Sex Hormone-binding Globulin Research Articles

Association of ultra-processed food-related metabolites with selected biochemical markers in the UK Biobank

BackgroundUltra-processed food (UPF) intake is positively associated with multiple adverse health outcomes. However, the underlying biological mechanisms remain unclear. Serum metabolites may elucidate these mechanisms. We investigated serum metabolites correlated with UPF and un/minimally processed food (UNPF) intake and evaluated their association with selected biochemical markers.MethodsCross-sectional study within the UK biobank, including a total of 72,817 participants with 24-hour recall dietary data and 134 nuclear magnetic resonance metabolites. UPF and UNPF intakes were evaluated using the NOVA classification, and related metabolites were identified using elastic net penalized regression. A UPF metabolomic signature was computed as a weighted sum of UPF-related metabolites, using elastic net coefficients as weights. Associations between UPF and UNPF-related metabolites, and serum C-reactive protein (CRP), insulin-like growth factor-1(IGF-1), sex hormone-binding globulin (SHBG), and testosterone were examined using multiple quantile regression.ResultsElastic net model identified 17 and 15 metabolites uniquely related to UPF and UNPF intake, respectively. Acetoacetate, acetone, high-density lipoprotein (HDL) diameter, docosahexaenoic acid, linoleic acid, ω-3 fatty acids (FA), total lipids in large HDL cholesterol, and valine levels were decreased, but free cholesterol in extremely small very low-density lipoproteins (LDL), glutamine, glycine, glycoprotein acetyls, lactate, saturated FA, sphingomyelins, triglycerides in large LDL, and triglycerides in medium HDL levels were increased with high UPF intake. Opposite relationships were observed for UNPF intake. Heterogeneous associations were observed between UPF-related metabolites and CRP, IGF-1, SHBG, and testosterone levels. A UPF metabolomic signature was positively associated with CRP (regression coefficient per standard deviation, 1.45, 95% confidence interval, 1.385, 1.515) and negatively associated with IGF-1 (-3.16, -4.493, -1.827) and SHBG (-13.878, -15.291, -12.465).ConclusionA UPF metabolomic profile, including VLDL free cholesterol, saturated FA, triglycerides, glutamine, glycine, and glycoprotein acetyl was associated with inflammatory, insulin signalling, and reproductive biomarkers. This metabolomic profile should be explored as a potential mediators of UPF-disease associations, and as an objective marker of UPF intake.

Characteristics of polymorphism of genes involved in the regulation of glucose metabolism and steroid hormone synthesis in patients with polycystic ovary syndrome

Background: Polycystic ovary syndrome is an urgent problem of gynecological endocrinology. Currently, a number of genes have been studied that control glucose metabolism and are involved in the synthesis, conversion into an active form and transport of steroid hormones, mutations in which with a certain degree of reliability can serve as a diagnostic criterion for polycystic ovary syndrome. Aim: The aim of this study was to evaluate the PPARG Pro12Ala, INS 223HphI AT, and SHBG (TAAAA)n gene polymorphisms in patients with polycystic ovary syndrome and in healthy individuals. Materials and methods: The polymerase chain reaction method and restriction fragment length polymorphism analysis were used. The frequencies of alleles and genotypes of polymorphic variants were studied in 136 women with polycystic ovary syndrome and 47 women in the control group: Pro12Ala (PPARG gene), 223HphI AT, (INS gene) and (TAAAA)n repeats (SHBG gene). Results: The distribution of the allele and genotype frequencies for the PPARG (rs1801282) and INS (rs689) genes in patients with polycystic ovary syndrome and in healthy individuals did not differ. The distribution of the genotype frequencies in the group of women with polycystic ovary syndrome differed (p = 0.02) from that in the control group for the (TAAAA)n polymorphism in the SHBG gene. In the presence of a long repeat in the SHBG gene in at least one of the homologous chromosomes, the probability of a woman having polycystic ovary syndrome increases by 2.5 times. Patients with a verified A/A genotype (INS), in the presence of an SHBG gene allele with a long repeat, have a ten-fold higher risk of developing polycystic ovary syndrome than women with SHBG gene short alleles. Conclusions: Patients with long repeats in the SHBG gene are at risk for developing polycystic ovary syndrome with phenotypes A, B, and C, especially in combination with the presence of the A/A genotype, class I (INS).

Comparison of GLP-1 Receptor Agonists Combined with Metformin Versus Metformin Alone in the Management of PCOS: A Comprehensive Meta-Analysis.

This study compared the efficacy and safety of glucogan-like peptide-1 receptor agonists (GLP1RAs) combined with metformin versus metformin alone in women with polycystic ovary syndrome (PCOS). A systematic search of "PubMed", "EMBASE", "Cochrane Library", and "Web of Science", "Google Scholar" was conducted up to September 2024. Studies were included if they were RCTs investigating the combination of GLP1RAs and metformin in women diagnosed with PCOS. Eligible studies compared this combination therapy to metformin alone. Primary outcomes included changes in body weight, BMI, waist circumference, fasting glucose, HOMA-IR, androgen levels, and sex hormone-binding globulin (SHBG). Meta-analysis was performed using RevMan 5.4 software. Eight RCTs with a total of 337 participants were included. The combination of GLP1RAs and metformin resulted in significant reductions in body weight (mean difference [MD]=-1.37kg, 95% CI [-2.07, -0.67]; P = 0.0001), BMI (MD= -0.88kg/m², 95% CI [-1.37, -0.39]; P = 0.0005), waist circumference (MD= -2.46cm, 95% CI [-3.59,-1.33]; P < 0.0001), fasting glucose level (MD= -0.30, 95% CI [-0.42,-0.17]; P < 0.0001), and glucose level at 2h after OGTT (MD= -1.58, 95% CI [-2.10,-1.06]; P < 0.0001) compared to metformin alone. Improvements in insulin sensitivity (HOMA-IR) in GLP1RA + Met group were also observed (MD=-1.58, 95% CI [-2.10, -1.06]; P < 0.0001) comparing to Met group. Hormonal outcomes demonstrated an increase in SHBG (MD = 10.04, 95% CI [7.06, 13.01]; P < 0.0001). Adverse events were not different between GLP1RA + Met and Met groups. Collectivley, combination of GLP1RAs and metformin provides superior benefits over metformin alone in reducing body weight, improving insulin sensitivity, and regulating hormonal imbalances in women with PCOS.

Biomarker Assessment of Cheese Intake and Stroke Risk: A Mendelian Randomization Study.

This study explores the association of cheese consumption with stroke using a Mendelian randomization (MR) approach, which leverages genetic variations to minimize confounding. The study analyzed the impact of cheese cheese dietary habits on stroke, mediated by 44 biomarkers, including blood cells, biochemical markers, and blood pressure indicators. The findings show that cheese consumption is associated with lower stroke risk (OR = 0.715, P = 0.000279). Seven key biomarkers were identified as intermediaries in this relationship: apolipoprotein B (1.70%), aspartate aminotransferase (1.68%), cystatin C (2.50%), glucose (4.40%), sex hormone binding globulin (2.14%), urate (3.70%), and diastolic blood pressure (11.94%). These biomarkers help explain the biological pathways through which cheese intake may influence stroke risk, with diastolic blood pressure contributing the most to the protective effect. Despite these findings, the study notes limitations, such as the absence of specific data on cheese types and the emphasis on individuals of European ancestry may restrict the applicability of the findings to broader populations. Further research is required to validate these results and clarify the underlying mechanisms of the identified biomarkers in stroke prevention.

Evaluating the association between lipidome and female reproductive diseases through comprehensive Mendelian randomization analyses

This study aimed to assess the causal relationship between lipidome and female reproductive diseases (FRDs) using an advanced series of Mendelian randomization (MR) methods. This study utilized genome-wide association study (GWAS) summary statistics encompassing 179 lipidomes and six prevalent FRDs, namely polycystic ovary syndrome (PCOS), endometriosis, uterine fibroid, female infertility, uterine endometrial cancer, and ovarian cancer. The two-sample MR (TSMR) approach was employed to investigate the causal relationships, with further validation using false discovery rate (FDR) and multivariable MR (MVMR) methods. Subsequently, a range of comprehensive evaluations were performed, including sensitivity analysis, mediation MR analysis, reverse MR analysis, and steiger test. Examining 179 lipidome traits as exposures and 6 FRDs as outcomes, this study identified significant causal effects of 56 lipids on FRDs. Following multiple testing correction and MVMR validation, sphingomyelin (d38:2) was found to have a protective effect against PCOS (β = -0.104, 95% CI: -0.199 ~ -0.010, P = 0.031). Phosphatidylcholine (18:0_22:6) was associated with a decreased risk of developing uterine fibroid (β = -0.111, 95% CI: -0.201~ -0.021, P = 0.016), and sterol ester (27:1/20:3) showed significance in uterine endometrial cancer (β = -0.248, 95% CI: -0.443 ~ -0.053, P = 0.013). Conversely, phosphatidylethanolamine (18:2_0:0) was associated with increased risk of endometriosis (β = 0.183, 95% CI: 0.015 ~ 0.350, P = 0.033), while sterol ester (27:1/18:1) posed a risk influence on uterine fibroid (β = 1.007, 95% CI: 0.925 ~ 1.089, P < 0.001), and phosphatidylcholine (16:0_22:6) on uterine endometrial cancer (β = 0.229, 95% CI: 0.039 ~ 0.420, P = 0.018). Furthermore, it was determined that the causal associations between these lipidome profiles and FRDs were independent of BMI, obesity, diabetes, smoking, alcohol use, physical activity, inflammation, depression, waist-hip ratio, vitamin D, dehydroepiandrosterone sulphate, sex hormone binding globulin, and testosterone levels. Most outcomes passed consistent tests without evidence of heterogeneity, pleiotropy, or reverse causality. The results indicated a close association between specific lipidomes, particularly sphingomyelin, lysophosphatidylethanolamine, cholesterol ester, and phosphatidylcholines, with FRDs. These lipid species may potentially serve as biomarkers and future drug targets for the treatment of FRDs.

Intracellular Retention of Estradiol is Mediated by GRAM Domain-Containing Protein ASTER-B in Breast Cancer Cells.

Elevated blood levels of estrogens are associated with poor prognosis in estrogen receptor-positive (ER+) breast cancers, but the relationship between circulating blood hormone levels and intracellular hormone concentrations are not well characterized. We observed that MCF-7 cells treated acutely with 17β-estradiol (E2) retain a substantial amount of the hormone even upon removal of the hormone from the culture medium. Moreover, global patterns of E2-dependent gene expression are sustained for hours after acute E2 treatment and hormone removal. While circulating E2 is sequestered by sex hormone binding globulin (SHBG), the potential mechanisms of intracellular E2 retention are poorly understood. We found that a mislocalization of a steroid-binding GRAM-domain containing protein, ASTER-B, to the nucleus, which is observed in a subset of breast cancer patients, is associated with higher cellular E2 retention. Accumulation and retention of E2 are related to the steroidal properties of E2, and require nuclear localization and steroid binding by ASTER-B, as shown using a panel of mutant ASTER-B proteins. Finally, we observed that nuclear ASTER-B-mediated E2 retention is required for sustained hormone-induced ERalpha chromatin occupancy at enhancers and gene expression, as well as subsequent cell growth responses. Our results add intracellular hormone retention as a mechanism controlling E2-dependent gene expression and downstream biological outcomes. Implications: Mislocalized nuclear ASTER-B, which binds estradiol to support the functions of ER, can provide an alternate means of enhancing the biological effects of E2 in breast cancers and may be a potential therapeutic target that addresses multiple aspects of estrogen bioavailability.

The Association of Menopausal Age with Sex Hormones and Anthropometric Measures Among Postmenopausal Women in the Multi-Ethnic Study of Atherosclerosis Study.

Introduction: We investigated associations of menopausal age category with body mass index (BMI), waist circumference, waist-hip ratio, and waist-height ratio. We also explored the moderating effect of anthropometric measures on associations of menopausal age category with prespecified sex hormones: estradiol, dehydroepiandrosterone (DHEA), sex hormone-binding globulin, bioavailable testosterone, and total testosterone-estradiol (T/E) ratio. Methods: In this cross-sectional study, we included 2,436 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis who had menopausal age, anthropometric, and sex hormone data at baseline. Menopausal age was categorized as <45 years (early menopause), 45-49 years, 50-54 years (referent), and ≥55 years (late menopause). Linear models were used for analysis. Results: The mean (standard deviation) age was 64.7 (9.2) years. After multivariable adjustment, women who experienced late menopause had higher waist circumference (2.28 cm), waist-hip ratio (0.013 units), and waist-height ratio (0.014 units) but not BMI than those in the referent category. The interaction terms between menopausal age category and anthropometric measures were not significant for prespecified sex hormones (all Pinteraction >0.05). When compared with the referent category, T/E ratio was 21% (4.72 - 39.8%) higher among women with late menopause while DHEA levels were 9% (1 - 16%) higher among women who experienced menopause between 45 and 49 years in multivariable adjusted models. Conclusion: Women with late menopause had higher abdominal adiposity but not generalized adiposity when compared with those who experienced menopause between 50 and 54 years of age. Androgenicity was higher among women who experienced menopause between 45 and 49 years of age and those with late menopause, based on DHEA and T/E ratios, respectively.

Sex-specific associations of serum testosterone with gray matter volume and cerebral blood flow in midlife individuals at risk for Alzheimer's disease.

Testosterone, an essential sex steroid hormone, influences brain health by impacting neurophysiology and neuropathology throughout the lifespan in both genders. However, human research in this area is limited, particularly in women. This study examines the associations between testosterone levels, gray matter volume (GMV) and cerebral blood flow (CBF) in midlife individuals at risk for Alzheimer's disease (AD), according to sex and menopausal status. A cohort of 294 cognitively normal midlife participants, 83% female, ages 35-65 years, with an AD family history and/or Apolipoprotein E epsilon 4 (APOE-4) genotype, underwent volumetric Magnetic Resonance Imaging (MRI) to measure GMV and MR-Arterial Spin Labeling (ASL) for measurement of CBF. We used voxel-based analysis and volumes of interest to test for associations between testosterone (both total and free testosterone) and brain imaging outcomes, stratified by sex and menopausal status. Higher total and free testosterone levels were associated with larger GMV in men, with peak effects in frontal and temporal regions. Conversely, in women, higher testosterone levels correlated with higher CBF, with peak effects in frontal and limbic regions, subcortical areas and hypothalamus. Among women, associations between testosterone and GMV were observed at the premenopausal and perimenopausal stages, but not postmenopause, whereas associations of testosterone with CBF were significant starting at the perimenopausal stage and were more pronounced among hormone therapy non-users. Results were independent of age, APOE-4 status, midlife health indicators, and sex hormone-binding globulin levels. These findings indicate sex-specific neurophysiological effects of testosterone in AD-vulnerable regions in midlife individuals at risk for AD, with variations observed across sex and menopausal status. This underscores the need for further research focusing on the neuroprotective potential of testosterone in both sexes.

Exploring the link between sex hormone-binding globulin levels and prostate cancer risk: a comprehensive systematic review and meta-analysis.

Sex hormone-binding globulin (SHBG) plays a critical role in regulating androgen bioavailability and has been hypothesized to influence prostate cancer risk, though existing evidence is inconsistent. This systematic review and meta-analysis aimed to evaluate the association between SHBG levels and prostate cancer risk. A comprehensive search was conducted across PubMed, Embase, and Web of Science for studies published up to December 1, 2024. Observational studies assessing SHBG levels and prostate cancer risk were included. Effect sizes were pooled using random-effects meta-analysis. Heterogeneity was evaluated using the I2 statistic, and quality assessment was performed using the Newcastle-Ottawa Scale. Statistical analysis was performed using R software version 4.4. Sixteen studies, including 720,298 participants and 90,799 prostate cancer cases, were analyzed. The pooled odds ratio (OR) for prostate cancer risk per unit increase in SHBG was 0.907 (95% CI 0.799-1.030), indicating no statistically significant association. Substantial heterogeneity was observed among the included studies (I2 = 79%; P < 0.0001). Subgroup analyses showed no significant variation in effect sizes by study design. However, a Mendelian randomization analysis conducted in 140,254 European-descent males, including 79,148 prostate cancer cases, suggested a modest protective effect of higher SHBG levels, with an OR of 0.944 (95% CI 0.897-0.993). Sensitivity analyses confirmed the robustness of the pooled findings. This meta-analysis showed a complex relationship between SHBG levels and prostate cancer risk. While overall findings do not support a statistically significant association, higher SHBG levels may confer a protective role in specific contexts. Further research is needed to elucidate mechanisms, reduce heterogeneity, and validate SHBG as a biomarker for risk stratification.

Sex steroid hormones mediate the association between neonicotinoids and obesity among children and adolescents.

Neonicotinoids are the most widely used insecticide worldwide. Toxicological and epidemiological studies suggest that exposure to neonicotinoid may be linked to the development of childhood obesity. However, the evidence is limited. To investigate the association between neonicotinoid exposure and obesity among U.S. children and adolescents and to explore underlying mechanism mediated by serum sex steroid hormones in these associations. Data from the 2015-2016 National Health and Nutrition Examination Survey were used for the analysis. Generalized linear regression was used to investigate the association between detectable neonicotinoids and ten measures of obesity. The interaction effects of multiple neonicotinoids were determined by Chi-squared Automatic Interaction Detection method. Mediation analysis was used to assess potential mediators of sex steroid hormones, including testosterone (T), estradiol (E2), T/E2, sex hormone-binding globulin (SHBG), and free androgen index (FAI). Clothianidin (β = -0.29, 95 % CI: -0.57, -0.01) and N-desmethyl-acetamiprid (β = -0.19, 95 % CI: -0.35, -0.03) were associated with reduced VFI z-score. After stratification, 5-hydroxy-imidacloprid was positively associated with the risk of general obesity in males (OR=2.24, 95 % CI: 1.20, 4.20) with a probability of 52.5 %. FAI mediated 15 % of the association between neonicotinoid exposure and reduced risk of obesity, and SHBG mediated 30 % of the association between neonicotinoid exposure and increased risk of obesity. Neonicotinoids showed associations with obesity, but the results were mixed and sex-specific. Sex steroid hormones may play a role in mediating the effects of neonicotinoids on obesity.

The impact of intermittent fasting on fertility: A focus on polycystic ovary syndrome and reproductive outcomes in Women-A systematic review.

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by hyperandrogenism, insulin resistance, and menstrual irregularities, leading to infertility in many women. Emerging evidence suggests intermittent fasting (IF), particularly time-restricted feeding (TRF), may improve reproductive and metabolic outcomes in women with PCOS by addressing core pathophysiological mechanisms. This systematic review examines the impact of IF on fertility and reproductive hormones in women with PCOS. A systematic search was conducted in PubMed, Scopus, and Cochrane Library using predefined search terms related to intermittent fasting, fertility, and PCOS. Eligible studies published between 2014 and 2024 were identified following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria targeted primary research evaluating the effects of IF on reproductive outcomes, menstrual irregularities, and metabolic parameters in women with PCOS. Data extraction and quality assessment were performed using the Caldwell framework. Three studies were included in the review. TRF interventions led to significant improvements in menstrual regularity, with 33-40% of participants reporting normalized cycles. Reductions in total testosterone, free androgen index, anti-Müllerian hormone (AMH), and luteinizing hormone (LH) levels were observed, alongside increased sex hormone-binding globulin (SHBG). TRF also improved insulin sensitivity, reduced body weight, and decreased inflammatory markers, all of which contribute to enhanced reproductive outcomes. Key outcomes included a 9% reduction in testosterone levels, 26% reduction in the free androgen index (FAI), and significant improvements in menstrual regularity (33-40%). Intermittent fasting, particularly TRF, shows potential as a non-pharmacological intervention to improve reproductive health and fertility in women with PCOS. By targeting hyperandrogenism, insulin resistance, and menstrual irregularities, TRF offers a promising lifestyle approach. However, larger randomized controlled trials with long-term follow-up are needed to confirm these findings and establish IF as a standard therapeutic option for PCOS management.

Causal influences of testosterone on brain structure change rate: A sex-stratified Mendelian randomization study.

The impact of testosterone levels on changes in brain structure has been reported. However, it is still unclear which specific brain region could be affected. This study approached Mendelian randomization method to reveal the causal relationship between testosterone levels and the rate of longitudinal structural changes in the brain. The testosterone-related GWAS data were determined from 425,097 European participants. The GWAS data on the rate of longitudinal structural changes in the brain came from the ENIGMA consortium, which included 15,640 all-age participants from 40 longitudinal cohorts. The inverse variance weighted was considered as the main estimate, MR Egger and weighted median methods were used to supplement IVW. A positive correlation was found between total testosterone levels and bioavailable testosterone levels in women and age-independent longitudinal changes in cerebral WM and surface area. The sex hormone-binding globulin levels were found a negative correlation with age-dependent longitudinal structural changes of cortical GM in men. Additionally, we also found that the bioavailable testosterone level in males was negatively associated with the quadratic age-dependent longitudinal change rate in the globus pallidum. We also found estradiol levels and sex hormone-binding globulin levels were negatively associated with the quadratic age-dependent longitudinal change rate of total brain in men. Moreover, we found a positive correlation between total testosterone levels and linear age-dependent longitudinal changes in the hippocampus in both males and females. The testosterone levels in different genders may have varying degrees of causal effects on the structural changes of brain regions. These findings provide evidence for the influence of the brain glandular axis on brain structure, particularly during female brain development.

SEX-SPECIFIC BIOMARKER PREDICTION OF FEMORAL NECK BONE LOSS AFTER HIP FRACTURE

Abstract Hip fracture exacerbates age-related inflammation and metabolic dysfunction, which could accelerate bone loss post-fracture. This study aimed to develop biomarker prediction models for declines in femoral neck bone mineral density (BMD) after hip fracture. Participants were Caucasian men (n=99) and women (n=75) from the Baltimore Hip Studies 7th cohort with a hip fracture who were not receiving glucocorticoids, sex-hormone therapy, or bone-active medications. Data were collected at baseline (within 15 days of admission) and 2-, 6-, and 12-months later. Biomarkers were categorized into tertiles: interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), soluble tumor necrosis factor-alpha (TNF-alpha) receptor type 1, estradiol (E), testosterone (T), intact parathyroid hormone (iPTH), sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), C-terminal telopeptide of type I collagen (CTX), and procollagen type I N-propeptide (PINP). Femoral neck BMD was measured using dual energy x-ray absorptiometry. Mixed-effects models adjusted for age, height, and weight estimated 1-year changes in femoral neck BMD after hip fracture. Bone loss was classified as accelerated for intra-individual changes that exceeded the mean decline. Logistic regression models were stratified by biological sex and implemented using stepwise selection. The area under the curve (AUC) estimate among men was 0.68, and biomarkers related to bone loss were E, IGF-1, SHBG, and CTX. Similarly, the AUC metric among women was 0.69, but identified biomarkers were IL-6, iPTH, IGF-1, and SHBG. Findings indicate that both inflammatory and hormonal biomarkers relate to accelerated bone loss post-fracture; however, there are differential associations in physiological mechanisms between men and women.

Bariatric Surgery as a Molecular Modulator: The Role of FSHR Polymorphisms in Enhancing eNOS Expression and Reproductive Hormone Dynamics in Women with Severe Obesity.

Severe obesity (BMI > 40 kg/m2) has a severe influence on vascular health and reproduction. This study looks at how bariatric surgery affects endothelial nitric oxide synthase (eNOS) expression and reproductive hormone regulation across different follicle-stimulating hormone receptor (FSHR) polymorphism groups in women with extreme obesity. Twenty-nine women with extreme obesity had bariatric surgery. Pre- and post-surgery levels of eNOS and reproductive hormones such as follicle-stimulating hormone (FSH), sex hormone-binding globulin (SHBG), anti-Müllerian hormone (AMH), and antral follicle count (AFC) were assessed. Patients were divided into three FSHR polymorphism groups (Ser/Ser, Asn/Asn, and Ser/Asn), and results were compared between them. Statistical techniques were used to determine changes and relationships. Bariatric surgery led to substantial increases in eNOS expression across all FSHR polymorphism groups (p < 0.0001), with the Ser/Ser group exhibiting the most variability. Prior to surgery, the Ser/Ser group had substantially higher FSH levels (7.41 ± 0.60 mIU/mL) than the Asn/Asn group (5.20 ± 0.63 mIU/mL, p < 0.001). Following surgery, FSH levels rose in the Ser/Ser group (9.45 ± 0.87 mIU/mL), with significant differences between the Ser/Ser and Ser/Asn groups (mean difference = 0.97, p = 0.019). SHBG levels had a negative connection with eNOS expression after surgery (r = -0.365, p = 0.049). AMH and AFC remained constant throughout polymorphism groups. BMI decreased uniformly, with an average of 15.2 ± 1.8 kg six months after surgery. Bariatric surgery improves vascular health and regulates reproductive hormones, especially in individuals with the Ser/Ser genotype. These findings indicate the possibility of combining genetic testing and bariatric therapies to improve infertility treatment in obese women.

Sex hormone-binding globulin, testosterone and type 2 diabetes risk in middle-aged African women: exploring the impact of HIV and menopause.

Sex hormone-binding globulin (SHBG) and testosterone are differentially associated with type 2 diabetes (T2D) risk. We investigated whether these associations differ by HIV and menopausal status in Black South African women living with (WLWH) and without HIV (WLWOH). Cross-sectional observational. Eighty one premenopausal (57 WLWOH, 24 WLWH) and 280 postmenopausal (236 WLWOH, 44 WLWH) women from the Middle-Aged Soweto Cohort (MASC) completed the following measures: circulating SHBG and sex hormones, body composition (dual energy x-ray absorptiometry), oral glucose tolerance test to estimate insulin sensitivity (Matsuda index), secretion (insulinogenic index, IGI) and clearance, and beta-cell function (disposition index, DI). Dysglycaemia was defined as either impaired fasting or postprandial glucose or T2D. SHBG was higher and total and free testosterone were lower in postmenopausal WLWH than WLWOH (all p≤0.023). Irrespective of HIV serostatus, SHBG was positively associated with Matsuda index, insulin clearance and DI and inversely with HOMA-IR (all p<0.011). The association between SHBG and Matsuda index was stronger in premenopausal than postmenopausal women (p=0.043 for interaction). Free testosterone (and not total testosterone) was only negatively associated with basal insulin clearance (p=0.021), and positively associated with HOMA-IR in premenopausal and not post-menopausal women (p=0.015 for interaction). We show for the first time that midlife African WLWH have higher SHBG and lower total and free testosterone than WLWOH, which corresponded to their higher beta-cell function, suggesting a putative protective effect of SHBG on T2D risk in WLWH.

The Role of Sex Hormones and Sex Hormone-binding Globulin in Functional Gatrointestinal Disorders: A Bidirectional Two-sample Mendelian Randomization Study.

Sex hormones and sex hormone-binding globulin (SHBG) have been confirmed to involve in the pathophysiology of functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS) and functional dyspepsia (FD). However, causal associations have not yet been investigated. Utilizing data from Genome-wide association studies, we conducted bidirectional two-sample mendelian randomization (MR) analyses to assess the causal relationships between sex hormones, SHBG and FGIDs. Data for sex hormones including testosterone and estradiol, and SHBG were collected from the UK Biobank and FinnGen study. Relevant single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs). Inverse variance weighted (IVW) analysis were performed to assess the causal relationships., supplemented with MR-Egger, weighted median, and weighted mode approaches. Additionally, we used Cochran's Q test to evaluate the heterogeneity of genetic variants and implemented leave-one-out analysis to assess the impact of individual SNPs on the causal estimates. Several sensitivity analyses were conducted to assess the robustness of the results. Significant negative causal relationship was found between genetically predicted testosterone and the risk of IBS (OR=0.90, 95%CI: 0.83-0.97; p=0.007). SHBG demonstrated an inverse correlation with the risk of IBS (OR=0.82, 95%CI: 0.68-0.98; p=0.035) and FD (OR=0.83, 95%CI: 0.69-0.99; p=0.048). However, no statistically significant association was found between testosterone and FD, while estradiol also showed no causal association with FGIDs. Our study revealed a negative causal relationship between testosterone and IBS risk, and SHBG appears to be inversely associated with FD. This provided new ideas for the prevention and control of IBS, and future research is warranted to elucidate the underlying mechanisms driving these associations and their potential clinical implications.

Probiotics as potential allies in hormonal harmony and metabolic management: unlocking the Gut- Poly Cystic Ovary Syndrome (PCOS)

The intricate interplay between gut microbiota and metabolic disorders has sparked interest in exploring probiotics as potential therapeutic agents for Polycystic Ovary Diseases (PCOD). It is a hormonal or endocrine disorder which is a combination of biochemical and clinical including an imbalance in reproductive hormones especially elevated androgen levels (male hormones) called hyperandrogenism. PCOD, also known as PCOS (Polycystic Ovary Syndrome). The endocrine disruption in PCOS can affect the menstrual cycle, ovulation, and other aspects of reproductive and metabolic health. The precise origin and development of this disease are not well understood, but it is believed that a multifaceted interplay involving external factors, surrounding conditions, hormone mediated factors, genetic susceptibility, social and financial status, toxic exposure, psychological stress, Sedentary lifestyle and eating habits are presumed to be the primary ethiopathogenic determinant. A regular exercise program and a diet free of fats and sugars are also recommended to all women with PCOS in order to manage the condition. In recent years, researchers have increasingly examined the gut microbiota and its positive impact on nutritional, immunological and metabolic functions in the host. The involvement of the gut microbiome in various metabolic complications linked to PCOS, such as impaired insulin action, excessive body weight, adiposity and systemic inflammatory status suggests its potential influence on the development of PCOS. Studies reveal that the gut microbiome of women with polycystic ovarian syndrome differs from that of healthy women. Interest in the relationship between gut health and PCOS has grown, and new studies suggest that the development of PCOS related symptoms may be connected to the gut microbiota. Probiotics are live bacteria that, when consumed in sufficient amounts, offer health benefits to the host. As such, they have been investigated for their potential to treat polycystic ovarian syndrome. Probiotic supplementation results in a significant decrease in free androgen index and malondialdehyde levels, along with an increase in nitric oxide and Sex Hormone Binding Globulin (SHBG). It also has an advantage of reduction in body weight and body mass index, hypertrichosis, HOMA-IR and total testosterone levels of PCOS patients. However, it is essential to highlight that studies in this area are still in their infancy, and further research is necessary to provide conclusive proof. The purpose of this review is to evaluate the importance of probiotic supplements in management PCOS symptoms.

Does irisin mediate metabolic effects of androgen deficiency? A cross-sectional study in men with chronic spinal cord injury.

Retrospective study. To check the hypothesis that irisin could mediate systemic metabolic effects of testosterone in men with chronic spinal cord injury (SCI). Spinal Unit of the San Raffaele Institute in Sulmona. Fifteen men with chronic SCI admitted to a rehabilitation program were involved. They underwent clinical and biochemical evaluations. Irisin levels were measured with a high-sensitivity ELISA kit. Free testosterone levels were calculated (cFT) from total testosterone, sex hormone binding globulin, and albumin concentrations using the Vermeulen formula. Androgen deficiency (total testosterone <3 ng/ml and cFT <64 pg/ml) was found in 53% of participants and was associated with significantly lower irisin levels, higher body mass index (BMI), and higher triglycerides. Participants were engaged in significantly poorer leisure time physical activity (LTPA). Circulating irisin correlated with cFT (r = 0.55; p = 0.03) and both were negatively correlated with triglycerides levels, homeostatic model assessment of insulin resistance (HOMA-IR) and systemic inflammation, as assessed by erythrocyte sedimentation rate (ESR). Correlations with irisin did not reach statistical significance for either BMI (r = -0.40; p = 0.13) or LTPA (r = 0.46; p = 0.08). In bivariate linear regression models, lower irisin levels were significantly associated with higher triglycerides (β = -0.46; 95% CI: -0.75 to -0.16), HOMA-IR (β = -0.32; 95% CI: -0.63 to -0.004) and ESR (β = -0.89; 95% CI: -1.69 to -0.10) independently of cFT. Conversely, the negative associations of cFT with the same variables were lost after adjustment for irisin levels. Spinal cord-injured men with androgen deficiency exhibit lower levels of irisin, which could mediate the systemic effects of testosterone.

Changes in Prolactin and Insulin Resistance in PCOS Patients Undergoing Metformin Treatment: A Retrospective Study

Background: Prolactin levels have been shown to influence metabolic outcomes, including insulin resistance. Metformin is known to be beneficial in polycystic ovary syndrome (PCOS) patients. PCOS women might react differently to metformin treatment depending on their baseline prolactin levels. Methods: In this retrospective study, the homeostasis model assessment for insulin resistance (HOMA-IR), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), the LH:FSH ratio, and total testosterone and sex hormone-binding globulin (SHBG) were measured in 75 obese/overweight women with PCOS and insulin resistance before initiation of metformin treatment and after 6–8 months. Results: At baseline, HOMA-IR was inversely correlated to SHBG (r = −0.408; p &lt; 0.001) and prolactin (r = −0.402; p &lt; 0.001). After 6–8 months of metformin treatment, the LH:FSH ratio and the HOMA-IR declined significantly (p &lt; 0.05). A significant positive correlation could be shown between basal prolactin and the difference in the HOMA-IR (r = 0.233; p = 0.044). Women with lower baseline prolactin (≤14.9 ng/mL) revealed a sharper decline in HOMA-IR (−0.8, IQR −1.0; −0.5 vs. −0.6, IQR −0.8; −0.3; p = 0.049) as well as an increase in prolactin at follow-up (1.6 ng/mL, IQR −0.2;3.8 vs. −1.3, IQR −4.6;3.2; p = 0.003) compared to patients with a baseline prolactin &gt; 14.9 ng/mL. Conclusions: In overweight/obese, insulin-resistant PCOS women, lower baseline prolactin levels are associated with higher baseline HOMA-IR levels as well as with a better response to metformin treatment. More data are necessary to prove these observations in larger populations.

Obesity and Polycystic Ovary Syndrome.

The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance. Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance. Additionally, obesity contributes to polycystic ovary syndrome by facilitating the conversion of precursor hormones to testosterone within adipose cells. Moreover, obesity can lead to relative hyperandrogenemia, which is marked by lower levels of sex hormone binding globulin and increased availability of free testosterone to target tissues. Also, obesity affects the secretion of gonadotropins, resulting in heightened luteinizing hormone secretion or increased sensitivity of thecal cells to luteinizing hormone. Obesity-related insulin resistance might be amplified by alterations in adipokine and inflammatory cytokine production. Ultimately, obesity and polycystic ovary syndrome might share a common genetic predisposition. The cornerstone of managing polycystic ovary syndrome is to address individual symptoms such as hyperandrogenism (hirsutism, acne, and female type boldness), menstrual irregularities, and infertility stemming from anovulation. However, obesity is integral to the pathophysiology of polycystic ovary syndrome and exacerbates all of its features. Therefore, lifestyle modifications aimed at weight reduction should be the primary strategy in overweight or obese women with polycystic ovary syndrome.