Increase In Sex Hormone-binding Globulin Research Articles

7467 Supplement Use Among Transgender Patients: Case Reports and Literature Review

Abstract Disclosure: H. Cunningham: None. Q. Jones: None. C. Kelley: None. The barriers to initiating gender affirming medical treatment are innumerable and increasing in the wake of wide-sweeping anti-trans legislation, leading many transgender individuals to utilize more accessible means of transitioning. We provide examples of patient-initiated supplement use at a gender medicine clinic in the Southeast. We describe a 60-year-old transgender woman who was unable to establish care due to lack of affirming providers in her region and insurance approval delays. She began taking Pueraria mirifica, along with saw palmetto and fenugreek, for feminization. Subsequently, her breast size increased from an A to B cup, and she noticed fat redistribution to her hips. When finally seen one year later, labs demonstrated suppressed luteinizing and follicle stimulating hormones and increased sex hormone binding globulin, with an associated decrease in estradiol and testosterone levels. Cessation of supplements resulted in lab normalization. Our second case describes masculinizing effects, including voice deepening, experienced by a transgender man using a supplement that contained "orchic extract.” Supplements used for gender affirmation can also have more adverse effects, including polycythemia in the setting of trenbolone, an illicit steroidogenic performance enhancing supplement used for masculinization by some patients assigned female at birth. Patients without access to gender affirming hormones through a medical provider, or who do not feel comfortable accessing health care, may be more likely to use supplements purchased online without a prescription. Considering this, we must create more safe spaces for gender affirming care and ask all transgender patients about supplement use. Providers should consider supplement use as a possible explanation for unexpected lab results. The literature on supplement use for gender-affirming effects is sparse; this presentation provides a summary of and contributes to the current literature on this topic. Presentation: 6/2/2024

Clomiphene citrate and optional human chorionic gonadotropin for treating male hypogonadism arising from long-term anabolic-androgenic steroid use—A pilot study

IntroductionLong-term anabolic-androgenic steroid (AAS) use poses several health risks, including secondary hypogonadism. There is a knowledge gap on treatment targeting the hypothalamic-pituitary-gonadal (HPG) axis among men with anabolic steroid-induced hypogonadism (ASIH). This study aims to gain insights into the potential utility of endocrine therapy to restore endogenous testosterone levels and alleviate ASIH symptoms in AAS dependent men. MethodsIn this proof-of-concept, single-site, open longitudinal pilot study, AAS dependent men with continuous AAS use and a desire to permanently discontinue use, were given endocrine therapy. The treatment included 25 mg clomiphene citrate (CC) every second day for 16 weeks, transdermal testosterone daily during the first four weeks, and if indicated, human chorionic gonadotropin (hCG) injections for a maximum of eight weeks. Physical exams including blood collection and online questionnaires were completed every four and two weeks, respectively. ResultsTen participants, with median age 32 years (interquartile range 30–45), with mean ± standard deviation AAS use of 11 ± 4 years, completed the CC intervention. Seven participants received hCG as part of their treatment protocol. Mild adverse events included headaches, dizziness, and mood swings, and no serious adverse events occurred. During the intervention, there was a decrease in levels of hematocrit, hemoglobin and ALT (alanine aminotransferase), as well as an increase in serum FSH (follicle stimulating hormone), LH (luteinizing hormone) and SHBG (sex hormone binding globulin). Five of ten participants reached a total testosterone level within normal range (9–30 nmol/l). The HPG axis response varied greatly among participants, and was not aligned with the severity of ASIH related withdrawal symptoms. ConclusionsThe findings from this proof-of-concept study may guide future randomized controlled trials aiming to investigate potential endocrine therapeutic approaches to ASIH.

Bisphenol A Exposure Interferes with Reproductive Hormones and Decreases Sperm Counts: A Systematic Review and Meta-Analysis of Epidemiological Studies.

Bisphenol A (BPA), an acknowledged endocrine disrupter, is easily exposed to humans via food packaging and container. However, a consensus has not been reached on the extent to which BPA exposure affects the reproductive system. We therefore conducted this systematic review and meta-analysis to elucidate the relationship between BPA exposure and male reproduction-related indicators. Up to October 2023, a comprehensive search was carried out in the PubMed, Embase, Cochrane and Web of Science, and 18 studies were ultimately included. β coefficients from multivariate linear regression analyses were pooled using a random effects model. The results showed that the urinary BPA concentration was negatively correlated with the sperm concentration (β coefficient = -0.03; 95% CI: -0.06 to -0.01; I2 = 0.0%, p = 0.003) and total sperm count (β coefficient = -0.05; 95% CI: -0.08 to -0.02; I2 = 0.0%, p < 0.001). In addition, BPA concentrations were associated with increased sex hormone-binding globulin (SHBG) levels, increased estradiol (E2) levels, and reduced biologically active androgen levels. However, the relationship between an increased risk of below-reference sperm quality and BPA exposure was not robust. This systematic review revealed that BPA exposure disrupts reproductive hormones, reduces sperm counts and may ultimately adversely affect male reproduction.

Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women's Health Across the Nation (SWAN).

To investigate the associations of longitudinal changes in sex hormone binding globulin (SHBG) and testosterone (T) over the menopause transition with the risk of diabetes. We followed 2,952 participants in the Study of Women's Health Across the Nation (SWAN) who were premenopausal or early perimenopausal and diabetes-free at baseline. SHBG,T, and estradiol (E2) levels were measured at up to 13 follow-up visits (over up to 17 years). We used complementary log-log-based discrete-time survival models anchored at baseline. Diabetes developed in 376 women. A 5-unit increase in time-varying SHBG was associated with a 10% reduced risk of diabetes (hazard ratio [HR] 0.91, 95% CI 0.87-0.95), adjusting for covariates, and baseline SHBG,T, and E2 levels. Time-varying T was not associated with diabetes risk. Compared with the lowest quartile for annual rate of change of SHBG since baseline (quartile 1 [Q1] -92.3 to -1.5 nmol/L), all other quartiles were associated with a decreased risk of diabetes adjusting for covariates and baseline SHBG; associations persisted after adjusting for rate of change of T and E2 (Q2 [> -1.5 to -0.2 nmol/L] HR 0.33, 95% CI 0.23-0.48; Q3 [> -0.2 to 1.3 nmol/L] HR 0.37, 95% CI 0.25-0.55; Q4 [>1.3 to 82.0 nmol/L] HR 0.43, 95% CI 0.30-0.63). Increasing levels of SHBG over the menopause transition were associated with a decreased risk of incident diabetes. Stable to increasing rates of change in SHBG were also independently associated with a decreased risk of diabetes compared with decreasing rates of change, suggesting SHBG may affect glucose through a mechanism beyond androgenicity.

Three Weeks on a Ketogenic Diet Reduces Free Testosterone and Free Estradiol in Middle-Aged Obese Men and Women.

Beta-hydroxybuturate (β-OHB) supplements are commonly utilized in sports by both recreational and professional athletes. In a recent study, we observed a drop in testosterone levels following the oral ingestion of racemic sodium-β-OHB. In this investigation, we aim to determine whether a single oral dose of ketone ester (study I) and prolonged endogenous ketosis (study II) also reduces testosterone levels. This investigation integrated samples from two distinct studies. Study I was a randomized, controlled, crossover trial with ten healthy, young male participants receiving either a weight-adjusted ketone ester or control (water, CTR) and vice versa following an overnight fast. Repeated blood sampling was used to monitor plasma β-OHB and testosterone levels. Study II, another randomized, controlled, crossover trial, included 11 middle-aged participants (five males). They followed either a ketogenic diet (KD) characterized by low carbohydrates and high fat content or a standard diet (SDD) for three weeks. After each study period, participants underwent examination following an overnight fast, with repeated measures employed to analyze concentrations of plasma β-OHB and sex hormone levels. Study I: Testosterone decreased from 23.8 ± 2.4 nmol/l to 22.3 ± 2.5 nmol/l 300 minutes after the ketone ester and increased from 20.9 ± 2.1 nmol/l to 22.2 ± 1.9 300 minutes after CTR. This difference was not significant, p = 0.06. Study II. Total testosterone was unaffected after the KD compared to the SDD in men (20.2 ± 1.23 nmol/l vs. 18.2 ± 1.23 nmol/l (p = 0.1)) and was lower after KD in women (0.87 ± 0.06 vs. 1.1 ± 0.06 nmol/l (p < 0.0001)). Sex hormone-binding globulin (SHBG) increased in men after KD compared with SDD (31.2 ± 2.6 nmol/l vs 25.0 ± 2.6 nmol/l, p < 0.0001) and women (26.5 ± 3.05 nmol/l vs 24.2 ± 3.05 nmol/l, p = 0.003). The free androgen index decreased after KD in men (ratio: 0.65 ± 0.05 vs. ratio: 0.74 ± 0.05, p = 0.04) and in women (ratio: 0.036 ± 0.006 vs. SDD 0.05 ± 0.006, p = 0.0001). Free estradiol index was also found lower after KD in men (ratio: 3.1 ± 0.8 vs. ratio: 4.8 ± 0.8, p = 0.0003) and in women (ratio: 1.2 ± 2.2 vs. 9.8 ± 2.2, p = 0.0001). Our findings indicate that the acute ingestion of ketone ester may not reduce testosterone levels in healthy young males. However, a three-week exposure to KB from a KD results in an increase in SHBG in men and women with obesity as well as it lowers free testosterone and estradiol for men and women. We thus present evidence of crosstalk between alterations in a metabolite, β-OHB, and the regulation of the hypothalamic-pituitary-gonadal axis from a KD. The clinical impact of this reduction remains to be investigated. This trial is registered with NCT04156477 and NCT05012748.

Effect of dapagliflozin on proteomics and metabolomics of serum from patients with type 2 diabetes

BackgroundSodium-glucose co-transporter 2 (SGLT2) inhibitors reduced the risk of cardiovascular and renal outcomes in patients with type 2 diabetes (T2D), but the underlying mechanism has not been well elucidated. The circulating levels of proteins and metabolites reflect the overall state of the human body. This study aimed to evaluate the effect of dapagliflozin on the proteome and metabolome in patients with newly diagnosed T2D.MethodsA total of 57 newly diagnosed T2D patients were enrolled, and received 12 weeks of dapagliflozin treatment (10 mg/d, AstraZeneca). Serum proteome and metabolome were investigated at the baseline and after dapagliflozin treatment.ResultsDapagliflozin significantly decreased HbA1c, BMI, and HOMA-IR in T2D patients (all p < 0.01). Multivariate models indicated clear separations of proteomics and metabolomics data between the baseline and after dapagliflozin treatment. A total of 38 differentially abundant proteins including 23 increased and 15 decreased proteins, and 35 differentially abundant metabolites including 17 increased and 18 decreased metabolites, were identified. In addition to influencing glucose metabolism (glycolysis/gluconeogenesis and pentose phosphate pathway), dapagliflozin significantly increased sex hormone-binding globulin, transferrin receptor protein 1, disintegrin, and metalloprotease-like decysin-1 and apolipoprotein A-IV levels, and decreased complement C3, fibronectin, afamin, attractin, xanthine, and uric acid levels.ConclusionsThe circulating proteome and metabolome in newly diagnosed T2D patients were significantly changed after dapagliflozin treatment. These changes in proteins and metabolites might be associated with the beneficial effect of dapagliflozin on cardiovascular and renal outcomes.

FRI435 A Grave Case Of Gynecomastia

Abstract Disclosure: S. Seltzer: None. A. illiams: None. T. Kader: None. Background: Gynecomastia is a common endocrinology referral. Our team saw a patient in the clinic with an unusual presentation. Clinical Case: A 28 year old male presented with worsening painful gynecomastia affecting one breast initially but eventually progressing to both breasts. His secondary concern was a 40lb weight loss and new onset tremor. He declined hypogonadal symptoms, palpitations, or new testicular growth. Exam revealed a resting pulse of 120 b.p.m., a palpable goiter, visible tremor, hyperdynamic heart sounds and bilateral tender gynecomastia. Labs revealed normal FSH, LH and hCG, high total testosterone (TT), thyroxine (T4) and triiodothyronine (T3) with positive thyroid receptor antibodies. Methimazole and beta blockade were started. He did develop an episode of atrial fibrillation requiring admission. Due to medication intolerance and patient preference the decision was made for total thyroidectomy. Three months post-surgery there was complete resolution of hyperthyroidism and gynecomastia.The differential for true gynecomastia is broad. The initial diagnostic approach includes a thorough history and physical exam followed by measuring serum testosterone (T), LH, hCG and estradiol (E2). Increased LH and low T indicates hypogonadism. Normal values may suggest an idiopathic cause. Elevated hCG warrants testicular imaging and if negative, chest and abdominal imaging to rule out extragonadal germ cell tumors. Elevated total T and LH should prompt measurement of TSH and T4 and if normal androgen resistance should be suspected. Elevated E2 and low/low normal LH should prompt testicular imaging and if normal an adrenal CT to rule out an adrenal neoplasm. If LH and T are low, prolactin should be measured as well as dedicated pituitary imaging.Any state which induces an increased E to T ratio may cause gynecomastia. The true pathophysiology in hyperthyroidism driving the increased sex hormone binding globulin (SHBG) production is unknown. It is postulated that this increase is driven by increased transcription and translation of hepatocyte nuclear factor-4ɑ secondary to elevated T41. SHBG more readily binds androgens than estrogens leading to a relative decrease in free T (FT). The lower FT levels result in negative feedback to the pituitary gland which causes increases in LH resulting in production of androgens, estradiol and peripheral aromatases. The increase in peripheral aromatization of testosterone leads to further elevation of the free estrogen levels. Conclusion: Hyperthyroidism should always be in the differential of gynecomastia as in our case the presentation may be atypical.

Sex hormone-binding globulin levels and development of hypertension in middle-aged men and women.

To investigate the association between sex hormone-binding globulin (SHBG) levels, change in blood pressure and development of hypertension. In a community-based study, we examined 2816 middle-aged participants with focus on cardiometabolic risk factors in 2002-2005. A representative sample of 1954 men and women was invited to follow-up in 2012-2014 and 1327 were included in a second study visit. Mean follow-up time was 9.7 years. Blood pressure was measured according to the guidelines from the seventh Joint National Committee of Hypertension, and new cases of hypertension were recorded. SHBG was measured at baseline. The association between SHBG, blood pressure and new cases of hypertension was investigated using linear regression analyses and logistic regression analyses after excluding individuals treated with blood pressure-lowering drugs. Mean SBP and DBP at follow-up was 123 and 72 mmHg, respectively, and mean increase from baseline was 5.8 and 2.9 mmHg. During the follow-up time, 167 new cases of hypertension (16.1%) were identified. One standard deviation (SD) increase in SHBG at baseline was inversely associated with the risk to develop hypertension at follow-up (OR = 0.74, 95% CI 0.58-0.95) in the fully adjusted model. Moreover, one SD increase in SHBG was associated with a decrease in mean SBP (delta = -1.5 mmHg, 95% CI - 2.2 to -0.8) and DBP (delta = - 1.0 mmHg, 95% CI - 1.5 to -0.4), after adjusting for covariates. SHBG levels are inversely associated with development of hypertension and change in blood pressure levels independent of major risk factors.

(013) Estetrol Combined with Drospirenone: An Investigational Oral Contraceptive With A Selective Impact on Endocrine Parameters

Abstract Introduction Combined oral hormone contraceptive use is associated with decreased circulating androgens (Burrows LJ, et al. J Sex Med. 2012) and increased hormone binding globulins (Mawet M, et al. Eu J Cont Rep Hlth Care. 2015). Estetrol (E4) is a human-specific estrogen produced by the fetal liver, and has selective action in different tissues. The combination of E4 and Drospirenone (DRSP) was evaluated in a Phase-2 study to determine the potential effects on endocrine parameters. Objectives To evaluate the change from baseline in serum concentration of various endocrine and liver protein markers at cycle 3 and 6 in subjects receiving E4/DRSP and two comparison combined oral contraceptive (COC) formulations. Methods In this randomized, open-label, three-arm parallel study, participants received E4 15 mg /DRSP 3mg (n = 38), or ethinyl-estradiol (EE) 30 g/Levonorgestrel (LNG) 150 g (n = 29) or EE 20 g/DRSP 3 mg (n = 31) in a 24/4-day regimen of 6 consecutive, 28-day treatment cycles. Changes from baseline in serum total testosterone (TT), free testosterone (FT), androstenedione, dehydroepiandrosterone sulfate (DHEA-S), cortisol binding globulin (CBG), sex hormone binding globulin (SHBG), and thyroxine binding globulin (TBG) were determined at cycle 3 and 6. Potential differences between baseline and cycle 3 and 6 for all treatments, as well as pairwise comparisons of E4/DRSP and each of the other two formulations are considered statistically significant with an exploratory P-value &amp;lt; 0.05. Results TBG was significantly increased with EE/LNG (47% and 37%) and EE/DRSP (80% and 70%) at cycle 3 and 6. TBG was also increased significantly but to a lesser extent with E4/DRSP (27% and 17%). CBG increased at cycle 6 in all treatments. The increase in CBG was significantly greater with EE/LNG (152%) and EE/DRSP (140%) than that noted for E4/DRSP (40%). A significant increase in SHBG was observed at cycle 3 (240%) and 6 (251%) with EE/DRSP as compared to baseline or E4/DRSP (52% and 55%). At cycle 3, a significant decrease in TT was observed for E4/DRSP (35%), EE/LNG (40.5%), and EE/DRSP (41%). FT was significantly reduced at cycle 3 for E4/DRSP, EE/LNG, and EE/DRSP at 50%, 60%, and 75%, respectively. At cycle 6, a similar pattern of significant reductions in both TT and FT was observed with each treatment. Pairwise comparison, revealed no significant differences in TT and FT among groups. There were significant decreases in androstenedione at cycle 3 and 6, with E4/DRSP (32% and 31%), EE/LNG (44% and 49%), and EE/DRSP (40% and 40%). DHEA-S was significantly reduced from baseline at cycle 3 and 6 in all treatments. There was a significant difference in DHEA-S at cycle 6 with EE/DRSP (27%) compared to E4/DRSP (11%). Conclusions E4/DRSP had lower increases in hormone binding globulins compared to EE/LNG or EE/DRSP. Increases in SHBG were significantly higher for EE/DRSP than E4/DRSP. A decrease in TT and FT with E4/DRSP was not significantly different from EE/LNG or EE/DRSP. E4/DRSP had a significantly lower impact on DHEA-S levels than EE/DRSP. Disclosure Yes - Mithra Women's Health. Industry initiated, executed and funded study – Yes.

Scoping Review: Dampak Penggunaan Kontrasepsi Hormonal Memengaruhi Disfungsi Seksual Pada Wanita

Hormonal contraception is very effective in preventing pregnancy, but this contraception has various side effects. The objective is to determine how hormonal contraceptive use affects sexual dysfunction in women. In this research, the author follows the Arksey and O'Malley framework by identifying questions, identifying relevant articles, selecting and selecting papers, mapping data, discussing, concluding, and reporting results. The prism flowchart displays the flow of article searches on four databases: PubMed, Wiley, EBSCO, and ProQuest. This Scoping Review found 14 articles out of 1441 selected based on inclusion and exclusion criteria into three themes. Hormonal changes due to using Combined Hormonal Contraceptive (CHC) contraception negatively affect sexual life, namely increasing Sex Hormone Binding Globulin (SHBG) and decreasing free testosterone. The effect of hormonal contraceptives on female sexual dysfunction decreases libido, pleasure, orgasm, difficulty in lubrication, and vaginal dryness. Other factors affecting women's sexual function include age, education, premenopause, marital status, consumption of antidepressants, differences in partner age, income, and household harmony. CHC hormonal contraceptives cause sexual dysfunction in women due to decreased androgen hormones in the ovaries.

Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women.

The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83-0.94]) and women (HR: 0.89 [0.83-0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74-0.89) and women (pooled RR: 0.86 [0.78-0.94]). Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

Sex-specific differences in bone mineral density loss after sleeve gastrectomy

Sleeve gastrectomy is an effective bariatric procedure; however, sleeve gastrectomy-related adverse skeletal outcomes have been increasingly reported. High levels of sex hormone-binding globulin (SHBG) have been documented to be a risk factor of bone mineral density (BMD) loss with different effects observed between sexes. The aim of this study was to identify sex-specific changes in BMD following sleeve gastrectomy and to evaluate the role of SHBG in this process. This retrospective study included 19 middle-aged men and 30 non-menopausal women with obesity who underwent sleeve gastrectomy in China. Anthropometrics, bone turnover markers, calciotropic hormones, BMD, SHBG, and gonadal steroids were measured preoperatively and at 6 and 12 months postoperatively. Longitudinal changes in BMD, bone turnover markers and SHBG were compared between sexes by linear mixed models. Multiple stepwise regression analysis was used to identify the predictors of BMD loss at the investigated bone sites. Over the 12-month study period, total hip and femoral neck BMD decreased, while lumbar spine BMD remained largely unchanged in both sexes. Linear mixed models revealed significant sex × time interaction effects in total hip BMD and SHBG, showing that men had a significantly greater reduction in total hip BMD and less increase in SHBG after sleeve gastrectomy than women. In the multivariate model, SHBG was significantly associated with total hip BMD loss in men (adjusted β = -0.533, P = 0.019) but not women while total estrogen was significantly associated with total hip BMD loss in women (adjusted β = 0.508, P = 0.01) but not men. Significant sex-specific BMD changes were observed after sleeve gastrectomy in the current study. Sleeve gastrectomy-related increase in SHBG may be a specific risk factor for total hip BMD loss in men. Our results indicate that sex-specific screening may be warranted to facilitate personalized postoperative bone care in this population.

Mendelian randomization identifies age at menarche as an independent causal effect factor for gestational diabetes mellitus.

The relationship between age at menarche (AAM) and gestational diabetes mellitus (GDM) risk is still inconclusive. This Mendelian randomization (MR) analysis was used to assess systematically the causal relationship between AAM and GDM risk in human beings. Single-nucleotide polymorphisms associated with AAM, oestradiol levels, sex hormone-binding globulin (SHBG) levels and bioavailable testosterone (BioT) levels were screened via the genome-wide association study enrolling individuals of European descent. Summary-level data for GDM (123 579 individuals) were extracted from the UK Biobank. An inverse-variance-weighted method was used for the primary MR analysis. Sensitivity analyses were examined via MR-Egger regression, heterogeneity tests, pleiotropy tests and leave-one-out tests. The directionality that exposure causes the outcome was verified using the MR-Steiger test. Genetically predicted early AAM was found to have a causal positive association with a higher risk of GDM (odds ratio=0.798, 95% confidence interval=0.649-0.980, p=.031). In the multivariable MR analysis adjusted for oestradiol, SHBG and BioT levels, the causal association between AAM and GDM risk remained (odds ratio=0.651, 95% confidence interval=0.481-0.881, p=.006). A 1-SD increase in SHBG or BioT levels was significantly associated with a 41.4% decrease or 20.8% increase in the overall GDM risk (p=3.71E-05 and .040), respectively. However, after controlling for AAM, oestradiol levels and BioT levels by multivariable MR analysis, there was no direct causal effect of SHBG levels on GDM risk (p=.084). Similarly, after adjusting for AAM, oestradiol levels and SHBG levels by multivariable MR analysis, there was no direct causal effect of BioT levels on the risk of GDM (p=.533). In addition, no direct causal association was identified between oestradiol levels and GDM risk in univariable MR analysis or multivariable MR analysis. Genetic variants predisposing individuals to early AAM were independently associated with higher GDM risk. Further research is required to understand the mechanisms underlying this putative causative association. In addition, AAM may be helpful in clinical practice to identify women at risk for GDM; pregnant women who are young for menarche may need to take precautions before GDM develops.

Effect of Intermittent Fasting on Reproductive Hormone Levels in Females and Males: A Review of Human Trials.

Intermittent fasting is a popular diet for weight loss, but concerns have been raised regarding the effects of fasting on the reproductive health of women and men. Accordingly, we conducted this literature review to clarify the effects of fasting on reproductive hormone levels in humans. Our results suggest that intermittent fasting decreases androgen markers (i.e., testosterone and the free androgen index (FAI)) while increasing sex hormone-binding globulin (SHBG) levels in premenopausal females with obesity. This effect was more likely to occur when food consumption was confined to earlier in the day (eating all food before 4 pm). In contrast, fasting did not have any effect on estrogen, gonadotropins, or prolactin levels in women. As for men, intermittent fasting reduced testosterone levels in lean, physically active, young males, but it did not affect SHBG concentrations. Interestingly, muscle mass and muscular strength were not negatively affected by these reductions in testosterone. In interpreting these findings, it is important to note that very few studies have been conducted on this topic. Thus, it is difficult to draw solid conclusions at present. From the limited data presented here, it is possible that intermittent fasting may decrease androgen markers in both genders. If this is the case, these results would have varied health implications. On the one hand, fasting may prove to be a valuable tool for treating hyperandrogenism in females with polycystic ovarian syndrome (PCOS) by improving menstruation and fertility. On the other hand, fasting may be shown to decrease androgens among males, which could negatively affect metabolic health and libido. More research is warranted to confirm these preliminary findings.

Associations between pyrethroid exposure and serum sex steroid hormones in adults: Findings from a nationally representative sample

BackgroundPyrethroids have been considered as potential endocrine-disrupting chemicals and have been shown to be associated with endocrine-related health outcomes. However, limited studies directly explored the link between pyrethroid exposure and sex hormones in the general population. ObjectivesTo explore the associations between exposure to pyrethroids and serum sex steroid hormones in adults. MethodsWe evaluated the cross-sectional associations in 1235 adults aged ≥20 years who had been assigned to the National Health and Nutrition Examination Survey (NHANES) 2013–2014. The urinary concentration of 3-phenoxybenzoic acid (3-PBA) was applied as a biomarker of human pyrethroid exposure levels. Information on sex steroid hormones, including total testosterone (TT), estradiol (E2), and sex hormone-binding globulin (SHBG) in serum were measured. Free androgen index (FAI) and the ratio of TT to E2 (TT/E2) were also calculated. The percent changes with 95% confidence intervals (CIs) for a doubling of 3-PBA concentrations in the serum sex hormone levels were estimated using generalized linear regression models. ResultsThe overall median concentrations of creatinine-adjusted 3-PBA were 0.58 μg/g creatinine, and 90.0% of adults had a detectable level of 3-PBA. In females, every two-fold increase in 3-PBA was associated with 4.34% (95% CI: 1.58%, 7.18%) higher levels of TT and 4.05% (95% CI: 7.03%, 1.16%) higher levels of SHBG, respectively. In males, a doubling in 3-PBA was associated with 3.02% (95% CI: 1.21%, 4.86%) increase in SHBG but 1.85% (−3.59%, −0.07%) decrease in FAI, respectively. In addition, significant non-linear associations of 3-PBA with SHBG in both males and females and TT in females were observed. ConclusionsEnvironmental pyrethroid exposure was associated with altered sex hormones in adults. This study provides important epidemiological evidence for the association of pyrethroids with endocrine disruption.

Can we rely on total testosterone measurement to exclude hypogonadism in erectile dysfunction?

Although male hypogonadism (MH) is a prevalent comorbidity in patients presenting for erectile dysfunction (ED), its screening relies solely on total testosterone (TT). Ageing and other conditions can increase sex hormone-binding globulin (SHBG) and lower free testosterone (FT) causing symptomatic MH despite normal TT. The primary objective was to measure the prevalence of normal TT/low FT among patients presenting for ED. From January 2019 to December 2020, 408 patients referred for sexual dysfunction were screened; 180 men with a confirmed diagnosis of ED were included. MH was screened using TT, SHBG, albumin and LH. FT was calculated (cFT). Low TT, high SHBG and low cFT were defined as <345 ng/dL, >50 nmol/L and <6.5 ng/dL, respectively. Patients were divided into groups according to TT/cFT status and to age group. The frequency of normal TT/low cFT was 17.2%. From all 31 patients with normal TT/low cFT, only four (12.9%) had either hyperthyroidism, hepatic disease or HIV infection, while 23 (74.2%) were older than 60 years. Patients with normal TT/low cFT were older (65.57 ± 10.43 vs. 56.79 ± 10.63 yo, p = 0.001) and had higher SHBG (78.48 ± 40.14 vs. 52.35 ± 20.39 nmol/L, p = 0.014) than patients with normal TT/cFT. Patients over 60 years represented 48.9% of the sample, 52.5% had elevated SHBG and their frequency of normal TT/low cFT was 26.3%. Normal TT/low cFT is frequent and can be missed by current screening recommendations for MH in patients presenting for ED. Ageing seems to be the main culprit as elevated SHBG prevalence increases steeply after the sixth decade. TT cannot solely be relied on to exclude biochemical MH in patients presenting for ED, especially in patients over 60 years old. Current guidelines for MH screening in ED should be amended.

High-intensity training elicits greater improvements in cardio-metabolic and reproductive outcomes than moderate-intensity training in women with polycystic ovary syndrome: a randomized clinical trial.

Does 12 weeks of high-intensity interval training (HIIT) result in greater improvements in cardio-metabolic and reproductive outcomes compared to standard moderate-intensity continuous training (MICT) in women with polycystic ovary syndrome (PCOS)? HIIT offers greater improvements in aerobic capacity, insulin sensitivity and menstrual cyclicity, and larger reductions in hyperandrogenism compared to MICT. Exercise training is recognized to improve clinical outcomes in women with PCOS, but little is known about whether HIIT results in greater health outcomes compared to standard MICT. This was a two-armed randomized clinical trial enrolling a total of 29 overweight women with PCOS between May 2016 and November 2019. Women with PCOS aged 18-45 years were randomly assigned to 12 weeks of either MICT (60-75% peak heart rate, N = 14) or HIIT (>90% peak heart rate, N = 15), each completed three times per week. The primary clinical outcomes were aerobic capacity (VO2peak) and insulin sensitivity (euglycaemic-hyperinsulinaemic clamp). Secondary outcomes included hormonal profiles, menstrual cyclicity and body composition. Both HIIT and MICT improved VO2peak (HIIT; Δ 5.8 ± 2.6 ml/kg/min, P < 0.001 and MICT; Δ 3.2 ± 2 ml/kg/min, P < 0.001), however, the HIIT group had a greater improvement in aerobic capacity compared to MICT (β = 2.73 ml/kg/min, P = 0.015). HIIT increased the insulin sensitivity index compared to baseline (Δ 2.3 ± 4.4 AU, P = 0.007) and MICT (β = 0.36 AU, P = 0.030), and caused higher increases in sex hormone-binding globulin compared to MICT (β = 0.25 nmol/l, P = 0.002). HIIT participants were 7.8 times more likely to report improved menstrual cyclicity than those in the MICT group (odds ratio 7.8, P = 0.04). This study has a small sample size and the findings of the effect of the exercise interventions are limited to overweight reproductive-aged women, who do not have any co-existing co-morbidities that require medication. Exercise, regardless of intensity, has clear health benefits for women with PCOS. HIIT appears to be a more beneficial strategy and should be considered for promoting health and reducing cardio-metabolic risk in overweight women with PCOS. This work was supported by a Project Support Grant from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence in PCOS. The authors have no conflicts of interest to disclose. ACTRN12615000242527. 19 February 2015. 27 May 2016.

Association between sex hormone-binding globulin and kidney function in men: results from the SPECT-China study.

The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population. A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR <60 mL·min -1 ·1.73 m -2 . After adjusting for age, smoking, metabolic factors, and testosterone, through increasing quartiles of SHBG, a significantly positive association between SHBG quartiles and eGFR was detected in men (Q1 vs. Q4, β -2.53, 95% confidence interval -3.89, -1.17, Ptrend < 0.001). Compared with the highest quartile of SHBG, SHBG in the lowest quartile was associated with 96% higher odds of low eGFR (odds ratio 1.96, 95% confidence interval 1.10, 3.48) in the model after full adjustment. According to the stratified analyses, the associations between a 1-standard deviation increase in serum SHBG and the prevalence of low eGFR were significant in men aged ≥60 years old, waist circumference <90 cm, diabetes (no), hypertension (yes), dyslipidemia (no), and nonalcoholic fatty liver disease (no). Lower serum SHBG levels were significantly associated with lower eGFR and a higher prevalence of low eGFR in Chinese men independent of demographics, lifestyle, metabolic-related risk factors, and testosterone. Large prospective cohort and basic mechanistic studies are warranted in the future.

Effect of aerobic exercise with diet on sex hormones and selected coagulation biomarkers in obese postmenopausal women: a randomized clinical trial.

The current study determined the effect of aerobic training and diet program versus diet only on sex hormones and selected coagulation biomarkers in obese postmenopausal women. Further, the correlation between the measured variables after the intervention was identified. Eligible 40 women were distributed into two equal groups: the experimental group that received aerobic training three times per week for 12 weeks along with a balanced diet, and the control group that received a balanced diet only. Changes in weight, body mass index, sex hormones, and coagulation biomarkers were assessed pre-and post-intervention. The correlation between evaluated variables was assessed. Both groups demonstrated a significant difference in sex hormones (i.e., a substantial decrease in estradiol, total testosterone, free testosterone, and a substantial increase in sex hormone-binding globulin) and coagulation biomarkers (a considerable reduction in plasminogen activator inhibitor-1 activity, fibrinogen, and a significant increase in tissue plasminogen activator, prothrombin time, and cephalin-kaolin coagulation time). This discrepancy was highly significant in the experimental group (p < 0.01) relative to the control group (p < 0.05), and there was a strong link between sex hormones and coagulation biomarkers (p ≤ 0.05). Conversely, no correlation between variables was noticed in the control group (p > 0.05). Aerobic exercise along with a balanced diet modulates sex hormones level, improves homeostasis balance in postmenopausal women, and reduces the potential risk of cardiovascular disease.

Characterization and comparison of recombinant full-length ursine and human sex hormone-binding globulin.

Sex hormone‐binding globulin (SHBG) regulates the bioavailability of sex steroid hormones in the blood. Levels of SHBG increase markedly in brown bears (Ursus arctos) during hibernation, suggesting that a key regulatory role of this protein is to quench sex steroid bioavailability in hibernation physiology. To enable characterization of ursine SHBG and a cross species comparison, we established an insect cell‐based expression system for recombinant full‐length ursine and human SHBG. Compared with human SHBG, we observed markedly lower secretion levels of ursine SHBG, resulting in a 10‐fold difference in purified protein yield. Both human and ursine recombinant SHBG appeared as dimeric proteins in solution, with a single unfolding temperature of ~ 58 °C. The thermal stability of ursine and human SHBG increased 5.4 and 9.5 °C, respectively, in the presence of dihydrotestosterone (DHT), suggesting a difference in affinity. The dissociation constants for [3H]DHT were determined to 0.21 ± 0.04 nm for human and 1.32 ± 0.10 nm for ursine SHBG, confirming a lower affinity of ursine SHBG. A similarly reduced affinity, determined from competitive steroid binding, was observed for most steroids. Overall, we found that ursine SHBG had similar characteristics to human SHBG, specifically, being a homodimeric glycoprotein capable of binding steroids with high affinity. Therefore, ursine SHBG likely has similar biological functions to those known for human SHBG. The determined properties of ursine SHBG will contribute to elucidating its potential regulatory role in hibernation physiology.