Sex-specific association between coffee consumption and incident chronic kidney disease: a population-based analysis of 359,906 participants from the UK Biobank.

BACKGROUND: The risk for chronic kidney disease (CKD) is influenced by genetic predisposition, sex, and lifestyle. Previous research indicates that coffee is a potentially protective factor in CKD. The current study aims to investigate whether sex disparity exists in the coffee-CKD association, and whether genetic risk of CKD or genetic polymorphisms of caffeine metabolism affect this association. METHODS: A total of 359,906 participants from the UK Biobank who were enrolled between 2006 and 2010 were included in this prospective cohort study, which aimed to estimate the hazard ratios for coffee intake and incident CKD using a Cox proportional hazard model. Allele scores of CKD and caffeine metabolism were additionally adjusted for in a subsample with qualified genetic data ( n = 255,343). Analyses stratified by genetic predisposition, comorbidities, and sex hormones were performed. Tests based on Bayesian model averaging were conducted to ascertain the robustness of the results. RESULTS: Coffee was inversely associated with CKD in a dose-dependent manner. The effects of coffee did not differ across different strata of genetic risk for CKD, but were more evident among slower genetically predicted caffeine metabolizers. Significant sex disparity was observed ( P value for interaction = 0.013), in that coffee drinking was only associated with the risk reduction of CKD in females. Subgroup analysis revealed that testosterone and sex hormone-binding globulin (SHBG), but not estradiol, modified the coffee-CKD association. CONCLUSIONS: In addition to the overall inverse coffee-CKD association that was observed in the general population, we could also establish that a sex disparity existed, in that females were more likely to experience the benefit of the association. Testosterone and SHBG may partly account for the sex disparity.

The effects of coenzyme Q10 supplementation on metabolic profiles and parameters of mental health in women with polycystic ovary syndrome.

OBJECTIVE: Evaluating the impact of coenzyme Q10 (CoQ10) supplementation on hormonal indices, mental health, and biomarkers of inflammatory responses and oxidative stress among female patients suffering from polycystic ovary syndrome (PCOS). METHODS: The present double-blinded, placebo-controlled randomized clinical trial consisted of 55 PCOS women (aged 18-40 years old), who were randomized into groups receiving 100 mg/day of CoQ10 (28 cases) or placebo (27 cases) for 12 weeks. RESULTS: The supplementation of CoQ10 decreased significantly the scores of Beck Depression Inventory (BDI) (p = .03) and Beck Anxiety Inventory (BAI) (p = .01) and high-sensitivity C-reactive protein (hs-CRP) level (p = .005) when comparing with the placebo group. Moreover, CoQ10 group exhibited a significant drop in total testosterone (p = .004), dehydroepiandrosterone sulfate (DHEAS) (p < .001), hirsutism (p = .002) and malondialdehyde (MDA) (p = .001) levels in the serum, and a significant rise in sex hormone-binding globulin (SHBG) (p < .001) and total antioxidant capacity (TAC) (p < .001) levels in the serum than the placebo group. CONCLUSIONS: 12-week supplementation of CoQ10 to PCOS women showed beneficial impact on BDI, BAI, hs-CRP, total testosterone, DHEAS, hirsutism, SHBG, TAC and MDA levels.

The effect of L-carnitine supplementation on insulin resistance, sex hormone-binding globulin and lipid profile in overweight/obese women with polycystic ovary syndrome: a randomized clinical trial.

PURPOSE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. Insulin resistance and dyslipidemia are linked to PCOS. L-Carnitine supplementation as a management strategy for women with PCOS has been proposed. The effect of L-carnitine supplementation on insulin resistance, sex hormone-binding globulin (SHBG) and lipid profile in overweight/obese women with PCOS was investigated. METHODS: This randomized, double-blind, controlled clinical trial, was conducted on 62overweight/obese women with PCOS. Participants were randomly assigned into two groups to receive 1000 mg/day L-carnitine or placebo (1000 mg starch) for 12 weeks. RESULTS: L-Carnitine supplementation compared to the placebo showed a significant improvement in insulin [- 0.7 (- 7.3 to 4.0) vs. 0.7 (- 3.0 to 5.2); P = 0.001], homeostatic model assessment for insulin resistance [- 0.4 (- 1.7 to 1.1) vs. 0.0 (- 0.7 to 1.3); P = 0.002], quantitative insulin sensitivity check index (+ 0.01 ± 0.02 vs. - 0.01 ± 0.01; P = 0.02) and a non-significant change toward improvement in SHBG (+ 11.5 ± 40.2 vs. - 3.2 ± 40.2; P = 0.2). However, there was no significant differences between the two groups in serum levels of fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein-cholesterol and high density lipoprotein cholesterol (P > 0.05). CONCLUSION: 12-week L-carnitine supplementation in overweight or obese women with PCOS ameliorate insulin resistance, but has no effect on SHBG and lipid profile. Studies with higher dosages and duration of L-carnitine intake are required. The trial was registered on 30 December 2019 at Iranian Registry of Clinical Trials IRCT20191016045131N1. TRIAL REGISTRATION: Registered on 30th December 2019 at Iranian Registry of Clinical Trials (IRCT20191016045131N1).

MANAGEMENT OF ENDOCRINE DISEASE: Rationale and current evidence for testosterone therapy in the management of obesity and its complications.

Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (TS) therapy. As obese men often display lower serum TS levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase in TS prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low TS predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low TS are truly hypogonadal. We further describe the mechanisms underlying the bi-directional relationships of TS levels with obesity and metabolic health, and finally assess the evidence for TS therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum sex hormone-binding globulin and total TS levels are highly prevalent in obese men, but that only those with low free TS levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low TS is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound TS therapy trials have shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate TS therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, the focus should remain on lifestyle measures and management of obesity-related consequences.

The role of LCPUFA-ω3 on the obesity-associated hyperandrogenemia of pubertal girls: secondary analysis of a randomized clinical trial.

Introduction Hyperandrogenism (HA), either clinical or biochemical, is associated with obesity in adolescent girls. Long chain polyunsaturated fatty acids ω3 (LCPUFA-ω3) play protective roles in some obesity-associated morbidities, but their contribution to preventing HA is unclear. Our aim was to examine the potential positive relationships between erythrocyte LCPUFA-ω3, with or without supplementation, and hyperandrogenemia. Methods Secondary analysis of a clinical trial that was conducted previously to analyze the effect of LCPUFA-ω3 on insulin resistance and body weight. Here, we present a cross-sectional analysis of 180 girls with obesity, and a longitudinal analysis of 117 girls who completed a 3-month supplementation period (57 LCPUFA-ω3 [DO3] and 60 placebo [DP)]). Dehydroepiandrosterone sulfate (DHEAS), total testosterone (TT) and steroid hormone binding globulin (SHBG) were measured with chemiluminescence; free testosterone (FT) was calculated. Erythrocyte fatty acids were determined by gas chromatography. Non-parametric statistics was used for analysis. Results In cross-sectional analysis, age (odds ratio [OR] = 1.35; 95% confidence interval [CI] = 1.03, 1.78; p = 0.027), insulin (OR = 1.05; 95% CI: 1.00, 1.10; p = 0.018), and erythrocytes eicosapentaenoic acid (EPA) (OR = 0.04; 95% CI: 0.01, 0.65; p = 0.012) were predictors of hyperandrogenemia (FT >0.63 ng/mL). In longitudinal analysis, EPA, adiponectin and SHBG increased, while FT decreased, in the DO3 group (p < 0.05). The risk of hyperandrogenemia at the end of follow-up was predicted by basal hyperandrogenemia (OR = 18.16, 95% CI: 5.37, 61.4; p < 0.001) and by increases in EPA (OR = 0.40; 95% CI: 0.01, 0.65; p = 0.06 marginal significance). Conclusions Our results suggest a preventive role of EPA on the risk for hyperandrogenemia in girls with obesity, but further studies are needed to demonstrate a benefit.

The Effect of Oligopin Supplementation on Hormonal and Metabolic Profiles in the Polycystic Ovary Syndrome: A Randomized Controlled Trial.

Background: A double blind clinical trial was performed to evaluate whether the polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in the women with PCOS during the three-month administration of oligopin. Methods: In this double-blind multicenter trial, we randomly assigned 80 PCOS women, based on a 1:1 ratio, to receive oligopin (n= 40) or maltodextrin as placebo (n = 40) for up to 3 months. As PCOS-specific outcomes, we investigated the changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from the baseline to the end of treatment. We investigated serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. Results: The first participant was enrolled on April 18, 2018, and the last study visit took place on May 14, 2019. PCOS-specific serum parameters did not change during the three-month administration of oligopin (p > 0.05), except for a small increase in the FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels was significantly increased in placebo group, as compared with oligopin (p=0.01). Conclusion: Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in the women with PCOS. Clinical Trial Registration: www.irct.ir, identifier IRCT20140406017139N3.

The effect of Trigonella foenum-graecum extract on prostate-specific antigen, and prostate function in otherwise healthy men with benign prostate hyperplasia.

The aim of this trial was to evaluate the effect of a standardised Trigonella foenum-graecum (Fenugreek) extract on the symptoms of benign prostate hyperplasia (BPH) using a double-blind randomised placebo controlled design. The study recruited 100 healthy males aged between 45 and 80 years with symptoms of BPH who recorded a minimum score of eight on the International Prostate Symptom Score. Participants were randomised to an oral dose of either 600mg Trigonella foenum-graceum per day or placebo for 12 weeks. The primary outcome measure was the International Prostate Symptom Score total and subdomain scores. The secondary outcomes were serum levels of the hormones (testosterone, free testosterone, and sex hormone binding globulin) prostate-specific antigen, and safety markers. The results indicated that Trigonella foenum-graceum did not have an effect on improving the symptoms of BPH. Hormone levels, safety markers, and prostate-specific antigen remained unchanged and within normal limits after 12 weeks, which adds to the safety profile of this specialised extract.

The effect of vitamin D supplementation on the androgenic profile in men: A systematic review and meta-analysis of clinical trials.

The aim of this systematic review and meta-analysis was to evaluate the effect of vitamin D supplementation on total testosterone (TT) and sex hormone-binding globulin (SHBG) in men. We searched PubMed, Scopus and Web of Science for randomized, controlled trials of vitamin D supplementation in men ≥18 years old up to September 2018, without language restrictions. Meta-analysis was based on a random effects model. The systematic review was registered as CRD42018094498. We identified 3,402 articles, of which eight studies with 10 effect sizes met the inclusion criteria. Vitamin D daily dose equivalents ranged from 600 to 4,000 per day to 60,000 IU per week; duration was 6 weeks to 36 months. In general, vitamin D supplementation had no significant effect on TT (MD = 0.20, 95% CI: -0.20, 0.60, p = 0.336) and SHBG (MD = 1.56, 95% CI: -0.85, 3.97, p = 0.204). Subgroup analysis conducted with duration of prescription, type (daily or weekly), dosing frequency and baseline vitamin D and TT concentration showed that vitamin D did not significantly affect TT. The present study did not find any evidence to support beneficial effect of vitamin D supplementation on TT and SHBG in men. Thus, further large-scale randomised controlled trials are required to evaluate the effects of vitamin D supplementation on androgen in men.

The effects of quercetin supplementation on metabolic and hormonal parameters as well as plasma concentration and gene expression of resistin in overweight or obese women with polycystic ovary syndrome.

The aim of this study was to investigate the effect of quercetin on metabolic and hormonal parameters as well as plasma concentration and gene expression of resistin in overweight or obese women with polycystic ovary syndrome (PCOS). In this randomized, double-blind, placebo-controlled trial, 78 overweight or obese women (25 ≤ BMI ≤ 40 kg/m2 , 20-40 years) with PCOS were recruited. Patients were randomized to receive 1,000 mg/day quercetin or placebo for 12 weeks. Resistin plasma concentration and gene expression in peripheral blood mononuclear cells, parameters of glucose homeostasis, circulatory testosterone, luteinizing hormone (LH), and sex hormone-binding globulin, and anthropometries were assessed at baseline and at the end of the study. Following supplementation, quercetin significantly decreased resistin concentration (2.07 ± 0.23 vs. 2.88 ± 0.40 ng/ml, p < 0.001) and mRNA level (0.64 ± 0.58 vs. 1 ± 0.56 fold change, p = 0.008), compared with placebo group. Moreover, testosterone (0.72 ± 0.15 vs. 0.76 ± 0.12 ng/ml, p = 0.001) and LH (8.05 ± 2.88 vs. 8.77 ± 1.99 mIU/ml, p = 0.035) concentrations were significantly lower in quercetin compared with placebo group. Fasting blood glucose (p < 0.001), insulin (p = 0.02), and homeostatic model assessment of insulin resistance (p = 0.009) decreased within the quercetin group; however, no significant differences were observed compared with the placebo group (p = 0.074, p = 0.226, p = 0.22, respectively). Quercetin supplementation decreased resistin plasma levels and gene expression, and testosterone and LH concentration in overweight or obese women with PCOS.

Dietary minerals, reproductive hormone levels and sporadic anovulation: associations in healthy women with regular menstrual cycles.

Although minerals are linked to several reproductive outcomes, it is unknown whether dietary minerals are associated with ovulatory function. We hypothesised that low intakes of minerals would be associated with an increased risk of anovulation. We investigated associations between dietary mineral intake and both reproductive hormones and anovulation in healthy women in the BioCycle Study, which prospectively followed up 259 regularly menstruating women aged 18-44 years who were not taking mineral supplements for two menstrual cycles. Intakes of ten selected minerals were assessed through 24-h dietary recalls at up to four times per cycle in each participant. Oestradiol, progesterone, luteinising hormone (LH), follicle-stimulating hormone (FSH), sex-hormone-binding globulin and testosterone were measured in serum up to eight times per cycle. We used weighted linear mixed models to evaluate associations between minerals and hormones and generalised linear models for risk of anovulation. Compared with Na intake ≥1500 mg, Na intake <1500 mg was associated with higher levels of FSH (21·3 %; 95 % CI 7·5, 36·9) and LH (36·8 %; 95 % CI 16·5, 60·5) and lower levels of progesterone (-36·9 %; 95 % CI -56·5, -8·5). Na intake <1500 mg (risk ratio (RR) 2·70; 95 % CI 1·00, 7·31) and Mn intake <1·8 mg (RR 2·00; 95 % CI 1·02, 3·94) were associated with an increased risk of anovulation, compared with higher intakes, respectively. Other measured dietary minerals were not associated with ovulatory function. As essential minerals are mostly obtained via diet, our results comparing insufficient levels with sufficient levels highlight the need for future research on dietary nutrients and their associations with ovulatory cycles.

Cross-sectional association of coffee and caffeine consumption with sex hormone-binding globulin in healthy nondiabetic women.

OBJECTIVE: Low sex hormone-binding globulin (SHBG) is a consistent risk factor for type 2 diabetes, particularly in women. Coffee consumption has been associated with a lower risk of type 2 diabetes, but its effects on SHBG are less known. DESIGN AND METHODS: This was a cross-sectional study of 2377 nondiabetic pre- and postmenopausal women from the E3N cohort study whose baseline SHBG was measured. Information on diet (including coffee and caffeine consumption), lifestyle and medical conditions was collected through questionnaires. The relationship between coffee and caffeine consumption and SHBG was modelled, with adjustment for covariates and stratification by body mass index (BMI) categories (< or ≥25 kg/m2 ) and menopausal status. RESULTS: The mean age was 57.2±6.4 years and 61% of the 2377 women were postmenopausal. High coffee (≥3 cups/day) and caffeine (≥265 mg/day) intakes were associated with a reduced risk of being in the 1st quartile of the SHBG level distribution (<46.3 nmol/L) in a multivariate adjusted model (OR: 0.72 [95% CI: 0.52-1.01] and OR: 0.71 [95% CI: 0.53-0.95], respectively). No association was found between tea consumption and SHBG levels. In multivariate models stratified on BMI categories and menopausal status, associations were restricted to women with a BMI ≥25 kg/m2 or being postmenopausal. The association with SHBG was consistently noted with consumption of both caffeinated coffee and caffeine, but not decaffeinated coffee. CONCLUSIONS: Consumption of high coffee and caffeine is associated with a reduced risk of low SHBG, an established risk marker for T2DM, which might contribute to the protective effects of coffee for type 2 diabetes.

Effects of selenium on short-term control of hyperthyroidism due to Graves' disease treated with methimazole: results of a randomized clinical trial.

OBJECTIVE: In spite of previous conflicting results, an adjuvant role of selenium in the treatment of Graves' disease (GD) hyperthyroidism has been proposed. To address this issue, a randomized clinical trial was carried out aimed at investigating whether selenium is beneficial on the short-term control of GD hyperthyroidism treated with methimazole (MMI). METHODS: Thirty newly diagnosed hyperthyroid GD patients were randomly assigned to treatment with: (i) MMI or (ii) MMI plus selenium. Primary outcomes were: control of hyperthyroidism and clinical and biochemical manifestations of hyperthyroidism [heart rate, cholesterol, sex hormone-binding globulin (SHBG), hyperthyroidism symptoms] at 90 days. RESULTS: Baseline features of the two groups did not differ. Serum selenium at baseline was similar in the two groups and within the recommended range to define selenium sufficiency. Selenium increased with treatment in the MMI-selenium group and became significantly higher than in the MMI group. Serum malondialdehyde, a marker of oxidative stress, was similar in the two groups and decreased significantly with treatment, with no difference between groups. Administration of MMI was followed by a reduction of FT3 and FT4, with no difference between groups. Heart rate, SHBG and symptoms of hyperthyroidism decreased, whereas total cholesterol increased in both groups with no difference between groups. CONCLUSIONS: Our study, carried out in a selenium-sufficient cohort of GD patients, failed to show an adjuvant role of selenium in the short-term control of hyperthyroidism. However, selenium might be beneficial in patients from selenium-deficient areas, as well as in the long-term outcome of antithyroid treatment.

The efficacy of antioxidant therapy against oxidative stress and androgen rise in ethylene glycol induced nephrolithiasis in Wistar rats.

Administration of natural antioxidants has been used to protect against nephrolithiasis. Urolithiasis was induced by ethylene glycol (EG) in Wistar rats. For 4 weeks, group 1 (control) was fed with a standard commercial diet. Group 2 received the same diet with 0.75% of EG. Group 3 received EG plus the diet and water added with antioxidant nutrients and lime juice as the dietary source of citrate (EG + AX). Group 4 same as group 3 with no EG in water. For 8 weeks, group 5 was fed the standard diet with EG in water for the first 28 days, followed by no EG. Group 6 received the diet with EG for the first 28 days, followed by discontinuation of EG and addition of antioxidant nutrients. Group 7 were provided the diet with antioxidant nutrients for 8 weeks. Group 8 received the diet with antioxidant nutrients for 4 weeks, followed by antioxidant nutrients with EG for the next 4 weeks. Blood samples were collected and kidneys were removed. The size and the mean number of crystal deposits in EG-treated groups was significantly higher than the EG-treated groups, added with antioxidant nutrients and lime juice. After 4 weeks, the mean concentration of malondialdehyde in group 2 was higher than the group 3, and significantly lower in group 4; and in groups 7 after 8 weeks, as well. After 8 weeks, supplementation developed less mean number of deposits in group 6 as compared to group 5; and in group 8, the crystal deposits was substantially less than either group 2 or group 5 (EG-treated rats). Elevated concentration of androgens (as promoters of the formation of renal calculi) as a result of EG consumption decreased following antioxidant supplementations. Results showed a beneficial effect of antioxidant and provided superior renal protection on treating and preventing stone deposition in the rat kidney.

Maca reduces blood pressure and depression, in a pilot study in postmenopausal women.

OBJECTIVE: Lepidium meyenii (Maca) has been used for centuries for its fertility-enhancing and aphrodisiac properties. In an Australian study, Maca improved anxiety and depressive scores. The effects of Maca on hormones, lipids, glucose, serum cytokines, blood pressure, menopausal symptoms and general well-being in Chinese postmenopausal women were evaluated. METHODS: A randomized, double-blind, placebo-controlled, cross-over study was conducted in 29 postmenopausal Hong Kong Chinese women. They received 3.3 g/day of Maca or placebo for 6 weeks each, in either order, over 12 weeks. At baseline, week 6 and week 12, estradiol, follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), thyroid stimulating hormone (TSH), full lipid profiles, glucose and serum cytokines were measured. The Greene Climacteric, SF-36 Version 2, Women's Health Questionnaire and Utian Quality of Life Scales were used to assess the severity of menopausal symptoms and health-related quality of life. RESULTS: There were no differences in estradiol, FSH, TSH, SHBG, glucose, lipid profiles and serum cytokines amongst those who received Maca as compared to the placebo group; however, significant decreases in diastolic blood pressure and depression were apparent after Maca treatment. CONCLUSIONS: Maca did not exert hormonal or immune biological action in the small cohort of patients studied; however, it appeared to reduce symptoms of depression and improve diastolic blood pressure in Chinese postmenopausal women. Although results are comparable to previous similar published studies in postmenopausal women, there might be a cultural difference among the Chinese postmenopausal women in terms of symptom reporting.

Association of serum androgen concentrations with cardiovascular risk factors in elderly male patients with chronic systolic heart failure in China.

OBJECTIVE: To survey the serum androgen concentrations and investigate the relationship between androgen levels and cardiovascular risk factors in elderly male patients with chronic systolic heart failure (HF) in China. METHODS: 106 consecutive male patients hospitalized for chronic systolic HF aged from 60 to 87 were enrolled. About 400 healthy age-matched men were compared as a control group. Total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS) and sex hormone binding globulin (SHBG) were measured. Differences of androgen levels between HF patients and healthy men were determined by t-test and associations of androgen with cardiovascular risk factors were evaluated by partial correlations analyses. RESULTS: Compared with healthy men, TT, FT and DHEAS levels in patients with HF decreased, whereas SHBG level increased significantly (both p < 0.01). TT was negatively correlated with TC, TG and DBP (p < 0.05), FT was negatively correlated with TC, LDL-C and DBP (p < 0.05). SHBG correlated with BMI and smoking history positively (p < 0.05). CONCLUSIONS: Level of bio-available testosterone decreased with advancing age, especially in men with HF. Men with low levels of bio-available testosterone had worse profiles of cardiovascular risk factors. Treatment of HF is still challenging and testosterone supplementation therapy may be an effective therapeutic option.

Peculiar observations in measuring testosterone in women treated with oral contraceptives supplemented with dehydroepiandrosterone (DHEA).

Total testosterone is considered to be decreased during the use of combined oral contraceptives. There is, however, considerable concern about the quality of testosterone assays, especially at low levels. We aimed to confirm testosterone levels measured by direct radioimmunoassay in a recent clinical trial with a state-of-the-art LC-MSMS method. Surplus specimens with known testosterone levels collected during the study (Clinical Trial Registration number ISRCTN06414473) were reanalyzed with an LC-MSMS method. This method was compared to another LC-MSMS method that had shown to concur excellently to a reference method. Follow-up experiments were designed to explain the results. In contrast to our expectation, LC-MSMS measurements did not corroborate the data obtained by radioimmunoassay. Subsequent experiments showed that this could be attributed to a strong dependency of the radioimmunoassay on SHBG. Testosterone results (n = 198) obtained by direct radioimmunoassay showed a negative correlation to SHBG levels (r = -0.676; p<0.001). By contrast, testosterone results obtained by LC-MSMS were not related to SHBG (r = 0.100; NS). In conclusion, our results indicate that total testosterone measurements during oral contraceptive use are unreliable when performed with assays sensitive to the SHBG concentration. The discrepancy with the literature can most likely be explained by the sensitivity of the immunoassay used to SHBG. Given the sharp increase in SHBG during the use of many oral contraceptives, total testosterone may not decrease, whereas its bioavailability, estimated by free testosterone levels, will be diminished. Studies aiming at restoration of testosterone homeostasis during oral contraception need to take this into account.

Oleic acid increases hepatic sex hormone binding globulin production in men.

SCOPE: Low circulating sex hormone-binding globulin (SHBG) is an independent risk factor for cardiovascular disease. Mediterranean diet has been associated with a decreased risk of cardiovascular disease. We aimed to test the hypothesis that the increase of circulating MUFA associated with olive oil consumption (primary fat source in Mediterranean diet) increases SHBG serum levels. METHODS AND RESULTS: A total of 315 men were included. In these patients, nutrition data and plasma samples for SHBG assessment were obtained. In vitro studies to examine the effects of oleic and linoleic acid on SHBG production using HepG2 cells were performed. We provided evidence that SHBG serum levels were significantly higher in subjects using olive oil for cooking in comparison with subjects using sunflower oil. The SHBG levels correlated positively with MUFA (p < 0.001) and negatively with saturated fatty acids (p = 0.003). In the multiple regression analysis, MUFA were independently associated with SHBG levels and accounted for the 20.4% of SHBG variance. In vitro studies revealed that oleoyl-CoA increases SHBG production by downregulating PPAR-γ levels in HepG2 cells. CONCLUSION: Olive oil consumption is associated with elevated SHBG serum levels. PPAR-γ downregulation induced by oleoyl-CoA is an important underlying mechanism of such regulation.

The effects of caffeinated and decaffeinated coffee on sex hormone-binding globulin and endogenous sex hormone levels: a randomized controlled trial.

BACKGROUND: Findings from observational studies suggest that sex hormone-binding globulin (SHBG) and endogenous sex hormones may be mediators of the putative relation between coffee consumption and lower risk of type 2 diabetes. The objective of this study was to evaluate the effects of caffeinated and decaffeinated coffee on SHBG and sex hormone levels. FINDINGS: After a two-week run-in phase with caffeine abstention, we conducted an 8-week parallel-arm randomized controlled trial. Healthy adults (n = 42) were recruited from the Boston community who were regular coffee consumers, nonsmokers, and overweight. Participants were randomized to five 6-ounce cups of caffeinated or decaffeinated instant coffee or water (control group) per day consumed with each meal, mid-morning, and mid-afternoon. The main outcome measures were SHBG and sex hormones [i.e., testosterone, estradiol, dehydroepiandrosterone sulfate]. No significant differences were found between treatment groups for any of the studied outcomes at week 8. At 4 weeks, decaffeinated coffee was associated with a borderline significant increase in SHBG in women, but not in men. At week 4, we also observed several differences in hormone concentrations between the treatment groups. Among men, consumption of caffeinated coffee increased total testosterone and decreased total and free estradiol. Among women, decaffeinated coffee decreased total and free testosterone and caffeinated coffee decreased total testosterone. CONCLUSIONS: Our data do not indicate a consistent effect of caffeinated coffee consumption on SHBG in men or women, however results should be interpreted with caution given the small sample size. This is the first randomized trial investigating the effects of caffeinated and decaffeinated coffee on SHBG and sex hormones and our findings necessitate further examination in a larger intervention trial.

Effects of exemestane and tamoxifen on hormone levels within the Tamoxifen Exemestane Adjuvant Multicentre (TEAM) trial: results of a German substudy.

AIM: The aim of this study was to compare the effects of exemestane and tamoxifen on hormone levels in postmenopausal patients with hormone receptor-positive breast cancer within a Germany substudy of the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. METHODS: Within the TEAM trial, patients were randomized to receive adjuvant treatment with exemestane for 5 years or tamoxifen for 2.5-3 years followed by exemestane for 2-2.5 years. Serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH) and parathyroid hormone (PTH)-intact were measured at screening and after 3, 6 and 12 months of treatment. RESULTS: Data on hormone levels were available from 63 patients in the tamoxifen arm and 68 patients in the exemestane arm. Treatment with exemestane resulted in decreases from baseline in SHBG and PTH-intact levels, and increases from baseline in testosterone, DHEAS and FSH levels. Tamoxifen treatment resulted in increases from baseline in SHBG and PTH-intact, whereas levels of testosterone and FSH decreased and DHEAS levels did not change. At all time points assessed, the absolute change from baseline was significantly different between tamoxifen and exemestane for testosterone, SHBG, FSH and PTH-intact (all p < 0.0001). CONCLUSIONS: Exemestane and tamoxifen had statistically significantly different effects on hormone levels, including testosterone, SHBG, FSH and PTH-intact.

Anthropometric, dietary, and hormonal correlates of serum adiponectin in Asian American women.

There is increasing evidence that adiponectin has a critical role in the development of breast cancer, but factors that influence adiponectin concentrations have not been well studied. We conducted a cross-sectional study among Asian-American controls who participated in a population-based case-control study of breast cancer. Participants were interviewed in-person and donated a blood specimen. Using multivariate models, we investigated the relationships between serum adiponectin concentrations and lifestyle factors (including adiposity and dietary factors) and serum sex-hormones and growth factors among postmenopausal women who were nonhormone-users at blood draw (n = 196). Adiponectin concentrations were significantly positively associated with green tea intake (P trend = 0.03); levels were 31% higher among those who drank green tea 4 or more times per wk (14.5 ± 1.10 µg/mL) compared with nongreen-tea-drinkers (11.0 ± 1.09 µg/mL); this association remained after adjustment for body mass index (BMI) and waist/hip ratio (WHR), both of which were significantly and inversely associated with adiponectin. Adiponectin concentrations were positively associated with sex-hormone-binding globulin (P trend < 0.0001) and the ratios of total testosterone (T)/total estradiol (E2) (P trend <0.004) after adjustment for BMI and WHR. Confirmation of our findings on green tea and adiponectin is needed.