Increase In Sex Hormone-binding Globulin Research Articles

SUN-535 Impact of Route of Estrogen Administration on Bone Turnover Markers in Oligoamenorrheic Athletes and Mediators of these Effects

Transdermal, but not oral, estrogen replacement improves bone mineral density (BMD) in athletes with oligo-amenorrhea (OA). Our objective was to determine mechanisms that may explain the impact of route of estrogen administration on bone outcomes. Whereas IGF-1 is bone anabolic, sclerostin, preadipocyte factor-1 (Pref-1) and brain derived neurotropic factor (BDNF) inhibit bone formation, and an effect of estrogen on these factors has been demonstrated in other populations. However, few studies have examined the impact of route of estrogen administration on these factors in adolescents and young adults. Further, it is unclear how the route of estrogen administration impacts bioavailable testosterone, which in turn may impact bone outcomes in young oligo-amenorrheic women. 73 OA 14-25 years old received (i) a 17β-estradiol transdermal patch continuously with cyclic oral micronized progesterone (PATCH), (ii) a combined ethinyl estradiol and desogestrel pill (PILL), or (iii) no estrogen/progesterone (NONE) for 12-months. We evaluated fasting morning levels of a marker of bone formation [N-terminal propeptide of type 1 procollagen (P1NP)], a marker of bone resorption [N-telopeptide (NTX)], IGF-1, insulin-like growth factor binding protein 3 (IGFBP3), total testosterone, estradiol, sex hormone-binding globulin (SHBG), sclerostin, Pref-1, BDNF, calcium, 25(OH) vitamin D, and parathyroid hormone (PTH) at baseline and 12-months. Groups did not differ for age, weight, exercise activity or markers of bone formation at baseline. We have previously reported increases in areal BMD Z-scores at the spine and femoral neck in the PATCH compared to PILL and NONE groups (Ackerman et al: BJSM Oct. 2018). Over 12 months, between group analysis showed greatest decreases of P1NP in the PILL group (p=0.03) associated with a decrease in IGF-1 and IGF1/IGFBP-3 ratio (r=0.33, p≤0.05), and an increase in SHBG (r=-0.28;p=0.02). Within group analysis showed that sclerostin, Pref-1 and BDNF decreased in the PATCH group over 12 months (p=0.01, 0.01 and 0.04 respectively). PATCH group had the greatest increases in estradiol (p=0.0009), and estradiol increases were associated with increases in BMD. Groups did not differ for changes in NTX. Transdermal 17β-estradiol does not cause the decrease in IGF-1 and SHBG observed with oral ethinyl estradiol. It leads to decreases in sclerostin, Pref-1 and BDNF. These effects may mediate the beneficial effects of transdermal estrogen on bone in young women.

Efficiency of the D-chiro-inositol for the polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that develops in 10–15% of reproductive aged women. Over the past two decades, the inositol effectiveness in normalizing the clinical and hormonal disorders associated with PCOS has been actively studied. Inositol and its stereoisomers are classified as insulin sensitizers and act as a second conductor for insulin transmission routes. Myo-inositol and D-chiro-inositol are two of the nine existing stereoisomers the most studied currently, which play an important role in the PCOS physiology and treatment. The aim of the study was to study the Protalis effectiveness in patients with PCOS. 40 women with PCOS (mean age 24.4 ± 0.8 years) who were resistant to previous treatment with clomiphene citrate were examined. Protalis was administered for three months, after the end of the drug intake clomiphene citrate was used according to the standard regimen to restore fertility. The levels of luteinizing hormone, follicle-stimulating hormone, sex hormone binding globulin, total testosterone, antiMullerian hormone, homocysteine, folic acid were determined, and free androgen index was calculated. Fasting insulin was tested in serum and 120 minutes after the glucose load, the HOMA-IR was calculated, and lipid metabolism parameters were studied. Monotherapy with Protalis normalized the menstrual cycle in 52.5%, restore ovulation in 40%, contributed to the pregnancy in 7.5% patients with PCOS, in combination with clomiphene citrate in 27.5% women previously resistant to clomiphene. No changes in body mass index, waist circumference/hip circumference or hirsutism were found. A decrease in hyperandrogenism due to a testosterone decrease and an sex hormone binding globulin increase was found, the carbohydrate, lipid metabolism, and folate status improved. Protalis monotherapy can be recommended for patients with PCOS as a preliminary preparation, potentiating the clomiphene citrate effects, on the background insulin resistance. It is advisable to consider the Protalis use in combination with drugs for standard treatment of PCOS.

Effects of exercise on circulating levels of sex hormones in overweight and obese postmenopausal women: A systematic review

Summary Objective This study aimed to examine the evidence regarding the regulatory role of exercise in circulating levels of sex hormones in overweight and obese postmenopausal women. News Exercise has shown to be an effective non-pharmacological tool in obesity and breast cancer prevention. Sex hormones have been proposed as a potential link by which exercise may modulate obesity and breast cancer after menopause, however, the response of sex hormones as a metabolic pathway responsible for the connection between both pathologies are not entirely understood. An extensive search was performed using PubMed, Medline, Scopus and SPORTDiscus databases for the period from inception of each database to May 2018. A total of 778 studies were found in the search. Of these, 9 met the inclusion criteria and were further analyzed. Despite the different exercise protocols performed, most studies found a decrease in circulating levels of estrone and estradiol, and an increase in sex hormone-binding globulin (SHBG). However, when the effect of exercise on these sex hormones was compared to an unexercised control group, conflicting results were obtained. A reduction in body mass was reported in those studies in which exercise caused a significant effect on estrone, estradiol and SHBG compared to a control group. Conclusion These results suggest that exercise-induced weight loss and the type of exercise performed may to be critical factors in the modification of the circulation expression of some sex hormones. Further studies are required to elucidate the most effective exercise dose to restore sex hormones homeostasis as potential obesity-breast cancer nexus in the postmenopausal woman.

Relationship between sex hormone binding globulin and blood coagulation in women on postmenopausal hormone treatment.

: Postmenopausal hormone therapy increases the risk of venous thrombosis. Sex hormone binding globulin (SHBG) is a suggested marker of 'total estrogenicity'. The study objective was to evaluate the impact of hormone therapy on SHBG and the association with coagulation variables. The study populations comprised 202 healthy postmenopausal women randomized to treatment with low-dose or conventional-dose hormone therapy, tibolone or raloxifene (RET-study) and 140 women with a history of venous thrombosis randomized to conventional-dose hormone therapy or placebo (EVTET-study). SHBG was determined in serum collected at baseline and after 12 weeks. In healthy women, conventional-dose hormone therapy increased SHBG with mean 9.7 (95% confidence interval 4.8-14.5) nmol/l, low-dose hormone therapy by mean 5.9 (0.4-11.5) nmol/l, raloxifene by mean 7.2 (3.9-10.4) nmol/l, while tibolone reduced SHBG with mean -25.1 (-29.9 to -20.4) nmol/l. SHBG correlated with protein S, tissue factor pathway inhibitor (TFPI) and protein C at baseline, and with protein S and TFPI after 12 weeks, but the change in SHBG from baseline to 12 weeks was only associated with the change in activated protein C (APC) resistance. In women with a history of venous thrombosis, the mean increase in SHBG was 13.6 (8.4-18.9) nmol/l in the conventional-dose hormone therapy group, with no change in the placebo group. Baseline SHBG was higher among women who developed recurrent venous thrombosis on conventional-dose hormone therapy. SHBG correlated with several coagulation inhibitors, but the change in SHBG induced by postmenopausal hormone therapy was only associated with the change in APC resistance.

Testosterone, sex hormone-binding globulin and risk of cardiovascular events: A report from the Outcome Reduction with an Initial Glargine Intervention trial.

Testosterone and its binding protein sex hormone-binding globulin have been associated with cardiovascular disease and dysglycaemia. However, information on the prognostic implication in patients at high cardiovascular risk with dysglycaemia is inconsistent. The study objective was to determine whether testosterone and/or sex hormone-binding globulin predict cardiovascular events or death in dysglycaemic patients. Dysglycaemic males at high cardiovascular risk ( n = 5553) who participated in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial and provided baseline blood samples were studied. Testosterone and sex hormone-binding globulin were measured at baseline and used to estimate free testosterone. Low levels of total and free testosterone were defined as ≤300 ng/dl and ≤7 ng/dl, respectively. Patients were followed for six years for cardiovascular events (defined as the composite of cardiovascular death, non-fatal myocardial infarction or stroke) and all-cause mortality. The mean total and free testosterone levels were 416.6 ng/dl and 8.4 ng/dl, and low levels were present in 13% and 37% of the patients. The median sex hormone-binding globulin level was 35 nmol/l. In Cox regression models adjusted for age, previous diseases and pharmacological treatment, neither total nor free testosterone predicted cardiovascular events. However, a one-standard-deviation increase in sex hormone-binding globulin predicted both cardiovascular events (hazard ratio 1.07; 95% confidence interval 1.00-1.14; p = 0.03) and all-cause mortality (hazard ratio 1.13; 95% confidence interval 1.06-1.21; p < 0.01). Sex hormone-binding globulin, but not total testosterone, predicts cardiovascular disease and all-cause mortality in dysglycaemic males at high cardiovascular risk.

Changes in Sex Hormones After Laparoscopic Sleeve Gastrectomy in Chinese Obese Men: a 12-Month Follow-Up.

To examine changes in sex hormones after laparoscopic sleeve gastrectomy (LSG) in Chinese obese male patients and their correlation with metabolic parameters including serum uric acid (SUA) METHODS: A total of 56 obese men with body mass index (BMI) 41.9 ± 5.8kg/m2 undergoing LSG were selected. Thirty-one healthy men with normal BMI were included as controls. Levels of total testosterone (TT), estradiol (E2), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), SUA, and other metabolic indices were compared pre- and 12months post-LSG. Calculated free testosterone (cFT) was calculated from TT and SHBG using an empirical equation. At baseline, low TT and hyperuricemia (HUA) were common in obese men. Twelve months after LSG, statistically significant reduction in weight, BMI, and glucolipid metabolism indices was noted. SUA levels declined remarkably from 474.9 ± 94.6 to 338.8 ± 81.9μmol/L and the percentage of HUA decreased from 76.8 to 54.1% (all P< 0.001). Additionally, significant increases in TT, SHBG, and cFT as well as a decrease in percentage of low TT were observed after LSG (all P< 0.05), while E2, FSH, and LH did not change significantly. Moreover, changes in TT levels were more pronounced than those of other sex hormones. After age and BMI were adjusted, increased TT levels were correlated significantly with decreased SUA (β = - 1.077, P < 0.05), BMI (β = - 0.712, P < 0.001), and HOMA-IR (β = - 0.652, P < 0.05), as well as increased SHBG (β =0.759, P < 0.001). LSG promotes a significant increase in TT levels in Chinese obese men, which may be mediated by substantial weight loss, SUA reduction, and improved insulin resistance (IR).

Association between sex hormones and ambulatory blood pressure.

Higher levels of total testosterone and lower levels of sex hormone-binding globulin (SHBG) have been associated with increased blood pressure (BP) in women with an inverse association between total testosterone and BP among men. Fewer studies have examined associations with 24-h ambulatory blood pressure (ABP), blunted nocturnal BP decline or the role of dehydroepiandrosterone sulfate (DHEAS), a precursor to androgens. Baseline blood samples were assayed for 229 normotensive men (≥50 years) and women (≥55 years) participating in the VITamin D and OmegA-3 TriaL. Standardized seated BP (SBP and DBP) and 24-h ABP were measured by trained technicians. Self-reported cardiovascular risk factors and sociodemographic variables were reported on baseline questionnaires. Sex stratified linear regression models adjusted for age, race/ethnicity, BMI, smoking and alcohol estimated the association between each sex hormone and measures of BP and 24-h ABP. Logistic regression used to estimate associations with blunted nocturnal decline (>10% reduction in SBP or DBP during sleeping hours). Total testosterone and SHBG demonstrated significant inverse correlations with SBP whereas DHEAS was not significantly associated with BP. Among men, in multivariable analyses, each 10% increase in DHEAS was associated with a 0.41 mmHg higher seated DBP (β = 4.29, 95% CI 0.84-7.73) and each 10% increase in total testosterone and SHBG was associated with a 0.54 mmHg (β = -5.65, 95% CI -10.45 to -0.84) and 0.60 mmHg (β = -6.30, 95% CI -11.38 to -1.21) decrease in seated DBP, respectively. No significant associations were observed among women. Among men only, we observed statistically significant inverse cross-sectional associations between total testosterone and SHBG with seated DBP, and a significant positive association with DHEAS levels.

Mammographic Density and Circulating Sex Hormones: a Cross-Sectional Study in Postmenopausal Korean Women.

Mammographic density (MD) is a strong independent risk factor for breast cancer. It has been suggested that breast cancer is related to the exposure to circulating sex hormones. However, relations between MD and hormones have been inconsistent. In addition, such relations are mainly evaluated in Western populations. Therefore, we conducted a cross-sectional study in 396 cancer-free postmenopausal Korean women who had never used hormone replacement therapy. We assayed estradiol, testosterone, and sex hormone-binding globulin (SHBG) levels. We then calculated free testosterone (cFT) levels. Total and dense areas of digital mammogram were measured using a computer-assisted thresholding method, and non-dense area and percent dense area were calculated. Linear mixed model was used for analyses. Estradiol and testosterone levels were not associated with any MD measures after adjusting for reproductive factors and body mass index. However, cFT was persistently associated with non-dense area even after adjusting for covariates, with non-dense area increased by 3.5% per 1 standard deviation increase of cFT. SHBG showed an inverse association with non-dense area, although it showed a positive association with dense area and percent dense area regardless of adjustment for covariates. Non-dense area was decreased by 5.6% while percent dense area was increased by 13.4% per 1 standard deviation increase of SHBG. These findings suggest that SHBG might be related with breast cancer risk, probably through its association with breast density.

Effects of clomiphene citrate on male obesity-associated hypogonadism: a randomized, double-blind, placebo-controlled study.

Obesity causes secondary hypogonadism (HG) in men. Standard testosterone (T) replacement therapy improves metabolic parameters but leads to infertility. To evaluate clomiphene citrate (CC) treatment of adult men with male obesity-associated secondary hypogonadism (MOSH). Single-center, randomized, double-blind, placebo-controlled trial. Seventy-eight men aged 36.5 ± 7.8 years with a body mass index (BMI) > 30 kg/m2, total testosterone (TT) ≤ 300 ng/dL, and symptoms in the ADAM questionnaire. Random allocation to receive 50 mg CC or placebo (PLB) for 12 weeks. (1) Clinical features: ADAM and sexual behavior questionnaires; (2) hormonal profile: serum TT, free T, estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG); (3) body composition: BMI, waist circumference, and bioelectric impedance analysis; (4) metabolic profile: blood pressure, fasting blood glucose, HbA1c, insulin, HOMA-IR, and lipid profile; (5) endothelial function: flow-mediated dilation of the brachial artery, quantitative assessment of endothelial progenitor cells and serum sICAM-1, sVCAM-1, and selectin-sE levels; (6) safety aspects: hematocrit, serum prostate-specific antigen, International Prostate Symptom Score, and self-reported adverse effects. There was an improvement in one sexual complaint (weaker erections; P < 0.001); increases (P < 0.001) in TT, free T, E2, LH, FSH, and SHBG; and improvements in lean mass (P < 0.001), fat-free mass (P = 0.004), and muscle mass (P < 0.001) in the CC group. CC reduced HDL (P < 0.001). No statistically significant differences were seen in endothelial function. CC appeared to effectively improve the hormonal profile and body composition. CC may be an alternative treatment for MOSH in adult men.

Consensus Statement on the Use of Oral Contraceptive Pills in Polycystic Ovarian Syndrome Women in India.

Objective:To provide consensus recommendations for health-care providers on the use of oral contraceptive pills (OCPs) in polycystic ovarian syndrome (PCOS) women in India.Participants:Extensive deliberations, discussions, and brainstorming were done with different fraternities (specialists) being involved. These included endocrinologists, gynecologists, reproductive endocrinologists, dermatologists, public health experts, researchers, and a project manager with a team to develop the guideline.Evidence:Published literature was retrieved through searches of Medline and The Cochrane Database from January 2003 to December 2017 using appropriate-controlled vocabulary (e.g., oral contraceptive pills, polycystic ovarian syndrome, long term outcomes, infertility). Clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies' publications and data were also reviewed to suggest the recommendations.Process:The working group for guideline committee included members from the PCOS Society (India), Indian Society for Assisted Reproduction, The Mumbai Obstetric and Gynecological Society, The Endocrine Society of India, Indian Association of Dermatologists, Venereologists and Leprologists, Cosmetic Dermatology Society (India), Academicians from Medical Colleges, National Institute for Research in Reproductive Health, and a Research Associate. The core team included five reproductive endocrinologists, five gynecologists, five dermatologists, three endocrinologists, two public health experts and one research associate.Conclusions:This consensus statement provides the guidance/recommendations for Indian practitioners regarding the use of OCP in women with PCOS. PCOS is one of the common endocrinopathies encountered in gynecological/endocrine practice. The spectrum of this disorder may range from prepubertal girls with premature pubarche, young girls with hirsutism, acne and anovulatory cycles, married women with infertility, and elderly women. Although obesity is a common feature for most PCOS patients, 'lean PCOS' also exists. For several years, OCPs have played an important role in the symptom management of PCOS women. This is due to the fact that OCPs decrease the luteinizing hormone, reduce androgen production, and increase sex hormone-binding globulin, which binds androgens. Several new formulations of OCPs have been developed to decrease the side effects. This includes use of less androgenic progestins and lower doses of ethinyl estradiol. These consensus recommendations help the health provider to choose the right type of OCPs, which will alleviate the symptoms with least side effects. It also gives insight into the indications, contraindications, and concerns regarding its short, intermediate and long-term use.

In utero and lactational exposure to metformin induces reproductive alterations in male rat offspring

Metformin (MET) is prescribed for the treatment of type 2 diabetes mellitus and gestational diabetes. Although MET crosses the placenta, it is considered safe throughout gestation. However, it has been shown in humans that maternal exposure to MET increases sex hormone binding globulin levels in newborns, and in rats it decreases the testosterone concentration at gestational day (GD) 16.5. Therefore, the present study evaluated if maternal exposure to MET could interfere with reproductive parameters of male offspring. Wistar female rats were treated with MET 293mg/kg/day, by gavage from GD0 to GD21 (METG) or GD0 until lactational day (LD) 21 (METGL) and the control groups received water. Sexual behavior of male offspring was affected in both MET groups. However, a decrease in the sperm count was observed only in METGL group. These results suggest that MET exposure induced alterations in reproductive parameters of male offspring in adulthood depending on exposure time.

Cross-sectional association between testosterone, sex hormone-binding globulin and metabolic syndrome: The Healthy Twin Study.

This study evaluated an association between testosterone, sex hormone-binding globulin (SHBG) and metabolic syndrome (MetS).We also evaluated the genetic and environmental influences on the association. Cross-sectional. Community-based study. A total of 1098 Korean adult men including 139 monozygotic twin pairs. MetS was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP ATP III) and International Diabetes Federation (IDF) criteria. The associations between MetS and sex hormones were evaluated using linear mixed model and generalized estimating equation model. After considering covariates such as smoking, alcohol consumption and physical exercises as well as SHBG or testosterone, the risk of MetS defined by NCEP ATP III criteria decreased by 31%, 29%, and 48%, respectively, with 1-standard deviation increase in total testosterone (TT), free testosterone (cFT) and SHBG. Similar findings were revealed with IDF criteria. Metabolic component specific analysis showed that sex hormones were inversely associated with several components of MetS: TT with abdominal obesity, low high-density lipoprotein cholesterol (HDL-C) and high blood pressure; cFT with abdominal obesity and high blood pressure; SHBG with all components except high blood pressure. Cotwin control analysis found an inverse correlation between within-pair differences in testosterone and SHBG levels and within-pair differences in waist circumference only. Both testosterone and SHBG were inversely associated with MetS although the inverse associations with the sex hormones were not consistently found across individual metabolic components. Findings from cotwin analysis suggest a significant contribution of unshared unique environmental effect to the association between testosterone and SHBG and abdominal obesity.

Pharmacodynamic effects of the fetal estrogen estetrol in postmenopausal women: results from a multiple-rising-dose study

Estetrol (E4) is an estrogen produced exclusively by the human fetal liver during pregnancy. In this study the pharmacodynamic effects of escalating doses of E4 in postmenopausal women were investigated. This was a partly randomized, open-label, multiple-rising-dose study in 49 postmenopausal women. Participants were randomized to receive either 2 mg E4 or 2 mg estradiol-valerate (E2 V) for 28 days. Subsequent dose-escalation groups were (non-randomized): 10, 20 and 40 mg E4. Blood samples were collected regularly for measuring endocrine and hemostasis variables, lipids and lipoproteins, fasting glucose and bone turnover markers. Estetrol treatment resulted in a decrease of follicle-stimulating hormone and luteinizing hormone and an increase of sex-hormone binding globulin. Changes in hemostasis variables were small. A lowering effect on low-density lipoprotein cholesterol was accompanied with an increase in high-density lipoprotein cholesterol and no or minimal changes in triglycerides. The considerable decrease in osteocalcin levels in the three highest E4 dose groups and the small decrease in C-telopeptide levels were comparable to the E2 V control group and suggest a preventive effect on bone loss. All changes observed were dose-dependent. In this study, estetrol treatment showed dose-dependent estrogenic effects on endocrine parameters, bone turnover markers, and lipids and lipoproteins. The effect on triglycerides was small as were the effects on hemostatic variables. These results support the further investigation of estetrol as a candidate for hormone therapy. Quantitatively, the effects of 10 mg estetrol were similar to the study comparator 2 mg estradiol valerate.

Association between changes in fat distribution and biomarkers for breast cancer.

We assessed the associations between changes in total and abdominal fat and changes in biomarkers for breast cancer risk using data of the SHAPE-2 trial. In the SHAPE-2 trial, 243 postmenopausal overweight women were included. The intervention in this trial consisted of 5-6 kg weight loss either by diet only or exercise plus diet. After 16 weeks, we measured serum sex hormones, inflammatory markers, total body fat (measured by DEXA scan) and intra and subcutaneous abdominal fat (measured by MRI). Associations between changes in different body fat depots and biomarkers were analysed by linear regression using the study cohort irrespective of randomisation to make maximal use of the distribution of changes in fat measures. We found that a loss in total body fat was associated with favourable changes in free oestradiol, free testosterone, leptin and sex hormone binding globulin (SHBG). The loss of intra-abdominal fat was associated with a decrease in free testosterone, hsCRP and leptin, and an increase in SHBG. In the multivariable analysis, the best fitted models for the biomarkers free oestradiol, SHBG leptin and adiponectin included only total body fat. For free testosterone, this was subcutaneous abdominal fat, and for hsCRP and IL-6, only intra-abdominal fat change was important. For IL-6 and adiponectin, however, associations were weak and not significant. We conclude that, in our population of healthy overweight postmenopausal women, loss of fat at different body locations was associated with changes in different types of biomarkers, known to be related to risk of breast cancer.

Effects of Combat Deployment on Anthropometrics and Physiological Status of U.S. Army Special Operations Forces Soldiers.

U.S. Army Special Operations Forces (SOF) soldiers deploy frequently and conduct military operations through special warfare and surgical strike capabilities. Tasks required to execute these capabilities may induce physical and mental stress and have the potential to degrade soldier physiological status. No investigations have longitudinally characterized whether combat deployment alters anthropometrics or biochemical markers of physiological status in a SOF population of frequent deployers. Effects of modern combat deployment on longitudinal changes in anthropometrics and physiological status of elite U.S. Army SOF soldiers (n = 50) were assessed. Changes in measures of body composition, grip strength, physiological status, and health behaviors from baseline to postdeployment were determined with paired t test and McNemar's statistic. Baseline measures were obtained between 4 and 8 weeks before deployment. Deployment length was a uniform duration of time between 3 and 6 months (all soldiers completed the same length of deployment). Post hoc analyses determined change in body mass within quartiles of baseline body mass with paired t test and associations between change in sex hormone-binding globulin (SHBG) and change in body mass with correlation coefficient. The study was approved by the Human Use Review Committee at the U.S. Army Research Institute of Environmental Medicine, Natick, Massachusetts. In response to deployment, increases in lean mass (77.1 ± 7.6 to 77.8 ± 7.5 kg), maximum grip strength (57.9 ± 7.2 to 61.6 ± 8.8 kg), and conduct of aerobic (156 ± 106 to 250 ± 182 minutes/week) and strength training (190 ± 101 to 336 ± 251 minutes/week) exercise were observed (p < 0.05). Increases in serum SHBG (35.42 ± 10.68 to 38.77 ± 12.26 nmol/L) and decreases in serum cortisol (443.2 ± 79.3 to 381.9 ± 111.6 nmol/L) were also observed (p < 0.05). Body mass changes were dependent on baseline body mass. Soldiers in the lowest quartile of baseline body mass increased body mass (75.6 ± 2.6 vs. 76.6 ± 2.8 kg, p = 0.03), as did those in the second quartile (81.6 ± 2.0 vs. 83.7 ± 3.5 kg, p = 0.02). Those in the third quartile also tended to increase body mass (89.2 ± 2.6 vs. 90.9 ± 3.3 kg, p = 0.05), while those in the upper quartile tended to decrease body mass (98.5 ± 3.6 vs. 96.7 kg, p = 0.06). Change in SHBG was inversely correlated with change in body mass (r = -0.33, p = 0.02). There were no changes in fat mass, body fat percentage, waist circumference, neck circumference, total testosterone, calculated bioavailable or free testosterone, high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin-1β, or interleukin-6. Inflammatory markers were skewed toward lower values. Overall, physiological status of elite SOF soldiers characterized by multiple prior deployments was minimally impacted by combat deployment, in the absence of major unit casualties. The majority experienced some adaptive changes, including increased lean mass, grip strength, time spent engaged in exercise, and decreased levels of the stress hormone cortisol. Mechanisms contributing to inverse correlations between change in SHBG and change in body mass may be further clarified. Future investigations may also more fully characterize the degradation and optimization of health and physiological status of SOF training and deployment cycles with in-theater data collection and repeated measures.

Effects of Dietary Approach to Stop Hypertension diet on androgens, antioxidant status and body composition in overweight and obese women with polycystic ovary syndrome: a randomised controlled trial.

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive age women. The present study aimed to determine the effects of Dietary Approaches to Stop Hypertension (DASH) diet on reproductive hormones, plasma total antioxidant status and anthropometric indices in overweight and obese PCOS women. In this randomised controlled clinical trial, 60 women with PCOS were randomly assigned to one of two diets with energy restriction: the DASH diet and a control diet. The DASH and control diets consisted of 50-55% carbohydrate, 15-20% protein and 25-30% total fat. The DASH diet was designed to be rich in vegetables, fruits, whole grains and low-fat dairy products, as well as low in saturated fats, cholesterol, refined grains and sweets. In the present study, the anthropometric indices, body composition, total testosterone, androstenedione, sex hormone binding globulin (SHBG), free androgen index and 2,2'-diphenyl-1-picryylhydrazyl (DPPH) scavenging activity were measured before and after 3 months. The consumption of DASH diet compared to the control diet was associated with a significant reduction in weight [-5.78 (1.91) kg versus -4.34 (2.87) kg, P = 0.032], body mass index (BMI) [-2.29 (0.15) kg m-2 versus -1.69 (0.20) kg m-2 , P = 0.02], fat mass [-3.23(1.66) kg versus -2.13 (1.26) kg, P = 0.008] and serum androstenedione [-1.75 (1.39) ng mL-1 versus -1.02 (0.72) ng mL-1 , P-value = 0.019]. Increased concentrations of SHBG [28.80 (21.71) versus 11.66(18.82) nmol L-1 , P = 0.003) and DPPH scavenging activity [30.23% (19.09) versus 12.97% (25.12) were also found in the DASH group. The DASH diet could improve weight loss, BMI and fat mass. Furthermore, it could result in a significant reduction in serum androstenedione and a significant increase in antioxidant status and SHBG.

Association between Pesticide Biomarkers and Reproductive and Thyroid Hormones in Pregnant Women

Introduction: Prenatal exposure to pesticides may be associated with health effects, including changes in maternal hormone levels that could potentially lead to adverse birth outcomes. The association of pesticides with reproductive and thyroid hormones were examined in the first 44 pregnant women (86 observations) recruited for a large prospective cohort study in Puerto Rico. Methods: Serum hormone levels (estrogen, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH)) and urinary pesticide biomarkers (parathion, a pyrethyroid metabolite, three DEET metabolites, and five organophospohate (OP) metabolites) were measured at two visits during pregnancy (16-20 and 24-28 weeks). We used linear mixed models with a random intercept to examine associations between the exposure biomarkers and hormones, adjusting for specific gravity, visit, maternal age, BMI and education. All pesticide biomarkers, progesterone and TSH were log-transformed. Results: The only significant association among reproductive hormones was a 9.13% increase (95% CI 2.90, 15.36) in SHBG with an IQR increase in diethylthiophosphate (OP metabolite). An IQR increase across all DEET metabolites (3-(diethylcarbamoyl)benzoic acid (DCBA), N-ethyl-3-methyl-benzamide and N,N-diethyl-3-(hydroxymethyl)benzamide) was associated with a 5.45% (95% CI -10.61, -0.29), 3.32% (95% CI -6.36, -0.28) and 1.66% (95% CI -3.67, 0.35) decrease in FT3, respectively. The results also suggested a 15.90% (95% CI -1.48, 36.33) and a 19.64% (95% CI -2.60, 46.97) increase in TSH with an IQR increase in DCBA and the pyrethroid metabolite, respectively. Conversely, a 9.16% decrease (95% CI -18.19, 0.86) in TSH was observed with an IQR increase in dimethyldithiophosphate (OP metabolite). Conclusions: In this exploratory study, pyrethroid, DEET and OP were associated with SHBG, TSH and FT3 which may potentially lead to adverse health effects.

Phenols and parabens in relation to reproductive and thyroid hormones in pregnant women

IntroductionPhenols and parabens are ubiquitous environmental contaminants. Evidence from animal studies and limited human data suggest they may be endocrine disruptors. In the current study, we examined associations of phenols and parabens with reproductive and thyroid hormones in 106 pregnant women recruited for the prospective cohort, “Puerto Rico Testsite for Exploring Contamination Threats (PROTECT)”. MethodsUrinary exposure biomarkers (bisphenol A, triclosan, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, butyl, methyl and propyl paraben) and serum hormone levels (estradiol, progesterone, sex hormone-binding globulin (SHBG), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone) were measured at up to two time points during pregnancy (16–20 weeks and 24–28 weeks). We used linear mixed models to assess relationships between exposure biomarkers and hormone levels across pregnancy, controlling for urinary specific gravity, maternal age, BMI and education. In sensitivity analyses, we evaluated cross-sectional relationships between exposure and hormone levels stratified by study visit using linear regression. ResultsAn IQR increase in methyl paraben was associated with a 7.70% increase (95% CI 1.50, 13.90) in SHBG. Furthermore, an IQR increase in butyl paraben as associated with an 8.46% decrease (95% CI 16.92, 0.00) in estradiol, as well as a 9.34% decrease (95% CI −18.31,−0.38) in estradiol/progesterone. Conversely, an IQR increase in butyl paraben was associated with a 5.64% increase (95% CI 1.26, 10.02) in FT4. Progesterone was consistently negatively associated with phenols, but none reached statistical significance. After stratification, methyl and propyl paraben were suggestively negatively associated with estradiol at the first time point (16–20 weeks), and suggestively positively associated with estradiol at the second time point (24–28 weeks). ConclusionsWithin this ongoing birth cohort, certain phenols and parabens were associated with altered reproductive and thyroid hormone levels during pregnancy. These changes may contribute to adverse health effects in mothers or their offspring, but additional research is required.

Progressive Temporal Change in Serum SHBG, But Not in Serum Testosterone or Estradiol, Is Associated With Bone Loss and Incident Fractures in Older Men: The Concord Health and Ageing in Men Project.

This study aimed to examine progressive temporal relationships between changes in major reproductive hormones across three waves of a cohort study of older men and (1) changes in bone mineral density (BMD) and (2) incident fractures (any, hip or non-vertebral) over an average of 6 years of follow-up. The CHAMP cohort of men aged 70 years and older were assessed at baseline (2005 to 2007, n = 1705), 2-year follow-up (n = 1367), and 5-year follow-up (n = 958). Serum testosterone (T), dihydrotestosterone (DHT), estradiol (E2), and estrone (E1) (by liquid chromatography-tandem mass spectrometry [LC-MS/MS]), and sex hormone-binding globulin (SHBG), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) (by immunoassay) were measured at all time-points, whereas free testosterone (cFT) was calculated using a well-validated formula. Hip BMD was measured by dual-energy X-ray absorptiometry (DXA) at all three time-points, and fracture data were verified radiographically. Statistical modeling was done using general estimating equations (GEEs). For total hip BMD, univariable analyses revealed inverse associations with temporal changes in serum SHBG, FSH, and LH and positive associations for serum E1 and cFT across the three time-points. In models adjusted for multiple covariables, serum SHBG (β = -0.029), FSH (β = -0.065), LH (β = -0.049), E1 (β = 0.019), and cFT (β = 0.033) remained significantly associated with hip BMD. However for femoral neck BMD, only FSH (β = -0.048) and LH (β = -0.036) remained associated in multivariable-adjusted models. Temporal change in serum SHBG, but not T, E2, or other hormonal variables, was significantly associated with any, nonvertebral or hip fracture incidence in univariable analyses. In multivariable-adjusted models, temporal increase in serum SHBG over time remained associated with any fracture (β = 0.060) and hip fracture (β = 0.041) incidence, but not nonvertebral fracture incidence. These data indicate that a progressive increase in circulating SHBG over time predicts bone loss and fracture risk in older men. Further studies are warranted to further characterize changes in circulating SHBG as a mechanism and/or biomarker of bone health during male ageing. © 2016 American Society for Bone and Mineral Research.

Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women.

The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program. Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32 ng/mL ("insufficient") were randomized to either weight loss + 2,000 IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P > 0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend = 0.01), and larger decreases in free and bioavailable estradiol (Ptrend = 0.04, Ptrend = 0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n = 38), to women who became replete (25-hydroxyvitamin D ≥32 ng/mL; n = 53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7 pg/mL), free testosterone (-0.8 vs -0.3 pg/mL), and bioavailable testosterone (-1.8 vs -0.6 ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7 nmol/L) (all P < 0.05), even after adjusting for differences in total 12-month weight loss. Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.