Radical scavenging activity of fruit extracts Tribulus Terrestris with natural antioxidant Ascorbic acid: A comparative study

The main aim of this work was to analyze through a systematic review the ability of Tribulusterrestris to promote the increase of hormonal levels as a mechanism for the relief of menopausal symptoms. The criteria used for the selection were: studies involving menopausal women and use of Tribulusterrestris as a treatment for sexual dysfunction and / or other menopausal symptoms. The survey of literature shows that women who used Tribulusterrestris had drastic improvement in symptoms such as vaginal lubrication, sensation in the genitals during intercourse and other constructive activities. In this study, we have found a significant increase in bioavailable testosterone after the use of the plant extracts which has great potential in the treatment of sexual intercourse and unique symptoms of menopause.

Male sex hormone as a correlate of endothelial function in middle-aged Indian males: a cross-sectional prospective observational study

Background: Data on relationship between serum testosterone and endothelial dysfunction measured by brachial artery flow-mediated dilatation (BAFMD) in Indian subset are scarce. The present study was envisaged to assess the correlation between serum testosterone and endothelial dysfunction measured by BAFMD.Methods: From October 2013 till September 2014, 92 Indian male patients aged 40-60 years who underwent investigation of flow-mediated dilatation of the brachial artery using ultra sonography were included. The association between serum testosterone and BAFMD percent-measured endothelial dysfunction was examined.Results: Multivariate regression analysis in 92 Indian male patients (mean age 53.12±6.3 years) revealed that low levels of total serum, serum free and serum bioavailable testosterone were significantly associated with BAFMD% and were independent of age, hypertension, diabetes, body mass index (BMI), current smoking and hyperlipidaemia (p<0.001). The total serum, serum free and serum bioavailable testosterone were positively correlated with BAFMD% with Pearson correlation coefficients of r=0.572, r=0.525 and r=0.547, respectively (p<0.001).Conclusions: Low levels of total serum, serum free and serum bioavailable testosterone were significantly associated with BAFMD%-measured endothelial dysfunction, irrespective of cardiovascular risk factors.

Identifying molecular mediators of the relationship between body mass index and endometrial cancer risk: a Mendelian randomization analysis

Background: Endometrial cancer is the most common gynaecological cancer in high-income countries. Elevated body mass index (BMI) is an established modifiable risk factor for this condition and is estimated to confer a larger effect on endometrial cancer risk than any other cancer site. However, the molecular mechanisms underpinning this association remain unclear. We used Mendelian randomization (MR) to evaluate the causal role of 14 molecular risk factors (hormonal, metabolic, and inflammatory markers) in endometrial cancer risk. We then evaluated and quantified the potential mediating role of these molecular traits in the relationship between BMI and endometrial cancer. Methods and Findings: Genetic instruments to proxy 14 molecular risk factors and BMI were constructed by identifying single-nucleotide polymorphisms (SNPs) reliably associated (P < 5.0 x 10-8) with each respective risk factor in previous genome-wide association studies (GWAS). Summary statistics for the association of these SNPs with overall and subtype-specific endometrial cancer risk (12,906 cases and 108,979 controls) were obtained from a GWAS meta-analysis of the Endometrial Cancer Association Consortium (ECAC), Epidemiology of Endometrial Cancer Consortium (E2C2), and UK Biobank. SNPs were combined into multi-allelic models and odds ratios (ORs) and 95% confidence intervals (95% CIs) were generated using inverse-variance weighted random-effects models. The mediating roles of the molecular risk factors in the relationship between BMI and endometrial cancer were then estimated using multivariable MR. In MR analyses, there was strong evidence that BMI (OR per SD increase: 1.88, 95% CI: 1.69 to 2.09, P = 3.87 x 10-31), total testosterone (OR per inverse normal transformed nmol/L increase: 1.64, 95% CI: 1.43 to 1.88, P = 1.71 x 10-12), bioavailable testosterone (OR per inverse normal transformed nmol/L increase: 1.46, 95% CI: 1.29 to 1.65, P = 3.48 x 10-9), fasting insulin (OR per natural log transformed pmol/L increase: 3.93, 95% CI: 2.29 to 6.74, P = 7.18 x 10-7) and sex hormone-binding globulin (SHBG, OR per inverse normal transformed nmol/L increase: 0.71, 95% CI: 0.59 to 0.85, P = 2.07 x 10-4) had a causal effect on endometrial cancer risk. Additionally, there was suggestive evidence that total serum cholesterol (OR per mg/dL increase: 0.90, 95% CI: 0.81 to 1.00, P = 4.01 x 10-2) had an effect on endometrial cancer risk. In mediation analysis using multivariable MR, we found evidence for a mediating role of fasting insulin (19% total effect mediated, 95% CI: 5 to 34%, P = 9.17 x 10-3), bioavailable testosterone (15% mediated, 95% CI: 10 to 20%, P = 1.43 x 10-8), and SHBG (7% mediated, 95% CI: 1 to 12%, P = 1.81 x 10-2) in the relationship between BMI and endometrial cancer risk. The primary limitations of this analysis include the assumption of linear relationships across univariable and multivariable analyses and the restriction of analyses to individuals of European ancestry. Conclusions: Our comprehensive Mendelian randomization analysis provides insight into potential causal mechanisms linking BMI with endometrial cancer risk and suggests pharmacological targeting of insulinemic and hormonal traits as a potential strategy for the prevention of endometrial cancer.

Correlative studies on vitamin D and total, free bioavailable testosterone levels in young, healthy men

The relationship between vitamin D levels and testicular hormonal function in men has not been clearly established. Therefore, we aimed to investigate the relationship between deficiency/insufficiency levels of 25(OH)D and luteinizing hormone (LH), follicle-stimulating hormone (FSH), total (TT), free (FT), and bioavailable testosterone (BT), and sex hormone binding globulin (SHBG) in young, healthy men. We enrolled 176 healthy, active young men aged 18–35 years from a genetically homogenous population of Lower Silesia, Poland. Serum levels of 25(OH)D, LH, FSH, and TT were measured by electrochemiluminescence (ECLIA). FT levels were measured by enzyme-linked immunosorbent assay (ELISA). BT levels were calculated from TT, SHBG, and albumin. SHBG was measured by chemiluminescent immunoassay CLIA. We did not find any significant differences between the mean hormonal values (LH, FSH, TT, FT, BT, and SHBG) and the status of 25(OH)D level (deficient and insufficient). Based on our results, we concluded that there is no relationship between deficient and insufficient 25(OH)D concentration and androgen levels in young, healthy men.

The impact of rosuvastatin on hypothalamic–pituitary–testicular axis activity in metformin-treated and metformin-naïve men with low testosterone levels: a pilot study

Background Intense statin therapy was found to impair testosterone production in men. Metformin administered to subjects with hypergonadotropic hypogonadism decreased gonadotropin production. The current study was aimed at investigating whether metformin treatment modulates the impact of high-dose rosuvastatin therapy on hypothalamic–pituitary–testicular axis activity in men. Methods The study included 43 very high cardiovascular risk men with late-onset hypogonadism, 20 of whom had been treated with metformin (1.7–3 g daily) for at least 6 months. In all subjects, unsuccessful initial statin treatment was replaced with rosuvastatin (20–40 mg daily). Plasma lipid levels, glucose homeostasis markers, as well as circulating levels of gonadotropins, testosterone, bioavailable testosterone, dehydroepiandrosterone-sulfate, prolactin, estradiol and creatinine were measured at the beginning of the study and 4 months later in 28 individuals in whom rosuvastatin reduced LDL cholesterol levels to below 70 mg/dL. Results There were no differences between treatment-induced changes in plasma lipids. In both study groups, rosuvastatin reduced total and bioavailable testosterone levels. However, only in metformin-naïve men, rosuvastatin increased LH and FSH levels and slightly impaired insulin sensitivity. The impact on gonadotropin concentrations correlated with treatment-induced decrease in testosterone levels. There were no significant differences between baseline and posttreatment values of dehydroepiandrosterone-sulfate, prolactin, estradiol and the glomerular filtration rate. Conclusion The obtained results suggest that metformin prevents the compensatory increase in gonadotrope function induced by intense statin therapy.

Prenatal Testosterone Associates With Blood Pressure in Young Adults

Preclinical evidence suggests that adult blood pressure (BP) may be modified by the prenatal endocrine environment. Specifically, in several animal models, higher prenatal testosterone exposure increases the risk of hypertension in later life. We investigated the prospective association between prenatal testosterone levels (as measured in umbilical cord blood) and BP at 20 to 27 years in 434 participants from the Raine Study. As expected, median bioavailable testosterone, the fraction of total testosterone either free or bound to serum albumin, was higher in males than females (0.12 [Q1–Q3, 0.09–0.19] versus 0.07 [Q1–Q3, 0.05–0.1] nmol/L; P <0.001). Mean (SD) systolic BP was 122.9 (±12.3) and 110.9 (±9.5) mm Hg at age 20 years and 122.4 (±11) and 111.2 (±9.1) mm Hg at 27 years in males and females, respectively. Using hierarchical mixed-effects models, higher cord blood bioavailable testosterone concentrations were associated with higher levels of systolic BP ( P =0.007) and diastolic BP ( P =0.002) in young adults at 20 and 27 years, after adjusting for change in BP over time and potential confounders. In these models, one SD increase in bioavailable testosterone equated to a 1 mm Hg increase in systolic BP (regression coefficient, 11.1 [95% CI, 4.1–21.11]) and diastolic BP (regression coefficient, 10.15 [95% CI, 3.67–15.93]). There was no significant difference detected between males and females in the association between bioavailable testosterone and adult BP. These data from a large unselected population indicate that higher fetal testosterone levels in late pregnancy are associated with higher BP in young adulthood.

The Association Between Clinical and Biochemical Hyperandrogenism in Women With Female Pattern Hair Loss

Background: The exact association between clinical and biochemical hyperandrogenism (HA) is heterogeneous and cannot be ascertained, especially in normoandrogenic women. Aim: Evaluate any association between clinical HA phenotypes and biochemical parameters in premenopausal women with female pattern hair loss (FPHL). Methods: A cross-sectional observational study on 362 women with different degrees of FPHL, who were assessed for general characteristics, the degree of FPHL by Sinclair’s score, hirsutism by modified Ferriman-Gallwey (mFG) score. Evaluation for biochemical HA included total testosterone (TT), sex-hormone-binding globulin (SHBG), calculated free testosterone (FT), calculated bioavailable testosterone (BT), and dehydroepiandrosterone sulfate (DHEA-S). The variables of clinical HA which were used in this study are FPHL, hirsutism, and acne. We used the Free and Bioavailable Testosterone Calculator to calculate the FT and BT. Results: The enrolled young premenopausal women’s age range was (14-47 years). Around 78% of them were overweight or obese. Eighty-percent of women had a mild FPHL, with a median duration of three years where 2/3 of women had a duration &lt; 3 years, and had no significant relationship to FPHL degree. About 73% of women had either a mild to moderate hirsutism, and around 16% had acne. The biochemical HA was confirmed in around 52% of women (n=188), who show high levels of calculated FT. The calculated BT is high in 78.5% of the enrolled women (n=284). The means of biochemical indicators for HA were in their reference ranges or slightly above, with no specific change pattern with the corresponding FPHL severity. None of these parameters had a significant relationship to the severity of FPHL. The duration of FPHL was not affected by any presumed variable of clinical or biochemical HA. Conclusions: FPHL severity is associated with other clinical HA signs like hirsutism and acne, but not to HA’s biochemical parameter. Other parameters, like SHBG, HOMA-IR, and BMI, had no significant relation to the severity of FPHL. Clinical implications: FPHL severity does not correlate with the magnitude of hyperandrogenism. The assessment of women with FPHL is primarily clinical. The biochemical picture assists the diagnostic process.

Do sex hormones confound or mediate the effect of chronotype on breast and prostate cancer? A Mendelian randomization study.

BACKGROUND Previous research has demonstrated that a morning-preference chronotype is protective against both breast and prostate cancer. Sex hormones have been implicated in relation to both chronotype and the development of both cancers. This study aims to assess whether sex hormones confound or mediate the effect of chronotype on breast and prostate cancer risk using a Mendelian Randomization (MR) framework. METHODS We obtained genetic variants strongly (p<5x10-8) associated with chronotype and sex hormones (total testosterone, bioavailable testosterone, sex hormone binding globulin (SHBG), and oestradiol from previously published genome-wide association studies (GWAS) that had been undertaken in UK Biobank and 23andMe (n=244,207 females and n=205,527 males). These variants were used to investigate causal relationships with risk of breast and prostate cancer using summary data from the largest available consortia in breast (nCases/nControls=133,384/ 113,789) and prostate cancer (nCases/nControls=79,148/61,106). This was achieved using a series of MR approaches: univariable, bidirectional and multivariable. Results Overall, we found evidence for a protective effect of genetically predicted tendency towards morning preference on both breast (OR=0.93, 95% CI:0.88, 1.00) and prostate (OR=0.90, 95% CI:0.83, 0.97) cancer risk. There was evidence that an increased tendency to morning preference reduces bioavailable testosterone levels in both females (mean SD difference=-0.08, 95% CI:-0.12, -0.05) and males (mean SD difference=-0.06, 95% CI:-0.09, -0.03), and reduces total testosterone levels in females (mean SD difference=-0.07, 95% CI:-0.10, -0.03). We also found evidence to support higher total and bioavailable testosterone increasing the risk of breast cancer (OR=1.15, 95% CI:1.07, 1.23, OR=1.10, 95% CI:1.01, 1.19 respectively) and higher bioavailable testosterone increasing prostate cancer risk (OR=1.22, 95% CI:1.08, 1.37). While findings from univariable and bidirectional MR analyses indicated that testosterone may lie on the causal pathway between chronotype and cancer risk, there was evidence for a bidirectional association between chronotype and testosterone in females, implicating testosterone as both a confounder and mediator of the chronotype effect on breast cancer risk. However, the effects of chronotype remained largely unchanged when accounting for testosterone in multivariable MR, suggesting that any confounding or mediating effect is likely to be minimal. Conclusions This study has extended previous findings regarding the protective effect of chronotype on breast cancer and found evidence to suggest that morning preference also reduces prostate cancer risk in men. While testosterone levels were found to be closely linked with both chronotype and cancer risk, there was inconsistent evidence for the role of testosterone in mediating the effect of morning preference chronotype on both breast and prostate cancer. Findings regarding the potential protective effect of chronotype on both breast and prostate cancer risk are clinically interesting. However, this may not serve as a direct target for intervention, since it is difficult to modify someone's morning/evening preference. Given this, further studies are needed to investigate the mechanisms underlying this effect and to identify other potential modifiable intermediates.

Comparison of Clinical and Biochemical Markers of Hirsutism in Polycystic Ovary Syndrome – A Study from a Teaching Hospital in Sri Ramachandra Institute, Chennai, India

BACKGROUND We wanted to analyse the clinical profile of polycystic ovarian syndrome (PCOS) women with history, examination and ultrasonogram and correlate hirsutism with biochemical markers as free testosterone, dehydro-epiandrosterone sulphate (DHEAS), sex hormone binding globulin (SHBG), free testosterone, DHEAS, and SHBG. METHODS This study is a prospective observational study conducted from 2011 to 2013 in the Department of Obstetrics and Gynaecology, Shree Balaji Medical College and Hospital, Chrompet in patients attending Gynaecology OPD. 100 women visiting the OPD were taken as control and 100 women were taken for PCOS study. RESULTS Hyperandrogenism was studied and all the biochemical markers were significantly higher in polycystic ovarian syndrome patients than in controls (P < 0.0001). The highest AUC-ROC was found for bioavailable testosterone (0.852) followed by free androgen index (0.847) and free testosterone (0.837). Lower AUC-ROC was found for androstenedione, total testosterone and SHBG (0.706, 0.799 and 0.76, respectively). When free androgen index of 4.97 was taken as a cut off value, sensitivity was 71.4 % and specificity was 85.2 %. A cut off of 0.78 nmol / L for bioavailable testosterone had even higher sensitivity of 75.9 %, but slightly lower specificity of 83.3 %. Bioavailable testosterone and free androgen index correlated significantly (all P < 0.05) with DHEAS, LH / FSH ratio, androstenedione and total testosterone. In addition, bioavailable testosterone, free androgen index, and free testosterone correlated significantly with follicle count, ovarian volume, and hirsutism scores. CONCLUSIONS White women have about 20 % of excess of dehydro-epiandrosterone sulphate (DHEAS) and black women have 30 % excess of dehydro-epiandrosterone sulphate (DHEAS) in those having poly cystic ovaries patients. There is an age-associated decline in DHEAS levels which is similar in both control and poly cystic ovaries women, regardless of the race which was seen in this study. KEY WORDS Free Testosterone, Dehydro–Epiandrosterone Sulphate (DHEAS), Sex Hormone Binding Globulin (SHBG)

Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort

Objective To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults. Methods The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic risk score (PRS) of sex hormone traits were calculated from individual-level genotype data of the United Kingdom (UK) Biobank cohort. We then used logistic and linear regression models to assess the associations between individual PRS of sex hormone traits and the frequency of alcohol consumption, anxiety, intelligence and so on. Finally, gene-environment-wide interaction study (GEWIS) was performed to detect novel candidate genes interacting with the sex hormone traits on the development of fluid intelligence and the frequency of smoking and alcohol consumption by PLINK2.0. Results We observed positive association between SHBG and the frequency of alcohol consumption (b = 0.0101, p = 3.84 × 10–11) in middle-aged males and females. In addition, estradiol was positively associated with the frequency of alcohol consumption (b = 0.0128, p = 1.96 × 10–8) in middle-aged males. Moreover, bioavailable testosterone was associated with the fluid intelligence (b = − 0.0136, p = 5.74 × 10–5) in middle-aged females. Finally, GEWIS identified one significant loci, Tenascin R (TNR) (rs34633780, p = 3.45 × 10–8) interacting with total testosterone for fluid intelligence. Conclusion Our study results support the genetic effects of sex hormone traits on the development of intelligence and the frequency of alcohol consumption in middle-aged adults in UK.