88.6% were non-Hispanic white, and < 10% had not completed high school. The never-user group was slightly older than the current or former user groups (average, 63.8 vs. 61.4 vs. 63.3 years; P < .001). Almost one-half (47.1%) of the current users had undergone hysterectomy, compared with 21.6% of never-users and 34.0% of former users (P < .001). Adjusted colorectal cancer incidence in current users compared to never-users was lower (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.69-0.94; P = .005), as was death from colorectal cancer (HR, 0.63; 95% CI, 0.47-0.85; P = .002) and all-cause mortality (HR, 0.76; 95% CI, 0.72-0.80; P < .001). Hormone replacement therapy is associated with a reduced risk of colorectal cancer incidence and improved colorectal cancer-specific survival, as well as all-cause mortality. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Comparison of combined hormonal vaginal ring and low dose combined oral hormonal pill for the treatment of idiopathic chronic pelvic pain: a randomised trial.

PubMed

Priya, Khushboo; Rajaram, Shalini; Goel, Neerja

2016-12-01

To compare the efficacy and acceptability of combined hormonal vaginal ring with combined oral hormonal pill in women with idiopathic chronic pelvic pain. Randomised prospective interventional trial conducted in 60 women with idiopathic chronic pelvic pain. Women were randomised into two groups of 30 each. In each group, treatment was given for 84 days using either combined vaginal ring or combined oral hormonal pill. Hormonal vaginal ring releases 15mcg of ethinyl estradiol and 120mcg of the etonogestrel per day while the hormonal pill contained 30mcg of ethinyl estradiol and 150mcg of levonorgestrel. There was no ring or pill free week. After every 28 days, pain relief was measured using visual analogue scale (VAS), and verbal rating score (VRS) calculated by summing dysmenorrhea, non-cyclic pelvic pain (NCCP) and deep dyspareunia scores. Side effects, compliance, satisfaction, and user acceptability were also measured. Data was analyzed using various parametric and non-parametric tests. Reduction in mean VAS score at end of treatment in ring group was 6.23 (95% confidence interval [CI], 5.45-7.01; p<0.001) as compared to 5.53 in pill group (95% CI, 4.83-6.23; p<0.001). Reduction in mean VRS score was 5.63 in ring users (95% CI, 4.84-6.42; p<0.001) versus 4.36 in pill users (95% CI, 3.63-5.10; p<0.001). A significantly higher persistent relief in NCPP score was observed in vaginal ring group as compared to oral pill group at end of one month after stopping treatment. Compliance, satisfaction, and user acceptability were higher in ring users (80%) than pill users (70%) and a higher incidence of nausea was seen in pill group. Present study demonstrates for first time that both vaginal and oral hormonal therapy are effective in treatment of idiopathic chronic pelvic pain and vaginal ring may be a better choice with higher satisfaction rate and fewer side effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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

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.

Reversal learning in gonadectomized marmosets with and without hormone replacement: are males more sensitive to punishment?

PubMed

LaClair, Matthew; Lacreuse, Agnès

2016-05-01

This study examined sex differences in executive function in middle-aged gonadectomized marmosets (Callithrix jacchus) with or without hormonal replacement. We tested ten castrated male (mean age 5.5 years) marmosets treated with testosterone cypionate (T, n = 5) or vehicle (n = 5) on Reversal Learning, which contributes to cognitive flexibility, and the Delayed Response task, measuring working memory. Their performance was compared to that of 11 ovariectomized females (mean age = 3.7 years) treated with Silastic capsules filled with 17-β estradiol (E2, n = 6) or empty capsules (n = 5), previously tested on the same tasks (Lacreuse et al. in J Neuroendocrinol 26:296-309, 2014. doi: 10.1111/jne.12147). Behavioral observations were conducted daily. Females exhibited more locomotor behaviors than males. Males and females did not differ in the number of trials taken to reach criterion on the reversals, but males had significantly longer response latencies, regardless of hormone replacement. They also had a greater number of refusals than females. Additionally, both control and T-treated males, but not females, had slower responses on incorrect trials, suggesting that males were making errors due to distraction, lack of motivation or uncertainty. Furthermore, although both males and females had slower responding following an incorrect compared to a correct trial, the sex difference in response latencies was disproportionally large following an incorrect trial. No sex difference was found in the Delayed Response task. Overall, slower response latencies in males than females during Reversal Learning, especially during and following an incorrect trial, may reflect greater sensitivity to punishment (omission of reward) and greater performance monitoring in males, compared to females. Because these differences occurred in gonadectomized animals and regardless of hormone replacement, they may be organized early in life.

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.

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

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.

Circadian hormone profiles and insulin sensitivity in patients with Addison's disease: a comparison of continuous subcutaneous hydrocortisone infusion with conventional glucocorticoid replacement therapy.

PubMed

Björnsdottir, Sigridur; Øksnes, Marianne; Isaksson, Magnus; Methlie, Paal; Nilsen, Roy M; Hustad, Steinar; Kämpe, Olle; Hulting, Anna-Lena; Husebye, Eystein S; Løvås, Kristian; Nyström, Thomas; Bensing, Sophie

2015-07-01

Conventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI). The aim of this study was to compare circadian hormone rhythms and insulin sensitivity in conventional thrice-daily regimen of glucocorticoid replacement therapy with CSHI treatment in patients with AD. An open, randomized, two-period, 12-week crossover multicentre trial in Norway and Sweden. Ten Norwegian patients were admitted for 24-h sampling of hormone profiles. Fifteen Swedish patients underwent euglycaemic-hyperinsulinaemic clamp. Thrice-daily regimen of oral hydrocortisone (OHC) and CSHI treatment. We measured the circadian rhythm of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH), insulin-like growth factor-1, (IGF-1), IGF-binding protein-3 (IGFBP-3), glucose, insulin and triglycerides during OHC and CSHI treatment. Euglycaemic-hyperinsulinaemic clamp was used to assess insulin sensitivity. Continuous subcutaneous hydrocortisone infusion provided a more physiological circadian cortisol curve including a late-night cortisol surge. ACTH levels showed a near normal circadian variation for CSHI. CSHI prevented a continuous decrease in glucose during the night. No difference in insulin sensitivity was observed between the two treatment arms. Continuous subcutaneous hydrocortisone infusion replacement re-established a circadian cortisol rhythm and normalized the ACTH levels. Patients with CSHI replacement had a more stable night-time glucose level compared with OHC without compromising insulin sensitivity. Thus, restoring night-time cortisol levels might be advantageous for patients with AD. © 2015 John Wiley & Sons Ltd.

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.

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)

Combination nicotine replacement therapy: strategies for initiation and tapering.

PubMed

Hsia, Stephanie L; Myers, Mark G; Chen, Timothy C

2017-04-01

Several studies and meta-analyses have demonstrated the efficacy of combination nicotine replacement therapy (NRT) for patients who wish to quit smoking. However, there is limited guidance with respect to initiation and tapering of combination NRT. We attempt to review the evidence and rationale behind combination NRT, present the dosing used in combination NRT studies, and propose a step-down approach for tapering of combination NRT with integration of behavioral strategies. Copyright © 2017. Published by Elsevier Inc.

Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

PubMed

Uppal, Surabhi; Jee, Youn Hee; Lightbourne, Marissa; Han, Joan C; Stratakis, Constantine A

2017-01-01

Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella. The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC. We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.

Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

PubMed

Cerbone, Manuela; Dattani, Mehul T

2017-12-01

Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary hormone deficits, with TSH deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary hormone deficiencies. Copyright © 2017 Elsevier Ltd. All rights reserved.

A novel KAL1 mutation is associated with combined pituitary hormone deficiency.

PubMed

Takagi, Masaki; Narumi, Satoshi; Hamada, Riku; Hasegawa, Yukihiro; Hasegawa, Tomonobu

2014-01-01

Using a next-generation sequencing strategy, we identified a novel KAL1 missense mutation (p.His568Gln) in a patient with combined pituitary hormone deficiency, right microphthalmia, right renal aplasia and severe developmental delay. Our findings will provide additional evidence that KAL1 mutations are associated with hypopituitarism, in addition to luteinizing hormone, and follicle-stimulating hormone deficiencies, and improve our understanding of the phenotypic features and developmental course associated with KAL1 mutations.

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.

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.

A novel KAL1 mutation is associated with combined pituitary hormone deficiency

PubMed Central

Takagi, Masaki; Narumi, Satoshi; Hamada, Riku; Hasegawa, Yukihiro; Hasegawa, Tomonobu

2014-01-01

Using a next-generation sequencing strategy, we identified a novel KAL1 missense mutation (p.His568Gln) in a patient with combined pituitary hormone deficiency, right microphthalmia, right renal aplasia and severe developmental delay. Our findings will provide additional evidence that KAL1 mutations are associated with hypopituitarism, in addition to luteinizing hormone, and follicle-stimulating hormone deficiencies, and improve our understanding of the phenotypic features and developmental course associated with KAL1 mutations. PMID:27081504

[Utilization of hormone replacement therapy in Spain: Trends in the period 2000-2014].

PubMed

Baladé Martínez, Laura; Montero Corominas, Dolores; Macías Saint-Gerons, Diego

2016-10-07

The objective of the study was to describe the trends of utilization, supply and prevalence of hormone replacement therapy (HRT) in Spain during the period 2000-2014. Annual prevalence of HRT use including the 95% CI was calculated for women aged≥40 using individual data from the national population-based database BIFAP. Annual and total-period consumptions were expressed in defined daily doses (DDD) per 1,000 inhabitants per day and were obtained from the databases of medications dispensed in community pharmacies and charged through official prescriptions to the Spanish National Health System. In the year 2000, overall HRT consumption was 33.12 DDDs/1000 inhabitans/day: 19.81 for oestrogen only, 6.88 for tibolone and 6.44 for combined oestrogen and progestagen. In 2014 overall HRT consumption was 5.32 DDDs/1000 inhabitans/day: 1.08 for oestrogen only, 1.61 for tibolone and 2.62 for combinations of oestrogen and progestagen. The marketed presentations of HRT decreased by 46.9%. Prevalence of HRT use in women aged≥40 in BIFAP was 7.19% (95% CI 6.97-7.40) in 2001 and 0.21% (95% CI 0.20-0.22) in 2014. Women aged 40-45 registered the highest prevalence of use in 2014: 0.71% (95% CI 0.66-0.76). A sharp decline in the consumption and prevalence of HRT has been observed in Spain since the publication of the Women's Health Initiative and Million Women Study and the regulatory measures taken restricting conditions of use, showing a similar trend to that of other western countries. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

The effects of treatment combining an agonist of gonadotropin-releasing hormone with growth hormone in pubertal patients with isolated growth hormone deficiency.

PubMed

Toublanc, J E; Couprie, C; Garnier, P; Job, J C

1989-06-01

The final height of patients treated with growth hormone for isolated growth hormone deficiency has, up to now, been subnormal, with a mean below -2 SD in the series reported, an insufficient height at the onset of puberty and a more or less accelerated bone maturation during puberty being two important factors of the poor results. A long-acting analogue of gonadoliberin, Trp6-GnRH, has been given to GH-treated patients with isolated growth hormone deficiency at the time they reached pubertal stage 2, in combination with unchanged doses of GH, for one year in 11 and for two years in 7 of them. It resulted in an increase in the height age/bone age ratio and a reduction of the height insufficiency for bone age. The increase was slight but significant after one year, and fair after two years, in spite of reduced annual growth rate. Post-analogue follow-up in 5 patients with continued GH treatment showed a good development of growth and of puberty. It is concluded that combination of the long-acting Trp6-GnRH analogue and GH for 1-2 years in patients with isolated growth hormone deficiency whose puberty starts with a very insufficient height may be an appropriate way to improve their growth parameters. Studies with increased doses of GH or increased frequency of injections could help to optimize the results. Several years of follow-up are needed for demonstrating the results on final height.

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.

The ethics of aggregation and hormone replacement therapy.

PubMed

Lyerly, A D; Myers, E R; Faden, R R

2001-01-01

The use of aggregated quality of life estimates in the formation of public policy and practice guidelines raises concerns about the moral relevance of variability in values in preferences for health care. This variability may reflect unique and deeply held beliefs that may be lost when averaged with the preferences of other individuals. Feminist moral theories which argue for attention to context and particularity underline the importance of ascertaining the extent to which differences in preferences for health states reveal information which is morally relevant to clinicians and policymakers. To facilitate these considerations, we present an empirical study of preferences for the timing and occurrence of health states associated with hormone replacement therapy (HRT). Sixteen women between the ages of 45 and 55 were enrolled in this pilot study. Their preferences regarding five health states associated with HRT (menopausal symptoms. side effects of HRT, breast cancer, myocardial infarction, and osteoporosis) were assessed in quantitative terms known as utilities. Two standard methods, the visual analog scale (VAS) and the standard gamble (SG), were used to assess utility and time preference (calculated as a discount rate). The wide variability of responses underlines the importance of tailoring health care to individual women's preferences. Policy guidelines which incorporate utility analysis must recognize the normative limitations of aggregated preferences, and the moral relevance of individual conceptions of health.

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.

New trends in combined use of gonadotropin-releasing hormone antagonists with gonadotropins or pulsatile gonadotropin-releasing hormone in ovulation induction and assisted reproductive technologies.

PubMed

Gordon, K; Danforth, D R; Williams, R F; Hodgen, G D

1992-10-01

The use of gonadotropin-releasing hormone agonists as adjunctive therapy with gonadotropins for ovulation induction in in vitro fertilization and other assisted reproductive technologies has become common clinical practice. With the recent advent of potent gonadotropin-releasing hormone antagonists free from the marked histamine-release effects that stymied earlier compounds, an attractive alternative method may be available. We have established the feasibility of combining gonadotropin-releasing hormone antagonist-induced inhibition of endogenous gonadotropins with exogenous gonadotropin therapy for ovulation induction in a nonhuman primate model. Here, the principal benefits to be gained from using the gonadotropin-releasing hormone antagonist rather than the gonadotropin-releasing hormone agonist are the immediate inhibition of pituitary gonadotropin secretion without the "flare effect," which brings greater safety and convenience for patients and the medical team and saves time and money. We have also recently demonstrated the feasibility of combining gonadotropin-releasing hormone antagonist with pulsatile gonadotropin-releasing hormone therapy for the controlled restoration of gonadotropin secretion and gonadal steroidogenesis culminating in apparently normal (singleton) ovulatory cycles. This is feasible only with gonadotropin-releasing hormone antagonists because, unlike gonadotropin-releasing hormone agonists, they achieve control of the pituitary-ovarian axis without down regulation of the gonadotropin-releasing hormone receptor system. This capacity to override gonadotropin-releasing hormone antagonist-induced suppression of pituitary-ovarian function may allow new treatment modalities to be employed for women who suffer from chronic hyperandrogenemia with polycystic ovarian disease.

Aorta-atria-septum combined incision for aortic valve re-replacement

PubMed Central

Xu, Yiwei; Ye, Xiaofeng; Li, Zhaolong

2018-01-01

This case report illustrates a patient who underwent supra-annular mechanical aortic valve replacement then suffered from prosthesis dysfunction, increasing pressure gradient with aortic valve. She was successfully underwent aortic valve re-replacement, sub-annular pannus removing and aortic annulus enlargement procedures through combined cardiac incision passing through aortic root, right atrium (RA), and upper atrial septum. This incision provides optimal visual operative field and simplifies dissection. PMID:29850170

Mutations in PROP1 cause familial combined pituitary hormone deficiency.

PubMed

Wu, W; Cogan, J D; Pfäffle, R W; Dasen, J S; Frisch, H; O'Connell, S M; Flynn, S E; Brown, M R; Mullis, P E; Parks, J S; Phillips, J A; Rosenfeld, M G

1998-02-01

Combined pituitary hormone deficiency (CPHD) in man denotes impaired production of growth hormone (GH) and one or more of the other five anterior pituitary hormones. Mutations of the pituitary transcription factor gene POU1F1 (the human homologue of mouse Pit1) are responsible for deficiencies of GH, prolactin and thyroid stimulating hormone (TSH) in Snell and Jackson dwarf mice and in man, while the production of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) is preserved. The Ames dwarf (df) mouse displays a similar phenotype, and appears to be epistatic to Snell and Jackson dwarfism. We have recently positionally cloned the putative Ames dwarf gene Prop1, which encodes a paired-like homeodomain protein that is expressed specifically in embryonic pituitary and is necessary for Pit1 expression. In this report, we have identified four CPHD families with homozygosity or compound heterozygosity for inactivating mutations of PROP1. These mutations in the human PROP1 gene result in a gene product with reduced DNA-binding and transcriptional activation ability in comparison to the product of the murine df mutation. In contrast to individuals with POU1F1 mutations, those with PROP1 mutations cannot produce LH and FSH at a sufficient level and do not enter puberty spontaneously. Our results identify a major cause of CPHD in humans and suggest a direct or indirect role for PROP1 in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

PubMed

Krysiak, Robert; Kowalska, Beata; Żmuda, Witold; Okopień, Bogusław

2015-04-01

Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

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.

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

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

PubMed

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

2014-07-01

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

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) - ...

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.

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.

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.

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

Elimination of Two Hormones by Ultrasonic and Ozone Combined Processes

NASA Astrophysics Data System (ADS)

Mingcan Cui,; Younggyu Son,; Myunghee Lim,; Seungmin Na,; Jeehyeong Khim,

2010-07-01

A direct ultrasonic (US) and ozone (O3) combination (US/O3) process for the removal of two hormones, estrone (E1) and estriol (E3), in aqueous solutions was investigated. These two hormones were detected in a wastewater treatment plant effluent in Korea. It was found that the ultrasonic/ozone process showed a higher removal performance than the US and O3 process even though the O3 process also showed approximately the same removal efficiency after 60 min. Chemical oxygen demand/total organic carbon (CODcr/TOC) ratios for E1 and E3 decreased, indicating that biodegradability could be increased significantly in the US/O3 process. The optimal pH condition was determined above the neutral pH condition.

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.

Genetic causes of isolated and combined pituitary hormone deficiency.

PubMed

Giordano, Mara

2016-12-01

Research over the last 20 years has led to the elucidation of the genetic aetiologies of Isolated Growth Hormone Deficiency (IGHD) and Combined Pituitary Hormone Deficiency (CPHD). The pituitary plays a central role in growth regulation, coordinating the multitude of central and peripheral signals to maintain the body's internal balance. Naturally occurring mutation in humans and in mice have demonstrated a role for several factors in the aetiology of IGHD/CPHD. Mutations in the GH1 and GHRHR genes shed light on the phenotype and pathogenesis of IGHD whereas mutations in transcription factors such as HESX1, PROP1, POU1F1, LHX3, LHX4, GLI2 and SOX3 contributed to the understanding of CPHD. Depending upon the expression patterns of these molecules, the phenotype may consist of isolated hypopituitarism, or more complex disorders such as septo-optic dysplasia (SOD) and holoprosencephaly. Although numerous monogenic causes of growth disorders have been identified, most of the patients with IGHD/CPHD remain with an explained aetiology as shown by the relatively low mutation detection rate. The introduction of novel diagnostic approaches is now leading to the disclosure of novel genetic causes in disorders characterized by pituitary hormone defects. Copyright © 2016. Published by Elsevier Ltd.

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.

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

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.

Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height.

PubMed

Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

2012-04-01

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin(®)) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.

Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height

PubMed Central

Tanaka, Toshiaki; Naiki, Yasuhiro; Horikawa, Reiko

2012-01-01

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin®) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone. PMID:23926409

[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.

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 ...

Drug synergistic antifertility effect of combined administration of low-dose gossypol with steroid hormones in rats.

PubMed

Chang, Qing; Liu, Zhe; Ma, Wen-Zhi; Hei, Chang-Chun; Shen, Xin-Sheng; Qian, Xiao-Jing; Xu, Zeng-Lu

2011-06-01

Our previous studies suggested that low-dose gossypol combined with steroid hormones has a reversible antifertility role in adult male rats, and the course of treatment was shorter than that of either gossypol or steroid hormones alone. This result suggested that low-dose gossypol and steroid hormones have a drug synergistic effect on antifertility. The aim of the study was to find the target organs of the antifertility synergistic effect of the combined regimen. Thirty-two adult male rats were divided into four groups randomly: group GH, rats were fed orally with gossypol acetic acid (GA, 12.5 mg×kg(-1)×d(-1)) and desogestrel (DSG, 0.125 mg×kg(-1)×d(-1))/ethinylestradiol (EE, 0.025 mg×kg(-1)×d(-1))/testosterone undecanoate (TU, 100 mg×kg(-1)×d(-1)); group G, a single dose of GA (12.5 mg×kg(-1)×d(-1)) was given; group H, the same dosage of DSG/EE/TU as in group GH were administered; group C, rats were treated with vehicle (1% methyl cellulose) as control. Testes and epididymis were removed at 8 weeks post-treatment for evaluating their weight, volumes, volume fraction, and total volume of testicular tissue structures and the seminiferous tubule diameter using stereological assay. Sperm cell numbers and the motility of epididymal sperm were quantitated by flow cytometry and morphological methods. Compared with group C, spermatogenesis was normal in group G and suppressed in groups H and GH. Similar changes of testicular tissue structures and sperm number were found in groups H and GH. The decreases of epididymal sperm number and motility in group GH were greater than that of the low-dose gossypol or steroid hormones alone group. The suppression of spermatogenesis was induced by steroid hormones in the combined regimen, and the epididymis was the target organ of low-dose gossypol. Combined use of low-dose gossypol and steroid hormones played a comprehensive antifertility role in their synergistic effect on reducing the number and motility of epididymal

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.

Addition of sucralose enhances the release of satiety hormones in combination with pea protein.

PubMed

Geraedts, Maartje C P; Troost, Freddy J; Saris, Wim H M

2012-03-01

Exposing the intestine to proteins or tastants, particularly sweet, affects satiety hormone release. There are indications that each sweetener has different effects on this release, and that combining sweeteners with other nutrients might exert synergistic effects on hormone release. STC-1 cells were incubated with acesulfame-K, aspartame, saccharine, sucralose, sucrose, pea, and pea with each sweetener. After a 2-h incubation period, cholecystokinin(CCK) and glucagon-like peptide 1 (GLP-1) concentrations were measured. Using Ussing chamber technology, the mucosal side of human duodenal biopsies was exposed to sucrose, sucralose, pea, and pea with each sweetener. CCK and GLP-1 levels were measured in basolateral secretions. In STC-1 cells, exposure to aspartame, sucralose, sucrose, pea, and pea with sucralose increased CCK levels, whereas GLP-1 levels increased after addition of all test products. Addition of sucrose and sucralose to human duodenal biopsies did not affect CCK and GLP-1 release; addition of pea stimulated CCK and GLP-1 secretion. Combining pea with sucrose and sucralose induced even higher levels of CCK and GLP-1. Synchronous addition of pea and sucralose to enteroendocrine cells induced higher levels of CCK and GLP-1 than addition of each compound alone. This study shows that combinations of dietary compounds synergize to enhance satiety hormone release. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome.

PubMed

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Won Kyoung; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-03-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD.

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

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.

COMBINED REPLACEMENT OF THE AORTIC VALVE AND ASCENDING AORTA IN JEHOVAH'S WITNESSES: REPORT OF TWO CASES

PubMed Central

Beddermann, Christoph; Norman, John C.; Cooley, Denton A.

1979-01-01

Two Jehovah's Witnesses with large ascending thoracic aortic aneurysms and aortic insufficiency secondary to annuloaortic ectasia underwent successful combined replacement of the aortic valve and the ascending aorta. One patient received a composite graft containing an aortic valve prosthesis, which necessitated supravalvular coronary ostia reimplantation; the other patient underwent separate aortic valve and left supracoronary ascending aneurysm replacement, with reimplantation of the right coronary ostium into the graft. No blood or blood derivatives were administered. Both patients had uneventful recoveries and continue to do well. To our knowledge, they represent the first reported cases of successful combined replacement of the aortic valve and ascending aorta in Jehovah's Witnesses. Images PMID:15216324

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

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

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.

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.

Thyroid Dysfunction, Thyroid Hormone Replacement and Colorectal Cancer Risk

PubMed Central

Boursi, Ben; Haynes, Kevin; Mamtani, Ronac

2015-01-01

Background: Current screening guidelines for colorectal cancer (CRC) do not consider thyroid dysfunction as a risk factor for disease development. We sought to determine the risk of developing CRC in patients with thyroid dysfunction, with and without thyroid hormone replacement (THR). Methods: We conducted a nested case-control study using a large population-based medical records database from the United Kingdom. Study case patients were defined as those with any medical code of CRC. Subjects with familial colorectal cancer syndromes or inflammatory bowel disease (IBD) were excluded. For every case patient, four eligible control patients matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was THR therapy before index date. We further divided the THR unexposed group into patients with hypothyroidism (TSH > 4mg/dl), patients with hyperthyroidism (TSH < 0.4mg/dl), and subjects without documented thyroid abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were estimated using conditional logistic regression. All statistical tests were two-sided. Results: We identified 20990 CRC patients and 82054 control patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI = 0.79 to 0.99, P = .03) and 0.68 (95% CI = 0.55 to 0.83, P < .001) for treatment initiated five to 10 years and more than 10 years before index date, respectively. This protective association increased with cumulative duration of therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36, P = .001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24, P < .001) were associated with increased risk of CRC. Conclusion: Long-term THR is associated with a decreased risk of CRC. Hyperthyroidism and untreated hypothyroidism are associated with modestly elevated risk of CRC. PMID:25855726

Combined sewer overflows: an environmental source of hormones and wastewater micropollutants

USGS Publications Warehouse

Phillips, P.J.; Chalmers, A.T.; Gray, J.L.; Kolpin, D.W.; Foreman, W.T.; Wall, G.R.

2012-01-01

Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40–90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency.

Combined Sewer Overflows as a Source of Hormones to Surface Water

NASA Astrophysics Data System (ADS)

Phillips, P.; Chalmers, A.; Gray, J. L.; Foreman, W.; Kolpin, D. W.; Wall, G.; Esposito, K.

2009-12-01

Some sources of hormones to surface water, such as wastewater-treatment-plant (WWTP) effluent, have been well documented, but other sources, particularly wet-weather discharges from combined-sewer-overflows (CSOs), are not well characterized. Flow-weighted composite samples of secondarily treated WWTP effluent and untreated sewage discharges from WWTP inflows and CSO discharges were collected during 12 storms and 6 non-storm conditions from November 2007-December 2008 at the main Burlington Vermont WWTP. Concentrations of many androgens and estrogens were highest in samples from untreated sewage, and lower in samples from treated sewage. For example, concentrations of estriol in CSO samples ranged from 5 to over 100 ng/L (nanograms per liter), but were generally less than 1 ng/L in treated sewage. Many androgens were detected in CSO discharge samples in concentrations ranging from 1 to over 1000 ng/L, but were not detected above 1 ng/L in treated samples. For many of the hormones, including androgens and estriol, CSO discharges comprised over half of the total load discharged by the WWTP, even though annual CSO discharge is less than 10% of the treated plant discharge. These results indicate that untreated discharges during CSO events can be a major source of some hormones and other wastewater compounds to the environment.

Combined Sewer Overflows: An Environmental Source of Hormones and Wastewater Micropollutants

PubMed Central

2012-01-01

Data were collected at a wastewater treatment plant (WWTP) in Burlington, Vermont, USA, (serving 30,000 people) to assess the relative contribution of CSO (combined sewer overflow) bypass flows and treated wastewater effluent to the load of steroid hormones and other wastewater micropollutants (WMPs) from a WWTP to a lake. Flow-weighted composite samples were collected over a 13 month period at this WWTP from CSO bypass flows or plant influent flows (n = 28) and treated effluent discharges (n = 22). Although CSO discharges represent 10% of the total annual water discharge (CSO plus treated plant effluent discharges) from the WWTP, CSO discharges contribute 40–90% of the annual load for hormones and WMPs with high (>90%) wastewater treatment removal efficiency. By contrast, compounds with low removal efficiencies (<90%) have less than 10% of annual load contributed by CSO discharges. Concentrations of estrogens, androgens, and WMPs generally are 10 times higher in CSO discharges compared to treated wastewater discharges. Compound concentrations in samples of CSO discharges generally decrease with increasing flow because of wastewater dilution by rainfall runoff. By contrast, concentrations of hormones and many WMPs in samples from treated discharges can increase with increasing flow due to decreasing removal efficiency. PMID:22540536

Growth hormone in combination with leuprorelin in pubertal children with idiopathic short stature

PubMed Central

Benabbad, Imane; Rosilio, Myriam; Tauber, Maité; Paris, Emmanuel; Paulsen, Anne; Berggren, Lovisa; Patel, Hiren; Carel, Jean-Claude

2018-01-01

Objective There is a scarcity of data from randomised controlled trials on the association of growth hormone (GH) with gonadotrophin-releasing hormone agonists in idiopathic short stature (ISS), although this off-label use is common. We aimed to test whether delaying pubertal progression could increase near-adult height (NAH) in GH-treated patients with ISS. Methods Patients with ISS at puberty onset were randomised to GH with leuprorelin (combination, n = 46) or GH alone (n = 45). NAH standard deviation score (SDS) was the primary outcome measure. The French regulatory authority requested premature discontinuation of study treatments after approximately 2.4 years; patients from France were followed for safety. Results Mean (s.d.) baseline height SDS was −2.5 (0.5) in both groups, increasing at 2 years to −2.3 (0.6) with combination and −1.8 (0.7) with GH alone. NAH SDS was −1.8 (0.5) with combination (n = 19) and −1.9 (0.8) with GH alone (n = 16). Treatment-emergent adverse events and bone fractures occurred more frequently with combination than GH alone. Conclusion Due to premature discontinuation of treatments, statistical comparison of NAH SDS between the two cohorts was not possible. During the first 2–3 years of treatment, patients treated with the combination grew more slowly than those receiving GH alone. However, mean NAH SDS was similar in the two groups. No new GH-related safety concerns were revealed. A potentially deleterious effect of combined treatment on bone fracture incidence was identified. PMID:29669803

Growth without growth hormone in combined pituitary hormone deficiency caused by pituitary stalk interruption syndrome

PubMed Central

Lee, Sang Soo; Han, A-Leum; Ahn, Moon Bae; Kim, Shin Hee; Cho, Kyoung Soon; Park, So Hyun; Jung, Min Ho; Suh, Byung-Kyu

2017-01-01

Growth hormone (GH) is an essential element for normal growth. However, reports of normal growth without GH have been made in patients who have undergone brain surgery for craniopharyngioma. Normal growth without GH can be explained by hyperinsulinemia, hyperprolactinemia, elevated leptin levels, and GH variants; however, its exact mechanism has not been elucidated yet. We diagnosed a female patient aged 13 with combined pituitary hormone deficiency (CPHD) caused by pituitary stalk interruption syndrome (PSIS). The patient has experienced recurrent hypoglycemic seizures since birth, but reached the height of 160 cm at the age of 13, showing normal growth. She grew another 8 cm for 3 years after the diagnosis, and she reached her final adult height of 168 cm which was greater than the midparental height, at the age of 16. The patient's blood GH and insulin-like growth factor-I levels were consistently subnormal, although her insulin levels were normal. Her physical examination conducted at the age of 15 showed truncal obesity, dyslipidemia, and osteoporosis, which are metabolic features of GH deficiency (GHD). Herein, we report a case in which a PSIS-induced CPHD patient attained her final height above mid parental height despite a severe GHD. PMID:28443260

Combined pituitary hormone deficiency in german shepherd dogs with dwarfism.

PubMed

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

2000-10-01

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

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.

Rarity of PIT1 involvement in children from Russia with combined pituitary hormone deficiency.

PubMed

Fofanova, O V; Takamura, N; Kinoshita, E; Yoshimoto, M; Tsuji, Y; Peterkova, V A; Evgrafov, O V; Dedov, I I; Goncharov, N P; Yamashita, S

1998-06-05

To ascertain the molecular background of combined pituitary hormone deficiency, screening for mutations in the pituitary-specific transcription factor (Pit-1/GHF-1) gene (PIT1) was performed on a cohort of 15 children from Russia with combined growth hormone (GH)/prolactin (Prl)/thyroid-stimulating hormone (TSH) deficiency. The group of patients, suspected of PIT1 mutations, consisted of four familial cases (seven patients) and eight sporadic cases. All had complete GH deficiency and complete or partial Prl and TSH deficiency. Direct sequencing of all six exons of PIT1 and its promoter region showed a C to T transition mutation at codon 14 of exon 1 in a 3 8/12-year-old girl. This novel PIT1 mutation results in a proline to leucine substitution (P14L). The patient was heterozygous for mutant and normal alleles. The heterozygous P14L mutation was also present in her mother as well as in her maternal aunt and grandmother, all of whom were phenotypically normal. There was no mutation in the father's DNA, suggesting the need for reevaluation of genomic imprinting. In other children of our series, no mutation in PIT1 or in its promotor region was identified. This is the first report on the analysis of PIT1 and its promoter region in Russian children with GH/Prl/TSH deficiency. However, as the involvement of PIT1 mutation is rare in Russia, the other negative cases need to be analyzed for another candidate gene responsible for combined GH/Pr/TSH deficiency.

Combined hormonal versus nonhormonal versus progestin-only contraception in lactation.

PubMed

Lopez, Laureen M; Grey, Thomas W; Stuebe, Alison M; Chen, Mario; Truitt, Sarah T; Gallo, Maria F

2015-03-20

Postpartum contraception improves the health of mothers and children by lengthening birth intervals. For lactating women, contraception choices are limited by concerns about hormonal effects on milk quality and quantity and passage of hormones to the infant. Ideally, the contraceptive chosen should not interfere with lactation or infant growth. Timing of contraception initiation is also important. Immediately postpartum, most women have contact with a health professional, but many do not return for follow-up contraceptive counseling. However, immediate initiation of hormonal methods may disrupt the onset of milk production. To determine the effects of hormonal contraceptives on lactation and infant growth We searched for eligible trials until 2 March 2015. Sources included the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, POPLINE, Web of Science, LILACS, ClinicalTrials.gov, and ICTRP. We also examined review articles and contacted investigators. We sought randomized controlled trials in any language that compared hormonal contraception versus another form of hormonal contraception, nonhormonal contraception, or placebo during lactation. Hormonal contraception includes combined or progestin-only oral contraceptives, injectable contraceptives, implants, and intrauterine devices.Trials had to have one of our primary outcomes: breast milk quantity or biochemical composition; lactation initiation, maintenance, or duration; infant growth; or timing of contraception initiation and effect on lactation. Secondary outcomes included contraceptive efficacy while breastfeeding and birth interval. For continuous variables, we calculated the mean difference (MD) with 95% confidence interval (CI). For dichotomous outcomes, we computed the Mantel-Haenszel odds ratio (OR) with 95% CI. Due to differing interventions and outcome measures, we did not aggregate the data in a meta-analysis. In 2014, we added seven trials for a new total of 11. Five reports were

A newborn with combined pituitary hormone deficiency developing shock and sludge.

PubMed

Ueda, Yasuhiro; Aoyagi, Hayato; Tajima, Toshihiro

2017-11-27

A male neonate was born at 41 weeks of gestation with a birth weight of 3320 g. Artificial respiratory management was required due to respiratory disturbance 1 h after birth, and subsequently catecholamine-refractory low cardiac output-induced shock occurred. Severe combined pituitary hormone deficiency (CPHD) was considered based on the presence of his respiratory disturbance, hypoglycemia and micropenis. After hydrocortisone (HDC) administration, circulatory dynamics rapidly improved. Brain magnetic resonance imaging (MRI) showed aplasia of the anterior pituitary gland and ectopic posterior gland. γ-Glutamyltranspeptidase (γ-GTP) increased from day 10 after birth and direct bilirubin increased from day 18. On ultrasonography, sludge filling the common bile duct and gall bladder was observed. After initiating treatment with both ursodeoxycholic acid and recombinant human growth hormone (rhGH), cholestasis improved and the sludge disappeared at 3 months after birth. In newborns with CPHD, severe central adrenal insufficiency might induce cardiogenic shock after birth. Early diagnosis and intervention are necessary.

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.

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

Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: A pilot study.

PubMed

Agarwal, N; Gupta, M; Kriplani, A; Bhatla, N; Singh, N

2016-01-01

The aim of this study was to compare combined hormonal vaginal ring with ultralow-dose combined oral contraceptive (COC) pills in management of heavy menstrual bleeding (HMB). Fifty patients were randomised into Group I: vaginal ring (n = 25) and group II: COC pills (n = 25). Menstrual blood loss (MBL) was assessed at baseline, 1, 3 and 6 months (while on treatment) and at 9 months (3 months after stopping therapy). There was significant reduction in baseline pictorial blood loss assessment chart (PBAC) score from 440 ± 188 (Mean ± SD) to 178 ± 95, 139 ± 117, 112 ± 84 and 120 ± 108 in group I and from 452 ± 206 to 204 ± 152, 179 ± 125, 176 ± 164 and 202 ± 167 in group II at 1, 3, 6 and 9 months, respectively (p = 0.001). Reduction in MBL was 72% and 62% at 6 months and up to 71% and 55% at 9 months in group I and group II, respectively (p = 0.001). Reduction in MBL with ring was greater at higher baseline PBAC score but lesser in patients with fibroid > 2 cm. Combined vaginal hormonal treatment for HMB is as effective as oral hormonal therapy, with minor and transient side effects and persistence of response after cessation of therapy.

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

A unique case of combined pituitary hormone deficiency caused by a PROP1 gene mutation (R120C) associated with normal height and absent puberty

PubMed Central

Arroyo, Armando; Pernasetti, Flavia; Vasilyev, Vyacheslav V.; Amato, Paula; Yen, Samuel S. C.; Mellon, Pamela L.

2010-01-01

Summary We report a 28-year-old-female who presented with primary amenorrhoea, absence of puberty, obesity and normal stature. The subject was clearly short as a child, with a height more than 2 SD below normal until the age of 15 years. The pubertal growth spurt failed to develop. She continued growing at a prepubertal rate until growth ceased at the age of 20 years, reaching her final adult height of 157 cm (SDS −0.86) without hormonal treatment. A combined pituitary hormone stimulation test of anterior pituitary function showed deficiencies of GH, LH and FSH, and low normal serum levels of TSH and PRL. Magnetic resonance imaging revealed a hypoplastic pituitary with markedly reduced pituitary height. In addition, a whole body dual energy X-ray absorptiometry scan showed high levels of body fat (54%). Combined pituitary hormone deficiencies with a hypoplastic pituitary suggested the diagnosis of a Prophet of Pit-1 (PROP1) gene mutation. Normal stature in this case, however, confounded this diagnosis. Sequencing of PROP1 revealed homozygosity for a single base-pair substitution (C to T), resulting in the replacement of an Arg by a Cys at codon 120 (R120C) in the third helix of the homeodomain of the Prop-1 protein. To our knowledge, this is the first report of a patient with a mutation in the PROP1 gene that attained normal height without hormonal treatment, indicating a new variability in the PROP1 phenotype, with important implications for the diagnosis of these patients. We suggest that this can be explained by (i) the presence of low levels of GH in the circulation during childhood and adolescence; (ii) the lack of circulating oestrogen delaying epiphyseal fusion, resulting in growth beyond the period of normal growth; and (iii) fusion of the epiphyseal plates, possibly as a result of circulating oestrogens originating from peripheral conversion of androgens by adipose tissue. PMID:12153609

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.

Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT).

PubMed

Nose, Osamu; Tatsumi, Keita; Nakano, Yukiko; Amino, Nobuyuki

2006-04-01

Combined pituitary hormone deficiency (CPHD) is an anterior pituitary disorder, commonly resulting in growth retardation. PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan. Two sisters (aged 8.4 and 4.3 years at presentation) exhibited proportional short stature from about 2 years of age. Genetic analysis determined the nature and location of mutations. Pituitary size by magnetic resonance imaging (MRI) indicated only slight hypoplasia, while hormone analysis revealed deficiencies in secretion of growth hormone (GH), thyroid stimulating hormone, prolactin and gonadotropins; adrenocortinotropin secretion appeared adequate. Genetic analysis revealed a novel familial inherited PROP1 mutation. A unique insertion mutation was found in codon 156 (467insT) located in the transcription-activating region of the PROP1 gene. The resulting PROP1 protein (191 amino acids) would lack the transcription activation domain and consequently be non-functional. Gene analysis suggested that the siblings had inherited a unique autosomal recessive PROP1 gene mutation resulting in severe GH deficiency and subsequent growth retardation.

Thyroid dysfunction, thyroid hormone replacement and colorectal cancer risk.

PubMed

Boursi, Ben; Haynes, Kevin; Mamtani, Ronac; Yang, Yu-Xiao

2015-06-01

Current screening guidelines for colorectal cancer (CRC) do not consider thyroid dysfunction as a risk factor for disease development. We sought to determine the risk of developing CRC in patients with thyroid dysfunction, with and without thyroid hormone replacement (THR). We conducted a nested case-control study using a large population-based medical records database from the United Kingdom. Study case patients were defined as those with any medical code of CRC. Subjects with familial colorectal cancer syndromes or inflammatory bowel disease (IBD) were excluded. For every case patient, four eligible control patients matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence density sampling. Exposure was THR therapy before index date. We further divided the THR unexposed group into patients with hypothyroidism (TSH > 4 mg/dl), patients with hyperthyroidism (TSH < 0.4 mg/dl), and subjects without documented thyroid abnormality. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for CRC were estimated using conditional logistic regression. All statistical tests were two-sided. We identified 20990 CRC patients and 82054 control patients. The adjusted odds ratio for CRC associated with THR was 0.88 (95% CI = 0.79 to 0.99, P = .03) and 0.68 (95% CI = 0.55 to 0.83, P < .001) for treatment initiated five to 10 years and more than 10 years before index date, respectively. This protective association increased with cumulative duration of therapy. In contrast, hyperthyroidism (adjusted OR = 1.21, 95% CI = 1.08 to 1.36, P = .001) or untreated hypothyroidism (adjusted OR = 1.16, 95% CI = 1.08 to 1.24, P < .001) were associated with increased risk of CRC. Long-term THR is associated with a decreased risk of CRC. Hyperthyroidism and untreated hypothyroidism are associated with modestly elevated risk of CRC. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e

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

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.

Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage.

PubMed

Chew, Fiona; Wu, Xianwei

2017-01-01

Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT) to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions). We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002-2003, 2008-2009 and 2012-14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians' HT recommendations from 2002 to 2009, and 2012 to 2014. Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks). While a majority of physician surveys were pro-HT 10/19), eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period. Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap.

Homozygous Resistance to Thyroid Hormone β: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?

PubMed

Moran, Carla; Habeb, Abdelhadi M; Kahaly, George J; Kampmann, Christoph; Hughes, Marina; Marek, Jan; Rajanayagam, Odelia; Kuczynski, Adam; Vargha-Khadem, Faraneh; Morsy, Mofeed; Offiah, Amaka C; Poole, Ken; Ward, Kate; Lyons, Greta; Halsall, David; Berman, Lol; Watson, Laura; Baguley, David; Mollon, John; Moore, Anthony T; Holder, Graham E; Dattani, Mehul; Chatterjee, Krishna

2017-09-01

Resistance to thyroid hormone β (RTH β ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTH β , with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTH β had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTH β in which life-threatening hyperthyroid features predominate.

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

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.

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.

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

Combined effects of sex hormone-binding globulin and sex hormones on risk of incident type 2 diabetes.

PubMed

Hu, Jinbo; Zhang, Aiping; Yang, Shumin; Wang, Yue; Goswami, Richa; Zhou, Huang; Zhang, Yi; Wang, Zhihong; Li, Rong; Cheng, Qingfeng; Zhen, Qianna; Li, Qifu

2016-07-01

The aim of the present study was to investigate the combined effects of sex hormone-binding globulin (SHBG) and sex hormones on the risk of type 2 diabetes (T2D). A nested case-control study of Chinese participants in the Environment, Inflammation and Metabolic Diseases Study (2008-13) was performed. Of the 3510 subjects free of diabetes, 145 men and 87 women developed diabetes over the 5-year follow-up. One age- and sex-matched control subject was selected for each case. Baseline concentrations of SHBG, estradiol, testosterone, and dehydroepiandrosterone sulfate (DHEA-S) were divided into tertiles and subjects were classified as having low, intermediate and high levels accordingly. After multivariate adjustment, men with low SHBG levels had a fourfold greater risk of T2D than men with high SHBG levels. Conversely, men with high estradiol levels had a fourfold greater risk of T2D than men with low estradiol levels. Men with low SHBG + high estradiol had a 20-fold greater risk of T2D than men with high SHBG + low estradiol (odds ratio [OR] 20.23; 95% confidence interval [CI] 4.62-51.33). These risk associations in men were not observed for testosterone or DHEA-S, alone or in combination with SHBG. Compared with low SHBG, the risk of T2D decreased with increasing SHBG tertile (OR 0.92 [95% CI 0.21-4.53], 0.14 [95% CI 0.10-0.74]; Ptrend  = 0.043) after multivariate adjustment in women. Estradiol, testosterone, and DHEA-S levels showed no association with T2D in women. Low SHBG in conjunction with high estradiol has an additive detrimental effect on the risk of T2D in men. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

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

Sources of information influencing the state-of-the-science gap in hormone replacement therapy usage

PubMed Central

Wu, Xianwei

2017-01-01

Objective Medical reviews and research comprise a key information source for news media stories on medical therapies and innovations as well as for physicians in updating their practice. The present study examined medical review journal articles, physician surveys and news media coverage of hormone replacement therapy (HT) to assess the relationship between the three information sources and whether/if they contributed to a state-of-the-science gap (a condition when the evaluation of a medical condition or therapy ascertained by the highest standards of investigation is incongruent with the science-in-practice such as physician recommendations and patient actions). Methods We content-analyzed 177 randomly sampled HT medical reviews between 2002 and 2014, and HT news valence in three major TV networks, newspapers and magazines/internet sites in 2002–2003, 2008–2009 and 2012–14. The focus in both analyses was whether HT benefits outweighed risks, risks outweighed benefits or both risks and benefits were presented. We also qualitatively content-analyzed all 19 surveys of US physicians’ HT recommendations from 2002 to 2009, and 2012 to 2014. Results Medical reviews yielded a mixed picture about HT (40.1% benefits, 26.0% risks, and 33.9% both benefits and risks). While a majority of physician surveys were pro-HT 10/19), eight showed varied attitudes and one was negative. Newspaper and television coverage reflected a pro and con balance while magazine stories were more positive in the later reporting period. Conclusion Medical journal review articles, physicians, and media reports all provide varying view points towards hormone therapy use thus leading to limited knowledge about the actual risks and benefits of HT among peri- and menopausal women and a state-of-the-science gap. PMID:28158240

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.

Use of hormone replacement therapy in the Hong Kong public health sector after the Women's Health Initiative trial.

PubMed

Leung, K Y; Ling, Matina; Tang, G W K

2005-01-01

To determine the impact of Women Health Initiative (WHI) trial on the use of hormone replacement therapy (HRT) in the Hong Kong public health sector. The central prescription database of the Hospital Authority was used to describe the half-yearly trend in the use of HRT between July 2000 and December 2003. The data of hysterectomy was retrieved from another clinical database. Before the publication of the WHI trial in July 2002, conjugated equine estrogens (CEE) and its related products dominated HRT prescribing. Relative to the first half of 2002, there was an immediate and substantial decline by 43.5% in the prescriptions of combined CEE/progestogen products and a modest decline by 22.4% in the prescriptions of CEE-alone therapy in the second half of 2002. In the first half of 2003, a decline in the prescriptions of all HRT preparations except raloxifene was observed. However, in the second half of 2003, there were no more declines in overall HRT users. Relative to the first half of 2002, the decline in the overall HRT users in the first half of 2003 was more than 46% in women aged 50-69. The decline was greater in women with a history of hysterectomy (60.3%) than women without (38.6%), but was similar between gynaecology specialty (41.7%) and non-gynaecology specialty (43.9%). Similar to the U.S., an immediate and substantial decline in the use of CEE and its related products was observed in Hong Kong after the publication of the WHI trial.

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.

Individual and combined effects of noise-like whole-body vibration and parathyroid hormone treatment on bone defect repair in ovariectomized mice.

PubMed

Matsumoto, Takeshi; Sato, Daisuke; Hashimoto, Yoshihiro

2016-01-01

The effectiveness of intermittent administration of parathyroid hormone and exposure to whole-body vibration on osteoporotic fracture healing has been previously investigated, but data on their concurrent use are lacking. Thus, we evaluated the effects of intermittent administration of parathyroid hormone, whole-body vibration, and their combination on bone repair in osteoporotic mice. Noise-like whole-body vibration with a broad frequency range was used instead of conventional sine-wave whole-body vibration at a specific frequency. Mice were ovariectomized at 9 weeks of age and subjected to drill-hole surgery in the right tibial diaphysis at 11 weeks. The animals were divided into four groups (n = 12 each): a control group, and groups treated with intermittent administration of parathyroid hormone, noise-like whole-body vibration, and both. From postoperative day 2, the groups treated with intermittent administration of parathyroid hormone and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were subcutaneously administered parathyroid hormone at a dose of 30 µg/kg/day. The groups treated with noise-like whole-body vibration and groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration were exposed to noise-like whole-body vibration at a root mean squared acceleration of 0.3g and frequency components of 45-100 Hz for 20 min/day. Following 18 days of interventions, the right tibiae were harvested, and the regenerated bone was analyzed by micro-computed tomography and nanoindentation testing. Compared with the control group, callus volume fraction was 40% higher in groups treated with intermittent administration of parathyroid hormone and 73% higher in groups treated with both intermittent administration of parathyroid hormone and noise-like whole-body vibration, and callus thickness was 35% wider in groups treated with both

Fixed-functional appliance treatment combined with growth hormone therapy.

PubMed

Jung, Min-Ho

2017-09-01

The purpose of this study was to illustrate the effects of growth hormone (GH) therapy and fixed functional appliance treatment in a 13-year-old Class II malocclusion patient without GH deficiency. GH has been shown to effectively increase endochondral growth and induce a more prognathic skeletal pattern. Although a major concern in Class II retrognathic patients is chin deficiency, long-term studies have shown that the mandibular growth enhancement effects of functional appliances are clinically insignificant. This case report demonstrates that the mandible grew significantly during fixed functional appliance treatment combined with GH therapy, with stable results during 2 years 11 months of retention. More studies are needed to evaluate GH therapy as a supplement in Class II treatment. Copyright © 2017 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.

Frequency of mutations in PROP-1 gene in Turkish children with combined pituitary hormone deficiency.

PubMed

Kandemir, Nurgün; Vurallı, Doğuş; Taşkıran, Ekim; Gönç, Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Yılmaz, Engin

2012-01-01

Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with CPHD were expected to be more prevalent in our population due to consanguinity, but it was found that these mutations were far less than expected and that it was rare in non-familial cases.

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.

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.

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 .

Temporal relations in hormone-withdrawal migraines and impact on prevention- a diary-based pilot study in combined hormonal contraceptive users.

PubMed

Merki-Feld, Gabriele S; Epple, Gina; Caveng, Nina; Imthurn, Bruno; Seifert, Burkhardt; Sandor, Peter; Gantenbein, Andreas R

2017-08-25

Menstrually related migraine (MRM) in the hormone-free interval (HFI) of combined hormonal contraceptives (CHC) are according to the ICHD definition also estrogen withdrawal migraines (EWH). MRMs are less responsive to acute medication. Therefore short-term prevention, initiated 1-2 days before onset of the anticipated bleeding and continued for 6 days, is recommended. Such a long prophylactic triptan use might increase the risk for medication overuse headache in women suffering in addition from non-menstrual migraines. In CHC users onset of hormone decline is predictable. It is however unknown, whether the EWHs are rather associated with onset of hormone withdrawal or onset of bleeding. Improved understanding of this relation might contribute to better define and shorten the time interval for prevention. For this observational diary-based pilot study we collected data from daily conducted headache diaries of CHC users with MRM in at least two of three cycles, visiting our clinic from 2009 to 2015. We analyzed frequency of migraines for each hormone free day, onset of migraine, onset of bleeding and the relation of migraine to onset of bleeding in the 7-day period following estrogen withdrawal. We identified in addition the onset of migraine attacks lasting more than 1 day (episodes). Forty patient charts met the inclusion criteria, what allowed us to analyze 103 cycles. The mean number of migraine days in the HFI was 2.2 ± 1.6. Migraine started typically on days 1-5 and bleeding on days 3-5. In relation to first day of bleeding, migraines started on days -1 to 4. Almost half of the migraine attacks lasted longer than 24 h, despite the use of rescue medication. MRM in CHC users starts on bleeding days -1 to 4, what differs from findings in the natural cycle. Referring to the HFI interval migraine started mostly on days 1-5. According to these data, it seems to be reasonable to initiate short-term prevention at the last day of pill use or the first day of

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.

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.

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.

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.

Sex hormones in the cardiovascular system.

PubMed

dos Santos, Roger Lyrio; da Silva, Fabrício Bragança; Ribeiro, Rogério Faustino; Stefanon, Ivanita

2014-05-01

Gender-associated differences in the development of cardiovascular diseases have been described in humans and animals. These differences could explain the low incidence of cardiovascular disease in women in the reproductive period, such as stroke, hypertension, and atherosclerosis. The cardiovascular protection observed in females has been attributed to the beneficial effects of estrogen on endothelial function. Besides estrogen, sex hormones are able to modulate blood pressure by acting on important systems as cardiovascular, renal, and neural. They can have complementary or antagonistic actions. For example, testosterone can raise blood pressure by stimulating the renin-angiotensin-aldosterone system, whereas estrogen alone or combined with progesterone has been associated with decreased blood pressure. The effects of testosterone in the development of cardiovascular disease are contradictory. Although some researchers suggest a positive effect, others indicate negative actions of testosterone. Estrogens physiologically stimulate the release of endothelium-derived vasodilator factors and inhibit the renin-angiotensin system. Although the cardioprotective effects of estrogen are widely appreciated, little is known about the effects of progesterone, which is commonly used in hormone replacement therapy. Progesterone has both vasodilatory and vasoconstrictive effects in the vasculature, depending on the location of the vessel and the level of exposure. Nevertheless, the mechanisms through which sex hormones modulate blood pressure have not been fully elucidated. Therefore, the characterization of those could lead to a better understanding of hypertension in women and men and perhaps to improved forms of therapy.

Combined pituitary hormone deficiency: current and future status.

PubMed

Castinetti, F; Reynaud, R; Quentien, M-H; Jullien, N; Marquant, E; Rochette, C; Herman, J-P; Saveanu, A; Barlier, A; Enjalbert, A; Brue, T

2015-01-01

Over the last two decades, the understanding of the mechanisms involved in pituitary ontogenesis has largely increased. Since the first description of POU1F1 human mutations responsible for a well-defined phenotype without extra-pituitary malformation, several other genetic defects of transcription factors have been reported with variable degrees of phenotype-genotype correlations. However, to date, despite the identification of an increased number of genetic causes of isolated or multiple pituitary deficiencies, the etiology of most (80-90 %) congenital cases of hypopituitarism remains unsolved. Identifying new etiologies is of importance as a post-natal diagnosis to better diagnose and treat the patients (delayed pituitary deficiencies, differential diagnosis of a pituitary mass on MRI, etc.), and as a prenatal diagnosis to decrease the risk of early death (undiagnosed corticotroph deficiency for instance). The aim of this review is to summarize the main etiologies and phenotypes of combined pituitary hormone deficiencies, associated or not with extra-pituitary anomalies, and to suggest how the identification of such etiologies could be improved in the near future.

Estrogen, vascular estrogen receptor and hormone therapy in postmenopausal vascular disease.

PubMed

Khalil, Raouf A

2013-12-15

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women's Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject's age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. Copyright © 2013 Elsevier Inc. All rights reserved.

Estrogen, Vascular Estrogen Receptor and Hormone Therapy in Postmenopausal Vascular Disease

PubMed Central

Khalil, Raouf A.

2013-01-01

Cardiovascular disease (CVD) is less common in premenopausal women than men of the same age or postmenopausal women, suggesting vascular benefits of estrogen. Estrogen activates estrogen receptors ERα, ERβ and GPR30 in endothelium and vascular smooth muscle (VSM), which trigger downstream signaling pathways and lead to genomic and non-genomic vascular effects such as vasodilation, decreased VSM contraction and growth and reduced vascular remodeling. However, randomized clinical trials (RCTs), such as the Women’s Health Initiative (WHI) and Heart and Estrogen/progestin Replacement Study (HERS), have shown little vascular benefits and even adverse events with menopausal hormone therapy (MHT), likely due to factors related to the MHT used, ER profile, and RCT design. Some MHT forms, dose, combinations or route of administration may have inadequate vascular effects. Age-related changes in ER amount, distribution, integrity and post-ER signaling could alter the vascular response to MHT. The subject’s age, preexisting CVD, and hormone environment could also reduce the effects of MHT. Further evaluation of natural and synthetic estrogens, phytoestrogens, and selective estrogen-receptor modulators (SERMs), and the design of appropriate MHT combinations, dose, route and 'timing' could improve the effectiveness of conventional MHT and provide alternative therapies in the peri-menopausal period. Targeting ER using specific ER agonists, localized MHT delivery, and activation of specific post-ER signaling pathways could counter age-related changes in ER. Examination of the hormone environment and conditions associated with hormone imbalance such as polycystic ovary syndrome may reveal the causes of abnormal hormone-receptor interactions. Consideration of these factors in new RCTs such as the Kronos Early Estrogen Prevention Study (KEEPS) could enhance the vascular benefits of estrogen in postmenopausal CVD. PMID:24099797

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.

A novel mutation of LHX3 is associated with combined pituitary hormone deficiency including ACTH deficiency, sensorineural hearing loss, and short neck-a case report and review of the literature.

PubMed

Bonfig, Walter; Krude, Heiko; Schmidt, Heinrich

2011-08-01

The LHX3 LIM-homeodomain transcription factor gene is required for normal pituitary and motoneuron development. LHX3 mutations are associated with growth hormone, prolactin, gonadotropin, and TSH deficiency; abnormal pituitary morphology; and may be accompanied with limited neck rotation and sensorineural hearing loss. We report on a boy, who presented with hypoglycemia in the newborn period. He is the second child of healthy unrelated parents. Short neck, growth hormone deficiency, and central hypothyroidism were diagnosed at a general pediatric hospital. Growth hormone and levothyroxine treatment were started, and blood sugar normalized with this treatment. On cerebral MRI, the anterior pituitary gland was hypoplastic. Sensorineural hearing loss was diagnosed by auditory testing. During follow-up, six repeatedly low morning cortisol levels (<1 μg/dl) and low ACTH levels (<10 pg/ml) were documented, so ACTH deficiency had developed over time and therefore hydrocortisone replacement was started at 1.5 years of age. Mutation analysis of the LHX3 gene revealed a homozygous stop mutation in exon 2: c.229C>T (CGA > TGA), Arg77stop (R77X). A complete loss of function is assumed with this homozygous stop mutation. We report a novel LHX3 mutation, which is associated with combined pituitary hormone deficiency including ACTH deficiency, short neck, and sensorineural hearing loss. All patients with LHX3 defects should undergo longitudinal screening for ACTH deficiency, since corticotrope function may decline over time. All patients should have auditory testing to allow for regular speech development.

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

PubMed

Liu, S; Liu, Q; Cheng, X; Luo, Y; Wen, Y

2016-10-01

This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD = 2.81 cm, 95 % CI 1.76-3.87, four CCTs; MD = 4.30 cm, 95 % CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD = 3.92 cm, 95 % CI 3.12-4.73, four CCTs; MD = 4.00 cm, 95 % CI 1.93-6.07, One RCT) and larger height gains (MD = 3.49 cm, 95 % CI 0.97-6.01, four CCTs; MD = 3.88 cm, 95 % CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

Successfully treated necrotizing fasciitis using extracorporeal life support combined with hemoadsorption device and continuous renal replacement therapy.

PubMed

Eid, Maroua; Fouquet, Olivier; Darreau, Cédric; Pierrot, Marc; Kouatchet, Achille; Mercat, Alain; Baufreton, Christophe

2018-03-01

Necrotizing fasciitis represents a life-threatening infectious condition that causes spreading necrotisis of superficial fascia and subcutaneous cellular tissues. We describe the case of a patient diagnosed with septic and toxic shocks leading to multiple organ failure successfully treated with a combination of extracorporeal life support, continuous renal replacement therapy, and a hemoadsorption device. A 41-year-old patient presented with necrotizing fasciitis and multi-organ failure. Initial extracorporeal life support therapy was implanted, compensating for systolic failure. Due to acute renal failure that persisted in time, continuous renal replacement therapy was added. Despite these treatments and as a last attempt to control the septic condition, a CytoSorb ® hemoadsorption device was installed in parallel to the extracorporeal life support circuit and two sessions were run. During the days following CytoSorb ® treatment, hemodynamic stabilization was observed, as well as normalization of lactic acidosis and blood parameters. This case describes the successful use of CytoSorb ® with continuous renal replacement therapy and extracorporeal life support in a combined way to overcome a critical phase of septic shock in a young adult patient. This combination of treatments turned out to be efficient for this patient in the context of necrotizing fasciitis.

Partisan perspectives in the medical literature: a study of high frequency editorialists favoring hormone replacement therapy.

PubMed

Tatsioni, Athina; Siontis, George C M; Ioannidis, John P A

2010-09-01

Unfavorable results of major studies have led to a large shrinkage of the market for hormone replacement therapy (HRT) in the last 6 years. Some scientists continue to strongly support the use of HRT. We analyzed a sample of partisan editorializing articles on HRT to examine their arguments, the reporting of competing interests, the journal venues and their sponsoring societies. Through Thomson ISI database, we selected articles without primary data written by the five most prolific editorialists that addressed clinical topics pertaining to HRT and that were published in regular journal issues in 2002-2008. We recorded the number of articles with a partisan stance and their arguments, the number of partisan articles that reported conflicting interests, and the journal venues and their sponsoring societies publishing the partisan editorials. We analyzed 114 eligible articles (58 editorials, 16 guidelines, 37 reviews, 3 letters), of which 110 (96%) had a partisan stance favoring HRT. Typical arguments were benefits for menopausal and related symptoms (64.9%), criticism of unfavorable studies (78.9%), preclinical data that showed favorable effects of HRT (50%), and benefits for major outcomes such as osteoporosis and fractures (49.1%), cardiovascular disease (31.6%), dementia (24.6%) or colorectal cancer (20.2%), but also even breast cancer (4.4%). All 5 prolific editorialists had financial relationships with hormone manufacturers, but these were reported in only 6 of the 110 partisan articles. Four journals published 15-37 partisan articles each. The medical societies of these journals reported on their websites that several pharmaceutical companies sponsored them or their conferences. There is a considerable body of editorializing articles favoring HRT use and very few of these articles report conflicts of interest. Full disclosure of conflicts of interest is needed, especially for articles without primary data.

Retrospective analysis of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide for hormone-refractory prostate cancer.

PubMed

Hatano, Koji; Nonomura, Norio; Nishimura, Kazuo; Kawashima, Atsunari; Mukai, Masatoshi; Nagahara, Akira; Nakai, Yasutomo; Nakayama, Masashi; Takayama, Hitoshi; Tsujimura, Akira; Okuyama, Akihiko

2011-02-01

To evaluate the clinical utility of an oral combination of dexamethasone, uracil plus tegafur and cyclophosphamide as a treatment for patients with hormone-refractory prostate cancer. Fifty-seven patients with hormone-refractory prostate cancer were treated with an oral administration of dexamethasone (1.0 mg/day), uracil plus tegafur (400 mg/day) and cyclophosphamide (100 mg/day). The median patient age was 71 years. Sixteen patients had symptomatic bone metastasis, 31 had asymptomatic bone metastasis and 8 showed lymph node metastasis. Eight patients presented with only biochemical progression as evaluated by serum prostate-specific antigen levels. Thirty-six (63%) of 57 patients demonstrated a ≥50% decline in serum prostate-specific antigen levels. The median time to prostate-specific antigen progression was 7.2 months. In patients with a prostate-specific antigen decline of ≥50%, the median time to progression was 13.3 months. With respect to pre-treatment markers, the duration of response to initial hormonal treatment was associated with the time to prostate-specific antigen progression. In 11 of 16 (69%) patients who complained of bone pain, the pain improved and became stable in 5 of those patients (31%). Most adverse events were mild and only three (5%) patients showed neutropenia of Grade 3 or higher. The combination of dexamethasone, uracil plus tegafur and cyclophosphamide is an effective and well tolerated regimen for hormone-refractory prostate cancer. To evaluate the survival benefits, further randomized studies are required.

Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea.

PubMed

Choi, Jin Ho; Jung, Chang Woo; Kang, Eungu; Kim, Yoon Myung; Heo, Sun Hee; Lee, Beom Hee; Kim, Gu Hwan; Yoo, Han Wook

2017-05-01

Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes. IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD. The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype. © Copyright: Yonsei University College of Medicine 2017

Rare Frequency of Mutations in Pituitary Transcription Factor Genes in Combined Pituitary Hormone or Isolated Growth Hormone Deficiencies in Korea

PubMed Central

Choi, Jin-Ho; Jung, Chang-Woo; Kang, Eungu; Kim, Yoon-Myung; Heo, Sun Hee; Lee, Beom Hee; Kim, Gu-Hwan

2017-01-01

Purpose Congenital hypopituitarism is caused by mutations in pituitary transcription factors involved in the development of the hypothalamic-pituitary axis. Mutation frequencies of genes involved in congenital hypopituitarism are extremely low and vary substantially between ethnicities. This study was undertaken to compare the clinical, endocrinological, and radiological features of patients with an isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD). Materials and Methods This study included 27 patients with sporadic IGHD and CPHD. A mutation analysis of the POU1F1, PROP1, LHX3, LHX4, and HESX1 genes was performed using genomic DNA from peripheral blood leukocytes. Results IGHD and CPHD were observed in 4 and 23 patients, respectively. Mean age at diagnosis was 8.28±7.25 years for IGHD and 13.48±10.46 years for CPHD (p=0.37). Serum insulin-like growth factor-1 and peak growth hormone (GH) levels following GH stimulation tests were significantly lower in patients with CPHD than in those with IGHD (p<0.05). Sellar MRI findings revealed structural abnormalities in 3 patients with IGHD (75%) and 21 patients with CPHD (91.3%) (p=0.62). A mutation analysis identified homozygous p.R109Q mutations in HESX1 in a patient with CPHD. Patients with CPHD had more severe GHD than those with IGHD. Conclusion The frequency of defects in the genes encoding pituitary transcription factors was extremely low in Korean patients with congenital hypopituitarism. Environmental factors and the impact of other causative genes may contribute to this clinical phenotype. PMID:28332357

Gene analysis of PROP1 in dwarfism with combined pituitary hormone deficiency.

PubMed

Takamura, N; Fofanova, O V; Kinoshita, E; Yamashita, S

1999-06-01

The prophet of Pit-1 gene (PROP1), a novel pituitary-specific homeodomain factor, has been proved to be one of the causative genes for combined pituitary hormone deficiency (CPHD). Recently, PROP1 mutations have been identified in CPHD families, including our Russian cohort. The 2-bp deletion, 296delGA (A301G302del), is the most common mutational hot spot. Furthermore, in our cohort, PROP1 mutations are more common in comparison with human POU1F1 gene mutations. Here we review the gene analysis of PROP1 in patients with CPHD.

Inhibition of growth of PC-82 human prostate cancer line xenografts in nude mice by bombesin antagonist RC-3095 or combination of agonist [D-Trp6]-luteinizing hormone-releasing hormone and somatostatin analog RC-160.

PubMed

Milovanovic, S R; Radulovic, S; Groot, K; Schally, A V

1992-01-01

The effects of treatment with a bombesin receptor antagonist [D-Tpi6, Leu13 psi (CH2NH) Leu14]BN(6-14)(RC-3095) and the combination of an agonist of luteinizing hormone-releasing hormone [D-Trp6]-LH-RH and somatostatin analog D-Phe-Cys-Tyr-D-Trp-Lys-Val- Cys-Trp-NH2 (RC-160) were studied in nude mice bearing xenografts of the hormone-dependent human prostate tumor PC-82. During the 5 weeks of treatment, tumor growth was decreased in all treated groups compared with controls. Bombesin antagonist RC-3095 and the combination of [D-Trp6]-LH-RH and RC-160 caused a greater inhibition of tumor growth than [D-Trp6]-LH-RH or RC-160 alone as based on measurement of tumor volume and percentage change in tumor volume. The largest decrease in tumor weight was also seen in the groups treated with the bombesin antagonist and with the combination of RC-160 and [D-Trp6]-LH-RH. Serum prostatic-specific antigen levels were greatly decreased, and insulin-like growth factor I (IGF-I) as well as growth hormone levels were reduced in all treated groups. Specific binding sites for [D-Trp6]-LH-RH, epidermal growth factor (EGF), IGF-I, and somatostatin (SS-14) were found in the tumor membranes. Receptors for EGF were significantly down-regulated by treatment with the bombesin antagonist or RC-160. Combination of LH-RH agonists with somatostatin analog RC-160 might be considered for improvement of hormonal therapy for prostate cancer. The finding that bombesin antagonist RC-3095 inhibits the growth of PC-82 prostate cancer suggests the merit of further studies to evaluate the possible usefulness of antagonists of bombesin in the management of prostatic carcinoma.

Independent and combined effects of eating rate and energy density on energy intake, appetite, and gut hormones.

PubMed

Karl, J Philip; Young, Andrew J; Rood, Jennifer C; Montain, Scott J

2013-03-01

Energy density (ED) and eating rate (ER) influence energy intake; their combined effects on intake and on postprandial pancreatic and gut hormone responses are undetermined. To determine the combined effects of ED and ER manipulation on voluntary food intake, subjective appetite, and postprandial pancreatic and gut hormone responses. Twenty nonobese volunteers each consumed high (1.6 kcal g(-1) ; HED) and low (1.2 kcal g(-1) ; LED) ED breakfasts slowly (20 g min(-1) ; SR) and quickly (80 g min(-1) ; FR) ad libitum to satiation. Appetite, and pancreatic and gut hormone concentrations were measured periodically over 3 h. Ad libitum energy intake during the subsequent lunch was then measured. Main effects of ED and ER on energy intake and a main effect of ER, but not ED, on mass of food consumed were observed, FR and HED being associated with increased intake (P < 0.05). Across all conditions, energy intake was highest during FR-HED (P ≤ 0.01). Area under the curve (AUC) of appetite ratings was not different between meals. Main effects of ED and ER on insulin, peptide-YY, and glucagon-like peptide-1 AUC (P < 0.05) were observed, FR and HED being associated with larger AUC. No effects on active or total ghrelin AUC were documented. Total energy intake over both meals was highest during the FR-HED trial with the greatest difference between FR-HED and SR-LED trials (P ≤ 0.01). Consuming an energy dense meal quickly compounds independent effects of ER and ED on energy intake. Energy compensation at the following meal may not occur despite altered gut hormone responses. Copyright © 2013 The Obesity Society.

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.

A primer on the hormone-free interval for combined oral contraceptives.

PubMed

Hauck, Brian A; Brown, Vivien

2015-01-01

The dosing, schedules, and other aspects of combined oral contraceptive (COC) design have evolved in recent years to address a variety of issues including short- and long-term safety, bleeding profiles, and contraceptive efficacy. In particular, several newer formulations have altered the length of the hormone-free interval (HFI), in order to minimize two key undesired effects that occur during this time: hormone-withdrawal-associated symptoms (HWaS) and follicular development. This primer reviews our current understanding of the key biological processes that occur during the HFI and how this understanding has led to changes in the dosing and schedule of newer COC formulations. In brief, HWaS are common, underappreciated, and a likely contributor to COC discontinuation; because of this, shortening the HFI and/or supplementing with estrogen during the progestin-free interval may provide relief from these symptoms and improve adherence. A short HFI (with or without estrogen supplementation) may also help maintain effective follicular suppression and contraceptive efficacy, even when the overall dose of estrogen throughout the cycle is low. Taken together, the available data about HWaS and follicular activity during the HFI support the rationale for recent COC designs that use a low estrogen dose and a short HFI. The availability of a variety of COC regimens gives physicians a range of choices when selecting the most appropriate COC for each woman's particular priorities and needs.

Sheep model for osteoporosis: The effects of peripheral hormone therapy on centrally induced systemic bone loss in an osteoporotic sheep model.

PubMed

Oheim, Ralf; Simon, Maciej J K; Steiner, Malte; Vettorazzi, Eik; Barvencik, Florian; Ignatius, Anita; Amling, Michael; Clarke, Iain J; Pogoda, Pia; Beil, F Timo

2017-04-01

Hypothalamic-pituitary disconnection (HPD) leads to low bone turnover followed by bone loss and reduced biomechanical properties in sheep. To investigate the role of peripheral hormones in this centrally induced systemic bone loss model, we planned a hormone replacement experiment. Therefore, estrogen (OHE), thyroxin (OHT) or a combination of both (OHTE) was substituted in ovariectomized HPD sheep, as both hormones are decreased in HPD sheep and are known to have a significant but yet not fully understood impact on bone metabolism. Bone turnover and structural parameters were analyzed in comparison to different control groups - untreated sheep (C), ovariectomized (O) and ovariectomized+HPD sheep (OH). We performed histomorphometric and HR-pQCT analyses nine months after the HPD procedure, as well as biomechanical testing of all ewes studied. In HPD sheep (OH) the low bone turnover led to a significant bone loss. Treatment with thyroxin alone (OHT) mainly increased bone resorption, leading to a further reduction in bone volume. In contrast, the treatment with estrogen alone (OHE) and the combined treatment with estrogen and thyroxin (OHTE) prevented HPD-induced bone loss completely. In conclusion, peripheral hormone substitution was able to prevent HPD-induced low-turnover osteoporosis in sheep. But only the treatment with estrogen alone or in combination with thyroxin was able to completely preserve bone mass and structure. These findings demonstrate the importance of peripheral hormones for a balanced bone remodeling and a physiological bone turnover. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Combined hormonal contraceptive trials: variable data collection and bleeding assessment methodologies influence study outcomes and physician perception.

PubMed

Mishell, Daniel R; Guillebaud, John; Westhoff, Carolyn; Nelson, Anita L; Kaunitz, Andrew M; Trussell, James; Davis, Ann Jeanette

2007-01-01

Initially approved for use in the United States nearly 50 years ago, oral hormonal contraceptives containing both estrogen and progestin have undergone steady improvements in safety and convenience. Concurrent with improvements in safety associated with decreasing doses of both steroids, there has been an increased incidence of unscheduled bleeding and spotting. There exist no standards regarding data collection techniques and methods, and reporting and analysis of bleeding and spotting events during combined hormonal contraceptive (CHC) trials. For the regulatory review of hormonal contraceptives, data regarding the incidence of bleeding and spotting events are not included in either of the traditional categories of efficacy and safety. Standardization of methods for collecting and analyzing data about cycle control in all clinical trials of CHCs is long overdue. Until such standards are developed and implemented, clinicians need to familiarize themselves with the techniques used in each study in order to provide correct information to their patients about the frequency of bleeding and spotting associated with different formulations and delivery systems.

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.

Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

PubMed

Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

2006-06-01

Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

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.

Androgen replacement for women.

PubMed Central

Basson, R.

1999-01-01

OBJECTIVES: To determine whether a postmenopausal syndrome comprising specific changes in sexual desire and response associated with low free testosterone exists. To determine whether this syndrome is ameliorated by testosterone replacement. QUALITY OF EVIDENCE: Literature documenting that replacement of physiological levels of testosterone is beneficial and safe is scant. Only one randomized prospective blinded study examines sexual outcome in detail. MAIN MESSAGE: Testosterone is an important metabolic and sex hormone produced by the ovary throughout life. The variable reduction in ovarian testosterone production coincident with menopause is sometimes associated with a syndrome of specific changes in sexual desire and sexual response. Estrogen deficiency also impairs sexual response, but its replacement will not improve and might exacerbate sexual symptoms from androgen loss. Diagnosis of androgen deficiency is clinical, based on accurate assessment of a woman's sexual status before and after menopause and only confirmed (rather than diagnosed) by a low level of free testosterone. Partial androgen replacement restores much of the sexual response and facilitates sexual desire that is triggered by external cues. Avoiding supraphysiological levels of testosterone lessens risk of masculinization. Avoiding alkylated testosterone lessens hepatic or lipid impairment. CONCLUSION: Further prospective randomized studies of replacement of physiological levels of testosterone in women with androgen deficiency syndrome are needed, using formulations of testosterone available in Canada. The consistency of sexual changes, the associated personal and relationship distress, together with our clinical experience of the gratifying response to physiological replacement, make further studies urgently needed. PMID:10509222

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.

Hormone therapy in acne.

PubMed

Lakshmi, Chembolli

2013-01-01

Underlying hormone imbalances may render acne unresponsive to conventional therapy. Relevant investigations followed by initiation of hormonal therapy in combination with regular anti-acne therapy may be necessary if signs of hyperandrogenism are present. In addition to other factors, androgen-stimulated sebum production plays an important role in the pathophysiology of acne in women. Sebum production is also regulated by other hormones, including estrogens, growth hormone, insulin, insulin-like growth factor-1, glucocorticoids, adrenocorticotropic hormone, and melanocortins. Hormonal therapy may also be beneficial in female acne patients with normal serum androgen levels. An understanding of the sebaceous gland and the hormonal influences in the pathogenesis of acne would be essential for optimizing hormonal therapy. Sebocytes form the sebaceous gland. Human sebocytes express a multitude of receptors, including receptors for peptide hormones, neurotransmitters and the receptors for steroid and thyroid hormones. Various hormones and mediators acting through the sebocyte receptors play a role in the orchestration of pathogenetic lesions of acne. Thus, the goal of hormonal treatment is a reduction in sebum production. This review shall focus on hormonal influences in the elicitation of acne via the sebocyte receptors, pathways of cutaneous androgen metabolism, various clinical scenarios and syndromes associated with acne, and the available therapeutic armamentarium of hormones and drugs having hormone-like actions in the treatment of acne.

Pre-operative ultrasound identification of thyroiditis helps predict the need for thyroid hormone replacement after thyroid lobectomy.

PubMed

Morris, Lilah F; Iupe, Isabella M; Edeiken-Monroe, Beth S; Warneke, Carla L; Hansen, Mandy O; Evans, Douglas B; Lee, Jeffrey E; Grubbs, Elizabeth G; Perrier, Nancy D

2013-01-01

To evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy. Data from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had ≥1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR. During follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 μ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 μIU/mL and US-identified thyroiditis had a 5.8-fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001). A pre-operative TSH level >2.5 μIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months).

Evaluation of various combinations of alternative protein feedstuffs to replace soybean meal in diets for pond-raised channel catfish

USDA-ARS?s Scientific Manuscript database

A study was conducted in earthen ponds to evaluate the use of combinations of two or three alternative protein sources to replace soybean meal in diets for Channel Catfish Ictalurus punctatus. Six 28% protein diets containing various combinations of alternative protein feedstuffs including cottonse...

Is the growth outcome of children with idiopathic short stature and isolated growth hormone deficiency following treatment with growth hormone and a luteinizing hormone-releasing hormone agonist superior to that obtained by GH alone?

PubMed

Colmenares, Ana; González, Laura; Gunczler, Peter; Lanes, Roberto

2012-01-01

The aim of this study was to evaluate the effect of combined therapy with growth hormone (GH) and luteinizing hormone-releasing hormone agonist (LHRHa) on the near-final height (NFH) of children with idiopathic short stature (ISS) and growth hormone deficiency (GHD) in early puberty. A retrospective analysis of 20 patients with ISS and 9 patients with GHD treated with combined therapy was undertaken. Twelve children with ISS and ten with GHD, treated with GH alone, served as controls. Patients were matched at baseline for chronological age, bone age, height standard deviation score (SDS), and pubertal development. Patients with ISS or GHD treated with combined therapy improved both their predicted adult height (PAH) at 2 years of therapy (ISS, p < 0.001; GHD, p = 0.03) and their NFH (ISS, p < 0.05; GHD, p = 0.05). Treatment with combined therapy did not generate additional benefits on the PAH after 2 years of therapy (ISS children, an increase of 7.9 +/- 4.9 cm with combined therapy vs. 7.3 +/- 6.0 cm with GH; GHD children, an increase of 6.8 +/- 7.8 cm with combined therapy vs. 5 +/- 5.9 cm with GH). The total height gain SDS was higher in patients treated with GH alone compared with those with combined therapy, but the difference was not significant (ISS children, a gain of 2.4 SDS with GH vs. 0.8 SDS with combined therapy; GHD children, a gain of 1.8 SDS with GH vs. 0.6 SDS with combined therapy). Although 2 years of combined treatment with GH and LHRHa improved the PAH and the NFH of ISS and GHD patients in early puberty, this improvement was not significant compared with that observed in similar subjects treated with GH alone.

Continuation rate of hormone replacement therapy in Hong Kong public health sector.

PubMed

Leung, K Y; Ling, M; Tang, G W K

2004-12-10

To assess the 1-year continuation rate of HRT prescribed in Hong Kong public health sector and to identify factors affecting this continuation rate. All women who received at least one dispensed prescription of estrogens between January 1998 and December 2000 from 36 specialist outpatient clinics of the Hospital Authority were selected, and observed for at least 2 years and at most 3 years. The duration of use and variables including age, types of hormones, routes of delivery, dose of estrogen, and prescribing specialty were retrieved from the central prescription database of the Hospital Authority. Of 12,711 incident users of HRT, more than half were aged 50-59. Most (78.5%) of the users took conjugated equine estrogens (CEE) 0.625 mg or related products. Only a small proportion (3.0%) of women used CEE 0.3 mg. Initial estrogen prescriptions were written by gynaecologists in 86.7%. The overall 1-year continuation rate was 68.3%. The highest and lowest continuation rates were observed in women aged 40-49 and the two extreme age groups (35-39 and 70-79), respectively. Better continuation rate was observed in women taking estrogen-only therapy such as CEE or estradiol (overall 76.3%) than in women using continuous combined therapy (58.6%), sequential combined therapy (64.8%), or transdermal estrogen (60.6%). In the age group 60-69, the use of CEE 0.3 mg was associated with better continuation rate than CEE 0.625 mg. Better continuation rate at 1 year was associated with age younger than 60, oral route of HRT and hysterectomy.

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.

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.

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.

Combined low-dose aspirin and warfarin anticoagulant therapy of postoperative atrial fibrillation following mechanical heart valve replacement.

PubMed

Wang, Jian-tang; Dong, Ming-feng; Song, Guang-min; Ma, Zeng-shan; Ma, Sheng-jun

2014-12-01

The safety and efficacy of combined low dose aspirin and warfarin therapy in patients with atrial fibrillation after mechanical heart valve replacement were evaluated. A total of 1016 patients (620 females, mean age of 36.8±7.7 years) admitted for cardiac valve replacement and complicated with atrial fibrillation after surgery were randomly divided into study (warfarin plus 75-100 mg aspirin) or control (warfarin only) groups. International normalized ratio (INR) and prothrombin time were maintained at 1.8-2.5 and 1.5-2.0 times the normal values, respectively. Thromboembolic events and major bleedings were registered during the follow-up period. Patients were followed up for 24±9 months. The average dose of warfarin in the study and control groups was 2.91±0.83 mg and 2.88±0.76 mg, respectively (P>0.05). The incidence of overall thromboembolic events in study group was lower than that in control group (2.16% vs. 4.35%, P=0.049). No statistically significant differences were found in hemorrhage events (3.53% vs. 3.95%, P=0.722) or mortality (0.20% vs. 0.40%, P=0.559) between the two groups. Combined low dose aspirin and warfarin therapy in the patients with atrial fibrillation following mechanical heart valve replacement significantly decreased thromboembolic events as compared with warfarin therapy alone. This combined treatment was not associated with an increase in the risk of major bleeding or mortality.

Thyroid-stimulating hormone pituitary adenomas.

PubMed

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

2008-07-01

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.

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.

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.

[Arterial diseases in women using combined hormonal contraceptives].

PubMed

Novotná, M; Unzeitig, V; Novotný, T

2002-05-01

To determine the association between myocardial infarction and cerebral stroke and use of combined oral contraceptives. Review of literature. Department of Obstetrics and Gynaecology, Hospital of Merciful Brothers, Brno, Czech Republic. Identification of methodologically sound studies able to address the topic. Studies were identified by Medline database search. Five the most recent and important studies were the main source of information (Oxford Family Planning Association Contraception Study 1984, Royal College of General Practitioners' Study 1994, WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception 1996, 1997, Transnational Study on Oral Contraceptives and the Health of Young Women 1997, Myocardial Infarction and Oral Contraceptives Study, 1997). Generally there was no evidence of a significantly increased risk of arterial wall disease in healthy non smoked users younger than 35 years. No difference between second and third generation oral contraceptives on risk of arterial wall disease were found. In the most of cases of myocardial infarction or stroke one or more risk factor were identified. Two of the most relevant risk factors are smoking and the absence of blood pressure control. The risk of arterial cardiovascular system diseases seems not to be increased at no-risk users (healthy non-smoker younger than 35 years).

Effects of a meal replacement system alone or in combination with phentermine on weight loss and food cravings.

PubMed

Moldovan, Christina P; Weldon, Abby J; Daher, Noha S; Schneider, Louise E; Bellinger, Denise L; Berk, Lee S; Hermé, Alyson C; Aréchiga, Adam L; Davis, Willie L; Peters, Warren R

2016-11-01

To examine the effects of phentermine combined with a meal replacement program on weight loss and food cravings and to investigate the relationship between food cravings and weight loss. In a 12-week randomized, double-blind, placebo-controlled clinical trial, 77 adults with obesity received either phentermine or placebo. All participants were provided Medifast ® meal replacements, were instructed to follow the Take Shape for Life ® Optimal Weight 5&1 Plan for weight loss, and received lifestyle coaching in the Habits of Health program. The Food Craving Inventory and the General Food Cravings State and Trait Questionnaires were used to measure food cravings. The phentermine group lost 12.1% of baseline body weight compared with 8.8% in the placebo group. Cravings for all food groups decreased in both groups; however, there was a greater reduction in cravings for fats and sweets in the phentermine group compared with the placebo group. Percent weight loss correlated significantly with reduced total food cravings (r = 0.332, P = 0.009), cravings for sweets (r = 0.412, P < 0.000), and state food cravings (r = 0.320, P = 0.007). Both phentermine combined with a meal replacement program and meal replacements alone significantly reduced body weight and food cravings; however, the addition of phentermine enhanced these effects. © 2016 The Obesity Society.

Long-term follow-up of combined pituitary hormone deficiency in two siblings with a Prophet of Pit-1 gene mutation.

PubMed

Georgopoulos, Neoklis A; Katsikis, Ilias; Giamalis, Petros; Koika, Vasiliki; Adonakis, George; Kourtis, Anargyros; Kourounis, George; Panidis, Dimitrios

2006-12-01

Combined pituitary hormone deficiency (CPHD) is a rare disorder resulting from an impaired pituitary function due to different causes, characterized by impaired secretion of growth hormone (GH) and one or more of the other anterior pituitary hormones. To date, 16 distinct human Prophet of Pit-1 (Prop1) gene mutations have been identified in patients with CPHD, inducing a phenotype involving GH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and thyroid-stimulating hormone (TSH), and rarely adrenocorticotropic hormone, deficiency. Herein we present two siblings of different sexes from a family with parental consanguinity presenting the 301-302delAG mutation in the Prop1 gene. The female presented failure of growth from the age of 6 years and was treated for 10 years with GH, ending in a final height (standard deviation score) of -0.28. TSH deficiency was manifested after the initiation of GH and was treated with thyroxine while puberty was initiated with conjugated estrogens. The male presented TSH deficiency since childhood, treated with thyroxine, and growth failure at the age of 14 years, treated for a period of 2 years with GH. Puberty was initiated with increasing doses of testosterone, while human chorionic gonadotropin was added in order to achieve increased testicular volume. In conclusion, these two siblings of different sexes with CPHD carrying the 301-302delAG mutation in the Prop1 gene presented a variable phenotype characterized by GH, TSH, LH and FSH deficiency.

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).

Bisphenol A influences oestrogen- and thyroid hormone-regulated thyroid hormone receptor expression in rat cerebellar cell culture.

PubMed

Somogyi, Virág; Horváth, Tamás L; Tóth, István; Bartha, Tibor; Frenyó, László Vilmos; Kiss, Dávid Sándor; Jócsák, Gergely; Kerti, Annamária; Naftolin, Frederick; Zsarnovszky, Attila

2016-12-01

Thyroid hormones (THs) and oestrogens are crucial in the regulation of cerebellar development. TH receptors (TRs) mediate these hormone effects and are regulated by both hormone families. We reported earlier that THs and oestradiol (E 2 ) determine TR levels in cerebellar cell culture. Here we demonstrate the effects of low concentrations (10 -10 M) of the endocrine disruptor (ED) bisphenol A (BPA) on the hormonal (THs, E 2 ) regulation of TRα,β in rat cerebellar cell culture. Primary cerebellar cell cultures, glia-containing and glia-destroyed, were treated with BPA or a combination of BPA and E 2 and/or THs. Oestrogen receptor and TH receptor mRNA and protein levels were determined by real-time qPCR and Western blot techniques. The results show that BPA alone decreases, while BPA in combination with THs and/or E 2 increases TR mRNA expression. In contrast, BPA alone increased receptor protein expressions, but did not further increase them in combination with THs and/or E 2 . The modulatory effects of BPA were mediated by the glia; however, the degree of changes also depended on the specific hormone ligand used. The results signify the importance of the regulatory mechanisms interposed between transcription and translation and raise the possibility that BPA could act to influence nuclear hormone receptor levels independently of ligand-receptor interaction.

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.

Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

PubMed Central

Rudolph, Anja; Hein, Rebecca; Lindström, Sara; Beckmann, Lars; Behrens, Sabine; Liu, Jianjun; Aschard, Hugues; Bolla, Manjeet K.; Wang, Jean; Truong, Thérèse; Cordina-Duverger, Emilie; Menegaux, Florence; Brüning, Thomas; Harth, Volker; Severi, Gianluca; Baglietto, Laura; Southey, Melissa; Chanock, Stephen J.; Lissowska, Jolanta; Figueroa, Jonine D.; Eriksson, Mikael; Humpreys, Keith; Darabi, Hatef; Olson, Janet E.; Stevens, Kristen N.; Vachon, Celine M.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Webb, Penny M.; Guénel, Pascal; Brauch, Hiltrud; Giles, Graham; García-Closas, Montserrat; Czene, Kamila; Chenevix-Trench, Georgia; Couch, Fergus J.; Andrulis, Irene L.; Swerdlow, Anthony; Hunter, David J.; Flesch-Janys, Dieter; Easton, Douglas F.; Hall, Per; Nevanlinna, Heli; Kraft, Peter; Chang-Claude, Jenny

2013-01-01

Women using menopausal hormone therapy (MHT) are at increased risk to develop breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in eleven case-control studies. We used a case-only design to assess interactions between single nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2,920 cases (541 lobular) from four genome-wide association studies. The top 1,391 SNPs showing P-values for interaction (Pint) <3.0×10−03 were selected for replication using pooled case-control data from eleven studies of the Breast Cancer Association Consortium, including 7,689 cases (676 lobular) and 9,266 controls. Fixed effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9×10−06), two SNPs in SLC25A21 (combined Pint≤4.8×10−05), and three SNPs in PLCG2 (combined Pint≤4.5×10−05). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7×10−05), one SNP in CD80 (combined Pint≤8.2×10−06), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10−06), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6×10−05). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies. PMID:24080446

Combined pituitary hormone deficiency (CPHD) due to a complete PROP1 deletion.

PubMed

Abrão, M G; Leite, M V; Carvalho, L R; Billerbeck, A E C; Nishi, M Y; Barbosa, A S; Martin, R M; Arnhold, I J P; Mendonca, B B

2006-09-01

PROP1 mutations are the most common cause of genetic combined pituitary hormone deficiency (CPHD). The aim of this study was to investigate the PROP1 gene in two siblings with CPHD. Pituitary function and imaging assessment and molecular analysis of PROP1. Two siblings, born to consanguineous parents, presented with GH deficiency associated with other pituitary hormone deficiencies (TSH, PRL and gonadotrophins). The male sibling also had an evolving cortisol deficiency. Pituitary size was evaluated by magnetic resonance imaging (MRI). PROP1 gene analysis was performed by polymerase chain reaction (PCR), automatic sequencing and Southern blotting. Amplification of sequence tag sites (STS) and the Q8N6H0 gene flanking PROP1 were performed to define the extension of PROP1 deletion. MRI revealed a hypoplastic anterior pituitary in the girl at 14 years and pituitary enlargement in the boy at 18 years. The PROP1 gene failed to amplify in both siblings, whereas other genes were amplified. Southern blotting analysis revealed the PROP1 band in the controls and confirmed complete PROP1 deletion in both siblings. The extension of the deletion was 18.4 kb. The region flanking PROP1 contains several Alu core sequences that might have facilitated stem-loop-mediated excision of PROP1. We report here a complete deletion of PROP1 in two siblings with CPHD phenotype.

Effect of barley flour, crude cinnamon, and their combination on glycemia, dyslipidemia, and adipose tissue hormones in type 2 diabetic rats.

PubMed

Shatwan, Israa Ali; Ahmed, Lamiaa Ali; Badkook, Maha Mohamed

2013-07-01

This study aimed to evaluate the effects of barley flour, crude cinnamon, and their combination on blood glucose, serum insulin, serum lipid profile, and serum adipose tissue hormones in streptozotocin-induced diabetic rats. Male Wistar rats (n=35) were divided into five groups: nondiabetic, diabetic, diabetic group fed 5% cinnamon, diabetic group fed 30% barley, and diabetic group fed 5% cinnamon and 30% barley. Fasting blood glucose, insulin, lipid profile, adiponectin, and leptin were measured after 8 weeks. Blood glucose significantly decreased in all treated diabetic rats compared with the diabetic group. Serum insulin and high-density lipoprotein significantly increased, while cholesterol, triglycerides, and low-density lipoprotein were significantly decreased after 8 weeks. Adiponectin significantly increased, while leptin significantly decreased with administration of either cinnamon, barley, or their combination. No significant differences were observed among the three treated groups on all parameters. A cinnamon and barley combination caused obvious improvement in insulin-positive cells of pancreatic tissue. In conclusion, consuming diets containing either cinnamon, barley, or their combination regulates blood glucose, lipid profile, and adipose tissue hormones in type 2 diabetic rats. The most effective treatment was the cinnamon and barley combination.

Progress and prospects in male hormonal contraception

PubMed Central

Amory, John K.

2009-01-01

Purpose of review Testosterone functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary. Low concentrations of these hormones deprive the testes of the signals required for spermatogenesis and results in markedly decreased sperm concentrations and effective contraception in a majority of men. Male hormonal contraception is well tolerated and acceptable to most men. Unfortunately, testosterone-alone regimens fail to completely suppress spermatogenesis in all men, meaning that in some the potential for fertility remains. Recent findings Because of this, novel combinations of testosterone and progestins, which synergistically suppress gonadotropins, have been studied. Two recently published testosterone/progestin trials are particularly noteworthy. In the first, a long-acting injectable testosterone ester, testosterone decanoate, was combined with etonogestrel implants and resulted in 80–90% of subjects achieving a fewer than 1 million sperm per milliliter. In the second, a daily testosterone gel was combined with 3-monthly injections of depot medroxyprogesterone acetate producing similar results. Summary Testosterone-based hormone combinations are able to reversibly suppress human spermatogenesis; however, a uniformly effective regimen has remained elusive. Nevertheless, improvements, such as the use of injectable testosterone undecanoate, may lead to a safe, reversible and effective male contraceptive. PMID:18438174

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

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.

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.

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

[Dynamics of hormone secretion during chronic emotional stress].

PubMed

Amiragova, M G; Kovalev, S V; Svirskaia, R I

1979-05-01

Study of spontaneous secretion of corticosteroids and thyroid hormones and the direct hormonal response to stress revealed the pathogenic effect of chronic combined emotional stress upon the hormonal function of adrenal glands. The hippocampus takes part in formation of the emotional tension in response to stress stimulus and of the following hormonal secretion.

Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination.

PubMed

Köhrle, Josef

2007-06-01

Thyroid hormone metabolism by the three deiodinase selenoproteins -- DIO1, DIO2, and DIO3 -- regulates the local availability of various iodothyronine metabolites and thus mediates their effects on gene expression, thermoregulation, energy metabolism, and many key reactions during the development and maintenance of an adult organism. Circulating serum levels of thyroid hormone and thyroid-stimulating hormone, used as a combined indicator of thyroid hormone status, reflect a composite picture of: thyroid secretion; tissue-specific production of T(3) by DIO1 and DIO2 activity, which both contribute to circulating levels of T(3); and degradation of the prohormone T4, of the thyromimetically active T(3), of the inactive rT(3), of other iodothyronines metabolites with a lower iodine content and of thyroid hormone conjugates. Degradation reactions are catalyzed by either DIO1 or DIO3. Aberrant expression of individual deiodinases in disease, single nucleotide polymorphisms in their genes, and novel regulators of DIO gene expression (such as bile acids) provide a more complex picture of the fine tuning and the adaptation of systemic and local bioavailability of thyroid hormones.

Evaluation of growth hormone release in children using arginine and L-dopa in combination.

PubMed

Weldon, V V; Gupta, S K; Klingensmith, G; Clarke, W L; Duck, S C; Haymond, M W; Pagliara, A S

1975-10-01

L-Dopa in a dose ranging from 125-500 mg and arginine monochloride in a dose of 0.5 gm/kg were given simultaneously to 56 children with short stature (height less than third percentile). Sixteen of these children were subsequently diagnosed as having growth hormone deficiency. The diagnosis of hyposomatotropism was based on clinical findings and on responses to the combination test and to arginine and L-dopa administered as separate tests. All of the remaining 40 children had a normal GH response of greater than 6 ng/ml to the combination test. However, in this group, nine children were identified who responded to the combination test but who failed to respond to arginine and L-dopa in individual tests. The data suggest that a positive response to arginine and L-dopa in combination in children, who do not respond to the usual provocative tests when administered individually, may fail to identify children with partial GH deficiency who would benefit from treatment. The integrated stimulated GH response in the 31 children in whom a normal GH response to all three tests occurred suggests that the effects of L-dopa and arginine are additive.

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.

[Electroacupuncture intervention combined with general anesthesia for 80 cases of heart valve replacement surgery under cardiopulmonary bypass].

PubMed

Chi, Hao; Zhou, Wen-Xiong; Wu, Yao-Yao; Chen, Tong-Yu; Ge, Wen; Yuan, Lan; Shen, Wei-Dong; Zhou, Jia

2014-02-01

To determine whether electroacupuncture (EA) intervention combined with general anesthesia (GA) strategy can reduce early post-operative morbidity and medical costs in patients undergoing heart valve replacement operation under cardiopulmonary bypass. A total of 160 heart valve replacement surgery patients undergoing cardiopulmonary bypass were randomly divided into GA and EA + GA groups (n = 80 in each group). Patients of the GA group were given with intravenous injection of Fentanyl, Midazolam, Vecuronium Bromide, etc. and routine tracheal intubation. EA (3-4 Hz, 2.0-2.2 mA) was applied to bilateral Zhongfu (LU 1), Chize (LU 5) and Ximen (PC 4) beginning about 20 mm before the surgery in the EA + GA group. Endotracheal intubation was not employed but only prepared as a standby for patients of the EA + GA group. The dosage of narcotic drugs, duration of surgery, duration of aertic blockage, rate of cardiac re-beating, volumes of post-operative blood transfusion, discharge volume, cases of post-operative pulmonary infection, vocal cord injury, and the time of first bed-off, first eating and duration in intensive care unit (IOU) residence. etc. were recorded. The successful rates of heart valve replacement surgery were similar in both GA and EA + GA groups. Compared with the GA group, the dosages of Fentanyl, Midazolam and Vecuronium of the EA + GA group were significantly lower (P < 0.05, P < 0.01), the numbers of patients needing blood-transfusion, antibiotics treatment, and suffering from pulmonary infection were fewer, the time of first bed-off and duration of hospitalizetion and IOU residence were considerably shorter (P < 0.05, P < 0.01) and the total medical cost was obviously lower (P < 0.05) in the EA + GA group. EA combined with general anesthesia strategy for heart valve replacement surgery without endotracheal intubation is safe and can reduce post-operative morbidity and medical costs in patients undergoing heart valve replacement surgery under

[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.

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…

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.

[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.

Kyolic and Pycnogenol increase human growth hormone secretion in genetically-engineered keratinocytes.

PubMed

Buz'Zard, Amber R; Peng, Qiaoling; Lau, Benjamin H S

2002-02-01

The amount of human growth hormone (HGH) decreases significantly after the age of 30. This decrease has been implicated as one of the major causes in the signs of aging, such as thinning of the skin and bones, a decrease in lean muscle mass and an increase in adipose tissue. Supplementing the body's dwindling supply with recombinant human growth hormone (rHGH) has been shown to reverse the signs and symptoms of aging. However, drawbacks in rHGH replacement therapy include prohibitively high cost, the need for repeated injection and side effects such as carpel tunnel syndrome, gynecomastia and insulin resistance. The purpose of this study was to establish an in vitro model using genetically-engineered keratinocytes to screen natural compounds for the ability to stimulate HGH secretion. We now report that a combination of equal amounts of L-arginine and L-lysine, aged garlic extract (Kyolic), S-allyl cysteine and Pycnogenol significantly increased secretion of HGH in this in vitro model. The data indicate that this in vitro model may be used to screen for other secretagogues.

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.

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

A novel mutation in HESX1 causes combined pituitary hormone deficiency without septo optic dysplasia phenotypes.

PubMed

Takagi, Masaki; Takahashi, Mai; Ohtsu, Yoshiaki; Sato, Takeshi; Narumi, Satoshi; Arakawa, Hirokazu; Hasegawa, Tomonobu

2016-04-25

Heterozygous and/or homozygous HESX1 mutations have been reported to cause isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD), in association with septo optic dysplasia (SOD). We report a novel heterozygous HESX1 mutation in a CPHD patient without SOD phenotypes. The propositus was a one-year-old Japanese girl. Shortly after birth, she was found to be hypoglycemic. She was diagnosed with central adrenal insufficiency based on low cortisol and ACTH at a time of severe hypoglycemia. Further endocrine studies indicated that the patient also had central hypothyroidism and growth hormone deficiency. Using a next-generation sequencing strategy, we identified a novel heterozygous HESX1 mutation, c.326G>A (p.Arg109Gln). Western blotting and subcellular localization revealed no significant difference between wild type and mutant HESX1. Electrophoretic mobility shift assays showed that the mutant HESX1 abrogated DNA-binding ability. Mutant HESX1 was unable to repress PROP1-mediated activation. In conclusion, this study identified Arg109 as a critical residue in the HESX1 protein and extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in HESX1. When multiple genes need to be analyzed for mutations simultaneously, targeted sequence analysis of interesting genomic regions is an attractive approach.

Hormonal control of euryhalinity

USGS Publications Warehouse

Takei, Yoshio; McCormick, Stephen D.; McCormick, Stephen D.; Farrell, Anthony Peter; Brauner, Colin J.

2013-01-01

Hormones play a critical role in maintaining body fluid balance in euryhaline fishes during changes in environmental salinity. The neuroendocrine axis senses osmotic and ionic changes, then signals and coordinates tissue-specific responses to regulate water and ion fluxes. Rapid-acting hormones, e.g. angiotensins, cope with immediate challenges by controlling drinking rate and the activity of ion transporters in the gill, gut, and kidney. Slow-acting hormones, e.g. prolactin and growth hormone/insulin-like growth factor-1, reorganize the body for long-term acclimation by altering the abundance of ion transporters and through cell proliferation and differentiation of ionocytes and other osmoregulatory cells. Euryhaline species exist in all groups of fish, including cyclostomes, and cartilaginous and teleost fishes. The diverse strategies for responding to changes in salinity have led to differential regulation and tissue-specific effects of hormones. Combining traditional physiological approaches with genomic, transcriptomic, and proteomic analyses will elucidate the patterns and diversity of the endocrine control of euryhalinity.

Long-term survival, valve durability, and reoperation for 4 aortic root procedures combined with ascending aorta replacement.

PubMed

Svensson, Lars G; Pillai, Saila T; Rajeswaran, Jeevanantham; Desai, Milind Y; Griffin, Brian; Grimm, Richard; Hammer, Donald F; Thamilarasan, Maran; Roselli, Eric E; Pettersson, Gösta B; Gillinov, A Marc; Navia, Jose L; Smedira, Nicholas G; Sabik, Joseph F; Lytle, Bruce W; Blackstone, Eugene H

2016-03-01

To evaluate long-term results of aortic root procedures combined with ascending aorta replacement for aneurysms, using 4 surgical strategies. From January 1995 to January 2011, 957 patients underwent 1 of 4 aortic root procedures: valve preservation (remodeling or modified reimplantation, n = 261); composite biologic graft (n = 297); composite mechanical graft (n = 156); or allograft root (n = 243). Seven deaths occurred (0.73%), none after valve-preserving procedures, and 13 strokes (1.4%). Composite grafts exhibited higher gradients than allografts or valve preservation, but the latter 2 exhibited more aortic regurgitation (2.7% biologic and 0% mechanical composite grafts vs 24% valve-preserving and 19% allografts at 10 years). Within 2 to 5 years, valve preservation exhibited the least left ventricular hypertrophy, allograft replacement the greatest; however, valve preservation had the highest early risk of reoperation, allograft replacement the lowest. Patients receiving allografts had the highest risk of late reoperation (P < .05), and those receiving composite mechanical grafts and valve preservation had the lowest. Composite bioprosthesis patients had the highest risk of late death (57% at 15 years vs 14%-26% for the remaining procedures, P < .0001), because they were substantially older and had more comorbidities (P < .0001). These 4 aortic root procedures, combined with ascending aorta replacement, provide excellent survival and good durability. Valve-preserving and allograft procedures have the lowest gradients and best ventricular remodeling, but they have more late regurgitation, and likely, less risk of valve-related complications, such as bleeding, hemorrhage, and endocarditis. Despite the early risk of reoperation, we recommend valve-preserving procedures for young patients when possible. Composite bioprostheses are preferable for the elderly. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights

A comprehensive combined experimental and computational framework for pre-clinical wear simulation of total knee replacements.

PubMed

Abdelgaied, A; Fisher, J; Jennings, L M

2018-02-01

A more robust pre-clinical wear simulation framework is required in order to simulate wider and higher ranges of activities, observed in different patient populations such as younger more active patients. Such a framework will help to understand and address the reported higher failure rates for younger and more active patients (National_Joint_Registry, 2016). The current study has developed and validated a comprehensive combined experimental and computational framework for pre-clinical wear simulation of total knee replacements (TKR). The input mechanical (elastic modulus and Poisson's ratio) and wear parameters of the moderately cross-linked ultra-high molecular weight polyethylene (UHMWPE) bearing material were independently measured from experimental studies under realistic test conditions, similar to the loading conditions found in the total knee replacements. The wear predictions from the computational wear simulation were validated against the direct experimental wear measurements for size 3 Sigma curved total knee replacements (DePuy, UK) in an independent experimental wear simulation study under three different daily activities; walking, deep squat, and stairs ascending kinematic conditions. The measured compressive mechanical properties of the moderately cross-linked UHMWPE material were more than 20% lower than that reported in the literature under tensile test conditions. The pin-on-plate wear coefficient of moderately cross-linked UHMWPE was significantly dependant of the contact stress and the degree of cross-shear at the articulating surfaces. The computational wear predictions for the TKR from the current framework were consistent and in a good agreement with the independent full TKR experimental wear simulation measurements, with 0.94 coefficient of determination of the framework. In addition, the comprehensive combined experimental and computational framework was able to explain the complex experimental wear trends from the three different daily

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.

Long-term outcomes of three-dimensional conformal radiation therapy combined with neoadjuvant hormonal therapy in Japanese patients with locally advanced prostate cancer.

PubMed

Sakamoto, Masato; Mizowaki, Takashi; Mitsumori, Michihide; Takayama, Kenji; Sasai, Keisuke; Norihisa, Yoshiki; Kamoto, Toshiyuki; Nakamura, Eijiro; Ogawa, Osamu; Hiraoka, Masahiro

2010-12-01

The outcomes of three-dimensional conformal radiation therapy (3D-CRT) combined with neoadjuvant hormonal therapy (NAHT) in Japanese patients with locally advanced prostate cancer who initiated salvage hormonal therapy (SHT) at a relatively early phase were evaluated. Between April 1998 and April 2003, 70 Japanese patients with T3N0M0 prostate cancer who received radical 3D-CRT treatment were evaluated. The median age, initial prostate-specific antigen (PSA) level, and duration of NAHT were 73 years old, 26.3 ng/ml, and 4 months, respectively. Seventy grays were given in 35 fractions that were confined to the prostate and seminal vesicles. Adjuvant hormonal therapy was not administered after 3D-CRT in any of the cases. The median follow-up period was 64.9 months. The median PSA value at the time of initiation of SHT was 5.0 ng/ml (range 0.1-21.6 ng/ml). Overall, disease-specific, PSA failure-free (based on the Phoenix definition) and SHT-free survival rates at 5 years were 90.3% (95% CI 86.5-94.0), 96.5% (94.0-98.9), 60.5% (48.2-72.7), and 63.5% (57.2-69.8), respectively. Therefore, two-thirds of the patients were still hormone-free at 5 years. PSA control rates in our series of Japanese patients with stage T3N0M0 prostate cancer treated with the standard dose of 3D-CRT combined with NAHT seemed higher than expected. This approach involving 3D-CRT combined with NAHT with the initiation of SHT at PSA values of around 5 ng/ml may be one option for Japanese patients with locally advanced prostate cancer, although further prospective study is required to confirm the validity.

Combined Growth Hormone and Thyroid-Stimulating Hormone Deficiency in a Japanese Patient with a Novel Frameshift Mutation in IGSF1.

PubMed

Asakura, Yumi; Abe, Kiyomi; Muroya, Koji; Hanakawa, Junko; Oto, Yuji; Narumi, Satoshi; Hasegawa, Tomonobu; Adachi, Masanori

2015-01-01

Recent reports have indicated that loss-of-function mutations in the immunoglobulin superfamily member 1 gene (IGSF1, OMIM 300888) cause congenital central hypothyroidism with macroorchidism. We conducted a next-generation sequencing-based comprehensive mutation screening for pituitary hormone deficiencies to elucidate molecular mechanisms other than anatomical abnormalities of the pituitary that might be responsible for multiple anterior hormone deficiency in a male patient who originally visited our institute complaining of short stature. He was born large for gestational age (4,370 g, +3.0 SD) after an obstructed labour. Endocrinological evaluation revealed growth hormone and thyroid-stimulating hormone deficiency. Magnetic resonance imaging showed a discontinuity of the pituitary stalk with an ectopic posterior lobe and a hypoplastic anterior lobe, likely explaining multiple anterior pituitary hormone deficiency. We identified a novel hemizygous IGSF1 mutation (c.1137_1138delCA, p.Asn380Glnfs*6) in the patient. In reviewing the literature, we noticed that all reported Japanese male IGSF1 mutation carriers were born larger than mean standards for gestational age (mean birth weight SD score of +2.0, 95% confidence interval 1.0-3.0). This case suggests that more attention should be paid to intrauterine growth and birth history when patients are suspected of having an IGSF1 mutation. © 2015 S. Karger AG, Basel.

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.

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)

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.

A monocentric experience of growth hormone replacement therapy in adult patients.

PubMed

Abdi, Lyès; Sahnoun-Fathallah, Mona; Morange, Isabelle; Albarel, Frédérique; Castinetti, Frédéric; Giorgi, Roch; Brue, Thierry

2014-07-01

To describe the results of growth hormone (GH) therapy in adult GH-deficient patients treated in a tertiary referral center, with a focus on quality of life and adherence. Retrospective study of patients followed over a total period of 11 years. Quality of life (QOL) was assessed by the QOL-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) score and adherence to treatment was measured by a specific questionnaire. Clinical, biological, body composition and bone mineralization parameters were also analyzed. Data from 81 patients were analyzed. After a median treatment duration of 7 years, 2/3 of patients reported improved QOL (mean decrease of AGHDA score of 3.0 points, P<0.001). A trend towards more frequent improvement was observed in middle-aged patients, women, childhood-onset GHD, and in patients with initially more impaired QOL. More than 60% of the patients reported continuing treatment without interruption. Seventy percent declared good adherence (≤2 missed injections/month). A majority reported enhanced well-being. Additionally, we observed a mean weight increase of 2 kg, while fat mass, waist/hip circumference ratio and lipids were unchanged. Bone mineral density was significantly increased at lumbar spine and femoral neck. Our study confirmed a sustained improvement in quality of life and showed that majority of patients were still on GH treatment after a median duration of 7 years. Copyright © 2014. Published by Elsevier Masson SAS.

Combined Ovarian and Adrenal Venous Sampling in the Localization of Adrenocorticotropic Hormone-Independent Ectopic Cushing Syndrome.

PubMed

Chen, Shi; Li, Ran; Zhang, Xiaobo; Lu, Lin; Li, Ji; Pan, Hui; Zhu, Huijuan

2018-03-01

Cushing syndrome is rarely caused by the secretion of cortisol from ovarian tumors. In clinical decision-making, it is important to determine whether the ovarian tumor is capable of secreting cortisol. Selective ovarian and adrenal venous sampling is scarcely reported in the localization of ACTH-independent ectopic Cushing syndrome. We present a case of 40-year-old Chinese woman who had weight gain, hirsutism, hypertension, and menstrual disorder over 6 months. Her physical examination and biochemical assessment revealed adrenocorticotropic hormone-independent Cushing syndrome. Adrenal computed tomography scan indicated no abnormality. A mass of 5.7 cm × 4.2 cm × 3.4 cm was discovered by pelvic ultrasonography. Somatostatin receptor scintigraphy revealed no abnormal radioactivity intake. Combined ovarian and adrenal venous sampling together with a cortisol assay were conducted. Results revealed cortisol concentration of the right-side ovarian vein, left-side ovarian vein, and peripheral vein of 268.60, 29.00, and 35.18 μg/dL, respectively, suggesting a right-side ovarian origin. A right-side salpingo-oophorectomy was performed and the pathological diagnosis revealed ovarian steroid cell tumor, not otherwise specified. The cortisol level was substantially lower after the patient underwent surgery and symptoms of Cushing syndrome disappeared. At 3-year follow-up, the patient remained disease free, and no tumor was observed on pelvic ultrasonogram. Combined ovarian and adrenal venous sampling is valuable in the localization of adrenocorticotropic hormone-independent ectopic Cushing syndrome.

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.

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.

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.

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.

Response to growth hormone therapy in adolescents with familial panhypopituitarism.

PubMed

Kulshreshtha, B; Eunice, M; Ammini, A C

2010-04-01

Familial combined pituitary hormone deficiency is a rare endocrine disorder. We describe growth patterns of four children (3 females and 1 male) from two families with combined pituitary hormone deficiency. These children received growth hormone at ages ranging from 14.5 years to 19 years. While all the female siblings reached their target height, the male sibling was much shorter than mid parental height. The reasons for sexual dimorphism in growth patterns in these children are unclear.

Hormonal Approaches to Male contraception

PubMed Central

Wang, Christina; Swerdloff, Ronald S.

2010-01-01

Purpose of review Condoms and vasectomy are male controlled family planning methods but suffer from limitations in compliance (condoms) and limited reversibility (vasectomy); thus many couples desire other options. Hormonal male contraceptive methods have undergone extensive clinical trials in healthy men and shown to be efficacious, reversible and appear to be safe. Recent Findings The success rate of male hormonal contraception using injectable testosterone alone is high and comparable to methods for women. Addition of progestins to androgens improved the rate of suppression of spermatogenesis. Supported by government or non-government organizations, current studies aim to find the best combination of testosterone and progestins for effective spermatogenesis suppression and to explore other delivery methods for these hormones. Translation of these advances to widespread use in the developed world will need the manufacturing and marketing skills of the pharmaceutical industry. Availability of male contraceptives to the developing world may require commitments of governmental and non-governmental agencies. In a time when imbalance of basic resources and population needs are obvious, this may prove to be a very wise investment. Summary Male hormonal contraception is efficacious, reversible and safe for the target population of younger men in stable relationships. Suppression of spermatogenesis is achieved with a combination of an androgen and a progestin. Partnership with industry will accelerate the marketing of a male hormonal contraceptive. Research is ongoing on selective androgen and progesterone receptor modulators that suppress spermatogenesis, minimize potential adverse events while retaining the androgenic actions. PMID:20808223

Hormonal approaches to male contraception.

PubMed

Wang, Christina; Swerdloff, Ronald S

2010-11-01

Condoms and vasectomy are male-controlled family planning methods but suffer from limitations in compliance (condoms) and limited reversibility (vasectomy); thus many couples desire other options. Hormonal male contraceptive methods have undergone extensive clinical trials in healthy men and shown to be efficacious, reversible and appear to be well tolerated. The success rate of male hormonal contraception using injectable testosterone alone is high and comparable to methods for women. Addition of progestins to androgens improved the rate of suppression of spermatogenesis. Supported by government or nongovernment organizations, current studies aim to find the best combination of testosterone and progestins for effective spermatogenesis suppression and to explore other delivery methods for these hormones. Translation of these advances to widespread use in the developed world will need the manufacturing and marketing skills of the pharmaceutical industry. Availability of male contraceptives to the developing world may require commitments of governmental and nongovernmental agencies. In a time when imbalance of basic resources and population needs are obvious, this may prove to be a very wise investment. Male hormonal contraception is efficacious, reversible and well tolerated for the target population of younger men in stable relationships. Suppression of spermatogenesis is achieved with a combination of an androgen and a progestin. Partnership with industry will accelerate the marketing of a male hormonal contraceptive. Research is ongoing on selective androgen and progesterone receptor modulators that suppress spermatogenesis, minimize potential adverse events while retaining the androgenic and gonadotropin suppressive actions.

Sex hormones and the female voice.

PubMed

Abitbol, J; Abitbol, P; Abitbol, B

1999-09-01

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.

Clinical trials in male hormonal contraception.

PubMed

Nieschlag, Eberhard

2010-11-01

Research has established the principle of hormonal male contraception based on suppression of gonadotropins and spermatogenesis. All hormonal male contraceptives use testosterone, but only in East Asian men can testosterone alone suppress spermatogenesis to a level compatible with contraceptive protection. In Caucasians, additional agents are required of which progestins are favored. Clinical trials concentrate on testosterone combined with norethisterone, desogestrel, etonogestrel or depot-medroxyprogesterone acetate. The first randomized, placebo-controlled clinical trial performed by the pharmaceutical industry demonstrated the effectiveness of a combination of testosterone undecanoate and etonogestrel in suppressing spermatogenesis in volunteers. Copyright © 2010 Elsevier Inc. All rights reserved.

Pharmacologic development of male hormonal contraceptive agents.

PubMed

Roth, M Y; Amory, J K

2011-01-01

The world population continues to increase dramatically despite the existence of contraceptive technology. The use of male hormonal contraception may help in preventing un intended pregnancies and managing future population growth. Male hormonal contraception relies on the administration of exogenous hormones to suppress spermatogenesis. Clinical trials have tested several regimens using testosterone, alone or in combination with a progestin. These regimens were shown to be >90% effective in preventing conception and were not associated with serious adverse events.

Hormone replacement therapy for women previously treated for endometrial cancer.

PubMed

Edey, Katharine A; Rundle, Stuart; Hickey, Martha

2018-05-15

Endometrial cancer is the sixth most common cancer in women worldwide and most commonly occurs after the menopause (75%) (globocan.iarc.fr). About 319,000 new cases were diagnosed worldwide in 2012. Endometrial cancer is commonly considered as a potentially 'curable cancer,' as approximately 75% of cases are diagnosed before disease has spread outside the uterus (FIGO (International Federation of Gynecology and Obstetrics) stage I). The overall five-year survival for all stages is about 86%, and, if the cancer is confined to the uterus, the five-year survival rate may increase to 97%. The majority of women diagnosed with endometrial cancer have early-stage disease, leading to a good prognosis after hysterectomy and removal of the ovaries (oophorectomy), with or without radiotherapy. However, women may have early physiological and psychological postmenopausal changes, either pre-existing or as a result of oophorectomy, depending on age and menopausal status at the time of diagnosis. Lack of oestrogen can cause hot flushes, night sweats, genital tract atrophy and longer-term adverse effects, such as osteoporosis and cardiovascular disease. These changes may be temporarily managed by using oestrogens, in the form of hormone replacement therapy (HRT). However, there is a theoretical risk of promoting residual tumour cell growth and increasing cancer recurrence. Therefore, this is a potential survival disadvantage in a woman who has a potentially curable cancer. In premenopausal women with endometrial cancer, treatment induces early menopause and this may adversely affect overall survival. Additionally, most women with early-stage disease will be cured of their cancer, making longer-term quality of life (QoL) issues more pertinent. Following bilateral oophorectomy, premenopausal women may develop significant and debilitating menopausal symptoms, so there is a need for information about the risk and benefits of taking HRT, enabling women to make an informed decision

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

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.

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.

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

A combined case of macroprolactinoma, growth hormone excess and Graves' disease.

PubMed

Hussein, Z; Tress, B; Colman, P G

2005-06-01

Thyrotoxicosis due to Graves disease is a relatively common endocrine disorder. The occurrence of a prolactinoma with co-secretion of growth hormone (GH) is on the other hand, rare. We report the rare co-existence of Graves' disease in a patient with macroprolactinoma and GH hypersecretion and describe the successful response to medical therapy with dopamine agonist and antithyroid therapy. We hypothesize that hyperprolactinaemia played a role in promoting autoimmune thyroid disease in our patient and that treatment of hyperprolactinaemia may have been important in suppressing autoimmune disease activity in Graves' disease. This case also reflects on the close and complex interactions between thyroid hormones, prolactin (PRL), GH and testosterone (T).

Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks.

PubMed

Brynhildsen, Jan

2014-10-01

Combined hormonal contraceptives [combined oral contraceptives (COCs)] have been available for over 50 years and the impact of this invention may not be overestimated. Today over 100 million women are current users and in Western Europe and the United States approximately 80% of women of fertile ages can be considered as ever-users. Over the years several drawbacks have been identified and media alarms on risks are frequently presented, resulting in suboptimal compliance and low compliance and continuation rates. Poor compliance and discontinuation is a big problem and is not generally identified by prescribers. During ideal use COCs offer very good protection against unwanted pregnancies, however there is a big problem with compliance and continuation and thus the 'real-life' efficacy is much lower. Reasons for poor compliance include side effects and fear of side effects and it is crucial that the prescriber gives the individual woman thorough and balanced information on the benefits and risks. Most well known is the increased risk of venous thromboembolism, but also an elevated risk of arterial thrombosis and several types of cancer has been reported. The risk estimates are low but according to the large number of users a substantial number of extra cases will occur. However, use of COCs also offers several additional health benefits with significant impact on morbidity and quality of life. COC use is associated with a substantial decrease in the risk of ovarian cancer, endometrial cancer and colorectal cancer. Moreover, COCs are a major option of treatment for women suffering from heavy menstrual bleeding and dysmenorrhea as well as hirsutism and acne vulgaris. The net effect of the additional health effects of COC- use may very well be positive, i.e. a slight increase in life expectancy.

Gut hormones: the future of obesity treatment?

PubMed Central

McGavigan, Anne K; Murphy, Kevin G

2012-01-01

Obesity is a major worldwide health problem. The treatment options are severely limited. The development of novel anti-obesity drugs is fraught with efficacy and safety issues. Consequently, several investigational anti-obesity drugs have failed to gain marketing approval in recent years. Anorectic gut hormones offer a potentially safe and viable option for the treatment of obesity. The prospective utility of gut hormones has improved drastically in recent years with the development of longer acting analogues. Additionally, specific combinations of gut hormones have been demonstrated to have additive anorectic effects. This article reviews the current stage of anti-obesity drugs in development, focusing on gut hormone-based therapies. PMID:22452339

Two years of replacement therapy in adults with growth hormone deficiency.

PubMed

Verhelst, J; Abs, R; Vandeweghe, M; Mockel, J; Legros, J J; Copinschi, G; Mahler, C; Velkeniers, B; Vanhaelst, L; Van Aelst, A; De Rijdt, D; Stevenaert, A; Beckers, A

1997-10-01

Although several studies have shown beneficial short-term effects of recombinant human growth hormone (rhGH) therapy in adult GH deficient (GHD) patients, few data are available on large groups of patients treated for more than one year. In addition, the optimal dose of rhGH for each patient and the baseline parameters that predict which patients will benefit most from therapy or will have adverse events are not entirely elucidated. 148 adult GHD patients were enrolled in a multicentre 2-year rhGH replacement study which was placebo controlled for the first six months. rhGH (Genotropin/Genotonorm Pharmacia & Upjohn) was given in a dose of 0.25 IU/kg/week sc (1.5 IU/m2/day). Every 3-6 months body composition was measured using body impedance analysis and general well being was assessed using the Nottingham Health Profile (NHP) and social self-reporting questionnaire. At the same time patients had a full clinical examination and blood was sampled for glucose, HbA1c, IGF-1, creatinine, full blood count, thyroid hormones and liver function tests. With rhGH therapy IGF-1 levels increased from -2.00 +/- 2.60 SDS to 1.47 +/- 2.6 SDS after six months (P < 0.001), continued to rise despite no change in dose to 1.84 +/- 2.8 SDS after one year and remained constant thereafter (1.98 +/- 2.4 after 2 years). 56% of patients ultimately attained supranormal IGF-1 levels (+2 SD), 22% had levels below the mean, of which 9% were below -2 SD. Within 3 months lean body mass (LBM) increased by +5.09% (P < 0.001), total body water (TBW) by +5.40% (P < 0.001), while body fat (BF) dropped by -10.89% (P < 0.001) and waist circumference by -1.42% (P < 0.004). These effects were maintained during the first year of therapy, but the effect was attenuated after 24 months: LBM, +3.91% (P < 0.001); TBW, +3.28%, P < 0.001, BF, -6.42% (P < 0.001) and waist -2.22% (P < 0.009). Individual differences in response were large and could not be predicted by any of the baseline parameters, except for a

Satisfactory outcomes following combined unicompartmental knee replacement and anterior cruciate ligament reconstruction.

PubMed

Volpin, Andrea; Kini, S G; Meuffels, D E

2017-03-31

There exist limited options for treatment of patients with combined medial compartment arthritis and anterior cruciate ligament (ACL) deficiency. Ideal treatment is one that offers lasting relief of symptoms not compromising any future surgery. Unicompartmental knee replacement has shown consistently good results in the relatively young and active population, but there is a high reported incidence of failure up to 20%, if performed in ACL-deficient knees. One of the recognized treatment modality is combined ACL reconstruction and unicompartmental arthroplasty. A systematic review was conducted looking at the demographics, techniques, complications and outcome of combined ACL reconstruction with unicompartmental knee arthroplasty. A systematic literature search within the online Medline, PubMed Database, EMBASE, Web of Science, Cochrane and Google Scholar was carried out until October 2016 to identify relevant articles. A study was defined eligible if it met the following inclusion criteria: the surgical procedure combined unicompartmental knee arthroplasty and anterior cruciate ligament reconstruction; patient's clinical and/or functional outcomes were reported; any complications intra-operatively and post-operatively were reported; and the full-text articles, written in English, German, Italian, Dutch or Spanish, were available. Quality and risk of bias assessments were done using standardized criteria set. A total of 8 studies met the inclusion criteria encompassing 186 patients who were treated with simultaneous ACL reconstruction and unicompartmental knee arthroplasty. The mean age was 50.5 years (range from 44 to 56) with a mean follow-up of 37.6 months (range from 24 to 60). There was an improvement in mean Oxford Score from 27.5 to 36.8. Complications reported included tibial inlay dislocation (n = 3), conversion to a total knee arthroplasty (n = 1), infection requiring two-stage revision (n = 2), deep-vein thrombosis (n = 1), stiffness requiring

Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy.

PubMed

Gilligan, Lorna C; Gondal, Ali; Tang, Vivien; Hussain, Maryam T; Arvaniti, Anastasia; Hewitt, Anne-Marie; Foster, Paul A

2017-01-01

Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E 1 S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E 1 S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E 1 S transport in intracellular STS substrate availability. As E 1 S transport is regulated by the expression pattern of certain solute carrier organic anion transporter polypeptides, we show that in CRC OATP4A1 is the most abundantly expressed transporter. All four CRC cell lines rapidly transported E 1 S into cells, with this effect significantly inhibited by the competitive OATP inhibitor BSP. Transient knockdown of OATP4A1 significantly disrupted E 1 S uptake. Examination of estrogen receptor status showed ERα was present in Colo205 and Caco2 cells. None of the cells expressed ERβ. Intriguingly, HCT116 and HT29 cells strongly expressed the G protein coupled estrogen receptor (GPER), and that stimulation of this receptor with estradiol (E 2 ) and G1, a GPER agonist, significantly ( p < 0.01) increased STS activity. Furthermore, tamoxifen and fulvestrant, known GPER agonist, also increased CRC STS activity, with this effect inhibited by the GPER antagonist G15. These results suggest that CRC can take up and hydrolyze E 1 S, and that subsequent GPER stimulation increases STS activity in a potentially novel positive feedback loop. As elevated STS expression is associated with poor prognosis in CRC, these results suggest HRT, tamoxifen and fulvestrant may negatively impact CRC patient outcomes.

ALX 111: ALX1-11, parathyroid hormone (1-84) - NPS Allelix, PREOS, PTH, recombinant human parathyroid hormone, rhPTH (1-84).

PubMed

2003-01-01

Parathyroid Hormone; TOP) has been designed to assess the bone-building and fracture-reducing potential of the drug, and over 2600 postmenopausal women with osteoporosis who have not received previous drug therapy for osteoporosis have been enrolled. Treatment will be completed in September 2003, but more than 75% of patients enrolled in the TOP study have chosen to enrol in an Open Label Extension Study (OLES), which allows for a total treatment period of up to 24 months. NPS Pharmaceuticals has signed an agreement with Bio-Imaging Technologies, which will provide all image handling and analysis for this trial. In September 2002, NPS Pharmaceuticals announced that it has met its patient enrolment target (n > 150) for its POWER (PTH for Osteoporotic Women on Estrogen Replacement) study; a 24-month phase III trial initiated in Europe in November 2001. In this trial, women with osteoporosis receive SC injections of ALX 111 or placebo, in combination with their existing hormone replacement therapies, to test the bone building potential of the drug. In addition to the POWER study, a clinical trial sponsored by the National Institutes of Health (NIH) is being conducted to evaluate the potential of ALX 111 to build bone in combination with another osteoporosis medication. The 'PaTH' study (PTH/alendronate) is designed to assess the effect of various combinations and sequential uses of ALX 111 and Merck's Fosamax, a drug for slowing the loss of bone due to osteoporosis. The PaTH study, initiated in May 2000 and scheduled to conclude in September 2003, involved 238 patients with postmenopausal osteoporosis. It is thought that alendronic acid and ALX 111, when administered in combination, may act in an additive manner to treat osteoporosis because they act in different ways; alendronic acid acts to inhibit resorption and ALX 111 speeds up bone formation and resorption, with a net increase in formation. Results of this study are still being analysed but preliminary results appear to be

Hepatic veno-occlusive disease in pediatric stem cell transplantation: impact of pre-emptive antithrombin III replacement and combined antithrombin III/defibrotide therapy.

PubMed

Haussmann, Ursula; Fischer, Joachim; Eber, Stefan; Scherer, Franziska; Seger, Reinhard; Gungor, Tayfun

2006-06-01

Hepatic veno-occlusive disease (VOD) remains a serious complication after hematopoietic stem cell transplantation (HSCT). Based on a protective effect of antithrombin III (ATIII) on endothelial cells, we assessed the incidence of VOD after pre-emptive ATIII replacement and the outcome of VOD after combined high dose defibrotide (DF) and ATIII therapy. This prospective case series comprised two phases. In the first phase 71 children did not receive any specific VOD prophylaxis or therapy (controls). In the second phase 91 children were given pre-emptive ATIII replacement in case of decreased ATIII activity (< or =70%). If VOD was diagnosed clinically (according to modified Seattle criteria), high dose defibrotide (60 mg/day) and ATIII replacement therapy were combined. The severity of VOD was determined according to the degree of multiple organ dysfunction. The incidence of VOD was similar in both groups (13/71, 18% vs. 14/91, 15%). All 14 patients in the second group who developed VOD showed decreased ATIII activity not more than 1 day prior to the clinical diagnosis of VOD. The resulting short duration of pre-emptive ATIII therapy failed to prevent VOD (OR 0.96). None of the patients (n=72) maintaining normal ATIII levels developed VOD. All 14 patients with VOD who received combined therapy achieved complete remission and 93 % (13/14) survived until day +100, compared to six survivors (46%) in the first group. Pre-emptive ATIII administration did not alter the incidence of VOD. Combination treatment with ATIII and defibrotide was safe and yielded excellent remission and survival rates.

Effects of milk replacer composition on selected blood metabolites and hormones in preweaned Holstein heifers.

PubMed

Daniels, K M; Hill, S R; Knowlton, K F; James, R E; McGilliard, M L; Akers, R M

2008-07-01

We investigated the effects of increasing dietary protein and energy on concentrations of selected blood metabolites and hormones in Holstein heifers. Twenty-four heifers were fed 1 of 4 milk replacer (MR) diets for 9 wk (n = 6/diet): control [20% crude protein (CP), 21% fat MR fed at 441 g of dry matter (DM)/d], HPLF (28% CP, 20% fat MR fed at 951 g of DM/d), HPHF (27% CP, 28% fat MR fed at 951 g of DM/d), and HPHF+ (27% CP, 28% fat MR fed at 1,431 g of DM/d). Heifers were fed twice daily; water and starter (20% CP, 1.43% fat) were offered free choice and starter orts recorded daily. Serum and plasma aliquots from blood samples collected twice weekly after a 12-h fast were analyzed for insulin-like growth factor (IGF)-I, IGF-binding proteins (IGFBP), growth hormone (GH), insulin, glucose, nonesterified fatty acids, triglyceride, and plasma urea nitrogen concentrations. Only plasma glucose, IGFBP-2, and IGFBP-3 were affected by diet. Dietary treatment differences were only noted when the control was compared with the average of the other 3 diets. The addition of fat to the MR (HPLF vs. HPHF) and increased volume of MR (HPHF vs. HPHF+) had no effect on plasma glucose concentration or relative abundance of IGFBP-2 or IGFBP-3. Heifers fed the control diet had less glucose, greater IGFBP-2, and less IGFBP-3 than the average of the other 3 diets. There was a diet by week interaction for IGF-I. Serum IGF-I concentration in control heifers varied in a quadratic manner with a nadir (20 +/- 4 ng/mL) at wk 4, whereas IGF-I increased linearly in heifers on other diets. Both insulin and triglyceride changed over time in a complex pattern (significant linear and quadratic contrast effects). The greatest concentrations were measured at wk 0.5 with nadirs at wk 6 for both insulin and triglyceride. Serum GH concentration decreased in a linear manner from wk 0.5 to wk 9 in all heifers. Relative abundance of IGFBP-2 was quadratic over time with the greatest amount of IGFBP-2

Two novel LHX3 mutations in patients with combined pituitary hormone deficiency including cervical rigidity and sensorineural hearing loss.

PubMed

Ramzan, Khushnooda; Bin-Abbas, Bassam; Al-Jomaa, Lolwa; Allam, Rabab; Al-Owain, Mohammed; Imtiaz, Faiqa

2017-03-16

Congenital combined pituitary hormone deficiency (CPHD) is a rare heterogeneous group of conditions. CPHD-type 3 (CPHD3; MIM# 221750) is caused by recessive mutations in LHX3, a LIM-homeodomain transcription factor gene. The isoforms of LHX3 are critical for pituitary gland formation and specification of the anterior pituitary hormone-secreting cell types. They also play distinct roles in the development of neuroendocrine and auditory systems. Here, we summarize the clinical, endocrinological, radiological and molecular features of three patients from two unrelated families. Clinical evaluation revealed severe CPHD coupled with cervical vertebral malformations (rigid neck, scoliosis), mild developmental delay and moderate sensorineural hearing loss (SNHL). The patients were diagnosed with CPHD3 based on the array of hormone deficiencies and other associated syndromic symptoms, suggestive of targeted LHX3 gene sequencing. A novel missense mutation c.437G > T (p. Cys146Phe) and a novel nonsense mutation c.466C > T (p. Arg156Ter), both in homozygous forms, were found. The altered Cys146 resides in the LIM2 domain of the encoded protein and is a phylogenetically conserved residue, which mediates LHX3 transcription factor binding with a zinc cation. The p. Arg156Ter is predicted to result in a severely truncated protein, lacking the DNA binding homeodomain. Considering genotype/phenotype correlation, we suggest that the presence of SNHL and limited neck rotation should be considered in the differential diagnosis of CPHD3 to facilitate molecular diagnosis. This report describes the first LHX3 mutations from Saudi patients and highlights the importance of combining molecular diagnosis with the clinical findings. In addition, it also expands the knowledge of LHX3-related CPHD3 phenotype and the allelic spectrum for this gene.

Frequent development of combined pituitary hormone deficiency in patients initially diagnosed as isolated growth hormone deficiency: a long term follow-up of patients from a single center.

PubMed

Otto, Aline P; França, Marcela M; Correa, Fernanda A; Costalonga, Everlayny F; Leite, Claudia C; Mendonca, Berenice B; Arnhold, Ivo J P; Carvalho, Luciani R S; Jorge, Alexander A L

2015-08-01

Children initially diagnosed with isolated GH deficiency (IGHD) have a variable rate to progress to combined pituitary hormone deficiency (CPHD) during follow-up. To evaluate the development of CPHD in a group of childhood-onset IGHD followed at a single tertiary center over a long period of time. We retrospectively analyzed data from 83 patients initially diagnosed as IGHD with a mean follow-up of 15.2 years. The Kaplan-Meier method and Cox regression analysis was used to estimate the temporal progression and to identify risk factors to development of CPHD over time. From 83 patients initially with IGHD, 37 (45%) developed CPHD after a median time of follow up of 5.4 years (range from 1.2 to 21 years). LH and FSH deficiencies were the most common pituitary hormone (38%) deficiencies developed followed by TSH (31%), ACTH (12%) and ADH deficiency (5%). ADH deficiency (3.1 ± 1 years from GHD diagnosis) presented earlier and ACTH deficiency (9.3 ± 3.5 years) presented later during follow up compared to LH/FSH (8.3 ± 4 years) and TSH (7.5 ± 5.6 years) deficiencies. In a Cox regression model, pituitary stalk abnormalities was the strongest risk factor for the development of CPHD (hazard ratio of 3.28; p = 0.002). Our study indicated a high frequency of development of CPHD in patients initially diagnosed as IGHD at childhood. Half of our patients with IGHD developed the second hormone deficiency after 5 years of diagnosis, reinforcing the need for lifelong monitoring of pituitary function in these patients.

[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.

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.

Activation of erythropoietin receptor in the absence of hormone by a peptide that binds to a domain different from the hormone binding site

PubMed Central

Naranda, Tatjana; Wong, Kenneth; Kaufman, R. Ilene; Goldstein, Avram; Olsson, Lennart

1999-01-01

Applying a homology search method previously described, we identified a sequence in the extracellular dimerization site of the erythropoietin receptor, distant from the hormone binding site. A peptide identical to that sequence was synthesized. Remarkably, it activated receptor signaling in the absence of erythropoietin. Neither the peptide nor the hormone altered the affinity of the other for the receptor; thus, the peptide does not bind to the hormone binding site. The combined activation of signal transduction by hormone and peptide was strongly synergistic. In mice, the peptide acted like the hormone, protecting against the decrease in hematocrit caused by carboplatin. PMID:10377456

Ovarian cancer and hormone replacement therapy in the Million Women Study.

PubMed

Beral, Valerie; Bull, Diana; Green, Jane; Reeves, Gillian

2007-05-19

Ovarian cancer is the fourth most common cancer in women in the UK, with about 6700 developing the malignancy and 4600 dying from it every year. However, there is limited information about the risk of ovarian cancer associated with the use of hormone replacement therapy (HRT). 948,576 postmenopausal women from the UK Million Women Study who did not have previous cancer or bilateral oophorectomy were followed-up for an average of 5.3 years for incident ovarian cancer and 6.9 years for death. Information on HRT use was obtained at recruitment and updated where possible. Relative risks for ovarian cancer were calculated, stratified by age and hysterectomy status, and adjusted by area of residence, socioeconomic group, time since menopause, parity, body-mass index, alcohol consumption, and use of oral contraceptives. When they last reported HRT use, 287,143 women (30%) were current users and 186 751 (20%) were past users. During follow-up, 2273 incident ovarian cancers and 1591 deaths from the malignancy were recorded. Current users were significantly more likely to develop and die from ovarian cancer than never users (relative risk 1.20 [95% CI 1.09-1.32; p=0.0002] for incident disease and 1.23 [1.09-1.38; p=0.0006] for death). For current users of HRT, incidence of ovarian cancer increased with increasing duration of use, but did not differ significantly by type of preparation used, its constituents, or mode of administration. Risks associated with HRT varied significantly according to tumour histology (p<0.0001), and in women with epithelial tumours the relative risk for current versus never use of HRT was greater for serous than for mucinous, endometroid, or clear cell tumours (1.53 [1.31-1.79], 0.72 [0.52-1.00], 1.05 [0.77-1.43], or 0.77 [0.48-1.23], respectively). Past users of HRT were not at an increased risk of ovarian cancer (0.98 [0.88-1.11] and 0.97 [0.84-1.11], respectively, for incident and fatal disease). Over 5 years, the standardised incidence rates

Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency.

PubMed

Birla, S; Khadgawat, R; Jyotsna, V P; Jain, V; Garg, M K; Bhalla, A S; Sharma, A

2016-12-01

Growth hormone deficiency (GHD) results from variations affecting the production and release of growth hormone (GH) and is of 2 types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD results from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1 , POU1F1 , and HESX1. The present study reports on screening of POU1F1 , PROP1 , and HESX1 in CPHD patients and the novel variations identified. Fifty-one CPHD patients from 49 unrelated families clinically diagnosed on the basis of biochemical and imaging investigations along with 100 controls were enrolled. Detailed family history was noted from all participants and 5 ml blood samples drawn were processed for DNA isolation followed by direct sequencing of POU1F1 , PROP1 , and HESX1 genes. Of the 51 patients, 8 were females and 43 were males. Mean height standard deviation score (SDS) and weight SDS were -5.50 and -2.76, respectively. Thirty-six of the 51 patients underwent MRI of which 9 (25%) had normal pituitary structure and morphology while 27 (75%) showed abnormalities. Molecular analysis revealed 10 (20%) patients to have POU1F1 and PROP1 mutations/variations of which 5 were novel and 2 previously reported. No mutations were identified in HESX1. The novel variations identified were absent in the 100 healthy individuals screened and the control database Exome Aggregation Consortium (ExAC). Reported POU1F1 and PROP1 mutation hotspots were absent in our patients. Instead, novel POU1F1 changes were identified suggesting existence of a distinct mutation spectrum in our population. © Georg Thieme Verlag KG Stuttgart · New York.

Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt?

PubMed

Cerqueira, Charlotte; Knudsen, Nils; Ovesen, Lars; Laurberg, Peter; Perrild, Hans; Rasmussen, Lone Banke; Jørgensen, Torben

2011-08-01

Iodization of salt is an effective strategy to prevent iodine deficiency disorders. Recent studies, however, indicate that increasing the iodine intake in a population may give rise to an increased incidence of hypothyroidism, but the association has not been fully clarified. In Denmark, iodization of salt was initiated in 1998 because of mild-to-moderate iodine deficiency. The aim of this study was to evaluate the effect of the raised iodine intake on the nationwide incident use of thyroid hormone replacement therapy (levothyroxine) to treat hypothyroidism. Data on all use of levothyroxine was extracted from the Register of Medicinal Product Statistics during the period 1995-2009 and linked to other nationwide registers by use of the Danish identification number. Persons with previous thyroid surgery were excluded. In the studied period 71,565 incident users were identified. The incidence rate increased 75% in the moderately iodine deficient region (72.2 incident users/100,000 person-years in 1997 to 126.6 in 2008) and 87% in the mildly deficient region (86.9-162.9). When stratified by sex and age-group (00-39, 40-64, 65+) the largest relative increase was seen among women in the youngest age-group, where more than a doubling was seen. The mechanisms behind the increase may be a result of iodine-induced hypothyroidism, although a higher diagnostic activity with regard to thyroid dysfunction and intensified treatment of subclinical hypothyroidism may also play a role. Our findings stress the need for caution when initiating iodine fortification programs to keep the intake within the optimal range, and the need for continuous monitoring.

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.

The role of hormones in muscle hypertrophy.

PubMed

Fink, Julius; Schoenfeld, Brad Jon; Nakazato, Koichi

2018-02-01

Anabolic-androgenic steroids (AAS) and other hormones such as growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been shown to increase muscle mass in patients suffering from various diseases related to muscle atrophy. Despite known side-effects associated with supraphysiologic doses of such drugs, their anabolic effects have led to their widespread use and abuse by bodybuilders and athletes such as strength athletes seeking to improve performance and muscle mass. On the other hand, resistance training (RT) has also been shown to induce significant endogenous hormonal (testosterone (T), GH, IGF-1) elevations. Therefore, some bodybuilders employ RT protocols designed to elevate hormonal levels in order to maximize anabolic responses. In this article, we reviewed current RT protocol outcomes with and without performance enhancing drug usage. Acute RT-induced hormonal elevations seem not to be directly correlated with muscle growth. On the other hand, supplementation with AAS and other hormones might lead to supraphysiological muscle hypertrophy, especially when different compounds are combined.

Effects of luteinizing hormone-releasing hormone and arginine-vasotocin on the sperm-release response of Günther's Toadlet, Pseudophryne guentheri

PubMed Central

2010-01-01

Background Luteinizing hormone-releasing hormone (LHRH) is an exogenous hormone commonly used to induce spermiation in anuran amphibians. Over the past few decades, the LHRH dose administered to individuals and the frequency of injection has been highly variable. The sperm-release responses reported have been correspondingly diverse, highlighting a need to quantify dose-response relationships on a species-specific basis. This study on the Australian anuran Pseudophryne guentheri first evaluated the spermiation response of males administered one of five LHRHa doses, and second, determined whether AVT administered in combination with the optimal LHRHa dose improved sperm-release. Methods Male toadlets were administered a single dose of 0, 1, 2, 4 or 8 micrograms/g body weight of LHRHa. A 4 micrograms/g dose of AVT was administered alone or in combination with 2 micrograms/g LHRHa. Spermiation responses were evaluated at 3, 7 and 12 h post hormone administration (PA), and sperm number and viability were quantified using fluorescent microscopy. Results LHRHa administration was highly effective at inducing spermiation in P. guentheri, with 100% of hormone-treated males producing sperm during the experimental period. The number of sperm released in response to 2 micrograms/g LHRHa was greater than all other doses administered and sperm viability was highest in the 1 microgram/g treatment. The administration of AVT alone or in combination with LHRHa resulted in the release of significantly lower sperm numbers. Conclusion Overall, results from this study suggest that in P. guentheri, LHRHa is effective at inducing spermiation, but that AVT inhibits sperm-release. PMID:21059269

Combined hormonal contraceptive (CHC) use among obese women and contraceptive effectiveness: a systematic review.

PubMed

Dragoman, Monica V; Simmons, Katharine B; Paulen, Melissa E; Curtis, Kathryn M

2017-02-01

To evaluate from the literature whether combined hormonal contraception (CHC), including combined oral contraception pills (COCs), transdermal patch, vaginal ring or combined injectables, have different effectiveness or failure rates by body weight or body mass index (BMI). We searched PubMed and the Cochrane Library databases for all articles in all languages published between inception and February 2016, for evidence relevant to body weight or BMI, CHC use and contraceptive effectiveness. The quality of each individual study was assessed using the system for evaluating evidence developed by the United States Preventive Services Task Force. From 2874 articles, we identified 15 reports for inclusion, all of fair to poor quality. Fourteen studies measured the association of obesity status and contraceptive failure among COC users. Three fair quality and one poor quality study reported increased COC failure among a heterogeneous population of overweight and obese women compared with normal weight women, while eight fair quality and two poor quality studies did not find an association. Two fair quality studies reported on contraceptive transdermal patches. One pooled analysis described a higher proportion of pregnancies among women using the patch who weighed ≥90 kg; another secondary analysis suggested BMI>30 was associated with increased failure. No studies directly compared contraceptive effectiveness using the combined vaginal ring or combined injectable. Current available evidence addressing the risk of CHC failure in obese compared to normal weight women is limited to fair and poor quality studies. Studies of COCs show mixed results, though absolute differences in COC failure by body weight and BMI are small. Based on limited evidence, it appears that increasing body weight and BMI may contribute to decreasing contraceptive patch effectiveness. Copyright © 2017. Published by Elsevier Inc.

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.

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.

Peer-support in coping with medical uncertainty: discussion of oophorectomy and hormone replacement therapy on a web-based message board.

PubMed

Kenen, Regina H; Shapiro, Pamela J; Friedman, Susan; Coyne, James C

2007-08-01

The Facing Our Risk of Cancer Empowered (FORCE) website is devoted to women at risk for hereditary breast and ovarian cancers (HBOC). To understand the unique health concerns and emotional support needs of these women, we examined threads on the FORCE archived message boards with relevance to the broader HBOC community. We report on a thread discussing the controversial decision to use hormone replacement therapy (HRT) following prophylactic oophorectomy (PO). We used a qualitative research inductive process involving close reading, coding and identification of recurrent patterns, relationships and processes in the data. Twenty-nine women posted 177 messages over 7 months. Two main groups of women posted: (1) Women who were BRCA+, had completed PO, and were debating or adjusting their HRT options in terms of optimizing both quality and quantity of life. (2) Women who were BRCA+, were contemplating PO, but wanted to better understand the potential physical and psychological consequences of surgical menopause before deciding. Frustrated by physicians' lack of knowledge and contradictory media articles about the long-term consequences of HRT in BRCA+ women, they sought resources, emotional support and specific experiential knowledge from each other and generated a unique sense of community and a high level of trust. Copyright (c) 2007 John Wiley & Sons, Ltd.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

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

Li, Xiaolin; Ye, Li; Wang, Xiaoxiang

2012-12-15

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 andmore » non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.« less

[TREATMENT OF SHORT STATURE PATIENTS WITH NOPMAL GROWTH HORMONE SECRETION OF HYPOPHIS].

PubMed

Sprinchuk, N A; Samson, O J; Bol'shova, E V

2014-12-01

The article presents the treatment outcome in 86 children with short stature associated with different endocrine pathology and saved growth hormone secretion (congenital adrenal hyperplasia chondrodystrophy, Turner syndrome, idiopathic short stature, syndrome biologically inactive growth hormone and other genetically determined pathology). This study extends prior knowledge about the outcomes of the treatment with recombinant growth hormone and luteinizing hormone--releasing hormone analogue (alone or in combination) in short patients with poor prognosis of final height.

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.

Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies.

PubMed

de Zegher, Francis; Reynaert, Nele; De Somer, Lien; Wouters, Carine; Roelants, Mathieu

2018-06-25

Biologicals targeting the interleukin (IL)-1β or IL-6 pathway are becoming prime choices for the treatment of children with systemic juvenile idiopathic arthritis (sJIA). Up to 1 in 3 sJIA children receiving such treatment continues to have inflammatory activity and to require supra-physiological glucocorticoid doses which may reduce growth velocity for years and may lead to an extremely short stature for age, if not for life. Currently, there is no long-term proposal to normalize the adult height of these children with sJIA. We present long-term (up to 10 years), proof-of-concept evidence that the adult stature and adipose body composition of short sJIA children can be normalized with a hormonal combination strategy: (i) pubertal onset is postponed with a gonadotropin-releasing hormone analog (triptorelin) until a minimum height is reached, or until prepubertal growth is exhausted, and (ii) height gain is promoted with growth hormone (≈50 μg/kg/day), once inflammation is under control and high glucocorticoid doses are no longer needed. The latter treatment takes advantage of the window of relative glucocorticoid deficiency, which is known to open after prolonged glucocorticoid administration, and to be uniquely favorable to height gain. A long-term combination of biological and hormonal treatments for short sJIA children can be guided by a simple concept that involves (i) postponement of pubertal development and (ii) growth-promoting therapy after the episodes of major inflammation and high-dose glucocorticoid treatment. Limited long-term experience in short sJIA children suggests that this strategy leads consistently - albeit late - to a normal adult stature. © 2018 S. Karger AG, Basel.

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

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

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

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

Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives.

PubMed

Guazzelli, Christina Aparecida Falbo; Lindsey, Prescilla Chow; de Araújo, Fabio Fernando; Barbieri, Márcia; Petta, Carlos Alberto; Aldrighi, Jose Mendes

2005-02-01

The study evaluated the effects of the long-term use of a combined oral hormonal contraceptive containing 30 microg ethinyl estradiol and 75 microg gestodene in adolescents. Thirty-three volunteers, aged from 14 to 19 years, who used the oral contraceptive for three consecutive years, were studied. Evaluation of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides was made before use and after 1, 2 and 3 years. During the 3-year study period, total cholesterol, HDL-C, LDL-C and triglyceride levels were significantly higher than previous measurements, but average values did not exceed the normal range. Compared to the first year, the second- and third-year cholesterol, HDL-C, LDL-C and triglyceride levels were not significantly different.

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

Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

PubMed

Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

2016-06-01

Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Immunoassay of serum polypeptide hormones by using 125I-labelled anti(-immunoglobulin G) antibodies.

PubMed

Beck, P; Nicholas, H

1975-03-01

1. A technique for indirectly labelling antibodies to polypeptide hormones, by combining them with radioactively labelled anti-(immunoglobulin G) is described. (a) 125I-labelled anti-(rabbit immunoglobulin G) and anti-(guinea-pig immunoglobulin G) antibodies with high specific radioactivity were prepared after purification of the antibodies on immunoadsorbents containing the respective antigens. (b) Rabbit immunoglobulin G antibodies to human growth hormone, porcine glucagon and guinea-pig immunoglobulin G antibodies to bovine insulin and bovine parathyroid hormone were combined with immunoadsorbents containing the respective polypeptide hormone antigen. (c) The immunoglobulin G antibodies to the polypeptide hormones were reacted with 125-I-labelled anti-(immunoglobulin G) antibodies directed against the appropriate species of immunoglobulin G,and the anti-hormone antibodies were combined with the hormone-containing immunoadsorbent. (d) 125I-labelled anti-(immunoglobulin G) antibodies and anti-hormone antibodies were simultaneously eluted from the hormone-containing immunoadsorbent by dilute HCl, pH 2.0. After elution the anti-(immunoglobulin G) antibodies and antihormone antibodies were allowed to recombine at pH 8.0 and 4 degrees C. 2. The resultant immunoglobulin G-anti-immunoglobulin G complex was used in immunoradiometric (labelled antibody) and two-site assays of the respective polypeptide hormone. 3. By using these immunoassays, concentrations down to 90pg of human growth hormone/ml, 100 pg of bovine insulin/ml, 80 pg of bovine parathyroid hormone/ml and 150 pg of glucagon/ml were readily detected. Assays of human plasma for growth hormone and insulin by these methods showed good agreement with results obtained by using a directly 125I-labelled anti-hormone antibody in an immunoradiometric assay of human growth hormone or by radioimmunoassay of human insulin. 4. The method described allows immunoradiometric or two-site assays to be performed starting with as

Physical activity, hormone replacement therapy and breast cancer risk: A meta-analysis of prospective studies.

PubMed

Pizot, Cécile; Boniol, Mathieu; Mullie, Patrick; Koechlin, Alice; Boniol, Magali; Boyle, Peter; Autier, Philippe

2016-01-01

Lower risk of breast cancer has been reported among physically active women, but the risk in women using hormone replacement therapy (HRT) appears to be higher. We quantified the association between physical activity and breast cancer, and we examined the influence that HRT use and other risk factors had on this association. After a systematic literature search, prospective studies were meta-analysed using random-effect models applied on highest versus lowest level of physical activity. Dose-response analyses were conducted with studies reporting physical activity either in hours per week or in hours of metabolic equivalent per week (MET-h/week). The literature search identified 38 independent prospective studies published between 1987 and 2014 that included 116,304 breast cancer cases. Compared to the lowest level of physical activity, the highest level was associated with a summary relative risk (SRR) of 0.88 (95% confidence interval [CI] 0.85, 0.90) for all breast cancer, 0.89 (95% CI 0.83, 0.95) for ER+/PR+ breast cancer and 0.80 (95% CI 0.69, 0.92) for ER-/PR- breast cancer. Risk reductions were not influenced by the type of physical activity (occupational or non-occupational), adiposity, and menopausal status. Risk reductions increased with increasing amounts of physical activity without threshold effect. In six studies, the SRR was 0.78 (95% CI 0.70, 0.87) in women who never used HRT and 0.97 (95% CI 0.88, 1.07) in women who ever used HRT, without heterogeneity in results. Findings indicate that a physically inactive women engaging in at least 150 min per week of vigorous physical activity would reduce their lifetime risk of breast cancer by 9%, a reduction that might be two times greater in women who never used HRT. Increasing physical activity is associated with meaningful reductions in the risk of breast cancer, but in women who ever used HRT, the preventative effect of physical activity seems to be cancelled out. Copyright © 2015 Elsevier Ltd. All

Knowledge-attitude-practice survey among Portuguese gynaecologists regarding combined hormonal contraceptives methods.

PubMed

Bombas, Teresa; Costa, Ana Rosa; Palma, Fátima; Vicente, Lisa; Sá, José Luís; Nogueira, Ana Maria; Andrade, Sofia

2012-04-01

ABSTRACT Objectives To evaluate knowledge, attitude and practices of Portuguese gynaecologists regarding combined hormonal contraceptives. Methods A cross-sectional survey was conducted among 303 gynaecologists. Results Ninety percent of the gynaecologists considered that deciding on contraceptive methods is a process wherein the woman has her say. Efficacy, safety and the woman's preference were the major factors influencing gynaecologists, while efficacy, tolerability and ease of use were the major factors perceived by the specialists to influence the women's choice. Gynaecologists believed that only 2% of women taking the pill were 100% compliant compared to 48% of those using the patch and 75% of those using the ring. The lower risk of omission was the strong point for the latter methods. Side effects were the main reason to change to another method. Vaginal manipulation was the most difficult topic to discuss. Conclusions Most gynaecologists decided with the woman on the contraceptive method. The main reasons for the gynaecologist's recommendation of a given contraceptive method and the women's choice were different. Counselling implies an open discussion and topics related to sexuality were considered difficult to discuss. Improving communication skills and understanding women's requirements are critical for contraceptive counselling.

Impact of a women's counselling programme on combined hormonal contraception in Portugal--the IMAGINE Study.

PubMed

Costa, Ana Rosa R; Palma, Fátima; Sá, José Luís; Vicente, Lisa; Bombas, Teresa; Nogueira, Ana Maria; Rocha, Pedro

2011-12-01

The aim of this health education project was to measure the impact of counselling about combined hormonal contraceptive (CHC) methods on the subsequent choice of method by Portuguese women. This was a multi-centre study with a representative population, at the national and regional levels, of 2951 Portuguese women≥16 years of age visiting the gynaecologist. Counselling on available CHC methods was provided using a single leaflet, and their CHC choice was assessed before and after counselling. A combined oral contraceptive (COC) was the method preferred by the majority of the women prior to counselling. After counselling, 35% of women who initially had chosen the pill, switched to either the vaginal ring or the transdermal patch, and the difference was statistically significant. Ease of use was the major reason for choosing the COC, while a lower probability of omission was the reason for choosing the vaginal ring and the patch. The implementation of a counselling programme significantly affected contraceptive choices leading in a number of cases to the selection of alternatives better suited to women's lifestyle. Age and educational level are socio-demographic factors which play an important role.

Effects of information framing on the intentions of family physicians to prescribe long-term hormone replacement therapy.

PubMed

Nikolajevic-Sarunac, J; Henry, D A; O'Connell, D L; Robertson, J

1999-10-01

To determine whether the way in which information on benefits and harms of long-term hormone replacement therapy (HRT) is presented influences family physicians' intentions to prescribe this treatment. Family physicians were randomized to receive information on treatment outcomes expressed in relative terms, or as the number needing to be treated (NNT) with HRT to prevent or cause an event. A control group received no information. Primary care. Family physicians practicing in the Hunter Valley, New South Wales, Australia. Estimates of the impact of long-term HRT on risk of coronary events, hip fractures, and breast cancer were summarized as relative (proportional) decreases or increases in risk, or as NNT. Intention to prescribe HRT for seven hypothetical patients was measured on Likert scales. Of 389 family physicians working in the Hunter Valley, 243 completed the baseline survey and 215 participated in the randomized trial. Baseline intention to prescribe varied across patients-it was highest in the presence of risk factors for hip fracture, but coexisting risk factors for breast cancer had a strong negative influence. Overall, a larger proportion of subjects receiving information expressed as NNT had reduced intentions, and a smaller proportion had increased intentions to prescribe HRT than those receiving the information expressed in relative terms, or the control group. However, the differences were small and only reached statistical significance for three hypothetical patients. Framing effects were minimal when the hypothetical patient had coexisting risk factors for breast cancer. Information framing had some effect on family physicians' intentions to prescribe HRT, but the effects were smaller than those previously reported, and they were modified by the presence of serious potential adverse treatment effects.

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.

Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation

PubMed Central

Asakura, Yumi; Muroya, Koji; Hanakawa, Junko; Sato, Takeshi; Aida, Noriko; Narumi, Satoshi; Hasegawa, Tomonobu; Adachi, Masanori

2015-01-01

Abstract Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient’s mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD. PMID:25678757

Combined pituitary hormone deficiency with unique pituitary dysplasia and morning glory syndrome related to a heterozygous PROKR2 mutation.

PubMed

Asakura, Yumi; Muroya, Koji; Hanakawa, Junko; Sato, Takeshi; Aida, Noriko; Narumi, Satoshi; Hasegawa, Tomonobu; Adachi, Masanori

2015-01-01

Recent reports have indicated the role of the prokineticin receptor 2 gene (PROKR2) in the etiology of congenital hypopituitarism, including septo-optic dysplasia and Kallmann syndrome. In the present study, using next-generation targeted sequencing, we identified a novel heterozygous PROKR2 variant (c.742C>T; p.R248W) in a female patient who had combined pituitary hormone deficiency (CPHD), morning glory syndrome and a severely malformed pituitary gland. No other mutation was present in 27 genes related to hypogonadotropic hypogonadism, pituitary hormone deficiency and optic nerve malformation. The substituted amino acid was located on the third intracellular loop of the PROKR2 protein, which is a G protein-coupled receptor. Computational analyses with two programs (SIFT and PolyPhen-2) showed that the substitution was deleterious to PROKR2 function. The p.R248W mutation was transmitted from the patient's mother, who had a slightly delayed menarche. Collectively, we provide further genetic evidence linking heterozygous PROKR2 mutations and the development of CPHD.

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.

Transition in Pediatric and Adolescent Hypogonadal Girls: Gynecological Aspects, Estrogen Replacement Therapy, and Contraception.

PubMed

Tønnes Pedersen, Anette; Cleemann, Line; Main, Katharina M; Juul, Anders

2018-01-01

Hypogonadism may be suspected if puberty is delayed. Pubertal delay may be caused by a normal physiological variant, by primary ovarian insufficiency (Turner syndrome), or reflect congenital hypogonadotropic hypogonadism (HH; genetic) or acquired HH (brain lesions). Any underlying chronic disease like inflammatory bowel disease, celiac disease, malnutrition (anorexia or orthorexia), or excessive physical activity may also result in functional HH. Thus, girls with delayed puberty should be evaluated for an underlying pathology before any treatment, including oral contraception, is initiated. Estrogen replacement is important and natural 17β-estradiol, preferably transdermally, is the preferred choice, whereas the oral route can be used as an alternative depending on patient preference and compliance. Sexual activity is often delayed in the hypogonadal adolescent girl. In the adolescent hypogonadal girl, hormone replacement therapy (HRT) most likely has been initiated at the time she becomes sexually active. If a risk of unwanted pregnancy cannot be ruled out, there is a need to consider contraception. This consideration does not contradict the principles of HRT but can be included as a part of the substitution, e.g. oral contraceptives containing 17β-estradiol or a progestogen intrauterine device combined with continuous 17β-estradiol (transdermal or oral). © 2018 S. Karger AG, Basel.

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.

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.

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.

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 levels

MedlinePlus

Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

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

A New Combination of Testosterone and Nestorone Transdermal Gels for Male Hormonal Contraception

PubMed Central

Ilani, Niloufar; Roth, Mara Y.; Amory, John K.; Swerdloff, Ronald S.; Dart, Clint; Page, Stephanie T.; Bremner, William J.; Sitruk-Ware, Regine; Kumar, Narender; Blithe, Diana L.

2012-01-01

Context: Combinations of testosterone (T) and nestorone (NES; a nonandrogenic progestin) transdermal gels may suppress spermatogenesis and prove appealing to men for contraception. Objective: The objective of the study was to determine the effectiveness of T gel alone or combined with NES gel in suppressing spermatogenesis. Design and Setting: This was a randomized, double-blind, comparator clinical trial conducted at two academic medical centers. Participants: Ninety-nine healthy male volunteers participated in the study. Interventions: Volunteers were randomized to one of three treatment groups applying daily transdermal gels (group 1: T gel 10 g + NES 0 mg/placebo gel; group 2: T gel 10 g + NES gel 8 mg; group 3: T gel 10 g + NES gel 12 mg). Main Outcome Variable: The main outcome variable of the study was the percentage of men whose sperm concentration was suppressed to 1 million/ml or less by 20–24 wk of treatment. Results: Efficacy data analyses were performed on 56 subjects who adhered to the protocol and completed at least 20 wk of treatment. The percentage of men whose sperm concentration was 1 million/ml or less was significantly higher for T + NES 8 mg (89%, P < 0.0001) and T + NES 12 mg (88%, P = 0.0002) compared with T + NES 0 mg group (23%). The median serum total and free T concentrations in all groups were maintained within the adult male range throughout the treatment period. Adverse effects were minimal in all groups. Conclusion: A combination of daily NES + T gels suppressed sperm concentration to 1 million/ml or less in 88.5% of men, with minimal adverse effects, and may be further studied as a male transdermal hormonal contraceptive. PMID:22791756

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era

PubMed Central

Fang, Qing; George, Akima S.; Brinkmeier, Michelle L.; Mortensen, Amanda H.; Gergics, Peter; Cheung, Leonard Y. M.; Daly, Alexandre Z.; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A. Bilge; Kitzman, Jacob O.; Mills, Ryan E.; Li, Jun Z.

2016-01-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD. PMID:27828722

Genetics of Combined Pituitary Hormone Deficiency: Roadmap into the Genome Era.

PubMed

Fang, Qing; George, Akima S; Brinkmeier, Michelle L; Mortensen, Amanda H; Gergics, Peter; Cheung, Leonard Y M; Daly, Alexandre Z; Ajmal, Adnan; Pérez Millán, María Ines; Ozel, A Bilge; Kitzman, Jacob O; Mills, Ryan E; Li, Jun Z; Camper, Sally A

2016-12-01

The genetic basis for combined pituitary hormone deficiency (CPHD) is complex, involving 30 genes in a variety of syndromic and nonsyndromic presentations. Molecular diagnosis of this disorder is valuable for predicting disease progression, avoiding unnecessary surgery, and family planning. We expect that the application of high throughput sequencing will uncover additional contributing genes and eventually become a valuable tool for molecular diagnosis. For example, in the last 3 years, six new genes have been implicated in CPHD using whole-exome sequencing. In this review, we present a historical perspective on gene discovery for CPHD and predict approaches that may facilitate future gene identification projects conducted by clinicians and basic scientists. Guidelines for systematic reporting of genetic variants and assigning causality are emerging. We apply these guidelines retrospectively to reports of the genetic basis of CPHD and summarize modes of inheritance and penetrance for each of the known genes. In recent years, there have been great improvements in databases of genetic information for diverse populations. Some issues remain that make molecular diagnosis challenging in some cases. These include the inherent genetic complexity of this disorder, technical challenges like uneven coverage, differing results from variant calling and interpretation pipelines, the number of tolerated genetic alterations, and imperfect methods for predicting pathogenicity. We discuss approaches for future research in the genetics of CPHD.

Fractures in pituitary adenoma patients from the Dutch National Registry of Growth Hormone Treatment in Adults.

PubMed

van Varsseveld, N C; van Bunderen, C C; Franken, A A M; Koppeschaar, H P F; van der Lely, A J; Drent, M L

2016-08-01

The effects of growth hormone (GH) replacement therapy on fracture risk in adult GH deficient (GHD) patients with different etiologies of pituitary GHD are not well known, due to limited data. The aim of this study was to investigate characteristics and fracture occurrence at start of (baseline) and during long-term GH replacement therapy in GHD adults previously treated for Cushing's disease (CD) or acromegaly, compared to patients with previous nonfunctioning pituitary adenoma (NFPA). From the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide surveillance study in severe GHD adults, all patients using ≥30 days of GH replacement therapy with previous NFPA (n = 783), CD (n = 180) and acromegaly (n = 65) were selected. Patient characteristics, fractures and potential influencing factors were investigated. At baseline, patients with previous CD were younger, more often female and had more often a history of osteopenia or osteoporosis, whereas patients with previous acromegaly had more often received cranial radiotherapy and a longer duration between treatment of their pituitary tumor and start of adult GH replacement therapy. During follow-up, a fracture occurred in 3.8 % (n = 39) of all patients. Compared to patients with previous NFPA, only patients with previous acromegaly had an increased fracture risk after 6 years of GH replacement therapy. During GH replacement therapy, an increased fracture risk was observed in severe GHD adult patients previously treated for acromegaly, but not in those previously treated for CD, compared to severe GHD adult patients using GH replacement therapy because of previous NFPA. Further studies are needed to confirm these findings and to elucidate potential underlying mechanisms.

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

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.

Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats

PubMed Central

Jin, Yeung Bae; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil

2013-01-01

Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method. PMID:23239176

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.

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.

[Hormonal methods of increasing fertility in swine].

PubMed

Kostov, L; Radev, G; Andreev, A

1976-01-01

Experiments were carried out to raise the conception rate in sows during the summer season under industrial conditions of breeding. Eight test groups of 365 animals were formed as well as four control ones with 137 pigs. The sucking period lasted 28 to 33 days. When in estrus the sows were mated with boars twice at a 24-hour interval. In five groups that were dried up from July to September was recorded the effect of several kinds of gonadotropic hormones administered alone or in combination with vitamin E and steroid hormones -- Gravohormone Tolligon, an oil emulsion of PMS (500 IU), with 250 Chorulon and 2 mg estradiol benzoicum; an oil solution of PMS (500 IU) with 2 mg estradiol, 25 mg testosterone and 30 mg vitamin E. During the same period three other groups of test sows were formed to use steroid hormones such as Gravignost, an oil solution of 2 mg estradiol benzoicum, and 40 mg testosterone propionate as well as the same preparation in combination with 30 mg vitamin E. The deterioration of the temperature and humidity regime in the summer at the industrial pig-breeding complexes was shown to inhibit the manifestation of estrus and lower the conception rate in sows. Either alone or in combination with vitamin E and estradiol the gonadotropic hormones largely raised the per cent of animals manifesting estrus for ten days in summer after weaning their piglets (89 to 100 per cent) as well as the number of lively born offsprings per sow (9.8 to 11.3). The optimal doses used were as follows: Gravohormone, 13--14 IU/kg liveweight; Folligon or PMS, 6--7 IU per kg; and choriogonadotropin at the rate of 500 IU per sow. One the other hand, the steroid hormonal preparations bring about estrus of a lower quality leading to a low conception rate and fertility at first insemination, disturb the sexual cyclicity. They should not be administered alone as cycle starters in pig-breeding.

Noncontraceptive use of oral combined hormonal contraceptives in polycystic ovary syndrome-risks versus benefits.

PubMed

Dokras, Anuja

2016-12-01

The use of steroid sex hormones for noncontraceptive benefits has been endorsed by several medical societies. In women with polycystic ovary syndrome (PCOS), hormonal contraceptives are first-line therapy for concurrent treatment of menstrual irregularity, acne, and hirsutism. The association of PCOS with obesity, diabetes, and dyslipidemia frequently brings up the debate regarding risks versus benefits of hormonal contraceptives in this population. In women with PCOS, the lack of large-scale studies evaluating the risks with varying doses of ethinyl estradiol, types of progestins, and presence of confounding factors such as obesity, smoking, and other cardiometabolic comorbidities is a significant limitation in these deliberations. Although it is important to assess the absolute risk for major morbidities including cardiovascular events, currently, there are a paucity of long-term data for these outcomes in PCOS. Most of the current studies do not suggest an increase in risk of prediabetes/diabetes, clinically significant dyslipidemia, inflammatory changes, or depressive/anxiety symptoms with oral contraceptive pill use. Screening of women with PCOS for cardiometabolic and psychiatric comorbidities is routinely recommended. This information should be used by health care providers to individualize the choice of hormonal contraceptive treatment, adequately counsel patients regarding risks and benefits, and formulate an appropriate follow-up plan. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

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

Effects of Information Framing on the Intentions of Family Physicians to Prescribe Long-Term Hormone Replacement Therapy

PubMed Central

Nikolajevic-Sarunac, Jasminka; Henry, David A; Henry, David A; O'Connell, Dianne L; Robertson, Jane; Robertson, Jane

1999-01-01

OBJECTIVE To determine whether the way in which information on benefits and harms of long-term hormone replacement therapy (HRT) is presented influences family physicians' intentions to prescribe this treatment. DESIGN Family physicians were randomized to receive information on treatment outcomes expressed in relative terms, or as the number needing to be treated (NNT) with HRT to prevent or cause an event. A control group received no information. SETTING Primary care. PARTICIPANTS Family physicians practicing in the Hunter Valley, New South Wales, Australia. INTERVENTION Estimates of the impact of long-term HRT on risk of coronary events, hip fractures, and breast cancer were summarized as relative (proportional) decreases or increases in risk, or as NNT. MEASUREMENTS AND MAIN RESULTS Intention to prescribe HRT for seven hypothetical patients was measured on Likert scales. Of 389 family physicians working in the Hunter Valley, 243 completed the baseline survey and 215 participated in the randomized trial. Baseline intention to prescribe varied across patients—it was highest in the presence of risk factors for hip fracture, but coexisting risk factors for breast cancer had a strong negative influence. Overall, a larger proportion of subjects receiving information expressed as NNT had reduced intentions, and a smaller proportion had increased intentions to prescribe HRT than those receiving the information expressed in relative terms, or the control group. However, the differences were small and only reached statistical significance for three hypothetical patients. Framing effects were minimal when the hypothetical patient had coexisting risk factors for breast cancer. CONCLUSIONS Information framing had some effect on family physicians' intentions to prescribe HRT, but the effects were smaller than those previously reported, and they were modified by the presence of serious potential adverse treatment effects. PMID:10571703

Does ethnicity matter in male hormonal contraceptive efficacy?

PubMed Central

Ilani, Niloufar; Liu, Peter Y; Swerdloff, Ronald S; Wang, Christina

2011-01-01

The development of male hormonal contraception has progressed significantly during the last three decades. The ultimate goal is to produce an effective, safe and reversible male method of contraception that are within reach of and can be used by all men globally. This review aims to outline the recent developments in male hormonal contraception with special emphasis on how ethnicity influences acceptability, extent of sperm suppression, and rate of recovery of spermatogenesis. Baseline differences in testicular histomorphology and testosterone metabolism between East Asian and Caucasian men have been reported, but whether this contributes significantly to varying degrees of sperm suppression in response to exogenous testosterone therapy is less known. Testosterone alone male hormonal contraceptive regimens are effective and applicable for East Asian men, and less so for Caucasians. Combinations of progestins with androgens are sufficient to optimize effectiveness of suppression and applicability to all ethnicities. New compounds such as steroidal or non-steroidal selective androgen receptor modulators with dual androgenic and progestational activities are potential compounds for further development as male hormonal contraceptive methods. At the present time, combined androgen and progestin contraceptive regimens appear to be effective, safe, reversible and convenient to use for all men with ethnic, cultural and environmental differences. Further refinements on the hormonal agent, methods of delivery, and dose optimization of the androgen relative to the progestin are necessary. This goal mandates further investment and large clinical trials in multiethnic populations to better define safety and efficacy. PMID:21317912

Treatment of hypothyroidism with levothyroxine or a combination of levothyroxine plus L-triiodothyronine.

PubMed

Escobar-Morreale, Héctor F; Botella-Carretero, José I; Morreale de Escobar, Gabriella

2015-01-01

At present, the drug of choice for the treatment of hypothyroidism is levothyroxine sodium, even though the thyroid gland secretes both thyroxine and 3',3,5-triiodothyronine; the latter is the more active of the two at the cellular level because of its higher affinity for the nuclear thyroid hormone receptors. To date, combined levothyroxine plus liothyronine treatment for hypothyroidism has been evaluated in 15 clinical trials in humans. In two studies, combined therapy seemed to have beneficial effects on mood, quality of life, and psychometric performance of patients, compared with levothyroxine alone; in some of these studies, the patients preferred levothyroxine plus liothyronine combinations. This preference should be balanced against the possibility of adverse events resulting from the addition of liothyronine to levothyroxine. Until clear advantages of levothyroxine plus liothyronine are demonstrated, the administration of levothyroxine alone should remain the treatment of choice for replacement therapy of hypothyroidism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Combination L-T3 and L-T4 therapy for hypothyroidism.

PubMed

Wartofsky, Leonard

2013-10-01

Because of the longstanding controversy regarding whether hypothyroid patients can be optimally replaced by treatment with levothyroxine (L-T4) alone, numerous studies have addressed potential benefits of combined therapy of triiodothyronine (T3) with L-T4. Results of these studies have failed to support a potential benefit of combined therapy. A strong argument for the addition of L-T3 to L-T4 monotherapy has been lacking until recent genetic studies indicated a rationale for such therapy among a small fraction of the hypothyroid patient population. Interest in this issue has focused on the importance of the deiodinases in maintaining the euthyroid state and the role of genetic polymorphisms in the deiodinase genes that would affect thyroid hormone concentrations in both blood and tissues. One such polymorphism in the D2 gene, Thr92Ala, is associated with reduced T4 to T3 activation in skeletal muscle and thyroid, linked to obesity and alterations in thyroid-pituitary feedback, and in responses to thyroid hormone treatment. Although our professional organizations continue to recommend L-T4 alone for the treatment of hypothyroidism, the possibility of a D2 gene polymorphism should be considered in patients on L-T4 monotherapy who continue to complain of fatigue in spite of dosage achieving low normal serum thyroid stimulating hormone levels. A suggestive clue to the presence of this polymorphism could be a higher than normal free T4/free T3 ratio. Clinicians could consider adding T3 as a therapeutic trial in selected patients. Future well controlled clinical trials will be required to more fully resolve the controversy.

Growth hormone deficiency: an update.

PubMed

Audí, L; Fernández-Cancio, M; Camats, N; Carrascosa, A

2013-03-01

Growth hormone (GH) deficiency (GHD) in humans manifests differently according to the individual developmental stage (early after birth, during childhood, at puberty or in adulthood), the cause or mechanism (genetic, acquired or idiopathic), deficiency intensity and whether it is the only pituitary-affected hormone or is combined with that of other pituitary hormones or forms part of a complex syndrome. Growing knowledge of the genetic basis of GH deficiency continues to provide us with useful information to further characterise mutation types and mechanisms for previously described and new candidate genes. Despite these advances, a high proportion of GH deficiencies with no recognisable acquired basis continue to be labelled as idiopathic, although less frequently when they are congenital and/or familial. The clinical and biochemical diagnoses continue to be a conundrum despite efforts to harmonise biochemical assays for GH and IGF-1 analysis, probably because the diagnosis based on the so-called GH secretion stimulation tests will prove to be of limited usefulness for predicting therapy indications.

[Male hormonal contraception: past, present, future].

PubMed

Pásztor, Norbert; Hegyi, Borbála Eszter; Badó, Attila; Németh, Gábor

2017-11-01

In certain regions of the world the enormous rate of population growth raises economic and public health concerns and widely accessible contraceptive methods would be desired. In contrast, in other countries the use of effective contraception is a question of individual preferences. Today, most of the reliable contraceptive methods are applied by women, while the options for male methods are quite limited. It is well known that significant portion of pregnancies are still unplanned and several data revealed men's willingness to take part in family planning. Based on these needs, remarkable efforts have been made to develop a suitable hormonal contraceptive agent for men. With the exogenous suppression of follicle stimulating hormone and luteinizing hormone secretion, the inhibition of the testicular testosterone production and the spermatogenesis can be achieved. In the beginning, testosterone-derivatives, or testosterone-progestin combinations were administered, later synthetic androgen agents were developed. Despite of these efforts, unfortunately, there is no safe, widely feasible male hormonal contraception to date, but in the future this goal can be achieved by solving the key hurdles. Orv Hetil. 2017; 158(46): 1819-1830.

Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency.

PubMed

Turton, J P; Strom, M; Langham, S; Dattani, M T; Le Tissier, P

2012-03-01

  Mutations in the POU1F1 gene severely affect the development and function of the anterior pituitary gland and lead to combined pituitary hormone deficiency (CPHD).   The clinical and genetic analysis of a patient presenting with CPHD and functional characterization of identified mutations.   We describe a male patient with extreme short stature, learning difficulties, anterior pituitary hypoplasia, secondary hypothyroidism and undetectable prolactin, growth hormone (GH) and insulin-like growth factor 1 (IGF1), with normal random cortisol.   The POU1F1 coding region was amplified by PCR and sequenced; the functional consequence of the mutations was analysed by cell transfection and in vitro assays.   Genetic analysis revealed compound heterozygosity for two novel putative loss of function mutations in POU1F1: a transition at position +3 of intron 1 [IVS1+3nt(A>G)] and a point mutation in exon 6 resulting in a substitution of arginine by tryptophan (R265W). Functional analysis revealed that IVS1+3nt(A>G) results in a reduction in the correctly spliced POU1F1 mRNA, which could be corrected by mutations of the +4, +5 and +6 nucleotides. Analysis of POU1F1(R265W) revealed complete loss of function resulting from severely reduced protein stability.   Combined pituitary hormone deficiency in this patient is caused by loss of POU1F1 function by two novel mechanisms, namely aberrant splicing (IVS1+3nt (A>G) and protein instability (R265W). Identification of the genetic basis of CPHD enabled the cessation of hydrocortisone therapy without the need for further assessment for evolving endocrinopathy. © 2012 Blackwell Publishing Ltd.

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.

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

Study of goldfish (Carassius auratus) growth hormone structure-function relationship by domain swapping.

PubMed

Chan, Y H; Cheng, C H K; Chan, K M

2007-03-01

Using goldfish as a model, the structure-function relationship of goldfish growth hormone was studied using the strategy of homologous domain swapping. Chimeric mutants were constructed by exchanging homologous regions between goldfish growth hormone (gfGH II) and goldfish prolactin (gfPRL) with their cloned complementary DNAs. Six mutants, with their domain-swapped, were generated to have different combinations of three target regions, including the helix a, helix d and the large section in between these helices (possess the helices b, c and other random coiled regions). After expression in E. coli and refolding, these mutants were characterized by using competitive receptor binding assay (RRA) and growth hormone responding promoter activation assay. The different activity profiles of mutants in Spi 2.1 gene promoter assays from that in RRA shows that, for gfGH, receptor binding dose not confer receptor signal activations. When either helices a or d of gfGH was maintained with other helices replaced by their gfPRL counterparts, both receptor binding and hence gene activation activities are reduced. In mutants with helices b and c in gfGH maintained, containing the gfGH middle section, and helices a and d swapped with gfPRL, the had reduced RRA activities but the promoter activation activities retained. In conclusion, as in the case of human GH, the gfGH molecule possesses two functional sites: one of them is composed of discontinuous epitopes located on the target regions of this study and is for receptor binding; another site is located on the middle section of the molecule that helices a and d are not involved, and it is for activation of GH receptor and intracellular signals.

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.

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.

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

Changes in elderly women's health-related quality of life following discontinuation of hormone replacement therapy

PubMed Central

Heller, Debra A; Gold, Carol H; Ahern, Frank M; Pringle, Kristine E; Brown, Theresa V; Glessner, Margaret R

2005-01-01

Background Many women have discontinued hormone replacement therapy (HRT) in view of recent findings. The goal of this study was to determine if HRT discontinuation is associated with changes in health-related quality of life (HRQOL) in elderly women. Methods We studied women enrolled in Pennsylvania's Pharmaceutical Assistance Contract for the Elderly (PACE) program, linking prescription claims with data from a longitudinal mail survey. HRQOL measures included the number of days out of the last 30 that physical health was not good and analogous measures for mental health, pain, and interference with activities, as well as a composite "healthy days" measure developed by CDC. Longitudinal analyses focused on 2,357 women who completed surveys in both 2002 and 2003, and who used HRT at baseline (mean age = 75.5, range = 65–102). Propensity scores were used to match HRT continuers and discontinuers according to HRT type, demographics, and baseline HRQOL. Analysis of covariance was used to compare HRQOL change in continuers and discontinuers. Results Between 2002 and 2003, 43% of HRT users discontinued therapy. Analysis of covariance to examine HRQOL change revealed complex interactions with age. Discontinuers aged 65–74 reported greater increases in days in which mental health was not good (p < .05), fewer "healthy days" (p < .05), more days in which health interfered with activities (p < .01), and more days with pain (p < .01). Among women aged 75–84, HRT discontinuers reported more days in which physical health was not good (p < .01); no other significant effects were observed in this group. Relative to HRT continuers, discontinuers aged 85 and older experienced apparent HRQOL improvements following cessation, with fewer days in which physical health was not good (p < .01), fewer days of poor mental health (p < .05), and more "healthy days" (p < .01). Conclusions These results suggest that there are substantial age differences in response to HRT discontinuation

Identification of SLC20A1 and SLC15A4 among other genes as potential risk factors for combined pituitary hormone deficiency.

PubMed

Simm, Franziska; Griesbeck, Anne; Choukair, Daniela; Weiß, Birgit; Paramasivam, Nagarajan; Klammt, Jürgen; Schlesner, Matthias; Wiemann, Stefan; Martinez, Cristina; Hoffmann, Georg F; Pfäffle, Roland W; Bettendorf, Markus; Rappold, Gudrun A

2017-10-26

PurposeCombined pituitary hormone deficiency (CPHD) is characterized by a malformed or underdeveloped pituitary gland resulting in an impaired pituitary hormone secretion. Several transcription factors have been described in its etiology, but defects in known genes account for only a small proportion of cases.MethodsTo identify novel genetic causes for congenital hypopituitarism, we performed exome-sequencing studies on 10 patients with CPHD and their unaffected parents. Two candidate genes were sequenced in further 200 patients. Genotype data of known hypopituitary genes are reviewed.ResultsWe discovered 51 likely damaging variants in 38 genes; 12 of the 51 variants represent de novo events (24%); 11 of the 38 genes (29%) were present in the E12.5/E14.5 pituitary transcriptome. Targeted sequencing of two candidate genes, SLC20A1 and SLC15A4, of the solute carrier membrane transport protein family in 200 additional patients demonstrated two further variants predicted as damaging. We also found combinations of de novo (SLC20A1/SLC15A4) and transmitted variants (GLI2/LHX3) in the same individuals, leading to the full-blown CPHD phenotype.ConclusionThese data expand the pituitary target genes repertoire for diagnostics and further functional studies. Exome sequencing has identified a combination of rare variants in different genes that might explain incomplete penetrance in CPHD.Genetics in Medicine advance online publication, 26 October 2017; doi:10.1038/gim.2017.165.

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

Maternal hormonal contraceptive use and offspring overweight or obesity.

PubMed

Jensen, E T; Daniels, J L; Stürmer, T; Robinson, W R; Williams, C J; Moster, D; Juliusson, P B; Vejrup, K; Magnus, P; Longnecker, M P

2014-10-01

Experiments in animal models have shown a positive association between in utero exposure to pharmacologic sex hormones and offspring obesity. The developmental effects of such hormones on human obesity are unknown. Using data from a large, prospective pregnancy cohort study (n=19 652), with linkage to a national prescription registry, we evaluated the association between use of hormonal contraceptives before and after conception (defined from dispensed prescription data and characterized by last date of use relative to conception, 12 to >4 months before (n=3392), 4 to >1 months before (n=2541), 1 to >0 months before (n=2997) and 0-12 weeks after (n=567)) in relation to offspring overweight or obesity at age 3 years. We observed a weak, inverse association between early pregnancy use of a combination oral contraceptive and offspring overweight or obesity at age 3 (adjusted odds ratio (OR): 0.75, 95% confidence interval (CI): 0.53, 1.08) and a positive, but imprecise, association with use of a progestin-only oral contraceptive in early pregnancy (adjusted OR: 1.26, 95% CI: 0.79, 2.02). In general, no association was observed between the use of a hormonal contraceptive before conception and offspring overweight or obesity. A sensitivity analysis comparing combination oral contraceptive users in early pregnancy to other unplanned pregnancies without hormonal contraceptive use further strengthened the inverse association (adjusted OR: 0.70, 95% CI: 0.48, 1.02). Other sensitivity analyses were conducted to evaluate the robustness of the associations observed given varying assumptions. Pharmacologic sex hormones in early pregnancy may be inversely or positively associated with offspring overweight or obesity at age 3, depending on the specific formulation used. The present study provides support for the potential for environmental sources of hormonally active agents to exert developmental effects.

Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.

PubMed

Harlid, Sophia; Butt, Salma; Ivarsson, Malin I L; Eyfjörd, Jorunn Erla; Lenner, Per; Manjer, Jonas; Dillner, Joakim; Carlson, Joyce

2012-06-22

Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT). We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model. One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction = 0.03). There were no significant interactions after correction for multiple testing. We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.

Combined effects of endogenous sex hormone levels and mammographic density on postmenopausal breast cancer risk: results from the Breakthrough Generations Study

PubMed Central

Schoemaker, M J; Folkerd, E J; Jones, M E; Rae, M; Allen, S; Ashworth, A; Dowsett, M; Swerdlow, A J

2014-01-01

Background: Mammographic density and sex hormone levels are strong risk factors for breast cancer, but it is unclear whether they represent the same aetiological entity or are independent risk factors. Methods: Within the Breakthrough Generations Study cohort, we conducted a case–control study of 265 postmenopausal breast cancer cases and 343 controls with prediagnostic mammograms and blood samples. Plasma was assayed for oestradiol, testosterone and sex hormone-binding globulin (SHBG) concentrations and mammographic density assessed by Cumulus. Results: Oestradiol and testosterone were negatively and SHBG positively associated with percentage density and absolute dense area, but after adjusting for body mass index the associations remained significant only for SHBG. Breast cancer risk was independently and significantly positively associated with percentage density (P=0.002), oestradiol (P=0.002) and testosterone (P=0.007) levels. Women in the highest tertile of both density and sex hormone level were at greatest risk, with an odds ratio of 7.81 (95% confidence interval (CI): 2.89–21.1) for oestradiol and 4.57 (95% CI: 1.75–11.9) for testosterone and high density compared with those who were in the lowest tertiles. The cumulative risk of breast cancer in the highest oestradiol and density tertiles, representing 8% of controls, was estimated as 12.8% at ages 50–69 years and 19.4% at ages 20–79 years, and in the lowest tertiles was 1.7% and 4.3%, respectively. Associations of breast cancer risk with tertiles of mammographic dense area were less strong than for percentage density. Conclusions: Endogenous sex hormone levels and mammographic density are independent risk factors for postmenopausal breast cancer, which in combination can identify women who might benefit from increased frequency of screening and chemoprophylaxis. PMID:24518596

Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones.

PubMed

Malik, Minnie; Britten, Joy; Cox, Jeris; Patel, Amrita; Catherino, William H

2016-01-01

To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy. Published by Elsevier Inc.

MECHANISMS IN ENDOCRINOLOGY: An update in the genetic aetiologies of combined pituitary hormone deficiency.

PubMed

Castinetti, Frederic; Reynaud, Rachel; Saveanu, Alexandru; Jullien, Nicolas; Quentien, Marie Helene; Rochette, Claire; Barlier, Anne; Enjalbert, Alain; Brue, Thierry

2016-06-01

Over the last 5 years, new actors involved in the pathogenesis of combined pituitary hormone deficiency in humans have been reported: they included a member of the immunoglobulin superfamily glycoprotein and ciliary G protein-coupled receptors, as well as new transcription factors and signalling molecules. New modes of inheritance for alterations of genes encoding transcription factors have also been described. Finally, actors known to be involved in a very specific phenotype (hypogonadotroph hypogonadism for instance) have been identified in a wider range of phenotypes. These data thus suggest that new mechanisms could explain the low rate of aetiological identification in this heterogeneous group of diseases. Taking into account the fact that several reviews have been published in recent years on classical aetiologies of CPHD such as mutations of POU1F1 or PROP1, we focused the present overview on the data published in the last 5 years, to provide the reader with an updated review on this rapidly evolving field of knowledge. © 2016 European Society of Endocrinology.

Growth Hormone Deficiency in the Transition Age.

PubMed

Loche, Sandro; Di Iorgi, Natascia; Patti, Giuseppa; Noli, Serena; Giaccardi, Marta; Olivieri, Irene; Ibba, Anastasia; Maghnie, Mohamad

2018-01-01

Growth hormone (GH) is essential not only for normal growth during childhood, but also for the acquisition of bone mass and muscle strength in both sexes. This process is completed after the achievement of adult height in the phase of transition from adolescence to adulthood. Adolescents with childhood onset GH deficiency (GHD) show reduction of bone mineral density, decrease in lean body mass, increase in fat mass, and deterioration of the lipid profile. For this reason, continuation of GH replacement therapy in the transition age is recommended in all patients with a confirmed diagnosis of GHD. To confirm the diagnosis of GHD, GH treatment should be discontinued for at least 1 month after the attainment of adult height, and the patient should be re-evaluated for GH secretion. Current guidelines indicate that retesting is not required for those with a transcription factor mutation, more than 3 pituitary hormone deficits, or isolated GHD associated with an identified mutation. The key predictors of persistent GHD are its severity, the presence of additional pituitary hormone deficits, low insulin-like growth factor I (IGF-I) concentration, and the presence of structural hypothalamic-pituitary abnormalities Treatment should be initiated with a low dose (0.2-0.5 mg/day s.c.) and then adjusted according to IGF-I concentrations. © 2018 S. Karger AG, Basel.

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.

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children.

PubMed

Loche, S; Carta, D; Muntoni, A C; Corda, R; Pintor, C

1993-10-01

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an i.v. bolus injection of growth hormone releasing hormone 1-29, 1 microgram/kg, significantly enhanced the growth hormone response to the neuropeptide, confirming the results of previous studies which used the i.v. route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.

Comparison of UV photolysis, nanofiltration, and their combination to remove hormones from a drinking water source and reduce endocrine disrupting activity.

PubMed

Sanches, Sandra; Rodrigues, Alexandre; Cardoso, Vitor V; Benoliel, Maria J; Crespo, João G; Pereira, Vanessa J

2016-06-01

A sequential water treatment combining low pressure ultraviolet direct photolysis with nanofiltration was evaluated to remove hormones from water, reduce endocrine disrupting activity, and overcome the drawbacks associated with the individual processes (production of a nanofiltration-concentrated retentate and formation of toxic by-products). 17β-Estradiol, 17α-ethinylestradiol, estrone, estriol, and progesterone were spiked into a real water sample collected after the sedimentation process of a drinking water treatment plant. Even though the nanofiltration process alone showed similar results to the combined treatment in terms of the water quality produced, the combined treatment offered advantage in terms of the load of the retentate and decrease in the endocrine-disrupting activity of the samples. Moreover, the photolysis by-products produced, with higher endocrine disrupting activity than the parent compounds, were effectively retained by the membrane. The combination of direct LP/UV photolysis with nanofiltration is promising for a drinking water utility that needs to cope with sudden punctual discharges or deterioration of the water quality and wants to decrease the levels of chemicals in the nanofiltration retentate.

Evolution of Hormone Signaling Networks in Plant Defense.

PubMed

Berens, Matthias L; Berry, Hannah M; Mine, Akira; Argueso, Cristiana T; Tsuda, Kenichi

2017-08-04

Studies with model plants such as Arabidopsis thaliana have revealed that phytohormones are central regulators of plant defense. The intricate network of phytohormone signaling pathways enables plants to activate appropriate and effective defense responses against pathogens as well as to balance defense and growth. The timing of the evolution of most phytohormone signaling pathways seems to coincide with the colonization of land, a likely requirement for plant adaptations to the more variable terrestrial environments, which included the presence of pathogens. In this review, we explore the evolution of defense hormone signaling networks by combining the model plant-based knowledge about molecular components mediating phytohormone signaling and cross talk with available genome information of other plant species. We highlight conserved hubs in hormone cross talk and discuss evolutionary advantages of defense hormone cross talk. Finally, we examine possibilities of engineering hormone cross talk for improvement of plant fitness and crop production.

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

PubMed

Hay, Cathy J; Brady, Brian M; Zitzmann, Michael; Osmanagaoglu, Kaan; Pollanen, Pasi; Apter, Dan; Wu, Frederick C W; Anderson, Richard A; Nieschlag, Eberhard; Devroey, Paul; Huhtaniemi, Ilpo; Kersemaekers, Wendy M

2005-04-01

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Hormonal Contraception and Risk of Psychiatric and Other Noncommunicable Diseases in HIV-Infected Women

PubMed Central

Jenkins, Cathy A.; Shepherd, Bryan E.; Bebawy, Sally S.; Turner, Megan; Sterling, Timothy R.; Melekhin, Vlada V.

2015-01-01

Abstract Background: Hormonal contraception use is common among human immunodeficiency virus (HIV)-infected women. Risk of psychiatric and other noninfectious complications of hormonal contraception use has not been described in this population. Methods: We performed a retrospective cohort study of HIV-infected women receiving care in Tennessee from 1998 to 2008 to examine the risks of incident psychiatric and other noncommunicable diseases (NCDs), including cardiovascular, hepatic, renal, and malignant diseases, and hormonal contraception use, including depot medroxyprogesterone acetate (DMPA) and combined estrogen- and progestin-containing hormonal contraceptives. We used marginal structural models with inverse probability weights to account for time-varying confounders associated with hormonal contraception use. Results: Of the 392 women included, 94 (24%) used hormonal contraception during the study period. Baseline psychiatric disease was similar between women who received and did not receive hormonal contraception. There were 69 incident psychiatric diagnoses and 72 NCDs. Only time-varying DMPA use was associated with increased risk of psychiatric disease (adjusted odds ratio [aOR] 3.70; 95% confidence interval [95% CI] 1.32–10.4) and mood disorders, specifically (aOR 4.70 [1.87–11.8]). Time-varying and cumulative combined hormonal contraception use were not statistically associated with other NCDs (aOR 1.64, 95% CI 0.64–4.12 and aOR 1.16, 95% CI 0.86–1.56, respectively). However, risk of incident NCDs was increased with cumulative DMPA exposure (per year exposure aOR 1.45, 95% CI 1.01–2.08). Conclusions: Among HIV-infected women, DMPA was associated with risk of incident psychiatric diseases, particularly mood disorders, during periods of use. Cumulative DMPA exposure was also associated with risk of other NCDs. However, combined estrogen and progestin-containing hormonal contraception use was not statistically associated with risk of any NCDs

Comparison of serum and cervical mucus hormone levels during hormone-free interval of 24/4 vs. 21/7 combined oral contraceptives.

PubMed

Fels, Heather; Steward, Rachel; Melamed, Alexander; Granat, Anna; Stanczyk, Frank Z; Mishell, Daniel R

2013-06-01

This study analyzes levels of progesterone, estradiol, norethindrone (NET) and ethinyl estradiol (EE) in serum and levels of NET in cervical mucus on the last day of the hormone-free interval (HFI) in users of 24/4 [norethindrone acetate (NETA)/EE-24] vs. 21/7 (NETA/EE-21) regimens. This was a randomized controlled, crossover, equivalency trial. Subjects were randomized to receive NETA/EE-24 or NETA/EE-21 for 2 months and then switched between study drugs. Blood and cervical mucus samples were obtained on Days 12-16 and on the last day of the HFI. From April 2010 to November 2011, 32 subjects were enrolled with 18 subjects completing all study visits. There were no statistically significant differences in either day 12-16 (p=.54) or last hormone-free day (p=.33) cervical mucus NET concentrations between the regimens. On the last day of the HFI, median serum progesterone levels did not differ significantly; however, users of NETA/EE-24 had higher levels of serum NET (p<.001) and users of NETA/EE-21 had higher levels of serum estradiol (p=.01). This data supports the fact that inhibition of the pituitary-ovarian axis occurs during oral contraceptive use and during the HFI. We demonstrated that a reduced HFI of 4 days resulted in better suppression of the ovarian hormone production, thereby reducing the risk of ovulation and potential contraceptive failure. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Efficacy and Safety of an Injectable Combination Hormonal Contraceptive for Men.

PubMed

Behre, Hermann M; Zitzmann, Michael; Anderson, Richard A; Handelsman, David J; Lestari, Silvia W; McLachlan, Robert I; Meriggiola, M Cristina; Misro, Man Mohan; Noe, Gabriela; Wu, Frederick C W; Festin, Mario Philip R; Habib, Ndema A; Vogelsong, Kirsten M; Callahan, Marianne M; Linton, Kim A; Colvard, Doug S

2016-12-01

The development of a safe and effective reversible method of male contraception is still an unmet need. Evaluation of suppression of spermatogenesis and contraceptive protection by coadministered im injections of progestogen and testosterone. Prospective multicentre study. Ten study centers. Healthy men, aged 18-45 years, and their 18- to 38-year-old female partners, both without known fertility problems. Intramuscular injections of 200-mg norethisterone enanthate combined with 1000-mg testosterone undecanoate, administered every 8 weeks. Suppression of spermatogenesis by ejaculate analysis, contraceptive protection by pregnancy rate. Of the 320 participants, 95.9 of 100 continuing users (95% confidence interval [CI], 92.8-97.9) suppressed to a sperm concentration less than or equal to 1 million/mL within 24 weeks (Kaplan-Meier method). During the efficacy phase of up to 56 weeks, 4 pregnancies occurred among the partners of the 266 male participants, with the rate of 1.57 per 100 continuing users (95% CI, 0.59-4.14). The cumulative reversibility of suppression of spermatogenesis after 52 weeks of recovery was 94.8 per 100 continuing users (95% CI, 91.5-97.1). The most common adverse events were acne, injection site pain, increased libido, and mood disorders. Following the recommendation of an external safety review committee the recruitment and hormone injections were terminated early. The study regimen led to near-complete and reversible suppression of spermatogenesis. The contraceptive efficacy was relatively good compared with other reversible methods available for men. The frequencies of mild to moderate mood disorders were relatively high.

Prioritizing equipment for replacement.

PubMed

Capuano, Mike

2010-01-01

It is suggested that clinical engineers take the lead in formulating evaluation processes to recommend equipment replacement. Their skill, knowledge, and experience, combined with access to equipment databases, make them a logical choice. Based on ideas from Fennigkoh's scheme, elements such as age, vendor support, accumulated maintenance cost, and function/risk were used.6 Other more subjective criteria such as cost benefits and efficacy of newer technology were not used. The element of downtime was also omitted due to the data element not being available. The resulting Periop Master Equipment List and its rationale was presented to the Perioperative Services Program Council. They deemed the criteria to be robust and provided overwhelming acceptance of the list. It was quickly put to use to estimate required capital funding, justify items already thought to need replacement, and identify high-priority ranked items for replacement. Incorporating prioritization criteria into an existing equipment database would be ideal. Some commercially available systems do have the basic elements of this. Maintaining replacement data can be labor-intensive regardless of the method used. There is usually little time to perform the tasks necessary for prioritizing equipment. However, where appropriate, a clinical engineering department might be able to conduct such an exercise as shown in the following case study.

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.

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.

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.

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 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.

Two coexisting heterozygous frameshift mutations in PROP1 are responsible for a different phenotype of combined pituitary hormone deficiency.

PubMed

Ziemnicka, K; Budny, B; Drobnik, K; Baszko-Błaszyk, D; Stajgis, M; Katulska, K; Waśko, R; Wrotkowska, E; Słomski, R; Ruchała, M

2016-08-01

The role of genetic background in childhood-onset combined pituitary hormone deficiency (CPHD) has been extensively studied. The major contributors are the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes coding transcription factors implicated in pituitary organogenesis. The clinical consequences of mutations encompass impaired synthesis of a growth hormone (GH) and one or more concurrent pituitary hormones (i.e. LH, FSH, TSH, PRL). Manifestation of the disorder may vary due to various mutation impacts on the final gene products or an influence of environmental factors during pituitary organogenesis. We describe the clinical and molecular characteristics of two brothers aged 47 and 39 years presenting an uncommon manifestation of congenital hypopituitarism. Sequencing of the PROP1, POU1F1, LHX3, LHX4 and HESX1 genes was performed to confirm the genetic origin of the disorder. A compound heterozygosity in the PROP1 gene has been identified for both probands. The first change represents a mutational hot spot (c.150delA, p.R53fsX164), whereas the second is a novel alteration (p.R112X) that leads to protein disruption. Based on precise genetic diagnosis, an in silico prediction of a p.R112X mutation on protein architecture was performed. The resulting clinical phenotype was surprisingly distinct compared to most patients with genetic alterations in PROP1 reported in the current literature. This may be caused by a residual activity of a newly identified p.R112X protein that preserves over 70 % of the homeodomain structure. This examination may confirm a key role of a DNA-binding homeodomain in maintaining PROP1 functionality and suggests a conceivable explanation of an unusual phenotype.

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.

Developmental analysis and influence of genetic background on the Lhx3 W227ter mouse model of combined pituitary hormone deficiency disease.

PubMed

Prince, Kelly L; Colvin, Stephanie C; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A; Rhodes, Simon J

2013-02-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3(W227ter/W227ter) mouse model. Lhx3(W227ter/W227ter) embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3(W227ter/W227ter) genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3(W227ter/W227ter) animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3(W227ter/W227ter) mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3(W227ter/W227ter) mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases.

Developmental Analysis and Influence of Genetic Background on the Lhx3 W227ter Mouse Model of Combined Pituitary Hormone Deficiency Disease

PubMed Central

Prince, Kelly L.; Colvin, Stephanie C.; Park, Soyoung; Lai, Xianyin; Witzmann, Frank A.

2013-01-01

Combined pituitary hormone deficiency (CPHD) diseases result in severe outcomes for patients including short stature, developmental delays, and reproductive deficiencies. Little is known about their etiology, especially the developmental profiles and the influences of genetic background on disease progression. Animal models for CPHD provide valuable tools to investigate disease mechanisms and inform diagnostic and treatment protocols. Here we examined hormone production during pituitary development and the influence of genetic background on phenotypic severity in the Lhx3W227ter/W227ter mouse model. Lhx3W227ter/W227ter embryos have deficiencies of ACTH, α-glycoprotein subunit, GH, PRL, TSHβ, and LHβ during prenatal development. Furthermore, mutant mice have significant reduction in the critical pituitary transcriptional activator-1 (PIT1). Through breeding, the Lhx3W227ter/W227ter genotype was placed onto the 129/Sv and C57BL/6 backgrounds. Intriguingly, the genetic background significantly affected viability: whereas Lhx3W227ter/W227ter animals were found in the expected frequencies in C57BL/6, homozygous animals were not viable in the 129/Sv genetic environment. The hormone marker and PIT1 reductions observed in Lhx3W227ter/W227ter mice on a mixed background were also seen in the separate strains but in some cases were more severe in 129/Sv. To further characterize the molecular changes in diseased mice, we conducted a quantitative proteomic analysis of pituitary proteins. This showed significantly lower levels of PRL, pro-opiomelanocortin (ACTH), and α-glycoprotein subunit proteins in Lhx3W227ter/W227ter mice. Together, these data show that hormone deficiency disease is apparent in early prenatal stages in this CPHD model system. Furthermore, as is noted in human disease, genetic background significantly impacts the phenotypic outcome of these monogenic endocrine diseases. PMID:23288907

Hormonal induction of spawning in 4 species of frogs by coinjection with a gonadotropin-releasing hormone agonist and a dopamine antagonist

PubMed Central

2010-01-01

Background It is well known that many anurans do not reproduce easily in captivity. Some methods are based on administration of mammalian hormones such as human chorionic gonadotropin, which are not effective in many frogs. There is a need for simple, cost-effective alternative techniques to induce spawning. Methods Our new method is based on the injection of a combination of a gonadotropin-releasing hormone (GnRH) agonist and a dopamine antagonist. We have named this formulation AMPHIPLEX, which is derived from the combination of the words amphibian and amplexus. This name refers to the specific reproductive behavior of frogs when the male mounts and clasps the female to induce ovulation and to fertilize the eggs as they are laid. Results We describe the use of the method and demonstrate its applicability for captive breeding in 3 different anuran families. We tested several combinations of GnRH agonists with dopamine antagonists using Lithobates pipiens. The combination of des-Gly10, D-Ala6, Pro-LHRH (0.4 microrams/g body weight) and metoclopramide (10 micrograms/g BWt. MET) was most effective. It was used in-season, after short-term captivity and in frogs artificially hibernated under laboratory conditions. The AMPHIPLEX method was also effective in 3 Argentinian frogs, Ceratophrys ornata, Ceratophrys cranwelli and Odontophrynus americanus. Conclusion Our approach offers some advantages over other hormonally-based techniques. Both sexes are injected only once and at the same time, reducing handling stress. AMPHIPLEX is a new reproductive management tool for captive breeding in Anura. PMID:20398399

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.

Pituitary Microsomal Autoantibodies in Patients with Childhood-Onset Combined Pituitary Hormone Deficiency: an Antigen Identification Attempt.

PubMed

Ziemnicka, Katarzyna; Gut, Paweł; Gołąb, Monika; Dworacki, Grzegorz; Wrotkowska, Elżbieta; Stajgis, Marek; Katulska, Katarzyna; Rabska-Pietrzak, Barbara; Obara-Moszyńska, Monika; Niedziela, Marek; Budny, Bartłomiej; Kałużna, Małgorzata; Waśko, Ryszard; Ruchała, Marek

2016-12-01

The role of autoimmunization in the pathogenesis of pituitary disorders is poorly understood. The presence of pituitary autoantibodies (APA) has been detected in various pituitary disorders. Their role, however, remains elusive. Childhood-onset combined pituitary hormone deficiency (CPHD) may be caused by environmental or genetic factors. In some of patients, causes of the disease remain unclear and contributions of autoimmune processes have been postulated. The aim of this study was to identify the microsomes-derived pituitary antigens (MPA) as potential immunogenic autoantigens in patients with hypopituitarism, therefore 62 CPHD patients, 100 healthy controls and five autoimmune polyglandular syndrome type II (APS II) patients were included in the study. The clinical evaluation included hormonal tests and magnetic resonance imaging of the pituitary. The sources of MPA were pituitary glands taken from autopsies. Isolated MPA were then separated on SDS-PAGE gel and incubated with sera obtained from patients and controls. Microsomal APA were detected using Western blot and radioimmunological method. In all CPHD and APS II patients and in 9 % individuals from control group marked immunoreactivity was detected against MPA. Antibodies showed high affinity to 67, 60, 50 and 36 kDa MPAs. Since the identified autoantigens were of unknown nature, an in silico exploration of UniProt database was applied and indicated their possible relationship with chaperones, golgins and already known autoantigens like GAD67. Reactivity against MPA indicates that these proteins certainly play a role in the processes undergoing within pituitary of CPHD patients. The identification and further detailed studies on their role in the pathogenesis of CPHD should be continued.

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.

Metabolic and cardiovascular outcomes in a group of adult patients with Turner's syndrome under hormonal replacement therapy.

PubMed

Giordano, Roberta; Forno, Daniela; Lanfranco, Fabio; Manieri, Chiara; Ghizzoni, Lucia; Ghigo, Ezio

2011-05-01

Turner's syndrome (TS) is a rare genetic disorder caused by complete or partial X chromosome monosomy in a phenotypic female, and it is associated with increased morbidity and mortality for cardiovascular diseases, impaired glucose tolerance, and dyslipidemia. In 30 adult TS patients under chronic hormonal replacement therapy (HRT), 17β-estradiol (E(2)), body mass index (BMI), waist circumference, fasting glucose and insulin, homeostatic model assessment (HOMA) index, serum lipids, oral glucose tolerance test (OGTT), 24 h ambulatory blood pressure monitoring (ABPM), and intima-media thickness (IMT) were evaluated and compared with those in 30 age- and sex-matched controls (CS). No difference was found between TS and CS in E(2) and BMI, whereas waist circumference was higher (P<0.05) in TS (77.7±2.5 cm) than in CS (69.8±1.0 cm). Fasting glucose in TS and in CS was similar, whereas fasting insulin, HOMA index, and 2 h glucose after OGTT were higher (P<0.0005) in TS (13.2±0.8 mUI/l, 2.5±0.2, and 108.9±5.5 mg/dl respectively) than in CS (9.1±0.5 mUI/l, 1.8±0.1, and 94.5 ± 3.8 mg/dl respectively). Total cholesterol was higher (P<0.05) in TS (199.4 ± 6.6 mg/dl) than in CS (173.9±4.6 mg/dl), whereas no significant differences in high-density lipoprotein, low-density lipoprotein, and triglycerides were found between the two groups. In 13% of TS, ABPM showed arterial hypertension, whereas IMT was <0.9 mm in all TS and CS. A negative correlation between insulin levels, HOMA index, or 2 h glucose after OGTT and E(2) was present in TS. Our results indicate that adult patients with TS under HRT are connoted by higher frequency of central obesity, insulin resistance, hypercholesterolemia, and hypertension.

Growth, development, puberty and adult height of patients with congenital multiple pituitary hormone deficiencies.

PubMed

Haim-Pinhas, Hadar; Kauli, Rivka; Lilos, Pearl; Laron, Zvi

2016-04-01

Congenital MPHD is a rare condition caused by mutations in pituitary transcription factors genes: PROP1, POU1F1 (PIT1), HESX1, LHX3, LHX4. We evaluated in a retrospective study the effects on growth and development in 29 patients with congenital MPHD (cMPHD), during hGH replacement therapy alone and combined with sex hormones. Twenty nine patients with cMPHD were included and diagnosed, treated and followed in our clinic from diagnosis to adult age. Measurements on growth and development were taken by the same medical team. Mean birth weight of 21/29 neonates was 3126 ± 536 g. Mean birth length of 7/29 neonates was 48.7 ± 2 cm. Neuromotor development was normal or slightly delayed. Mean age at referral was 9.5 ± 7 years (m), 6.7 ± 3.5 years (f) (p=0.17). Height (SDS) before treatment was -2.8 ± 1.0 (m), -2.8 ± 1.0 (f) (p=0.99). Mean age at initiation of hGH treatment was 9.9 ± 6.7 years (m), 10.3 ± 4.2 years (f) (p=0.85). Mean age at initiation of sex hormone treatment was 17.0 ± 3.5 years (m), 17.1 ± 2.3 years (f) (p=0.88). Penile and testicular sizes were below normal before and after treatment. Head circumference (SD) was -1.9 ± 0.9 before and -0.6 ± 1.8 at end of treatment (p<0.001). Adult height (SDS) reached -1.1 ± 0.6 (p<0.001) for both males and females. Despite the multiple pituitary hormone deficiencies including hGH, children with congenital MPHD present with a better auxological development than children with congenital IGHD or congenital IGF-1 deficiency. These findings may be due to irregular and incomplete hormone deficiencies increasing with progressive age and late initiation of puberty. Copyright © 2016. Published by Elsevier Ltd.

Lifetime hormonal factors may predict late-life depression in women

PubMed Central

Ryan, Joanne; Carrière, Isabelle; Scali, Jacqueline; Ritchie, Karen; Ancelin, Marie-Laure

2008-01-01

Background Fluctuating hormone levels are known to influence a woman’s mood and well-being. This study aimed to determine whether lifetime hormonal markers are associated with late-life depression symptoms among elderly community-dwelling women. Method Detailed reproductive histories of 1013 women aged 65 years and over were obtained using questionnaires and depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale. Multivariate logistic regression models were generated to determine whether any lifetime endogenous or exogenous hormonal factors were associated with late-life depression. Results The prevalence of depressive symptoms was 17%. Age at menopause was associated with depressive symptoms, but only among women with a lower education level. For these women, an earlier age at menopause increased their risk of late-life depression (linear effect, OR=0.95, 95%CI: 0.91–0.99). The odds of late-life depression were also increased for women who were past (OR=1.6, 95%CI: 1.1–2.5), but not current hormonal replacement users. On the other hand, long-term oral contraceptive use (≥10 years) was protective against depression (OR=0.3, 95%CI: 0.1–0.9). These associations remained significant even after extensive adjustment for a range of potential confounding factors, including socio-demographic factors, mental and physical incapacities, antidepressant use and past depression. The other factors examined, including age at first menses, parity, age at childbirth and surgical menopause, were not associated with late-life depressive symptoms. Conclusions Lifetime hormonal factors that are significantly associated with depression symptoms in later life have been identified. Further work is needed to determine how potential hormonal interventions could be used in the treatment of late-life depression in certain sub-groups of women. PMID:18533067

Effects of combined stress during intense training on cellular immunity, hormones and respiratory infections.

PubMed

Gomez-Merino, Danielle; Drogou, Catherine; Chennaoui, Mounir; Tiollier, Eve; Mathieu, Jacques; Guezennec, Charles Yannick

2005-01-01

This study was designed to determine immune and hormonal changes and their relationship with the incidence of upper respiratory tract infections (URTIs) during an extremely stressful military training (3 weeks of physical conditioning followed by a 5-day combat course with energy restriction, sleep deprivation and psychological stress). Blood samples were collected from 21 cadets (21 +/- 2 years old) before training and after the combat course for analysis of leukocyte and lymphocyte subpopulations, serum cytokines [interleukin-6 (IL-6), IL-1beta and IL-10], and hormones [catecholamines, cortisol, leptin, total insulin-like growth factor I (IGF-I), prolactin, dehydroepiandrosterone sulfate (DHEAS) and testosterone]. Symptoms of URTI were recorded from health logs and medical examinations during training. After the combat course, total leukocyte and neutrophil counts were significantly increased while total lymphocytes were unchanged. In lymphocyte subsets, NK cells were reduced (p < 0.01), while CD4+ and CD19+ (B) cells were increased. Levels of IL-6 were increased (p < 0.01), while those of IL-1beta and IL-10 were unchanged. Norepinephrine and dopamine levels were increased, while those of cortisol were reduced. Levels of leptin, testosterone, prolactin and total IGF-I were reduced, while those of DHEAS were increased. The incidence of URTI increased during the training (chi(2) = 53.48, p < 0.05). After training data analysis showed a significant correlation between URTIs and NK cells (p = 0.0023). Training-induced changes in immune and hormonal parameters were correlated. Blood NK cell levels are related to increased respiratory infections during physical training in a multistressor environment. The training-induced decreases in immunostimulatory hormone levels may have triggered immunosuppression. Copyright (c) 2005 S. Karger AG, Basel.

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

Physicochemical properties of low sodium frankfurter with added walnut: effect of transglutaminase combined with caseinate, KCl and dietary fibre as salt replacers.

PubMed

Colmenero, F Jiménez; Ayo, M J; Carballo, J

2005-04-01

This study compares the effects of combinations of microbial transglutaminase (TGase) and various non-meat ingredients (caseinate, KCl and wheat fibre) used as salt replacers, with the effects of NaCl on the physicochemical properties (cooking loss, emulsion stability, texture and colour) of frankfurters with added walnuts. The combination of TGase with caseinate, KCl or fibre led to harder, springier and chewier (P<0.05) frankfurters with better water- and fat-binding properties (emulsion stability and cooking loss) (P<0.05) than those made with TGase only. Ranking of ingredient efficiency in combination with TGase showed that caseinate>KCl>fibre. Frankfurters with caseinate presented the highest lightness and the lowest redness values. Frankfurter with NaCl had a harder, springier and chewier gel/emulsion network with lower cooking loss than those NaCl free.

Electrodiagnostic studies in presumptive primary hypothyroidism and polyneuropathy in dogs with reevaluation during hormone replacement therapy.

PubMed

Giza, Elżbieta Gabriela; Płonek, Marta; Nicpoń, Józef Marian; Wrzosek, Marcin Adam

2016-05-21

Peripheral neuropathy is the most common neurological manifestation of canine hypothyroidism. Data concerning electrodiagnostic studies in hypothyroid associated polyneuropathy in dogs are very limited and usually lack a reevaluation after hormone replacement therapy. The objective of this study was to perform a detailed, retrospective analysis of electromyographic (EMG), motor nerve conduction velocity (MNCV), F-wave and brainstem auditory evoked response (BAER) findings in 24 dogs with presumptive primary hypothyroidism and polyneuropathy with a comparison of the results before and after initiation of levothyroxine treatment with the assessment of the clinical outcome. The results obtained from hypothyroid dogs showed a significant reduction in MNCV at a proximal-distal and middle-distal stimulation, decreased amplitudes of compound muscle action potentials (CMAP), an increased CMAP duration and a prolonged distal latency prior to treatment. Fifty percent of the dogs had an increased F-wave latency. A normal BAER recording was found in 78 % of the hypothyroid patients without vestibular impairment. Bilaterally increased peak V latencies and increased interpeak I-V latencies were found in the remaining individuals. Dogs with concurrent vestibular impairment had ipsilaterally increased peak latencies with normal interpeak latencies and decreased amplitudes of wave I and II. A comparison of the findings before and after 2 months of treatment revealed a decrease in the pathological activity on EMG, an improvement of proximal, middle and distal CMAP amplitudes and an increase in the proximal-distal conduction velocity in all dogs. F-wave latency improved in 38 % of dogs. The BAER reexamination revealed a persistent prolongation of peak I, II, III and V latencies and decreased wave I amplitude on the affected side in all dogs manifesting vestibular signs. Conversely, in dogs without vestibular signs, the peak V and interpeak I-V latencies decreased to normal values

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

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.

Obesity and hormonal contraceptive efficacy.

PubMed

Robinson, Jennifer A; Burke, Anne E

2013-09-01

Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.

Hormone Therapy Improves Femur Geometry Among Ethnically Diverse Postmenopausal Participants in the Women's Health Initiative Hormone Intervention Trials

PubMed Central

Chen, Zhao; Beck, Thomas J; Cauley, Jane A; Lewis, Cora E; LaCroix, Andrea; Bassford, Tamsen; Wu, Guanglin; Sherrill, Duane; Going, Scott

2008-01-01

Loss of bone strength underlies osteoporotic fragility fractures. We hypothesized that hormone interventions significantly improve the structural geometry of proximal femur cross-sections. Study participants were from the Women's Health Initiative hormone intervention trials: either the conjugated equine estrogen (CEE) only (N placebo = 447, N CEE = 422) trial or the estrogen (E) plus progestin (P) (N placebo = 441, N E+P = 503) trial, who were 50–79 yr old at baseline and were followed up to 6 yr. BMD scans by DXA were conducted at baseline, year 1, year 3, and year 6. Femur geometry was derived from hip DXA scans using the hip structural analysis (HSA) method. Mixed effects models with the intent-to-treat analysis approach were used. There were no significant differences in treatment effects between the E-alone and the E + P trial, so the analyses were conducted with participants combined from both trials. Treatment benefits (p < 0.05) on femur geometry were observed as early as 1 yr after the intervention. From baseline to year 6, section modulus (a measure of maximum bending stress) was preserved, and buckling ratio (an index of cortical instability under compression) was reduced by hormone interventions (p < 0.05); the differences in the percent changes from baseline to year 6 between women on hormone intervention versus women on placebo were 2.3–3.6% for section modulus and –5.3% to – 4.3% for buckling ratio. Hormone interventions led to favorable changes in femur geometry, which may help explain the reduced fracture risk observed in hormone interventions. PMID:18665788

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

PubMed

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

2001-12-01

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

Combined modified en bloc corpectomy with replacement of the aorta in curative interdisciplinary treatment of a large osteosarcoma infiltrating the aorta.

PubMed

Pilger, Amrei; Tsilimparis, Nikolaos; Bockhorn, Maximilian; Trepel, Martin; Dreimann, Marc

2016-05-01

We report a case of a large three-level spinal osteosarcoma infiltrating the adjacent aorta. This is the first case in which a combined modified three-level en bloc corpectomy with resection and replacement of the adjacent aorta was successful as a part of interdisciplinary curative treatment. Case report. The surgical procedure was performed as a two-step treatment. A heart lung machine (HLM) was not used, in order to avoid cerebral and spinal ischemia and to decrease the risk of hematogenous tumor metastases. Instead, a bypass from the left subclavian artery the distal descending aorta was used. We modified the en bloc corpectomy procedure, leaving a dorsal segment of the vertebral bodies to enable rapid surgery. The procedure was successful and the en bloc resection of the vertebral body with aortal resection could be achieved. Except for pallhypesthesia in the left dermatomes Th7-Th10, the patient does not have any postoperative neurologic deficits. Combined corpectomy with aortic replacement should be considered as a reasonable option in the curative treatment of osteosarcoma with consideration of the immense surgical risks. The use of an HLM is not necessary, especially considering the inherent risk of hematogenous tumor metastases. Modified corpectomy leaving a dorsal vertebral body segment was considered a reasonable variation since tumor-free margins could still be expected.

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.

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.

[Combined hormonal contraception in cycles artificially extended].

PubMed

Bustillos-Alamilla, Edgardo; Zepeda-Zaragoza, J; Hernández-Ruiz, M A; Briones-Landa, Carlos Humberto

2010-01-01

To compare the bleeding patterns, satisfaction and tolerability of 3 different contraceptive in an extended regimens in the service of Family Planning of the North Central Hospital of PEMEX. Healthy, adult women with desire of contraception for one year (N 120) were randomly assigned to receive oral contraceptive drospirenone/ethinyl E2 (group1), the norelgestromin/ethinyl E2 transdermal patch (group 2) and vaginal ring etonogestrel/ ethinyl E2 (group 3) in an extended regimen (42 consecutive days, 1 hormone-free week). Study assessments were conducted at scheduled visits at the time of initial screening, at baseline after 1, 3, 6, and 12 months. Subjects recorded menstrual associated symptoms bleeding data and completed satisfaction questionnaires. Subjects and investigators provided overall assessments of the regimens. Extended use of 3 different contraceptive resulted in fewer bleeding days in every group (66.6%, 55% and 58.3% P 0.0024), and less mastalgia and menstrual pain. Subjects were highly satisfied with three regimens (93.3%, 96.6% and 91.6% P 0.00421). Although not mayor adverse events were reported with this regimen, there was an increase in spotting days; it decreased with each successive cycle of therapy. Efficacy and safety were similar to those reported for traditional cycle. Extended-contraceptive regimen delays menses and reduces bleeding, a profile that may be preferred by women who seek flexibility with their contraceptive method.

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

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

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.

Hormones

MedlinePlus

Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

Potentiation of cytotoxic chemotherapy by growth hormone-releasing hormone agonists.

PubMed

Jaszberenyi, Miklos; Rick, Ferenc G; Popovics, Petra; Block, Norman L; Zarandi, Marta; Cai, Ren-Zhi; Vidaurre, Irving; Szalontay, Luca; Jayakumar, Arumugam R; Schally, Andrew V

2014-01-14

The dismal prognosis of malignant brain tumors drives the development of new treatment modalities. In view of the multiple activities of growth hormone-releasing hormone (GHRH), we hypothesized that pretreatment with a GHRH agonist, JI-34, might increase the susceptibility of U-87 MG glioblastoma multiforme (GBM) cells to subsequent treatment with the cytotoxic drug, doxorubicin (DOX). This concept was corroborated by our findings, in vivo, showing that the combination of the GHRH agonist, JI-34, and DOX inhibited the growth of GBM tumors, transplanted into nude mice, more than DOX alone. In vitro, the pretreatment of GBM cells with JI-34 potentiated inhibitory effects of DOX on cell proliferation, diminished cell size and viability, and promoted apoptotic processes, as shown by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide proliferation assay, ApoLive-Glo multiplex assay, and cell volumetric assay. Proteomic studies further revealed that the pretreatment with GHRH agonist evoked differentiation decreasing the expression of the neuroectodermal stem cell antigen, nestin, and up-regulating the glial maturation marker, GFAP. The GHRH agonist also reduced the release of humoral regulators of glial growth, such as FGF basic and TGFβ. Proteomic and gene-expression (RT-PCR) studies confirmed the strong proapoptotic activity (increase in p53, decrease in v-myc and Bcl-2) and anti-invasive potential (decrease in integrin α3) of the combination of GHRH agonist and DOX. These findings indicate that the GHRH agonists can potentiate the anticancer activity of the traditional chemotherapeutic drug, DOX, by multiple mechanisms including the induction of differentiation of cancer cells.

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.

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.

[Cox/maze III procedure combined with mitral valve replacement in treatment of rheumatic mitral valve disease with atrial fibrilation].

PubMed

Chen, Rukun; Wang, Yongqing; Chen, Yongbing; Chen, Suocheng

2002-06-25

To compare the curative effect of Cox/maze III procedure combined with mitral replacement and that of mitral valve replacement (MVR). Fifty-six patients suffering from rheumatic heart disease with atrial fibrillation (AF) were treated by Cox/maze III procedure combined with MVR (maze group). Another 56 age, sex, and heart function-matched patients with the same diagnosis underwent MVR alone during the same period. Warfarin was administered after operation in both groups. Comparison of operative complication and curative effects was made. The aortic cross-clamp time and cardio pulmonary bypass time (CPB) were longer in maze group than in MVT group (75 +/- 22 min vs 41 +/- 11 min, P < 0.05 and 124 +/- 40 min VS 68 +/- 19 min, P < 0.05). Bleeding happened after the heart reatored beating in 2 patients in maze group and in one patient in MVT group, all these 3 patients responding satisfactorily to hemostasis. The early post-operative mortality was 1.79% (1/56) in both groups. In maze group, AF disappeared in all patients but one who had node rhythm. Normal sinus rhythm was restored in 98.18% of the patients (54/55). Atrial contractility was restored in all patients with sinus rhythm. One year after operation, 98.18% patients' cardiac function changed to grade and 1.82% changed to grade II. In MVR group AF disappeared after operation temporarily for 24 hours in 7 patients and re-appeared, and AF disappeared in one patients for 2 years so far. One year after operation, the cardiac function of 94.6% patients in MVR group changed to grade I, of 3.6% patients to grade II, and of 1.8% patients to grade III. No serious hemorrhage relate d to anticoagulant therapy happened. One patient in MVR group suffered from hemiplegia due to cerebral embolism. The late mortality was 1.8% on maze group amd 3.6% in MVR group. Cox/maze III procedure combined with NVR is safe and effective in treating rheumatic heart disease with AF.

A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo

PubMed Central

Machado, Danielle S.; Sabet, Amin; Santiago, Leticia A.; Sidhaye, Aniket R.; Chiamolera, Maria I.; Ortiga-Carvalho, Tania M.; Wondisford, Fredric E.

2009-01-01

Resistance to thyroid hormone (RTH) is most often due to point mutations in the β-isoform of the thyroid hormone (TH) receptor (TR-β). The majority of mutations involve the ligand-binding domain, where they block TH binding and receptor function on both stimulatory and inhibitory TH response elements. In contrast, a few mutations in the ligand-binding domain are reported to maintain TH binding and yet cause RTH in certain tissues. We introduced one such naturally occurring human RTH mutation (R429Q) into the germline of mice at the TR-β locus. R429Q knock-in (KI) mice demonstrated elevated serum TH and inappropriately normal thyroid-stimulating hormone (TSH) levels, consistent with hypothalamic–pituitary RTH. In contrast, 3 hepatic genes positively regulated by TH (Dio1, Gpd1, and Thrsp) were increased in R429Q KI animals. Mice were then rendered hypothyroid, followed by graded T3 replacement. Hypothyroid R429Q KI mice displayed elevated TSH subunit mRNA levels, and T3 treatment failed to normally suppress these levels. T3 treatment, however, stimulated pituitary Gh levels to a greater degree in R429Q KI than in control mice. Gsta, a hepatic gene negatively regulated by TH, was not suppressed in R429Q KI mice after T3 treatment, but hepatic Dio1 and Thrsp mRNA levels increased in response to TH. Cardiac myosin heavy chain isoform gene expression also showed a specific defect in TH inhibition. In summary, the R429Q mutation is associated with selective impairment of TH-mediated gene repression, suggesting that the affected domain, necessary for TR homodimerization and corepressor binding, has a critical role in negative gene regulation by TH. PMID:19439650

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

Trends in thyroid hormone prescribing and consumption in the UK

PubMed Central

Mitchell, Anna L; Hickey, Bryan; Hickey, Janis L; Pearce, Simon HS

2009-01-01

Background Thyroid hormone replacement is one of the most commonly prescribed and cost effective treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications. This study aimed to provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine. Methods Data on community prescriptions for thyroid hormones in England between 1998 and 2007, provided by the Department of Health, were collated and analysed. A survey of UK members of a patient support organisation (the British Thyroid Foundation) who were taking levothyroxine was carried out. Results The amount of prescribed thyroid hormones used in England has more than doubled, from 7 to almost 19 million prescriptions, over the last 10 years. The duration of prescriptions has reduced from 60 to 45 days, on average over the same time. Two thousand five hundred and fifty one responses to the patient survey were received. Thirty eight percent of levothyroxine users reported receiving prescriptions of 28 days' duration. 59% of respondents reported being dissatisfied with 28-day prescribing. Conclusion Amongst users of levothyroxine, there is widespread patient dissatisfaction with 28-day prescription duration. Analysis of the full costs of 28-day dispensing balanced against the potential savings of reduced wastage of thyroid medications, suggests that this is unlikely to be an economically effective public health policy. PMID:19432950

[Medical treatment of endometriosis: Hormonal treatment of pain, impact on evolution and future perspectives].

PubMed

Geoffron, Sophie; Legendre, Guillaume; Daraï, Emile; Chabbert-Buffet, Nathalie

2017-12-01

Endometriosis is a chronic painful disease, for which hormone therapy is usually offered as a first line option to women not willing to conceive. To analyse and synthesize the literature, from 2006 onwards, on pain control, and disease evolution in oemn using combined hormonal contraceptives, progestins and GnRH analogs. Data on other current and future treatment perspectives is included as well. Medline (Pubmed), the Cochrane Library, and endometriosis treatment recommendations published by European Society of Human Reproduction and Embryology (ESHRE), National Institute for health and Care Excellence (NICE), American College of Obstetricians and Gynecologists (ACOG), Royal College of Obstetricians and Gynaecologists (RCOG) and Société des Obstétriciens et Gynécologues du Canada (SOGC). Meta-analysis and clinical trials are included. Study quality is heterogeneous in general. Hormone therapy inconstantly allows pain relief and prevention of endometrioma and rectovaginal wall nodules recurrence. Available molecules and routes of administration as well as risk benefit balance are evaluated. Data on future perspectives are limited to date and do not allow use in routine. Hormonal treatment of endometriosis relies on combined hormonal contraceptives (using different routes of administration), progestins and particularly the levonorgestrel-releasing IUS, and GnRH analogs as a last option, in combination with an add-back therapy. Promising alternatives are currently under preclinical and clinical evaluation. Copyright © 2017. Published by Elsevier Masson SAS.

Can anti-Mullerian hormone replace ultrasonographic evaluation in polycystic ovary syndrome? A review of current progress

PubMed Central

Singh, Awadhesh Kumar; Singh, Ritu

2015-01-01

Several studies over the past decade have now consistently indicated that the serum anti-Mullerian hormone (AMH) levels are at least 2–3-fold higher in the patients with polycystic ovary syndrome (PCOS), which also corresponds to the increased number of AMH producing preantral and small antral follicles. Moreover, AMH levels have been found to be associated in direct proportion to the follicle numbers per ovary or antral follicular count, assessed by the transvaginal ultrasound (TVS). Furthermore, AMH correlates directly with the rising serum testosterone and luteinizing hormone levels in PCOS. Hence, serum AMH in women with oligo-anovulation and/or hyperandrogenemia could indicate the presence of underlying PCOS, when reliable TVS is not feasible, or not acceptable, either due to the virginal status or psycho-social issue. In addition, the imaging quality of abdominal ultrasound is often impaired by obesity, which typically occurs in PCOS women. Indeed, PCOS occurs most commonly in young females who cannot be subjected to invasive TVS for various reasons; therefore, a desirable alternative to TVS is urgently required to diagnose the most prevalent endocrine abnormality of young women. This review will analyze the currently available evidence regarding the role of AMH in the diagnosis of PCOS. PMID:26693422

The Effects of Hormonal Contraception on the Voice: History of Its Evolution in the Literature.

PubMed

Rodney, Jennifer P; Sataloff, Robert Thayer

2016-11-01

Women of reproductive age commonly use hormonal contraceptives, the vocal effects of which have been studied. Otolaryngologists should be aware of this relationship to make recommendations on hormonal contraception as it relates to each patient's voice requirements. A comprehensive literature review of PubMed was completed. The terms "contraception," "vocal folds," "vocal cords," and "voice" were searched in various combinations. Articles from 1971 to 2015 that addressed the effects of contraception on the vocal folds were included. In total, 24 articles were available for review. Historically, contraception was believed to affect the voice negatively. However, more recent studies using low-dose oral contraceptive pills (OCPs) show that they stabilize the voice. However, stabilization generally occurs only during sustained vowel production; connected speech appears unaffected. Therefore, singers may be the only population that experiences clinically increased vocal stability as a result of taking hormonal contraceptives. Only combined OCPs have been studied; other forms of hormonal contraception have not been evaluated for effects on the voice. Significant variability exists between studies in the physical attributes of patients and parameters tested. Hormonal contraception likely has no clinically perceptible effects on the speaking voice. Singers may experience increased vocal stability with low-dose, combined OCP use. Other available forms of contraception have not been studied. Greater consistency in methodology is needed in future research, and other forms of hormonal contraception require study. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Takotsubo Cardiomyopathy Associated with Levothyroxine Over-replacement.

PubMed

Balsa, Ana Margarida; Ferreira, Ana Raquel; Alves, Márcia; Guimarães, Joana

2017-04-01

Takotsubo cardiomyopathy (TC) is characterised by acute, transient left ventricular apical ballooning precipitated by emotional or physiologically stressful stimuli and has been previously associated with Grave's disease based on a few clinical reports. More recently, the association with exogenous thyrotoxicosis and radioiodine-induced thyroiditis has also been described. Iatrogenic hyperthyroidism on patients on levothyroxine replacement therapy for hypothyroidism has not been reported as a cause of TC. The authors describe two female patients with TC associated with levothyroxine over-replacement. A 74-year-old and a 48-year-old female patient, medicated with levothyroxine (respectively, 2.27 μg/kg and 1.85 μg/kg) for autoimmune thyroiditis were admitted to our emergency room with precordial pain. The first had an electrocardiogram with ST-segment elevation in the anterior precordial leads, and the latter had sinus tachycardia with deep T-wave inversion and QT interval prolongation. Further investigation revealed a mild elevation of cardiac biomarker levels and severe apical hypokinesis, but no significant coronary lesions on catheterisation. The suppressed thyroid stimulating hormone (TSH) levels were verified in the cardiac intensive care unit: 0.21 and 0.07 mIU/l (0.35-5.50) respectively. Both patients showed improvement of the apical hypokinesis on the discharge echocardiogram and normalisation of cardiac biomarker levels. Levothyroxine dose was reduced. This case report focuses on the cardiovascular risks of thyrotoxicosis, emphasises the importance of correct dose adjustment on patients under levothyroxine replacement therapy and stresses that TSH should be determined in patients presenting with acute coronary syndrome and typical findings of TC.

Mathematical Modeling and Optimizing of in Vitro Hormonal Combination for G × N15 Vegetative Rootstock Proliferation Using Artificial Neural Network-Genetic Algorithm (ANN-GA)

PubMed Central

Arab, Mohammad M.; Yadollahi, Abbas; Ahmadi, Hamed; Eftekhari, Maliheh; Maleki, Masoud

2017-01-01

The efficiency of a hybrid systems method which combined artificial neural networks (ANNs) as a modeling tool and genetic algorithms (GAs) as an optimizing method for input variables used in ANN modeling was assessed. Hence, as a new technique, it was applied for the prediction and optimization of the plant hormones concentrations and combinations for in vitro proliferation of Garnem (G × N15) rootstock as a case study. Optimizing hormones combination was surveyed by modeling the effects of various concentrations of cytokinin–auxin, i.e., BAP, KIN, TDZ, IBA, and NAA combinations (inputs) on four growth parameters (outputs), i.e., micro-shoots number per explant, length of micro-shoots, developed callus weight (CW) and the quality index (QI) of plantlets. Calculation of statistical values such as R2 (coefficient of determination) related to the accuracy of ANN-GA models showed a considerably higher prediction accuracy for ANN models, i.e., micro-shoots number: R2 = 0.81, length of micro-shoots: R2 = 0.87, CW: R2 = 0.88, QI: R2 = 0.87. According to the results, among the input variables, BAP (19.3), KIN (9.64), and IBA (2.63) showed the highest values of variable sensitivity ratio for proliferation rate. The GA showed that media containing 1.02 mg/l BAP in combination with 0.098 mg/l IBA could lead to the optimal proliferation rate (10.53) for G × N15 rootstock. Another objective of the present study was to compare the performance of predicted and optimized cytokinin–auxin combination with the best optimized obtained concentrations of our other experiments. Considering three growth parameters (length of micro-shoots, micro-shoots number, and proliferation rate), the last treatment was found to be superior to the rest of treatments for G × N15 rootstock in vitro multiplication. Very little difference between the ANN predicted and experimental data confirmed high capability of ANN-GA method in predicting new optimized protocols for plant in vitro propagation

Combination of continuous renal replacement therapies (CRRT) and extracorporeal membrane oxygenation (ECMO) for advanced cardiac patients.

PubMed

Yap, Hon-Jek; Chen, Yung-Chang; Fang, Ji-Tseng; Huang, Chiu-Ching

2003-03-01

The critically ill patients may require mechanical ventilation, cardiac mechanical support, and other types of critical support. Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, which provides good cardiopulmonary and end-organ support. Continuous renal replacement therapies (CRRT) exhibit important advantages in terms of clinical tolerance and blood purification. This investigation aims to evaluate the acute renal failure in cardiac patients under ECMO, and assess the effect of combining these two technologies, ECMO and CRRT. Between December 1998 and June 2001, 10 adult cardiac patients were treated on ECMO. Five of them were treated with both ECMO and CRRT. The clinical outcomes were retrospectively analyzed. Of the 10 patients studied, five were men and five were women. The mean age of survivors and non-survivors was 37.00 +/- 14.54 years and 46.17 +/- 7.41 years, respectively. The overall mortality rate was 60%. Survivors did not differ significantly from non-survivors in age or gender. The APACHE II scores on the first day of ECMO support between survival and non-survival were 19.00 +/- 9.38 and 24.67 +/- 3.50 (P value = 0.392) (Table 2), which demonstrates no significant differences too. The cause of death in most patients was related to organ system failure during the 24 h immediately before ECMO started. Five patients with acute renal failure treated by CRRT were eventually died. The median and mean survival in this group on CRRT was 40.50 +/- 18.07 h and 92.60 +/- 60.50 h. We conclude that mortality rate for acute renal failure in cardiac patients under ECMO continues to be high. Our data suggest that acute renal failure is generally a part of multiorgan failure. This unique form of acute renal failure, causes generalized edema and fluid overload despite still low serum creatinine and azotemia, and deteriorates rapidly to death. From this study shows, advanced cardiac failure may need more aggressive and early initiation of ECMO support

Pulsatile GnRH Therapy May Restore Hypothalamus-Pituitary-Testis Axis Function in Patients With Congenital Combined Pituitary Hormone Deficiency: A Prospective, Self-Controlled Trial.

PubMed

Zheng, Junjie; Mao, Jiangfeng; Xu, Hongli; Wang, Xi; Huang, Bingkun; Liu, Zhaoxiang; Cui, Mingxuan; Xiong, Shuyu; Ma, Wanlu; Min, Le; Kaiser, Ursula B; Nie, Min; Wu, Xueyan

2017-07-01

The effectiveness of pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with congenital combined pituitary hormone deficiency (CCPHD) has not been investigated because of the limited number of patients, as well as these patients' presumed pituitary hypoplasia, poor gonadotrophic cell reserve, and impaired gonadotrophic response to GnRH. To assess the pituitary response to pulsatile GnRH therapy in men with CCPHD. Prospective, self-controlled, 3-month clinical trial. University endocrine clinic. Men with hypogonadotropic hypogonadism caused by CCPHD. Pulsatile GnRH was administered subcutaneously for 3 months. Primary endpoints were total serum testosterone, testicular volume, and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Secondary endpoints included occurrence of spermatogenesis. A total of 40 men with CCPHD completed the study. Of these, 60% (24 of 40) showed a good response to pulsatile GnRH treatment (response group). At 3 months, their LH and FSH levels increased to within the normal range and their testosterone levels increased to 8.67 ± 4.83 nmol/L. Of the patients in the response group, 33.3% (8 of 24) of them achieved spermatogenesis. The remaining 40% (16 of 40) of patients had a poor response to pulsatile GnRH treatment. Magnetic resonance imaging (MRI) did not reveal any correlation between pituitary response and pituitary height and/or integrity of the pituitary stalk. This study suggests that gonadotrophs in patients with CCPHD can exist and be functional-even with MRI evidence of pituitary hypoplasia or dysplasia. Pulsatile GnRH therapy restored pituitary-testis axis function in 60% of patients with CCPHD. These results may directly guide the clinical therapeutic choice. Copyright © 2017 Endocrine Society

Postero-Lateral Disc Prosthesis Combined With a Unilateral Facet Replacement Device Maintains Quantity and Quality of Motion at a Single Lumbar Level

PubMed Central

Nayak, Aniruddh N.; Doarn, Michael C.; Gaskins, Roger B.; James, Chris R.; Cabezas, Andres F.; Castellvi, Antonio E.

2014-01-01

Background Mechanically replacing one or more pain generating articulations in the functional spinal unit (FSU) may be a motion preservation alternative to arthrodesis at the affected level. Baseline biomechanical data elucidating the quantity and quality of motion in such arthroplasty constructs is non-existent. Purpose The purpose of the study was to quantify the motion-preserving effect of a posterior total disc replacement (PDR) combined with a unilateral facet replacement (FR) system at a single lumbar level (L4-L5). We hypothesized that reinforcement of the FSU with unilateral FR to replace the resected, native facet joint following PDR implantation would restore quality and quantity of motion and additionally not change biomechanics at the adjacent levels. Study Design In-vitro study using human cadaveric lumbar spines. Methods Six (n = 6) cadaveric lumbar spines (L1-S1) were evaluated using a pure-moment stability testing protocol (±7.5 Nm) in flexion-extension (F/E), lateral bending (LB) and axial rotation (AR). Each specimen was tested in: (1) intact; (2) unilateral FR; and (3) unilateral FR + PDR conditions. Index and adjacent level ROM (using hybrid protocol) were determined opto-electronically. Interpedicular travel (IPT) and instantaneous center of rotation (ICR) at the index level were radiographically determined for each condition. ROM, ICR, and IPT measurements were compared (repeated measures ANOVA) between the three conditions. Results Compared to the intact spine, no significant changes in F/E, LB or AR ROM were identified as a result of unilateral FR or unilateral FR + PDR. No significant changes in adjacent L3-L4 or L5-S1 ROM were identified in any loading mode. No significant differences in IPT were identified between the three test conditions in F/E, LB or AR at the L4-L5 level. The ICRs qualitatively were similar for the intact and unilateral FR conditions and appeared to follow placement (along the anterior-posterior (AP) direction) of

Liganded and unliganded activation of estrogen receptor and hormone replacement therapies

PubMed Central

Maggi, Adriana

2011-01-01

Over the past two decades, our understanding of estrogen receptor physiology in mammals widened considerably as we acquired a deeper appreciation of the roles of estrogen receptor alpha and beta (ERα and ERβ) in reproduction as well as in bone and metabolic homeostasis, depression, vascular disorders, neurodegenerative diseases and cancer. In addition, our insights on ER transcriptional functions in cells increased considerably with the demonstration that ER activity is not strictly dependent on ligand availability. Indeed, unliganded ERs may be transcriptionally active and post-translational modifications play a major role in this context. The finding that several intracellular transduction molecules may regulate ER transcriptional programs indicates that ERs may act as a hub where several molecular pathways converge: this allows to maintain ER transcriptional activity in tune with all cell functions. Likely, the biological relevant role of ER was favored by evolution as a mean of integration between reproductive and metabolic functions. We here review the post-translational modifications modulating ER transcriptional activity in the presence or in the absence of estrogens and underline their potential role for ER tissue-specific activities. In our opinion, a better comprehension of the variety of molecular events that control ER activity in reproductive and non-reproductive organs is the foundation for the design of safer and more efficacious hormone-based therapies, particularly for menopause. PMID:21605666

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.

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.

The effects of a low-calorie diet or an isocaloric diet combined with metformin on sex hormones In obese women of child-bearing age.

PubMed

Swora-Cwynar, Ewelina; Kujawska-Łuczak, Magdalena; Suliburska, Joanna; Reguła, Julita; Kargulewicz, Angelika; Kręgielska-Narożna, Matylda; Marcinkowska, Emilia; Kanikowska, Alina; Bielas, Marzena; Grzymisławski, Marian; Bogdański, Paweł

2016-01-01

The influence of weight loss treatment on sex hormones profile has been studied mainly in women with polycystic ovary syndrome (PCOS), but in obese premenopausal women without PCOS it still remains unclear. The aim of the study was to evaluate the effect of two approaches to obesity treatment on the serum level of sex hormones in obese women of child-bearing age without PCOS. 77 obese Caucasian women (aged 31.2 ±8.3 years) were randomized into two groups: 39 women received a low-calorie diet (LC) and 38 received an isocaloric diet plus metformin (IM), for 12 weeks. Anthropometric parameters, body composition and serum concentrations of estradiol (E2), testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH) and dehydroepiandrosterone (DHEA-S) sulfate were evaluated at baseline and after the study. Reductions in body weight, body mass index (BMI), waist and body fat content with an increase  in lean body percent were significant and comparable between the LC and IM group after the trial. The concentrations of serum FSH, LH, E2, DHEA and T did not change in either group after treatment. A tendency towards an increase in the E2 concentration in both groups and a decrease in the T level in the LC group  was observed. The correlations between a change in BMI, fat content, waist-hip ratio and a change in T were documented in the LC group. A 12-week low-calorie diet and an isocaloric diet combined with metformin produced comparable and significant weight loss with improvements in body composition. Both interventions did not significantly affect FSH, LH and DHEA sulfate serum concentrations, only a trend towards an E2 increase and a T decrease was observed, stronger in LC group. The significant correlations shown between the changes in anthropometric and body composition parameters and T serum levels in women treated with a low-calorie diet alone show the beneficial effect of a lifestyle intervention on the sex hormone in obese premenopausal women.

Pituitary gene mutations and the growth hormone pathway.

PubMed

Moseley, C T; Phillips, J A

2000-01-01

Hereditary forms of pituitary insufficiency not associated with anatomic defects of the central nervous system, hypothalamus, or pituitary are a heterogeneous group of disorders that result from interruptions at different points in the hypothalamic-pituitary-somatomedin-peripheral tissue axis. These different types of pituitary dwarfism can be classified on the level of the defect; mode of inheritance; whether the phenotype is isolated growth hormone deficiency (IGHD) or combined pituitary hormone deficiency (CPHD); whether the hormone is absent, deficient, or abnormal; and, in patients with GH resistance, whether insulin-like growth factor 1 (IGF1) is deficient due to GH receptor or IGF1 defects. Information on each disorder is summarized. More detailed information can be obtained through the electronic database Online Mendelian Inheritance in Man which is available at http://www3.ncbi.nlm.nih.gov/Omim/.

The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

PubMed

Root, A W; Shulman, D; Root, J; Diamond, F

1986-01-01

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

Parathyroid hormone therapy mollifies radiation-induced biomechanical degradation in murine distraction osteogenesis.

PubMed

Deshpande, Sagar S; Gallagher, Katherine K; Donneys, Alexis; Tchanque-Fossuo, Catherine N; Sarhaddi, Deniz; Nelson, Noah S; Chepeha, Douglas B; Buchman, Steven R

2013-07-01

Descriptions of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for defects caused by osteoradionecrosis have been limited. Previous work demonstrated radiation decreases union formation, cellularity and mineral density in mandibular distraction osteogenesis. The authors posit that intermittent systemic administration of parathyroid hormone will serve as a stimulant to cellular function, reversing radiation-induced damage and enhancing bone regeneration. Twenty male Lewis rats were randomly assigned to three groups: group 1 (radiation and distraction osteogenesis, n = 7) and group 2 (radiation, distraction osteogenesis, and parathyroid hormone, n = 5) received a human-equivalent dose of 35 Gy of radiation (human bioequivalent, 70 Gy) fractionated over 5 days. All groups, including group 3 (distraction osteogenesis, n = 8), underwent a left unilateral mandibular osteotomy with bilateral external fixator placement. Distraction osteogenesis was performed at a rate of 0.3 mm every 12 hours to reach a gap of 5.1 mm. Group 2 was injected with parathyroid hormone (60 µg/kg) subcutaneously daily for 3 weeks after the start of distraction osteogenesis. On postoperative day 40, all left hemimandibles were harvested. Biomechanical response parameters were generated. Statistical significance was considered at p ≤ 0.05. Parathyroid hormone-treated mandibles had significantly higher failure load and higher yield than did untreated mandibles. However, these values were still significantly lower than those of nonirradiated mandibles. The authors have successfully demonstrated the therapeutic efficacy of parathyroid hormone to stimulate and enhance bone regeneration in their irradiated murine mandibular model of distraction osteogenesis. Anabolic regimens of parathyroid hormone, a U.S. Food and Drug Administration-approved drug on formulary, significantly improve outcomes in a model of postoncologic craniofacial reconstruction.

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...

Metabolic and hormonal changes during aerobic exercise in distance runners.

PubMed

Fernández-Pastor, V J; Ruiz, M; Diego-Acosta, A M; Avila, C; García, J C; Pérez, F; Guirado, F; Noguer, N

1999-03-01

A group of long-distance runners is studied in order to clarify aspects concerning neuroendocrine mechanisms regulating organic adaptation to maximum effort, with special interest in the function of the growth hormone in fat metabolism and the possible use of ketone bodies as an alternative source of energy. A test is designed on a treadmill with a gradient of 3% and progressive increases in speed of 2 Km/h every 10 min, starting at 6 Km/h, and continuing until exhaustion. Masks are worn to enable the breath by breath measurement of expired gases and the subjects are monitored electrocardiographically using V5. For blood sample collection an antecubital vein is catheterized with a system enabling the replacement of the blood volume extracted by means of perfusion with physiological saline solution, and the increasing concentration of hormones in the blood is evaluated. The results obtained, indicate that epinephrine as well as GH hormones increase significatively from 20 min of exercise in runners promoting changes from carbohydrates to lipids as fuels to carry out exercise. The concomitant variations in energy substrates support the former hypothesis of work. Moreover, the muscle could employ acetylCoA originating from acetoacetate as an alternative metabolic source of fuel during maximum effort.

SYNERGISTIC WOOD PRESERVATIVES FOR REPLACEMENT OF CCA

EPA Science Inventory

The objective of this project was to evaluate the potential synergistic combinations of environmentally-safe biocides as wood preservatives. These wood preservatives could be potential replacements for the heavy-metal based CCA.

Didecyldimethylammonium chloride [DDAC] was...

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.

Hormone replacement therapy advertising: sense and nonsense on the web pages of the best-selling pharmaceuticals in Spain.

PubMed

Chilet-Rosell, Elisa; Martín Llaguno, Marta; Ruiz Cantero, María Teresa; Alonso-Coello, Pablo

2010-03-16

The balance of the benefits and risks of long term use of hormone replacement therapy (HRT) have been a matter of debate for decades. In Europe, HRT requires medical prescription and its advertising is only permitted when aimed at health professionals (direct to consumer advertising is allowed in some non European countries). The objective of this study is to analyse the appropriateness and quality of Internet advertising about HRT in Spain. A search was carried out on the Internet (January 2009) using the eight best-selling HRT drugs in Spain. The brand name of each drug was entered into Google's search engine. The web sites appearing on the first page of results and the corresponding companies were analysed using the European Code of Good Practice as the reference point. Five corporate web pages: none of them included bibliographic references or measures to ensure that the advertising was only accessible by health professionals. Regarding non-corporate web pages (n = 27): 41% did not include the company name or address, 44% made no distinction between patient and health professional information, 7% contained bibliographic references, 26% provided unspecific information for the use of HRT for osteoporosis and 19% included menstrual cycle regulation or boosting feminity as an indication. Two online pharmacies sold HRT drugs which could be bought online in Spain, did not include the name or contact details of the registered company, nor did they stipulate the need for a medical prescription or differentiate between patient and health professional information. Even though pharmaceutical companies have committed themselves to compliance with codes of good practice, deficiencies were observed regarding the identification, information and promotion of HRT medications on their web pages. Unaffected by legislation, non-corporate web pages are an ideal place for indirect HRT advertising, but they often contain misleading information. HRT can be bought online from Spain

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.

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.

ReplacementMatrix: a web server for maximum-likelihood estimation of amino acid replacement rate matrices.

PubMed

Dang, Cuong Cao; Lefort, Vincent; Le, Vinh Sy; Le, Quang Si; Gascuel, Olivier

2011-10-01

Amino acid replacement rate matrices are an essential basis of protein studies (e.g. in phylogenetics and alignment). A number of general purpose matrices have been proposed (e.g. JTT, WAG, LG) since the seminal work of Margaret Dayhoff and co-workers. However, it has been shown that matrices specific to certain protein groups (e.g. mitochondrial) or life domains (e.g. viruses) differ significantly from general average matrices, and thus perform better when applied to the data to which they are dedicated. This Web server implements the maximum-likelihood estimation procedure that was used to estimate LG, and provides a number of tools and facilities. Users upload a set of multiple protein alignments from their domain of interest and receive the resulting matrix by email, along with statistics and comparisons with other matrices. A non-parametric bootstrap is performed optionally to assess the variability of replacement rate estimates. Maximum-likelihood trees, inferred using the estimated rate matrix, are also computed optionally for each input alignment. Finely tuned procedures and up-to-date ML software (PhyML 3.0, XRATE) are combined to perform all these heavy calculations on our clusters. http://www.atgc-montpellier.fr/ReplacementMatrix/ olivier.gascuel@lirmm.fr Supplementary data are available at http://www.atgc-montpellier.fr/ReplacementMatrix/

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.

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

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.

Single-nucleotide variants in two Hedgehog genes, SHH and HHIP, as genetic cause of combined pituitary hormone deficiency.

PubMed

Gorbenko del Blanco, Darya; de Graaff, Laura C G; Visser, Theo J; Hokken-Koelega, Anita C S

2013-03-01

Combined pituitary hormone deficiency (CPHD) is characterized by deficiencies of two or more anterior pituitary hormones. Its genetic cause is unknown in the majority of cases. The Hedgehog (Hh) signalling pathway has been implicated in disorders associated with pituitary development. Mutations in Sonic Hedgehog (SHH) have been described in patients with holoprosencephaly (with or without pituitary involvement). Hedgehog interacting protein (HHIP) has been associated with variations in adult height in genome wide association studies. We investigated whether mutations in these two genes of the Hh pathway, SHH and HHIP, could result in 'idiopathic' CPHD. We directly sequenced the coding regions and exon - intron boundaries of SHH and HHIP in 93 CPHD patients of the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3 and LHX4 had been ruled out. We compared the expression of Hh genes in Hep3B transfected cells between wild-type proteins and mutants. We identified three single-nucleotide variants (p.Ala226Thr, c.1078C>T and c.*8G>T) in SHH. The function of the latter was severely affected in our in vitro assay. In HHIP, we detected a new activating variant c.-1G>C, which increases HHIP's inhibiting function on the Hh pathway. Our results suggest involvement of the Hedgehog pathway in CPHD. We suggest that both SHH and HHIP are investigated as a second screening in CPHD, after mutations in the classical CPHD genes have been ruled out. © 2012 Blackwell Publishing Ltd.

[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.

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

Liganded and unliganded activation of estrogen receptor and hormone replacement therapies.

PubMed

Maggi, Adriana

2011-08-01

Over the past two decades, our understanding of estrogen receptor physiology in mammals widened considerably as we acquired a deeper appreciation of the roles of estrogen receptor alpha and beta (ERα and ERβ) in reproduction as well as in bone and metabolic homeostasis, depression, vascular disorders, neurodegenerative diseases and cancer. In addition, our insights on ER transcriptional functions in cells increased considerably with the demonstration that ER activity is not strictly dependent on ligand availability. Indeed, unliganded ERs may be transcriptionally active and post-translational modifications play a major role in this context. The finding that several intracellular transduction molecules may regulate ER transcriptional programs indicates that ERs may act as a hub where several molecular pathways converge: this allows to maintain ER transcriptional activity in tune with all cell functions. Likely, the biological relevant role of ER was favored by evolution as a mean of integration between reproductive and metabolic functions. We here review the post-translational modifications modulating ER transcriptional activity in the presence or in the absence of estrogens and underline their potential role for ER tissue-specific activities. In our opinion, a better comprehension of the variety of molecular events that control ER activity in reproductive and non-reproductive organs is the foundation for the design of safer and more efficacious hormone-based therapies, particularly for menopause. This article is part of a Special Issue entitled: Translating Nuclear receptors from health to disease. Copyright © 2011 Elsevier B.V. All rights reserved.

Replacement predictions for drinking water networks through historical data.

PubMed

Malm, Annika; Ljunggren, Olle; Bergstedt, Olof; Pettersson, Thomas J R; Morrison, Gregory M

2012-05-01

Lifetime distribution functions and current network age data can be combined to provide an assessment of the future replacement needs for drinking water distribution networks. Reliable lifetime predictions are limited by a lack of understanding of deterioration processes for different pipe materials under varied conditions. An alternative approach is the use of real historical data for replacement over an extended time series. In this paper, future replacement needs are predicted through historical data representing more than one hundred years of drinking water pipe replacement in Gothenburg, Sweden. The verified data fits well with commonly used lifetime distribution curves. Predictions for the future are discussed in the context of path dependence theory. Copyright © 2012 Elsevier Ltd. All rights reserved.

Thyroid hormones and their effects: a new perspective.

PubMed

Hulbert, A J

2000-11-01

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3',5',3,5-L-tetraiodothyronine (T4), 3',5,3-L-triiodothyronine (T3), 3',5',3-L-triiodothyronine (rT3) and 3,5',-L-diiothyronine (3,5-T2). At physiological pH, dissociation of the phenolic -OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non-ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein-bound T4 and T3 are maintained in the nanomolar range. The function of thyroid-hormone-binding plasma proteins is to ensure an even distrubtion throughout the body. Various iodothyronines are produced by three types of membrane-bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones. (1) the nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid-hormone-induced membrane rigidificataion. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellulara matrix. The effects of thyroid hormones are reviewed and appear to b combinations of these various modes of action. During

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

PubMed

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

2009-08-01

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

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.

Circuit lifespan during continuous renal replacement therapy for combined liver and kidney failure.

PubMed

Chua, Horng-Ruey; Baldwin, Ian; Bailey, Michael; Subramaniam, Ashwin; Bellomo, Rinaldo

2012-12-01

To evaluate circuit lifespan (CL) and bleeding risk during continuous renal replacement therapy (CRRT), in combined liver and renal failure. Single-center retrospective analysis of adults with acute liver failure or decompensated cirrhosis who received CRRT, without anticoagulation or with heparinization in intensive care unit. Seventy-one patients with 539 CRRT circuits were evaluated. Median overall CL was 9 (6-16) hours. CL was 12 (7-24) hours in 51 patients never anticoagulated for CRRT. In 20 patients who subsequently received heparinization, CL was 7 (5-11) hours without anticoagulation, which did not improve with systemic or regional heparinization (P = .231), despite higher peri-circuit activated partial thromboplastin time (APTT) and heparin dose. Using multivariate linear regression, patients with higher baseline APTT or serum bilirubin, or who were not mechanically ventilated, had longer CL (P < .05). Additionally, peri-circuit thrombocytopenia (P < .0001) or higher international normalized ratio (P < .05) predicted longer CL. Of 71 patients, 33 had significant bleeding events. Using multivariate logistic regression, patients with higher baseline APTT, vasoactive drug use >24 hours, or thrombocytopenia, had more bleeding complications (P < .05). Decreasing platelet counts (especially <50 × 10(9)/mm(3)) had an incremental effect on CL (P < .0001). CRRT CL is short in patients with liver failure despite apparent coagulopathy. Thrombocytopenia predicts longer CL and bleeding complications. Copyright © 2012 Elsevier Inc. All rights reserved.

HormoneBase, a population-level database of steroid hormone levels across vertebrates

PubMed Central

Vitousek, Maren N.; Johnson, Michele A.; Donald, Jeremy W.; Francis, Clinton D.; Fuxjager, Matthew J.; Goymann, Wolfgang; Hau, Michaela; Husak, Jerry F.; Kircher, Bonnie K.; Knapp, Rosemary; Martin, Lynn B.; Miller, Eliot T.; Schoenle, Laura A.; Uehling, Jennifer J.; Williams, Tony D.

2018-01-01

Hormones are central regulators of organismal function and flexibility that mediate a diversity of phenotypic traits from early development through senescence. Yet despite these important roles, basic questions about how and why hormone systems vary within and across species remain unanswered. Here we describe HormoneBase, a database of circulating steroid hormone levels and their variation across vertebrates. This database aims to provide all available data on the mean, variation, and range of plasma glucocorticoids (both baseline and stress-induced) and androgens in free-living and un-manipulated adult vertebrates. HormoneBase (www.HormoneBase.org) currently includes >6,580 entries from 476 species, reported in 648 publications from 1967 to 2015, and unpublished datasets. Entries are associated with data on the species and population, sex, year and month of study, geographic coordinates, life history stage, method and latency of hormone sampling, and analysis technique. This novel resource could be used for analyses of the function and evolution of hormone systems, and the relationships between hormonal variation and a variety of processes including phenotypic variation, fitness, and species distributions. PMID:29786693

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...

Is human chorionic gonadotropin supplementation beneficial for frozen and thawed embryo transfer in estrogen/progesterone replacement cycles?: A randomized clinical trial.

PubMed

Shiotani, Masahide; Matsumoto, Yukiko; Okamoto, Eri; Yamada, Satoshi; Mizusawa, Yuri; Furuhashi, Kohyu; Ogata, Hiromi; Ogata, Seiji; Kokeguchi, Shoji

2017-04-01

Human chorionic gonadotropin (hCG) is used frequently for luteal support in fresh in vitro fertilization cycles as it induces progesterone secretion from the ovaries after oocyte retrieval and modulates the endometrium for implantation in fresh cycles. In contrast, hCG is not usually used for the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement cycles because ovulation is suppressed. However, several studies have shown that luteinizing hormone and hCG receptors are present in the human endometrium and that hCG can directly induce the decidualization of endometrial stromal cells in vitro. Thus, this study evaluated whether hCG supplementation can be beneficial for cryopreserved-thawed embryo transfer in estrogen/progesterone replacement cycles. One-hundred-and seventy-three cryopreserved-thawed embryo transfer cycles with estrogen/progesterone replacement were divided randomly into two groups. Transdermal oestradiol was used in combination with vaginal progesterone suppositories for HR. The embryo transfer was performed on day 17 and/or day 20 of the HR therapy cycle in both groups. In Group A, 3000 IU of hCG was administered on days 17, 20, and 23. In Group B, hCG was not used. There was no significant difference in the average age of the patients, the average number of previous assisted reproductive technology cycles, or the average number of embryo transfers between the two groups. The rates of pregnancy and implantation per embryo were 37.2% and 25.3%, respectively, in Group A and 35.6% and 21.7%, respectively, in Group B. The pregnancy and implantation rates were similar in both groups. Supplementation with hCG is not beneficial for cryopreserved-thawed embryo transfer in estrogen/progesterone replacement cycles.

Replacing methyl bromide with a combination of 1,3-dichloropropene and metam sodium for cucumber production in China

PubMed Central

Mao, Liangang; Zhang, Lan; Zhang, Yanning; Sial, Muhammad Umair; Yu, Haitao; Cao, Aocheng

2017-01-01

The combination of 1,3-dichloropropene (1,3-D) and metam sodium (MNa) is a potential resource to replace methyl bromide (MB) as a soil fumigant. The efficacy of 1,3-D+MNa as a crucial factor to limit soil-borne pests was evaluated in one laboratory experiment and two cucumber greenhouse studies conducted in commercial operations. Laboratory results revealed that 1,3-D and MNa (10+20 mg a.i. kg−1 soil) provided the best complementary control of the root-knot nematode, Fusarium oxysporum and two species of weed seeds. Greenhouse trials revealed that the blend of 1,3-D and MNa (10+20 g a.i. m−2) greatly inhibited the ability of Meloidogyne incognita to form root galls. In addition, the number of colony-forming units of F. oxysporum declined substantially after growth on media, resulting in higher fruit yields and greater economic benefits. The combined use of 1,3-D and MNa exhibited a higher control efficacy than when 1,3-D or MNa was utilized alone. The ability of this chemical combination to control soil-borne organisms did not differ significantly from the MB treatment and maintained high cucumber yields, enhancing the income of the farmers. Compared to the untreated control group, all the chemical treatments prominently improved the control of the pests. These results show that applying a combination of 1,3-D and MNa provides a promising alternative to MB that enables the sustained growth of cucumber production in China. PMID:29145472

Biological and psychological influences of cross sex hormone in transgender.

PubMed

Ling, Ling Shiao; Sidi, Hatta; Lope, Raja Adam Raja; Das, Srijit; Baharudin, Azlin

2018-05-11

Transgender is a complex state of bio-psycho-social dimension of human sexuality. It encompasses cognitive-emotional-behavior component that makes the person unique in his or her sexual expression. Transgender tend to use cross sex hormone in order to eradicate their secondary sexual characteristics and to facilitate the shift to their experienced gender. The common masculinising sex hormone use, i.e. Female to Male Treatment Options (FMTO) is testosterone and for feminising hormone i.e. Male to Female Treatment Options (MFTO) is a combination of estrogen with anti-androgen, respectively. Cross sex hormone, i.e. FMTO, or MFTO has biological and psychological influences on the transgender individuals. Nevertheless, cross sex hormone may also poses a range of side effect profiles, varies from the biological to psychosocial impact. The psychological impact can be paramount until it causes severe mental-health problems and even suicide. Numerous ranges of bio-psycho-social influence of cross-sex hormone were highlighted in this review as fundamental core knowledge in the art to know practice when dealing with the treatment options. In psychiatry, the change in the biological appearance may have great influence in the transgender individual, especially in the context of psychosocial and cultural perspective. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Plant hormone signaling in flowering: An epigenetic point of view.

PubMed

Campos-Rivero, Gerardo; Osorio-Montalvo, Pedro; Sánchez-Borges, Rafael; Us-Camas, Rosa; Duarte-Aké, Fátima; De-la-Peña, Clelia

2017-07-01

Reproduction is one of the most important phases in an organism's lifecycle. In the case of angiosperm plants, flowering provides the major developmental transition from the vegetative to the reproductive stage, and requires genetic and epigenetic reprogramming to ensure the success of seed production. Flowering is regulated by a complex network of genes that integrate multiple environmental cues and endogenous signals so that flowering occurs at the right time; hormone regulation, signaling and homeostasis are very important in this process. Working alone or in combination, hormones are able to promote flowering by epigenetic regulation. Some plant hormones, such as gibberellins, jasmonic acid, abscisic acid and auxins, have important effects on chromatin compaction mediated by DNA methylation and histone posttranslational modifications, which hints at the role that epigenetic regulation may play in flowering through hormone action. miRNAs have been viewed as acting independently from DNA methylation and histone modification, ignoring their potential to interact with hormone signaling - including the signaling of auxins, gibberellins, ethylene, jasmonic acid, salicylic acid and others - to regulate flowering. Therefore, in this review we examine new findings about interactions between epigenetic mechanisms and key players in hormone signaling to coordinate flowering. Copyright © 2017 Elsevier GmbH. All rights reserved.

Psychological stress during exercise: cardiorespiratory and hormonal responses.

PubMed

Webb, Heather E; Weldy, Michael L; Fabianke-Kadue, Emily C; Orndorff, G R; Kamimori, Gary H; Acevedo, Edmund O

2008-12-01

The purpose of this study was to examine the cardiorespiratory (CR) and stress hormone responses to a combined physical and mental stress. Eight participants (VO2(max) = 41.24 +/- 6.20 ml kg(-1) min(-1)) completed two experimental conditions, a treatment condition including a 37 min ride at 60% of VO2(max) with participants responding to a computerized mental challenge dual stress condition (DSC) and a control condition of the same duration and intensity without the mental challenge exercise alone condition (EAC). Significant interactions across time were found for CR responses, with heart rate, ventilation, and respiration rate demonstrating higher increases in the DSC. Additionally, norepinephrine was significantly greater in the DSC at the end of the combined challenge. Furthermore, cortisol area-under-the-curve (AUC) was also significantly elevated during the DSC. These results demonstrate that a mental challenge during exercise can exacerbate the stress response, including the release of hormones that have been linked to negative health consequences (cardiovascular, metabolic, autoimmune illnesses).

Genetic Overlap in Kallmann Syndrome, Combined Pituitary Hormone Deficiency, and Septo-Optic Dysplasia

PubMed Central

Raivio, Taneli; Avbelj, Magdalena; McCabe, Mark J.; Romero, Christopher J.; Dwyer, Andrew A.; Tommiska, Johanna; Sykiotis, Gerasimos P.; Gregory, Louise C.; Diaczok, Daniel; Tziaferi, Vaitsa; Elting, Mariet W.; Padidela, Raja; Plummer, Lacey; Martin, Cecilia; Feng, Bihua; Zhang, Chengkang; Zhou, Qun-Yong; Chen, Huaibin; Mohammadi, Moosa; Quinton, Richard; Sidis, Yisrael; Radovick, Sally; Dattani, Mehul T.

2012-01-01

Context: Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain. Objective: The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins. Design and Participants: A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro. Results: Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C>T, p.T112T). One patient had a synonymous change in FGF8 (c.216G>A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C). Conclusions: Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain. PMID:22319038

Gastrointestinal Hormones and Bariatric Surgery-induced Weight Loss

PubMed Central

Ionut, Viorica; Burch, Miguel; Youdim, Adrienne; Bergman, Richard N.

2015-01-01

Obesity continues to be a major public health problem in the United States and worldwide. While recent statistics have demonstrated that obesity rates have begun to plateau, more severe classes of obesity are accelerating at a faster pace with important implications in regards to treatment. Bariatric surgery has a profound and durable effect on weight loss, being to date one of the most successful interventions for obesity. Objective To provide updates to the possible role of gut hormones in post bariatric surgery weight loss and weight loss maintenance. Design and Methods The current review examines the changes in gastro-intestinal hormones with bariatric surgery and the potential mechanisms by which these changes could result in decreased weight and adiposity. Results The mechanism by which bariatric surgery results in body weight changes is incompletely elucidated, but it clearly goes beyond caloric restriction and malabsorption. Conclusion Changes in gastro-intestinal hormones, including increases in GLP-1, PYY, and oxyntomodulin, decreases in GIP and ghrelin, or the combined action of all these hormones might play a role in induction and long-term maintenance of weight loss. PMID:23512841

Molecular replacement: tricks and treats

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

Abergel, Chantal, E-mail: chantal.abergel@igs.cnrs-mrs.fr

2013-11-01

To be successful, molecular replacement relies on the quality of the model and of the crystallographic data. Some tricks that could be applied to the models or to the crystal to increase the success rate of MR are discussed here. Molecular replacement is the method of choice for X-ray crystallographic structure determination provided that suitable structural homologues are available in the PDB. Presently, there are ∼80 000 structures in the PDB (8074 were deposited in the year 2012 alone), of which ∼70% have been solved by molecular replacement. For successful molecular replacement the model must cover at least 50% ofmore » the total structure and the C{sub α} r.m.s.d. between the core model and the structure to be solved must be less than 2 Å. Here, an approach originally implemented in the CaspR server (http://www.igs.cnrs-mrs.fr/Caspr2/index.cgi) based on homology modelling to search for a molecular-replacement solution is discussed. How the use of as much information as possible from different sources can improve the model(s) is briefly described. The combination of structural information with distantly related sequences is crucial to optimize the multiple alignment that will define the boundaries of the core domains. PDB clusters (sequences with ≥30% identical residues) can also provide information on the eventual changes in conformation and will help to explore the relative orientations assumed by protein subdomains. Normal-mode analysis can also help in generating series of conformational models in the search for a molecular-replacement solution. Of course, finding a correct solution is only the first step and the accuracy of the identified solution is as important as the data quality to proceed through refinement. Here, some possible reasons for failure are discussed and solutions are proposed using a set of successful examples.« less

Behavioural and hormonal effects of member replacement in captive groups of blue-fronted amazon parrots (Amazona aestiva).

PubMed

Silva de Souza Matos, Laerciana; Palme, Rupert; Silva Vasconcellos, Angélica

2017-05-01

Social species in captivity may face allostatic overload due to artificial grouping and other social constraints. In rescue centres, groups of psittacines are constantly mixed due to the arrival and/or release of individuals; this procedure is potentially harmful to animal welfare. This study aimed at evaluating the possible impacts of mate replacement on the stress levels of captive blue-fronted amazon parrots (Amazona aestiva). During five weeks, we recorded agonistic interactions and dropping-glucocorticoid metabolites (GCM) concentrations of individuals allocated in a group whose members were kept constant and in a group subjected to frequent member replacement. In both groups, non-linear hierarchies developed, without sex differences regarding aggression or hierarchical positions. The replacement of individuals had no effect on the number of agonistic interactions or on the animals' stress levels. In both groups, higher-ranking individuals had higher stress loads than subordinates. Our study, the first to investigate the social dynamics of A. aestiva, indicated that introducing or removing individuals in captive groups does not seem to affect the welfare of the birds in the short term. This information favours release and reintroduction programs and is relevant for conservation management of this, and possibly other parrot species with similar environmental requirements. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioidentical Hormones and Menopause

MedlinePlus

... Endocrinologist Search Featured Resource Menopause Map™ View Bioidentical Hormones January 2012 Download PDFs English Espanol Editors Howard ... take HT for symptom relief. What are bioidentical hormones? Bioidentical hormones are identical to the hormones that ...

Multiple-scale neuroendocrine signals connect brain and pituitary hormone rhythms

PubMed Central

Romanò, Nicola; Guillou, Anne; Martin, Agnès O; Mollard, Patrice

2017-01-01

Small assemblies of hypothalamic “parvocellular” neurons release their neuroendocrine signals at the median eminence (ME) to control long-lasting pituitary hormone rhythms essential for homeostasis. How such rapid hypothalamic neurotransmission leads to slowly evolving hormonal signals remains unknown. Here, we show that the temporal organization of dopamine (DA) release events in freely behaving animals relies on a set of characteristic features that are adapted to the dynamic dopaminergic control of pituitary prolactin secretion, a key reproductive hormone. First, locally generated DA release signals are organized over more than four orders of magnitude (0.001 Hz–10 Hz). Second, these DA events are finely tuned within and between frequency domains as building blocks that recur over days to weeks. Third, an integration time window is detected across the ME and consists of high-frequency DA discharges that are coordinated within the minutes range. Thus, a hierarchical combination of time-scaled neuroendocrine signals displays local–global integration to connect brain–pituitary rhythms and pace hormone secretion. PMID:28193889

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.

Effects of growth hormone plus a hyperproteic diet on methotrexate-induced injury in rat intestines.

PubMed

Ortega, M; Gomez-de-Segura, I A; Vázquez, I; López, J M; de Guevara, C L; De-Miguel, E

2001-01-01

The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.

Effects of botanicals and combined hormone therapy on cognition in postmenopausal women.

PubMed

Maki, Pauline M; Rubin, Leah H; Fornelli, Deanne; Drogos, Lauren; Banuvar, Suzanne; Shulman, Lee P; Geller, Stacie E

2009-01-01

The aim of this study was to characterize the effects of red clover, black cohosh, and combined hormone therapy on cognitive function in comparison to placebo in women with moderate to severe vasomotor symptoms. In a phase II randomized, double-blind, placebo-controlled study, 66 midlife women (of 89 from a parent study; mean age, 53 y) with 35 or more weekly hot flashes were randomized to receive red clover (120 mg), black cohosh (128 mg), 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA), or placebo. Participants completed measures of verbal memory (primary outcome) and other cognitive measures (secondary outcomes) before and during the 12th treatment month. A subset of 19 women completed objective, physiological measures of hot flashes using ambulatory skin conductance monitors. Neither of the botanical treatments had an impact on any cognitive measure. Compared with placebo, CEE/MPA led to a greater decline in verbal learning (one of five verbal memory measures). This effect just missed statistical significance (P = 0.057) in unadjusted analyses but reached significance (P = 0.02) after adjusting for vasomotor symptoms. Neither of the botanical treatment groups showed a change in verbal memory that differed from the placebo group (Ps > 0.28), even after controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led to a decrease in immediate digit recall and an improvement in letter fluency. Only CEE/MPA significantly reduced objective hot flashes. Results indicate that a red clover (phytoestrogen) supplement or black cohosh has no effects on cognitive function. CEE/MPA reduces objective hot flashes but worsens some aspects of verbal memory.

Effects of Botanicals and Combined Hormone Therapy on Cognition in Postmenopausal Women

PubMed Central

Maki, Pauline M.; Rubin, Leah H.; Fornelli, Deanne; Drogos, Lauren; Banuvar, Suzanne; Shulman, Lee P.; Geller, Stacie E.

2009-01-01

Objective To characterize the effects of red clover, black cohosh, and combined hormone therapy on cognitive function in comparison to placebo in women with moderate to severe vasomotor symptoms. Design In a Phase II randomized, double-blind, placebo-controlled study, 66 midlife women (out of 89 from a parent study; mean age=53 y) with ≥ 35 weekly hot flashes were randomized to receive red clover (120 mg), black cohosh (128 mg), CEE/MPA (0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate), or placebo. Participants completed measures of verbal memory (primary outcome) and other cognitive measures (secondary outcomes) before and during the 12th treatment month. A subset of 19 women completed objective, physiological measures of hot flashes using ambulatory skin conductance monitors. Results There was no impact of either of the botanical treatments on any cognitive measure. Compared to placebo, CEE/MPA led to greater decline in verbal learning (one of five verbal memory measures). This effect just missed statistical significance (p=0.057) in unadjusted analyses, but reached significance (p=.02) after adjusting for vasomotor symptoms. Neither botanical treatment group showed a change in verbal memory that differed from the placebo group (ps>0.28), even after controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led to a decrease in immediate digit recall and an improvement in letter fluency. Only CEE/MPA significantly reduced objective hot flashes. Conclusions Results indicate no effects of a red clover (phytoestrogen) supplement or black cohosh on cognitive function. CEE/MPA reduces objective hot flashes but worsens some aspects of verbal memory. PMID:19590458

The de novo Q167K mutation in the POU1F1 gene leads to combined pituitary hormone deficiency in an Italian patient.

PubMed

Malvagia, Sabrina; Poggi, Giovanni Maria; Pasquini, Elisabetta; Donati, Maria Alice; Pela, Ivana; Morrone, Amelia; Zammarchi, Enrico

2003-11-01

The POU1F1 gene encodes a transcription factor that is important for the development and differentiation of the cells producing GH, prolactin, and TSH in the anterior pituitary gland. Patients with POU1F1 mutations show a combined pituitary hormone deficiency with low or absent levels of GH, prolactin, and TSH. Fourteen mutations have been reported in the POU1F1 gene up to now. These genetic lesions can be inherited either in an autosomal dominant or an autosomal recessive mode. We report on the first Italian patient, a girl, affected by combined pituitary hormone deficiency. The patient was found to be positive for congenital hypothyroidism (with low TSH levels) at neonatal screening. Substitutive therapy was started, but subsequent growth was very poor, although psychomotor development was substantially normal. Hospitalized at 10 mo she showed hypotonic crises, growth retardation, delayed bone age, and facial dysmorphism. In addition to congenital hypothyroidism, GH and prolactin deficiencies were found. Mutation DNA analysis of the patient's POU1F1 gene identified the novel Q167K amino acid change at the heterozygous level. The highly conserved Q167 residue is located in the POU-specific domain. No mutation was detected in the other allele. DNA analysis in the proband's parents did not identify this amino acid substitution, suggesting a de novo genetic lesion. From these data it can be hypothesized that the Q167K mutation has a dominant negative effect.

Bioprocessing for elimination antibiotics and hormones from swine wastewater.

PubMed

Cheng, D L; Ngo, H H; Guo, W S; Liu, Y W; Zhou, J L; Chang, S W; Nguyen, D D; Bui, X T; Zhang, X B

2018-04-15

Antibiotics and hormones in swine wastewater have become a critical concern worldwide due to the severe threats to human health and the eco-environment. Removal of most detectable antibiotics and hormones, such as sulfonamides (SAs), SMs, tetracyclines (TCs), macrolides, and estrogenic hormones from swine wastewater utilizing various biological processes were summarized and compared. In biological processes, biosorption and biodegradation are the two major removal mechanisms for antibiotics and hormones. The residuals in treated effluents and sludge of conventional activated sludge and anaerobic digestion processes can still pose risks to the surrounding environment, and the anaerobic processes' removal efficiencies were inferior to those of aerobic processes. In contrast, membrane bioreactors (MBRs), constructed wetlands (CWs) and modified processes performed better because of their higher biodegradation of toxicants. Process modification on activated sludge, anaerobic digestion and conventional MBRs could also enhance the performance (e.g. removing up to 98% SMs, 88.9% TCs, and 99.6% hormones from wastewater). The hybrid process combining MBRs with biological or physical technology also led to better removal efficiency. As such, modified conventional biological processes, advanced biological technologies and MBR hybrid systems are considered as a promising technology for removing toxicants from swine wastewater. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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.

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.

Comparison of the effects of combined nicotine replacement therapy vs. cigarette smoking in males.

PubMed

Haustein, Knut-Olaf; Krause, Jörn; Haustein, Heidi; Rasmussen, Thomas; Cort, Nicholas

2003-04-01

This open study assessed the effects of nicotine replacement therapy (NRT) on the normalizing of exhaled carbon monoxide (CO), transcutaneous partial oxygen tension (tcpO(2)), plasma cotinine and thiocyanate levels, and cardiovascular risk markers in abstinent subjects compared with untreated smokers after 4, 8, 12, and 26 weeks. The trial enrolled 197 subjects in two parallel groups: 164 subjects who received NRT (patch plus gum) for 12 weeks and 33 untreated smokers (controls). At 26 weeks, 123/164 participants in the treatment group had completed the study; 51/123 (41.5%) sustained abstinence from smoking, whereas 72/123 (58.5%) had relapsed. Changes in cotinine (abstainers: 291.6 ng/ml at baseline vs. 27.3 ng/ml at week 26; p<.0001) and thiocyanate levels (abstainers: 10.4 ng/ml at baseline vs. 6.2 ng/ml at week 26; p<.0001) and expired CO (abstainers: 30.4 ppm at baseline vs. 4.2 ppm at week 26; p<.0001) accurately reflected the changes in smoking and/or NRT use in both abstainers and relapsers. After they stopping smoking, tcpO(2) significantly improved in abstainers (34.9 mmHg at baseline vs. 50.4 mmHg at week 26; p<0.0001). Inverse correlations between the number of daily cigarettes and plasma cotinine, thiocyanate, and exhaled CO levels were observed in both relapsers and smokers. A clinically significant increase in HDL cholesterol (39.0 vs. 44.7 mg/dl; p<.0001) occurred in the abstainers between baseline and study end. Use of combination NRT to achieve abstinence resulted in marked improvements in biochemical parameters in abstainers and partial improvements in relapsers. The safety of combination NRT was confirmed by the absence of overdose-related adverse events.

Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors: A nationwide case-control study.

PubMed

Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian; Baandrup, Louise; Junge, Jette; Vang, Russell; Kurman, Robert J; Kjaer, Susanne K

2017-03-01

Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p<0.01). Older age at first birth also decreased the SBT risk (p=0.03). An increased SBT risk was associated with infertility (OR=3.31; 95% CI: 2.44-4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR=1.32; 95% CI: 1.02-1.72), whereas OC use decreased the risk (OR=0.40; 95% CI: 0.26-0.62). Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. Copyright © 2017 Elsevier Inc. All rights reserved.