Free Estradiol Research Articles

Influence of malignant growth and chronic neurogenic pain on neurosteroid levels in rat brain

The aim of the study was to determine the level of sex steroid hormones in white matter of the brain of rats with tumors combined with chronic neurogenic pain (CNP), which was modeled by bilateral sciatic nerve ligation. The study included albino male rats (n=74). In the main group, M1 sarcoma was transplanted subcutaneously (n=11) or into the subclavian vein (n=11) 45 days after CNP modeling. Two comparison groups (n=13 each) included sham operated animals (without CNP) with M1 sarcoma transplanted subcutaneously and intravenously. Control groups included animals with CNP and sham operated animals. Rats were euthanized on day 21 of the carcinogenesis. Levels of total and free testosterone (T), estrone (E1), estradiol (E2), estriol (E3) and progesterone (P4) in the brain white matter were measured using ELISA kits ("Cusabio", China). CNP caused a decrease in the total and free T by 1.5 times (p<0.05), E2 and P4 by 1.9 and 3 times, respectively, E3 by 1.6 times (p<0.05), as well as an increase in E1 by 1.4 times (p<0.05) as compared to the corresponding levels in the brain white matter of rats without CNP. CNP stimulated M1 sarcoma growth in both subcutaneous and intravenous transplantation. Regardless of the tumor site, the dynamics of total T, E2 and E3 in the brain had similar features, but the dynamics of free T, P4 and E1 differed. Thus, changes in the level of neurosteroids in the white matter of rat brain with CNP and tumor growth alone or associated with CNP are a reaction to stress.

Clinical Analysis of Elevated Free Oestradiol in Men of Eket: An Insight into Preventing Prostate Proliferation

Clinical Analysis of Elevated Free Oestradiol in Men of Eket: An Insight into Preventing Prostate Proliferation

Baicalin ameliorates polycystic ovary syndrome through AMP-activated protein kinase

Polycystic ovary syndrome (PCOS) is a complex endocrine disorder and regarded as the leading cause of anovulatory infertility. PCOS is characterized by reproductive dysfunction and metabolic disorders. Baicalin (BAL) is one of the most potent bioactive flavonoids isolated from the radix of Scutellaria baicalensis. In the present study, we investigated the potential effects of BAL on PCOS in dehydroepiandrosterone-treated rats. We found that BAL notably reduced the serum levels of free testosterone, total testosterone, follicle-stimulating hormone, luteinizing hormone, progesterone, and estradiol in PCOS rats. The increase of serum insulin level and HOMA-IR was markedly inhibited by BAL. Moreover, BAL decreased body weights, increased the number of rats with the regular estrous cycle, and ameliorated ovarian histological changes and follicular development in the DHEA-treated PCOS rats. The increase of pro-inflammatory cytokines (TNFα, IL-1β, and IL-18) and decrease of anti-inflammatory cytokine (IL-10) in PCOS rats were suppressed by BAL. BAL induced a significant decrease in the mRNA expression of steroidogenic enzymes, including 3β-HSD, CYP11A1, CYP19A1, StAR, in ovarian tissues in PCOS rats. Furthermore, BAL inhibited the decrease of AMPK protein level and phosphorylation, the decrease of Akt phosphorylation and the increase of 5α-reductase enzyme 1 expression in ovarian tissues in PCOS rats. The effects of BAL were inhibited by an inhibitor of AMPK, dorsomorphin. The upregulation of AMPK contributed to the beneficial effects of BAL. The results highlight the potential role of BAL for the intervention of PCOS.

Endogenous sex hormones and risk of venous thromboembolism in young women

BackgroundThe risk of venous thromboembolism (VTE) in young women can predominantly be attributed to exogenous hormone use. The influence of (abnormalities in) endogenous sex hormones, as in polycystic ovary syndrome (PCOS) or primary ovarian insufficiency (POI), on VTE risk is uncertain. ObjectivesTh assess the association between endogenous sex hormone levels and VTE risk. MethodsWomen aged ≤45 years from the MEGA case‐control study who provided a blood sample in the absence of exogenous hormone exposure or pregnancy were included. Sex hormone–binding globulin (SHBG), estradiol, follicle‐stimulating hormone (FSH) and testosterone were measured. The free androgen index (FAI) and estradiol to testosterone ratio (E:T) were calculated. VTE risk was assessed according to quartiles (Qs) of levels and clinical cut‐offs as proxies for PCOS (FAI > 4.5) and POI (FSH > 40 U/L). Logistic regression models were used to estimate adjusted odds ratios (ORs) with 95% confidence intervals (CIs). ResultsSix hundred and sixty‐five women (369 cases; 296 controls) were eligible for the analyses. Testosterone and FSH levels, E:T and POI (FSH > 40 U/L vs FSH ≤ 40 U/L) were not associated with VTE risk. For estradiol, VTE risk was increased with levels in Q4 vs Q1 (OR 1.6; 95% CI 1.0‐2.5). There was a dose‐response relationship between SHBG levels and VTE risk, with the highest OR at Q4 vs Q1: 2.0 (95% CI 1.2‐3.3). FAI > 4.5 (PCOS proxy) vs FAI ≤ 4.5 was associated with increased VTE risk (OR 3.3; 95% CI 0.9‐11.8). ConclusionsEstradiol, SHBG and FAI were associated with VTE risk, suggesting a role for endogenous sex hormones in the pathophysiology of VTE in young women.

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

Age-Specific Serum Total and Free Estradiol Concentrations in Healthy Men in US Nationally Representative Samples.

PurposeTo report age-specific serum estradiol concentration in nonsmoking, lean US men without comorbidities. We provide concentrations from 30 and 15 to 20 years ago given previously described declines in serum estradiol in US men over time.MethodsWe used data from the Third National Health and Nutrition Examination Survey (NHANES III; 1988 to 1991) and continuous NHANES (1999 to 2004). Serum estradiol and SHBG were previously measured by competitive electrochemiluminescence immunoassays. Free estradiol was estimated from estradiol, SHBG, and albumin. By age, we calculated median concentrations overall and for nonsmoking, lean (body mass index <25 kg/m2 and waist <102 cm) men without diabetes, cardiovascular disease, or cancer.ResultsOverall, respective total estradiol medians for men ages 20 to 39, 40 to 59, and ≥60 years old were 37.0, 33.9, and 33.5 pg/mL in NHANES III and 31.3, 30.5, and 27.0 pg/mL in continuous NHANES. In nonsmoking, lean men without comorbidities, respective total estradiol medians were 32.0, 32.1, and 32.0 pg/mL in NHANES III and 29.1, 22.7, and 26.1 pg/mL in continuous NHANES. Overall, respective free estradiol medians were 0.82, 0.72, and 0.64 pg/mL in NHANES III and 0.67, 0.61, and 0.47 pg/mL in continuous NHANES. In nonsmoking, lean men without comorbidities, respective free estradiol medians were 0.64, 0.67, and 0.62 pg/mL in NHANES III and 0.58, 0.42, and 0.40 pg/mL continuous NHANES.ConclusionWe report US nationally representative serum estradiol concentrations in healthy men, which could be used for targeting estradiol during testosterone supplementation and for general good health.

Cross-sectional associations between healthy eating index and sex steroid hormones in men-National Health and Nutrition Examination Survey 1999-2002.

Diet plays an important role in health and is a modifiable risk factor for chronic diseases. In men, sex steroid hormones influence, and are influenced by, a number of health states. Specific dietary patterns have been found to alter sex steroid hormone levels in observational and intervention studies. Thus, we hypothesized that dietary patterns captured by the Healthy Eating Index (HEI) are associated with serum concentrations of sex steroid hormones and sex hormone-binding globulin (SHBG). The objective is investigating the association between HEI and sex steroid hormones and SHBG in a general US population of men. We used data on serum sex steroid hormones and SHBG levels, HEI, and other variables collected in the National Health and Nutrition Examination Survey (NHANES), 1999-2002. A total of 550 men >20years old were included in the analysis. The cross-sectional associations between HEI (from 0 to 100 points, higher score equates to a healthier diet) with natural logarithm transformed concentrations of total and free testosterone, total and free estradiol, and SHBG were evaluated with multivariable linear regression models and adjusted for potential confounders. We also stratified by the body mass index (BMI) and race/ethnicity and tested for interactions. HEI showed a significant inverse association with free estradiol (p=0.03), but was not associated with total or free testosterone, total estradiol, or SHBG concentrations. Neither BMI nor race/ethnicity statistically significantly modified the association between HEI and sex steroid hormone levels. The present cross-sectional analysis in a representative sample of US men showed no consistent association between eating habits, sex steroid hormones, and SHBG. Longitudinal studies are needed to further investigate potential associations.

Increase in Osteocalcin Following Testosterone Therapy in Men With Type 2 Diabetes and Subnormal Free Testosterone.

ContextOne-third of men with type 2 diabetes have subnormal free testosterone concentrations. We evaluated the following: (i) whether bone mineral density (BMD) and bone strength are affected by gonadal status in type 2 diabetes and (ii) the effect of testosterone replacement on markers of osteoblast and osteoclast activity.DesignThis is a secondary analysis of a previously completed, randomized, placebo-controlled trial. Ninety-four men with type 2 diabetes were recruited; 44 had subnormal free testosterone concentrations. Men with subnormal free testosterone concentrations were randomized to receive intramuscular injections of testosterone or placebo every 2 weeks for 22 weeks. Dual energy X-ray absorptiometry scans were performed at baseline and at 23 weeks.ResultsMen with subnormal free testosterone had similar BMD compared with men with normal free testosterone. However, bone strength indices were lower in men with subnormal free testosterone. BMD was related to free estradiol concentrations (r = 0.37, P = 0.004 at hip), whereas bone strength was related to free testosterone concentrations (r = 0.41, P < 0.001). Testosterone replacement increased osteocalcin concentrations [mean change (95% CI), 3.52 (0.45, 6.59), P = 0.008]. C-Terminal telopeptide (CTx) concentrations also increased at 15 weeks but reverted to baseline following that. There were no changes in other bone turnover markers or BMD.ConclusionWe conclude that testosterone replacement resulted in an increase in osteocalcin and a transient increase in CTx, indicating an increase in osteoblastic activity and transient increase in bone breakdown. Therefore, a major action of testosterone is to increase bone turnover in men with type 2 diabetes.

Adiposity and estrogen receptor-positive, postmenopausal breast cancer risk: Quantification of the mediating effects of fasting insulin and free estradiol.

Adiposity increases estrogen receptor (ER)-positive postmenopausal breast cancer risk. While mechanisms underlying this relationship are uncertain, dysregulated sex-steroid hormone production and insulin signaling are likely pathways. Our aim was to quantify mediating effects of fasting insulin and free estradiol in the adiposity and ER-positive postmenopausal breast cancer association. We used data from a case-cohort study of sex hormones and insulin signaling nested within the Melbourne Collaborative Cohort Study. Eligible women, at baseline, were not diagnosed with cancer, were postmenopausal, did not use hormone therapy and had no history of diabetes or diabetes medication use. Women with ER-negative disease or breast cancer diagnosis within the first follow-up year were excluded. We analyzed the study as a cumulative sampling case-control study with 149 cases and 1,029 controls. Missing values for insulin and free estradiol were multiply imputed with chained equations. Interventional direct (IDE) and indirect (IIE) effects were estimated using regression-based multiple-mediator approach. For women with body mass index (BMI) >30 kg/m2 compared to women with BMI 18.5-25 kg/m2 , the risk ratio (RR) of breast cancer was 1.75 (95% confidence interval [CI] 1.05-2.91). The estimated IDE (RR) not through the mediators was 1.03 (95% CI 0.43-2.48). Percentage mediated effect through free estradiol was 72% (IIE-RR 1.56; 95% CI 1.11-2.19). There was no evidence for an indirect effect through insulin (IIE-RR 1.12; 95% CI 0.68-1.84; 28% mediated). Our results suggest that circulating free estradiol plays an important mediating role in the adiposity-breast cancer relationship but does not explain all of the association.

Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort.

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.

Long-term weight loss maintenance, sex steroid hormones, and sex hormone-binding globulin.

We tested the effects of weight loss on serum estradiol, estrone, testosterone, and sex hormone-binding globulin (SHBG) in overweight/obese women 18 months after completing a year-long, 4-arm, randomized-controlled dietary weight loss and/or exercise trial. From 2005 to 2008, 439 overweight/obese, postmenopausal women (BMI >25 kg/m), 50 to 75 years, were randomized to a year-long intervention: diet (reduced calorie, 10% weight loss, N = 118), exercise (225 min/wk moderate-to-vigorous activity, N = 117), combined diet + exercise (N = 117), or control (N = 87). At 12 months, 399 women provided blood; of these, 156 returned at 30 months and gave a blood sample. Hormones and SHBG were measured by immunoassay. Changes were compared using generalized estimating equations, adjusting for confounders. At 30 months, participants randomized to the diet + exercise intervention had statistically significant increases in SHBG levels versus controls (P = 0.001). There was no statistically significant change in SHBG in the exercise or diet intervention arms. Hormone levels did not vary by intervention arm from baseline to 30 months. Participants who maintained weight loss at 30 months had statistically significantly greater decreases in free estradiol and free testosterone (Ptrend = 0.02 and Ptrend = 0.04, respectively) and increases in SHBG (Ptrend < 0.0001) versus those who did not have sustained weight loss. Levels of other analytes did not vary by weight loss at 30 months. Sustained weight loss results in reductions in free estradiol and testosterone and increases in SHBG 18-month post-intervention.

Selenium and Sex Steroid Hormones in a U.S. Nationally Representative Sample of Men: A Role for the Link between Selenium and Estradiol in Prostate Carcinogenesis?

Given the recent findings from pooled studies about a potential inverse association between selenium levels and prostate cancer risk, this cross-sectional study aimed to investigate the association between serum selenium and serum concentrations of sex steroid hormones including estradiol in a nationally representative sample of U.S. men to investigate one mechanism by which selenium may influence prostate cancer risk. The study included 1,420 men ages 20 years or older who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We calculated age/race-ethnicity-adjusted and multivariable-adjusted geometric mean serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide, and sex hormone binding globulin, and compared them across quartiles of serum selenium. Adjusting for age, race/ethnicity, smoking status, serum cotinine, household income, physical activity, alcohol consumption, and percent body fat, mean total estradiol [e.g., Q1, 38.00 pg/mL (95% confidence interval (CI), 36.03-40.08) vs. Q4, 35.29 pg/mL (95% CI, 33.53-37.14); P trend = 0.050] and free estradiol [e.g., Q1, 0.96 pg/mL (95% CI, 0.92-1.01) vs. Q4, 0.90 (95% CI, 0.85-0.95); P trend = 0.065] concentrations decreased over quartiles of selenium. Stratification by smoking and alcohol consumption, showed that the latter observation was stronger for never smokers (P interaction = 0.073) and those with limited alcohol intake (P interaction = 0.017). No associations were observed for the other sex steroid hormones studied. Our findings suggests that a possible mechanism by which selenium may be protective for prostate cancer is related to estrogen. Further studies of longitudinal measurements of serum and toenail selenium in relation to serum measurements of sex steroid hormones are needed.

Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals

Coffee consumption has been linked to lower risk of various health outcomes. However, the biological pathways mediating the associations remain poorly understood. The aim of this study was to assess the association between coffee consumption and concentrations of plasma biomarkers in key metabolic and inflammatory pathways underlying common chronic diseases. We investigated the associations of total, caffeinated, and decaffeinated coffee consumption with 14 plasma biomarkers, including C-peptide, insulin-like growth factor 1 (IGF-1), IGF binding protein (IGFBP) 1, IGFBP-3, estrone, total and free estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), total adiponectin, high-molecular-weight (HMW) adiponectin, leptin, C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor receptor 2 (sTNFR-2). Data were derived from 2 cohorts of 15,551 women (Nurses' Health Study) and 7397 men (Health Professionals Follow-Up Study), who provided detailed dietary data before blood draw and were free of diabetes, cardiovascular disease, or cancer at the time of blood draw. Multivariable linear regression was used to calculate the percentage difference of biomarker concentrations comparing coffee drinkers with nondrinkers, after adjusting for a variety of demographic, clinical, and lifestyle factors. Compared with nondrinkers, participants who drank ≥4 cups of total coffee/d had lower concentrations of C-peptide (-8.7%), IGFBP-3 (-2.2%), estrone (-6.4%), total estradiol (-5.7%), free estradiol (-8.1%), leptin (-6.4%), CRP (-16.6%), IL-6 (-8.1%), and sTNFR-2 (-5.8%) and higher concentrations of SHBG (5.0%), total testosterone (7.3% in women and 5.3% in men), total adiponectin (9.3%), and HMW adiponectin (17.2%). The results were largely similar for caffeinated and decaffeinated coffee. Our data indicate that coffee consumption is associated with favorable profiles of numerous biomarkers in key metabolic and inflammatory pathways. This trial was registered at clinicaltrials.gov as NCT03419455.

Impact of Bariatric Surgery on Male Sex Hormones and Sperm Quality: a Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aims to establish the effects of bariatric surgery on male sex hormones, sperm parameters, and sexual function. We searched MEDLINE, EMBASE, Web of Science, and Scopus from database inception through June 2018. Articles were eligible for inclusion if they examined the effect of bariatric surgery on male sex hormones and sperm parameters in patients with obesity. Primary outcomes of interest were sex hormones and sperm quality. Secondary outcome was sexual function (International Index of Erectile Function (IIEF) score). Pooled estimates were calculated using random effects meta-analysis. A total of 28 cohort studies with 1022 patients were identified from 3896 potentially relevant citations. Both free and calculated testosterone levels were significantly increased after bariatric surgery (mean difference (MD) - 7.47nM, 95% CI - 8.62 to - 6.31, p < 0.001 and MD - 0.05nM, 95% CI - 0.07 to - 0.02, p < 0.001, respectively). Consistent with the increase in testosterone, LH, FSH, and SHBG levels were also significantly increased after surgery. In contrast, free and total estradiol and prolactin levels were significantly decreased after bariatric surgery. From studies that reported the IIEF score, bariatric surgery led to a significant increase in erectile function after surgery (MD - 0.46, 95% CI - 0.89 to - 0.02, p = 0.04). However, bariatric surgery did not affect sperm quality, DHEA, androstenedione, and inhibin B levels. Sustained weight-loss induced by bariatric surgery had a significant effect on increasing male sex hormones and decreasing female sex hormones in male patients with obesity. However, sperm quality and function were not improved after surgery.

Serum chemerin levels are negatively associated with male fertility and reproductive hormones.

Are chemerin levels different in subfertile men compared to men from the general population, and how does chemerin relate to reproductive hormonal status? Chemerin is negatively associated to LH, SHBG and estradiol and lower levels of chemerin are detected among subfertile men compared to controls. Adipokines have pleiotropic effects on tissue homeostasis and have been shown to affect both sex steroid production and action. Among adipokines the newly characterized chemokine chemerin is suggested to influence testosterone production in males, but whether serum levels associate with testosterone or male subfertility has not yet been reported. Case control study comprising a consecutive group of men from infertile couples referred to Reproductive Medicine Centre at Skane University Hospital from 2006 through 2012, and age-matched controls. Participants were enrolled in years 2011-2013. Males from infertile couples (n = 180) aged 18-50 years with sperm concentration <20 × 106/ml and age-matched controls (n = 139) from the general population were enrolled. Serum concentrations of total testosterone (TT), calculated free testosterone (cFT), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and sex-hormone binding globuline (SHBG) as well as the adipokines chemerin, adiponectin and leptin were measured. Anthropometrics and biochemical parameters of glucose and lipid metabolism were assessed. Chemerin levels were lower in subfertile men compared to controls (mean diff. 7.1 ng/ml; 95% CI, 3.7; 11 ng/ml; P < 0.001) even after adjustment for BMI. After adjustment for age, BMI, smoking, leptin and adiponectin, chemerin associated negatively with LH (ß = -4.2; P = 0.02), E2 (ß = -10; P = 0.004) and SHBG (ß = -7.4, P = 0.003). Men with elevated LH levels had lower chemerin levels compared to those with LH levels within the normal range (mean diff. 4.8 ng/ml; 95% CI, 0.16; 9.4 ng/ml; P = 0.04). Single sample blood test with immunoassays for determination of hormone levels. Heterogeneous group of subfertile subjects. Even though chemerin has been positively associated with BMI, inverse association with subfertility suggests that it is independently linked to reproductive function, a hypothesis that warrants further assessment. This work was supported by grants from EU Interreg V (ReproUnion) program as well as Swedish Governmental Fund for Clinical Research. The authors have no conflicts of interest.

Oestradiol level, oestrogen receptors, and mortality in elderly men: The three-city cohort study.

Although endogenous oestradiol, generally considered as the female hormone, has been little investigated in men, it could play a role in men's health, mortality in particular. The influence of oestrogen receptors (ER) genetic polymorphisms on this relationship has never been studied. The Three-City cohort study included (1999-2001) 3650 men ≥65years who were followed for mortality over 12years. At baseline, total oestradiol (tE2) was measured and ER genotyped in a random subsample of 472 men without hormonal treatment. Free oestradiol (fE2) was estimated using Vermeulen and Södergard algorithms. Mortality data were obtained from death certificates.We used inverse probability weighted Cox models to examine the association of oestradiol with all-cause and cause-specific mortality and its interaction with ER genetic polymorphisms. A total of 183 men died over the follow-up (cardiovascular disease (CVD), n=44; cancer, n=57; other causes, n=82). After adjustment, there was a quadratic relationship of all-cause mortality with tE2 and fE2 (P-quadratic=0.04 and 0.05, respectively), with higher mortality for the top and bottom tertiles compared to the middle one. These associations were stronger for CVD mortality (P-quadratic=0.01 and 0.02 for tE2 and fE2, respectively) and disappeared for cancer mortality. There was no evidence of an interaction of oestradiol with any ER polymorphisms on all-cause mortality. In elderly men, we showed a nonlinear association of tE2 and fE2 with all-cause mortality. These quadratic relationships were stronger for CVD mortality and did not exist for cancer mortality. ER genetic polymorphisms did not modify this association.

Testosterone, myocardial function, and mortality.

The cardiovascular system is particularly sensitive to androgens, but some controversies exist regarding the effect of testosterone on the heart. While among anabolic abusers, cases of sudden cardiac death have been described, recently it was reported that low serum level of testosterone was correlated with increased risk of cardiovascular diseases (CVD) and mortality rate. This review aims to evaluate the effect of testosterone on myocardial tissue function, coronary artery disease (CAD), and death. Low testosterone level is associated with increased incidence of CAD and mortality. Testosterone administration in hypogonadal elderly men and women has a positive effect on cardiovascular function and improved clinical outcomes and survival time. Although at supraphysiologic doses, androgen may have a toxic effect, and at physiological levels, testosterone is safe and exerts a beneficial effect on myocardial function including mechanisms at cellular and mitochondrial level. The interaction with free testosterone and estradiol should be considered. Further studies are necessary to better understand the interaction mechanisms for an optimal androgen therapy in CVD.

Sex hormone–binding globulin is a biomarker associated with nonvertebral fracture in men on dialysis therapy

Gonadal hormones impact bone health and higher values of sex hormone-binding globulin (SHBG) have been independently associated with fracture risk in men without chronic kidney disease. People with chronic kidney disease have a greatly increased fracture risk, and gonadal dysfunction is common in men receiving dialysis treatment. Nevertheless, in these men the effect of gonadal steroids and SHBG on bone mineral density (BMD) and fracture risk is unknown. Here we investigate relationships between gonadal steroids, SHBG, BMD and fracture in men on long-term dialysis therapy, awaiting kidney or simultaneous pancreas kidney transplantation. Results of serum biochemistry, SHBG, gonadal steroids (total testosterone, calculated free testosterone and estradiol), BMD by dual-energy X-ray absorptiometry and thoracolumbar X-rays were obtained. Multivariable regression models were used to examine associations between SHBG, gonadal steroids, BMD and fracture of 321 men with a mean age of 47 years. Diabetes mellitus was present in 45% and their median dialysis vintage was 24 months. Prior fractures occurred in 42%, 18% had vertebral fracture on lateral spine X-ray, 17% had non-vertebral fragility fracture within 10 years and 7% had both. After adjustment for age, body mass index and dialysis vintage, higher SHBG levels were significantly associated with nonvertebral fractures [odds ratio 1.81 (1.30-2.53)] and remained significant after adjustment for BMD. Calculated free testosterone and estradiol values were not associated with fracture. Prevalent fracture rates were high in relatively young men on dialysis awaiting transplantation. Thus, SHBG is a novel biomarker associated with fracture, which warrants investigation in prospective studies.

Associations Between Prediagnostic Concentrations of Circulating Sex Steroid Hormones and Esophageal/Gastric Cardia Adenocarcinoma Among Men

Esophageal adenocarcinoma (EA) and gastric cardia adenocarcinoma (GCA) are characterized by a strong male predominance. Concentrations of sex steroid hormones have been hypothesized to explain this sex disparity. However, no prospective population-based study has examined sex steroid hormones in relation to EA/GCA risk. Thus, we investigated whether prediagnostic circulating sex steroid hormone concentrations were associated with EA/GCA in a nested case-control study drawn from participants in three prospective cohort studies. Using gas chromatography-mass spectrometry (GC-MS) and electrochemiluminescence immunoassay, we quantitated sex steroid hormones and sex hormone binding globulin, respectively, in serum from 259 EA/GCA male case participants and 259 matched male control participants from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study II Nutrition Cohort. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between circulating hormones and EA/GCA risk. All statistical tests were two-sided. Higher concentrations of dehydroepiandrosterone (DHEA) were associated with a 38% decreased risk of EA/GCA (OR per unit increase in log2 DHEA = 0.62, 95% CI = 0.47 to 0.82, Ptrend = .001). Higher estradiol concentrations were associated with a 34% reduced risk of EA/GCA (OR = 0.66, 95% CI = 0.45 to 0.98, Ptrend = .05), and the association with free estradiol was similar. No other associations between baseline hormone concentrations and future EA/GCA risk were observed. This study provides the first evidence that higher concentrations of circulating DHEA, estradiol, and free estradiol may be associated with lower risks of EA/GCA in men.

Associations between circulating sex steroid hormones and leukocyte telomere length in men in the National Health and Nutrition Examination Survey.

Preliminary evidence suggests that sex steroid hormones, such as danazol (a synthetic sex steroid hormone), may be involved in enhancing telomerase activity. Elucidating underlying mechanisms of telomerase activity may further therapeutic options for individuals with telomeropathies and potentially avert certain age-related conditions. Therefore, we conducted a cross-sectional study to investigate the relationship between circulating sex steroid hormones and SHBG with leukocyte telomere length among 499 males in NHANES (1999-2002 surveys). Sample-weighted linear regression analyses were conducted to assess age-adjusted and multivariable-adjusted estimates of associations. Estimates were rescaled to represent telomere length change in base pairs per half the value of the interquartile range of the independent variable. Estradiol and free estradiol were significantly inversely associated with leukocyte telomere length (βcontinuous per §IQR =-61, p=0.04; free estradiol βcontinuous per §IQR =-67, p=0.03). Testosterone, free testosterone, androstanediol glucuronide, and SHBG were not associated with leukocyte telomere length. The inverse association seen in this study indicates that a danazol-induced hypoestrogenic state could partly underlie the previously observed association between danazol therapy and increased leukocyte telomere length.