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1.
A decade in female reproduction: an endocrine view of the past and into the future.
Macut, D, Milutinović, DV, Rašić-Marković, A, Nestorov, J, Bjekić-Macut, J, Stanojlović, O
Hormones (Athens, Greece). 2018;(4):497-505
Abstract
Over the last decade, huge achievements have been made in the fields of neurophysiology, molecular endocrinology, and biochemistry, as well as in the successful translation of clinical research into diseases into clinical practice. As regards female reproduction, most of the advances made in this area were achieved in gonadal axis regulation, regulation of behavior through sex steroids, reproductive genetics, preservation of ovarian reproductive function, steroid profiling, and metabolic and overall reproductive outcomes. The coming years are expected to bring further understanding of the relationships between nutrition, energy metabolism, and reproductive function and to succeed in identifying new genetic markers linked to adverse metabolic and unfavorable cardiovascular outcomes in women. From our perspective, future research in the field of female reproduction should be directed toward doing research into genetic reproductive abnormalities and neuroendocrine diseases, pathophysiology, long-term health outcomes for oligo/amenorrhea, hyperandrogenism, and ovulatory dysfunction. It is additionally expected that a better understanding will be gained of the endocrinology of the placenta and of pregnancy, the role of the microbiome in female reproduction, the role of insulin sensitizers, anti-obesity and anti-diabetic drugs, and various advances in the prevention of ovarian damage caused by various oncology therapies, while new therapeutic options for the treatment of infertility, including kisspeptin, will be developed.
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2.
Regulation of sex hormone receptors in sexual dimorphism of human cancers.
Zheng, D, Williams, C, Vold, JA, Nguyen, JH, Harnois, DM, Bagaria, SP, McLaughlin, SA, Li, Z
Cancer letters. 2018;:24-31
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Abstract
Gender differences in the incidences of cancers have been found in almost all human cancers. However, the mechanisms that underlie gender disparities in most human cancer types have been under-investigated. Here, we provide a comprehensive overview of potential mechanisms underlying sexual dimorphism of each cancer regarding sex hormone signaling. Fully addressing the mechanisms of sexual dimorphism in human cancers will greatly benefit current development of precision medicine. Our discussions of potential mechanisms underlying sexual dimorphism in each cancer will be instructive for future cancer research on gender disparities.
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3.
Targeting hypothalamic-pituitary-adrenal axis hormones and sex steroids for improving cognition in major mood disorders and schizophrenia: a systematic review and narrative synthesis.
Soria, V, González-Rodríguez, A, Huerta-Ramos, E, Usall, J, Cobo, J, Bioque, M, Barbero, JD, García-Rizo, C, Tost, M, Monreal, JA, et al
Psychoneuroendocrinology. 2018;:8-19
Abstract
Cognitive deficits are a core feature of serious mental illnesses such as schizophrenia, major depressive disorder (MDD) and bipolar disorder (BD) and are a common cause of functional disability. There is limited efficacy of pharmacological interventions for improving the cognitive deficits in these disorders. As pro-cognitive pharmacological treatments are lacking, hormones or drugs that target the endocrine system may become potential candidates for 'repurposing' trials aiming to improve cognition. We aimed to study whether treatment with drugs targeting the hypothalamic-pituitary-adrenal (HPA) axis and sex steroids can improve cognition in patients with schizophrenia, MDD or BD. A systematic search was performed using PubMed (Medline), PsychInfo and clinicaltrials.gov, and a narrative synthesis was included. The systematic review identified 12 studies dealing with HPA-related drugs (mifepristone [n = 3], cortisol synthesis inhibitors [ketoconazole, n = 2], dehydroepiandrosterone [n = 5], fludrocortisone [n = 2]) and 14 studies dealing with sex steroids (oestradiol [n = 2], selective oestrogen receptor modulators [raloxifene, n = 7], pregnenolone [n = 5]). Positive trials were found for BD (mifepristone), MDD (dehydroepiandrosterone and fludrocortisone) and schizophrenia (dehydroepiandrosterone, raloxifene and pregnenolone). A replication of positive findings by at least two clinical trials was found for mifepristone in BD and raloxifene and pregnenolone in schizophrenia. The use of drugs targeting hormones related to the HPA axis and sex steroids is a promising field of research that might help to improve the cognitive outcome of patients with schizophrenia, bipolar disorder and major depressive disorder in the near future.
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Effect of exercise and/or reduced calorie dietary interventions on breast cancer-related endogenous sex hormones in healthy postmenopausal women.
de Roon, M, May, AM, McTiernan, A, Scholten, RJPM, Peeters, PHM, Friedenreich, CM, Monninkhof, EM
Breast cancer research : BCR. 2018;(1):81
Abstract
BACKGROUND Physical inactivity and being overweight are modifiable lifestyle risk factors that consistently have been associated with a higher risk of postmenopausal breast cancer in observational studies. One biologic hypothesis underlying this relationship may be via endogenous sex hormone levels. It is unclear if changes in dietary intake, physical activity, or both, are most effective in changing these hormone levels. OBJECTIVE This systematic review and meta-analysis examines the effect of reduced caloric dietary intake and/or increased exercise levels on breast cancer-related endogenous sex hormones. METHODS We conducted a systematic literature search in MEDLINE, Embase, and Cochrane's Central Register of Controlled Trials (CENTRAL) up to March 2017. Main outcome measures were breast cancer-related endogenous sex hormones. Randomized controlled trials (RCTs) reporting effects of reduced caloric intake and/or exercise interventions on endogenous sex hormones in healthy, physically inactive postmenopausal women were included. Studies including women using hormone therapy were excluded. The methodological quality of each study was assessed by the Cochrane's risk of bias tool. RESULTS From the 2599 articles retrieved, seven articles from six RCTs were included in this meta-analysis. These trials investigated 1588 healthy postmenopausal women with a mean age ranging from 58 to 61 years. A combined intervention of reduced caloric intake and exercise, with durations ranging from 16 to 52 weeks, compared with a control group (without an intervention to achieve weight loss) resulted in the largest beneficial effects on estrone treatment effect ratio (TER) = 0.90 (95% confidence interval (CI) = 0.83-0.97), total estradiol TER = 0.82 (0.75-0.90), free estradiol TER = 0.73 (0.66-0.81), free testosterone TER = 0.86 (0.79-0.93), and sex hormone biding globulin (SHBG) TER = 1.23 (1.15-1.31). A reduced caloric intake without an exercise intervention resulted in significant effects compared with control on total estradiol TER = 0.86 (0.77-0.95), free estradiol TER = 0.77 (0.69-0.84), free testosterone TER = 0.91 (0.84-0.98), and SHBG TER = 1.20 (1.06-1.36). Exercise without dietary change, versus control, resulted in borderline significant effects on androstenedione TER = 0.97 (0.94-1.00), total estradiol TER = 0. 97 (0.94-1.00), and free testosterone TER = 0. 0.97 (0.95-1.00). CONCLUSIONS AND RELEVANCE This meta-analysis of six RCTs demonstrated that there are beneficial effects of exercise, reduced caloric dietary intake or, preferably, a combination of exercise and diet on breast cancer-related endogenous sex hormones in physically inactive postmenopausal women.
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Circulating steroid levels as correlates of adipose tissue phenotype in premenopausal women.
Marchand, GB, Carreau, AM, Laforest, S, Côté, JA, Daris, M, Cianflone, K, Prehn, C, Adamski, J, Tchernof, A
Hormone molecular biology and clinical investigation. 2018;(1)
Abstract
Background Obesity-related alterations in the circulating steroid hormone profile remain equivocal in women. Our objective was to identify circulating steroid levels that relate to increased adiposity and altered adipose phenotype in premenopausal women. Materials and methods In a sample of 42 premenopausal women [age 46 ± 3 years; body mass index (BMI) 27.1 ± 4.2 kg/m2], 19 plasma steroids were quantified by electrospray ionization-liquid chromatography-tandem mass spectroscopy (ESI-LC-MS/MS). Body composition and fat distribution were assessed by dual-energy X-ray absorptiometry (DXA) and computed tomography (CT), respectively. Markers of adipose tissue function including adipocyte size distributions, radiological attenuation and macrophage infiltration were also analyzed in surgically obtained visceral and subcutaneous fat samples. Results Many negative correlations were observed between adiposity measurements such as BMI, body fat percentage or total abdominal adipose tissue area and plasma levels of androstenedione (Δ4) (r = -0.33 to -0.39, p ≤ 0.04), androsterone (ADT) (r = -0.30 to -0.38, p ≤ 0.05) and steroid precursor pregnenolone (PREG) (r = -0.36 to -0.46, p ≤ 0.02). Visceral adipocyte hypertrophy was observed in patients with low PREG concentrations (p < 0.05). Visceral adipose tissue radiologic attenuation, a potential marker of adipocyte size, was also positively correlated with PREG levels (r = 0.33, p < 0.05). Low levels of PREG were related to increased number of macrophages infiltrating visceral and subcutaneous adipose tissue (p < 0.05). Conclusion Plasma levels of androgens and their precursors are lower in women with increased adiposity and visceral adipocyte hypertrophy. Low circulating PREG concentration may represent a marker of adipose tissue dysfunction.
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Stroke Risk Factors Unique to Women.
Demel, SL, Kittner, S, Ley, SH, McDermott, M, Rexrode, KM
Stroke. 2018;(3):518-523
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7.
Sex differences, endogenous sex-hormone hormones, sex-hormone binding globulin, and exogenous disruptors in diabetes and related metabolic outcomes.
Liu, S, Sun, Q
Journal of diabetes. 2018;(6):428-441
Abstract
In assessing clinical and pathophysiological development of type 2 diabetes (T2D), the critical role of the sex steroids axis is underappreciated, particularly concerning the sex-specific relationships with many relevant cardiometabolic outcomes. In this issue of the Journal of Diabetes, we provide a comprehensive overview of these significant associations of germline variants in the genes governing the sex steroid pathways, plasma levels of steroid hormones, and sex hormone-binding globulin (SHBG) with T2D risk that have been observed in many clinical and high-quality large prospective cohorts of men and women across ethnic populations. Together, this body of evidence indicates that sex steroids and SHBG should be routinely incorporated into clinical characterization of T2D patients, particularly in screening prediabetic patients, such as those with metabolic syndrome, using plasma levels of SHBG. Given that several germline mutations in the SHBG gene have also been directly related to both plasma concentrations of SHBG and clinical manifestation of T2D, targeting signals in the sex steroid axis, particularly SHBG, may have significant utility in the prediction and treatment of T2D. Further, many of the environmental endocrine disrupting chemicals may exert their potential adverse effects on cardiometabolic outcomes via either estrogenic or androgenic signaling pathways, highlighting the importance of using the sex steroids and SHBG as important biochemical markers in both clinical and population studies in studying sex-specific mechanisms in the pathogenesis of T2D and its complications, as well as the need to equitably allocate resources in studying both men and women.
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8.
Chromium supplementation does not improve weight loss or metabolic and hormonal variables in patients with polycystic ovary syndrome: A systematic review.
Maleki, V, Izadi, A, Farsad-Naeimi, A, Alizadeh, M
Nutrition research (New York, N.Y.). 2018;:1-10
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age, and recently, chromium was discussed as an adjuvant way to manage it. Herein, a systematic review was conducted which centered on the effects of chromium on ovarian physiology with a focus on body mass index, as well as hormonal and metabolic dysfunctions in women suffering from PCOS. This review was performed using the guidelines from Preferred Reporting Items for Systematic Reviews. Clinical trials investigating chromium in women with PCOS with outcome measures related to metabolic and hormonal status were included. The search was conducted using PubMed, Scopus, and Google Scholar databases for clinical trials in the English language from the inception of the resources until May 2017 with the terms: chromium, chromium picolinate, CrP, polycystic ovary syndrome, PCOS, and sclerocystic ovary syndrome. The search resulted in 89 articles, and after inclusion and exclusion criteria were applied, 6 articles were selected for analysis. Two studies that evaluated the effect of chromium on body weight or body mass index reported no effect. Another study reported the beneficial effect of chromium on weight reduction. It seems that the effect of chromium in the reduction of blood glucose is insignificant, and results are inconsistent in relation to dyslipidemia. With regard to the effects of chromium on concentrations of sex hormones, a longer duration of treatment is needed to produce significant changes. The articles reviewed demonstrated that chromium supplementation has limited effects on weight reduction, glucose control, lipid profile, and hormonal disturbance of women with PCOS; however, more studies are needed due to the clinical changes observed in patients with PCOS after chromium supplementation.
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The effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.
Nasri, K, Jamilian, M, Rahmani, E, Bahmani, F, Tajabadi-Ebrahimi, M, Asemi, Z
BMC endocrine disorders. 2018;(1):21
Abstract
BACKGROUND To our knowledge, no reports are available indicating the effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with polycystic ovary syndrome (PCOS). This research was done to assess the effects of synbiotic supplementation on hormonal status, biomarkers of inflammation and oxidative stress in subjects with PCOS. METHODS This randomized double-blind, placebo-controlled trial was conducted on 60 subjects diagnosed with PCOS according to the Rotterdam criteria. Subjects were randomly assigned into two groups to take either synbiotic (n = 30) or placebo (n = 30) for 12 weeks. Endocrine, inflammation and oxidative stress biomarkers were quantified at baseline and after the 12-week intervention. RESULTS After the 12-week intervention, compared with the placebo, synbiotic supplementation significantly increased serum sex hormone-binding globulin (SHBG) (changes from baseline in synbiotic group: + 19.8 ± 47.3 vs. in placebo group: + 0.5 ± 5.4 nmol/L, p = 0.01), plasma nitric oxide (NO) (changes from baseline in synbiotic group: + 5.5 ± 4.8 vs. in placebo group: + 0.3 ± 9.1 μmol/L, p = 0.006), and decreased modified Ferriman Gallwey (mF-G) scores (changes from baseline in synbiotic group: - 1.3 ± 2.5 vs. in placebo group: - 0.1 ± 0.5, p = 0.01) and serum high-sensitivity C-reactive protein (hs-CRP) (changes from baseline in synbiotic group: - 950.0 ± 2246.6 vs. in placebo group: + 335.3 ± 2466.9 ng/mL, p = 0.02). We did not observe any significant effect of synbiotic supplementation on other hormonal status and biomarkers of oxidative stress. CONCLUSIONS Overall, synbiotic supplementation for 12 weeks in PCOS women had beneficial effects on SHBG, mFG scores, hs-CRP and NO levels, but did not affect other hormonal status and biomarkers of oxidative stress. TRIAL REGISTRATION This study was retrospectively registered in the Iranian website ( www.irct.ir ) for registration of clinical trials ( IRCT201509115623N53 ), on 2015-09-27.
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10.
The Physiology of Childhood Growth: Hormonal Regulation.
Benyi, E, Sävendahl, L
Hormone research in paediatrics. 2017;(1):6-14
Abstract
The growth patterns of a child changes from uterine life until the end of puberty. Height velocity is highest in utero and declines after birth until puberty when it rises again. Important hormonal regulators of childhood growth are growth hormone, insulin-like growth factor 1, sex steroids, and thyroid hormone. This review gives an overview of these hormonal regulators of growth and their interplay with nutrition and other key players such as inflammatory cytokines.