Sex Hormone-binding Globulin Concentrations Research Articles

EXPRESS: Association of exposure to non-persistent endocrine disruptors with sex hormones and metabolic health in US females.

Endocrine disruptive chemicals (EDCs) are considered as the potential attributes for the increasing trend in obesity and metabolic syndrome (MS) through disruption of sex hormones, particularly in women. We evaluated the association of understudied EDC compounds with total testosterone (TT), sex hormone-binding globulin (SHBG), obesity, and metabolic syndrome (MS). A population-based cross-sectional study was conducted using the National Health and Nutrition Examination Survey datasets collected during the years 2013-2016. Women of age ≥15 years with urinary measurements of non-persistent EDCs including bisphenol, triclosan, triclocarban, dichlorophenol, and paraben compounds were included in this study. Data were analyzed using the modified Poisson models to estimate the adjusted relative risk (RR) and 95% confidence interval (CI). The associations were also validated by considering TT and SHBG concentrations as the outcomes. The study included 1974 women with 11% high TT, 10.5% low SHBG, 40% obesity, and 46.2% MS. A medium to high exposure to bisphenol-A (RR=1.64; 95%CI: 1.14, 2.35, p=0.009), bisphenol-F (RR=1.83; 95%CI: 1.35, 2.49, p<0.001), bisphenol-S (RR=1.83; 95%CI: 1.35, 2.49, p=0.041) and 2, 4- dichlorophenol (RR=1.61; 95%CI: 1.06, 2.45, p=0.026) were associated with low SHBG but not with high TT. In addition, high exposure to triclosan was also inversely associated with lower SHBG concentrations (regression coefficient=-0.09; 95%CI: -0.15, -0.02, p=0.013). However, these EDCs were found to be associated with SHBG, obesity, and MS according to menopausal status. High exposure to certain non-persistent EDCs was associated with low SHBG, obesity, and MS according to menopausal status.

Associations of body composition measures with circulating insulin-like growth factor-I, testosterone, and sex hormone-binding globulin concentrations in 16,000 men.

Adiposity is positively associated with risk of some cancer sites and other health conditions in men; however, it is unclear if endogenous hormones play a role in these associations. We examined how body composition, measured from magnetic resonance imaging (MRI) and common measures of adiposity (e.g., body mass index (BMI)), are related to hormone concentrations in men from the UK Biobank study. Up to 16,237 men with available body composition data (including visceral, subcutaneous, and liver fat, muscle fat infiltration (MFI), lean tissue, and common adiposity measures) and serum hormone measurements (insulin-like growth factor-I (IGF-I), total testosterone, sex hormone-binding globulin (SHBG), and calculated free testosterone) were included. Multivariable-adjusted linear regression models were used to determine the geometric mean hormone and SHBG concentrations across categories of each exposure. Common measurements of adiposity were highly correlated with MRI measures of central and total adiposity (r = 0.76-0.91), although correlations with ectopic fat (liver fat and MFI) were lower (r = 0.43-0.54). Most adiposity measurements showed an inverse U- or J-shaped association with circulating IGF-I and free testosterone; however, MFI was linearly inversely associated, and lean tissue volume was positively associated with both IGF-I and free testosterone concentrations. All body composition measures were inversely associated with total testosterone and SHBG concentrations (relative geometric mean difference between Q5 vs. Q1: 20-30%). Our results show that common adiposity and most MRI measures of adiposity relate similarly to serum hormone concentrations; however, associations with ectopic fat (particularly MFI) and lean tissue were different.

Prenatal phthalate exposure and pubertal development in 16-year-old daughters: reproductive hormones and number of ovarian follicles.

Is there a possible association between prenatal phthalate exposure and late effects in teenage daughters with respect to reproductive hormone levels, uterine volume, and number of ovarian follicles? Our study showed subtle associations between phthalate metabolite concentrations in maternal serum from pregnancy or cord blood and LH and insulin-like growth factor 1 (IGF-1) levels as well as uterine volume in their daughters 16 years later. Endocrine-disrupting environmental chemicals may adversely affect human reproductive health, and many societies have experienced a trend toward earlier puberty and an increasing prevalence of infertility in young couples. The scientific evidence of adverse effects of foetal exposure to a large range of chemicals, including phthalates, on male reproductive health is growing, but very few studies have explored effects on female reproduction. This follow-up study included 317 teenage daughters who were part of the Copenhagen Mother-Child Cohort, a population-based longitudinal birth cohort of 1210 females born between 1997 and 2002. A total of 317 female participants (median age 16 years) were examined for weight, height, and menstrual pattern. A serum sample was analysed for concentrations of reproductive hormones, and trans-abdominal 3D ultrasonography was performed to obtain the number of ovarian follicles, ovarian and uterine size. Prenatal maternal serum samples were available for 115 females, and cord blood samples were available for 118 females. These were analysed for concentrations of 32 phthalate metabolites. Weighted quantile sum regression was used for modelling associations of combined prenatal phthalate exposure with the reproductive outcomes in post-menarcheal females. In bivariate correlation analyses, negative significant associations were found between several prenatal phthalate metabolite concentrations and serum hormone concentrations (testosterone, 17-OH-progesterone, and IGF-1) as well as number of ovarian follicles in puberty. Positive significant correlations were found between prenatal phthalate exposure and FSH and sex hormone-binding globulin concentrations. Combined analyses of phthalate exposure (weighted quantile sums) showed significant negative associations with IGF-1 concentration and uterine volume as well as a significant positive association with LH concentration. Phthalate metabolites were measured in serum from single prenatal maternal blood samples and cord blood samples. Potential concomitant exposure to other endocrine-disrupting environmental chemicals before or after birth was not controlled for. The study population size was limited. Our results support the need for further research into possible adverse effects of environmental chemicals during foetal development of the female reproductive system. The work was supported by The Center on Endocrine Disruptors (CeHoS) under The Danish Environmental Protection Agency and The Ministry of Environment and Food (grant number: MST-621-00 065). No conflicts of interest are declared. N/A.

8377 Associations of Serum Testosterone and Sex Hormone-Binding Globulin with Incident Fractures in Middle-Aged to Older Men

Abstract Disclosure: L. Grahnemo: None. R.J. Marriott: None. K. Murray: None. L. Tyack: None. M. Nethander: None. A.M. Matsumoto: None. E.S. Orwoll: None. D. Vanderschueren: None. B.B. Yeap: None. C. Ohlsson: None. As men age, their circulating testosterone (T) decreases, circulating sex-hormone binding globulin (SHBG) increases, and risk of bone fracture increases. Unexpectedly, a recent large clinical trial reported that T treatment increased fracture risk in men. It is unclear if circulating T, independently of comorbidities, is associated with male fracture risk. We tested the hypothesis that serum T concentration is an independent risk predictor for incident bone fractures in men. We analyzed associations for T and SHBG with incident fractures in the large and well-characterized UK Biobank cohort (205,973 male participants median age 58 years, excluding men on androgen-related therapies). Baseline serum total T and SHBG were measured by immunoassay, and incident fractures documented over a median follow-up of 13.6 years (11,088 any fracture cases; 1,680 hip fracture cases; 1,366 forearm fracture cases). Associations of hormonal variables with fracture outcomes were modelled using Cox regression, adjusted for multiple comorbidities/covariates, with imputation for missing data, and non-linearity assessed using cubic splines. For total T, in multivariable models not including SHBG, there was a non-linear association with any fracture and hip fractures but not forearm fractures, with the lowest risk in the second quintile (Q2; hazard ratio (HR), 95% confidence intervals (CIs) Q2 vs Q5 any fracture 0.89, 0.84-0.94; hip fracture 0.76, 0.66-0.87; forearm fracture 0.97, 0.83-1.13). However, in multivariable models analyzing total T which were adjusted for SHBG, lower total T was associated with higher risk for fractures at all evaluated bone sites (HR, 95% CIs Q1 vs Q5 any fracture 1.24, 1.16-1.33; hip fracture 1.28, 1.08-1.51; forearm fracture 1.51, 1.25-1.82). Similar results were seen in multivariable models using calculated free T values. Lower SHBG concentration was associated with lower risk of any fracture, hip fractures, and forearm fractures, in multivariable models not including total T (HR, 95% CIs Q1 vs Q5, any fracture 0.71, 0.67-0.75; hip fracture 0.55, 0.47-0.65; forearm fracture 0.62, 0.52-0.74), with similar results following additional adjustment for total T. In conclusion, associations of total T concentrations with fracture risk without adjustment for SHBG are non-linear and inconsistent, whereas lower total T concentration, adjusted for SHBG, was independently associated with higher risks of any fracture, hip fractures, and forearm fractures. Lower circulating SHBG, without or with adjustment for total T, was strongly associated with lower risk of fractures at all three sites, consistent with SHBG being a major independent biomarker of fracture risk in men. When examining the relationship of endogenous T concentrations with health outcomes influenced by androgen-sensitive tissues in middle-aged to older men, both total T and SHBG concentrations should be assessed. Presentation: 6/2/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

9240 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

8039 Role Of Genetics In The Age-Related Testosterone Decline In Men: A UK Biobank Study

Abstract Disclosure: L. Ogoniak: None. S. Sandmann: None. J. Varghese: None. A.S. Busch: None. Background: Age-related decline in circulating serum testosterone concentrations is a well-established phenomenon in men. While the decline is partially linked to comorbidities such as obesity, type 2 diabetes (T2D), and cardiovascular disease (CVD), healthy ageing men present with rather stable levels. Recent genetic mapping studies demonstrated a large influence of common genetic variation on testosterone levels in men. However, increasing incidence rates of comorbidities in the ageing population are posing a challenge for the disentanglement of effects. Objective: Our study aims to investigate the genetic component of age-dependent testosterone decline in men. We hypothesize that the decline in testosterone levels in ageing men is primarily influenced by comorbidities, without significant alterations in the genetic architecture of testosterone levels. Material and Methods: We included 6,406 men with baseline and follow-up measurements of circulating serum concentrations of total testosterone (T), bioavailable testosterone (BAT) and sex hormone-binding globulin (SHBG) representing an independent sub-cohort of the UK Biobank study. We 1) assessed the association of baseline levels with the decline in sex steroids and 2) developed and verified polygenic risk score (PRS) models for T, BAT and SHBG based on 183,909 men from the UK Biobank (sub cohorts: 70% base, 15% target and 15% validation, follow-up cohort excluded for PRS development). Results: In the follow-up sub cohort, mean age (SD) at baseline was 58.2 yrs ( 7.5) and mean (SD) follow-up period was 4.3 (1.0) yrs. Mean (SD) BAT at baseline were 5.2 (1.32) nmol/L with a mean (SD) decline of 1.6 (24.4) % at follow-up. Baseline BAT, T and SHBG levels were significantly associated with the relative change of the respective biomarker at follow-up (-7.8, -2.9 and -0.4% per nmol/L, respectively, all p &amp;lt;0.001). After correcting for age at baseline, follow-up period and principal components 1-10, PGSTestosterone and PGSBAT were not associated with relative decline of the respective biomarker (both p = n.s.). Conclusion: Our study did not find evidence supporting a genetic component in the age-related decline of circulating serum T or BAT concentrations. Instead, in accordance to previous observational studies, our results suggest that rather non-genetic factors, e.g. increasing incidence rates of comorbidities, drive the age-related decline in sex steroid levels in men. Our study contributes to understanding the intricate relationship between genetic and non-genetic factors with age-related testosterone decline in men and offers valuable insights for potential interventions targeting age-related hormonal changes and associated health outcomes. Presentation: 6/2/2024

The Concentration of Follistatin and Activin A in Serum and Selected Biochemical Parameters in Women with Polycystic Ovary Syndrome: Stratification by Tobacco Smoke Exposure, Insulin Resistance, and Overweight/Obesity.

Background/Objectives: The aim of the study was to investigate the concentrations of follistatin and activin A in the serum of women with polycystic ovary syndrome (PCOS) and to assess their relationship with selected biochemical parameters, specifically stratifying the analysis based on tobacco smoke, insulin resistance, and abnormal weight. Methods: The research was carried out within a cohort of 88 women (60 women with and 28 without PCOS). Results: We observed significant differences (p < 0.05) in follistatin concentrations between women with PCOS stratified by homeostatic model assessment for insulin resistance (HOMA-IR) values. These differences were consistent across both smoking and non-smoking subgroups with PCOS. Similar results were observed when comparing normal-weight women with PCOS to those with overweight or obesity. Additionally, activin A concentrations were significantly increased by higher body mass index (BMI) and HOMA-IR values in non-smoking women with PCOS. Moreover, we identified a negative correlation (r = -0.30; p < 0.023) between cotinine levels and Anti-Müllerian hormone. Among smoking women with PCOS, we noted decreased concentrations of sex hormone-binding globulin and high-density lipoproteins, alongside increased fasting glucose, insulin, HOMA-IR, and free androgen index values. Conclusions: Our findings suggest that activin A and follistatin concentrations are more strongly influenced by disruptions in glucose metabolism and BMI than by tobacco smoke exposure. The observed changes were more pronounced in follistatin than in activin A level.

The influence of anthropometric parameters on the concentration of globulin that binds sex hormones during the menopausal transition

&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;Aim &amp;lt;/strong&amp;gt;To determine the effect of body mass index (BMI) and waist-hip ratio (WHR) on the concentration of circulating sex hormone-binding globulin (SHBG) throughout the menopausal transition.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Methods &amp;lt;/strong&amp;gt;This cross-sectional study included 150 women divided into three groups: premenopausal (n=50), perimenopausal (n=50), and postmenopausal (n=50). The processing of the test women consisted of three phases: inter-view, blood sampling and determination of BMI and WHR. The SHBG concentration was determined from the blood, and BMI and WHR were measured.&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Results &amp;lt;/strong&amp;gt;The BMI and WHR of the post-menopausal women were significantly higher comparing to the other two groups, while the postmenopausal SHBG was significantly lower compared to the premenopausal con-centration. In all three groups, a significant negative correlation was found between SHBG and BMI (Rho= -0.385; p&amp;amp;lt;0.05), and between SHBG and WHR (Rho= -0.411; p&amp;amp;lt;0.05). By the univariate regression analysis model, it was determined that BMI (&amp;amp;beta;= -0.594; p&amp;amp;lt;0.001) and WHR (&amp;amp;beta;= -0.407; p=0.003) were independently negative predictors of SHBG in postmenopausal women, while in the multivariate regression analysis model only BMI as an independently negative predictor of SHBG in postmenopausal women was found (&amp;amp;beta;= -0.263; p=0.024).&amp;lt;br /&amp;gt;&amp;lt;strong&amp;gt;Conclusion &amp;lt;/strong&amp;gt;The value of SHBG during the menopausal transition decreases and women with higher BMI and WHR have lower values of SHBG regardless of the duration of menopause.&amp;amp;nbsp;&amp;lt;br /&amp;gt;Considering the connection between SHBG and anthropometric parameters, and the drop in its values upon entering and passing through the menopausal transition as such it can be used as a predictor for an increased risk of cardiovascular diseases and metabolic syndrome in a selected group of women.&amp;lt;/p&amp;gt;

Direct and indirect connections of androgen status with ejaculate parameters in men from infertile couples

In men from infertile couples the serum level of total testosterone (tT) has been shown to vary widely. Is it possible to expect that there is an association of tT content with spermogram disorders in men from infertile couples? Aim of the study was to investigate the patterns of changes in the spermiological status of men from infertile couples depending on tT level in blood serum. Material and methods. Design – observational, retrospective, one-stage study. The analysis of medical histories of 358 men with infertility in marriage was carried out. The sample was divided into comparison groups according to tT level: group 1 – less than 12.1, group 2 – from 12.1 to 20.9, group 3 – 21.0 nmol/l or more. Results. From group 1 to group 3, tT content increases more than twice, as well as concentration of indicators related to the level of T – sex hormone binding globulin (SHBG) and free testosterone (fT). There are no significant differences in luteinizing hormone (LH) and follicle stimulating hormone (FSH) level, although there is a tendency to its increase from group 1 to group 3. From group 1 of men with androgen deficiency to group 3, not only body weight and body mass index (BMI), but also waist circumference (WC) and hip circumference (HC), as well as the WC/HC index, characterizing the degree of abdominal obesity, decrease. The groups examined did not differ in the values of all studied ejaculate parameters. In group 1, a pronounced correlation between the content of tT and fT was found, in groups 2 and 3 – statistically significant inverse relationships between the level of Tob and the values of anthropometric indicators (body weight, BMI, WC and HC), as well as direct ones - with the concentration of SHBG, tT, LH and estradiol, in group 3 – with FSH levels. There were no correlations between tT content and spermogram indicators in any group of examined men. Conclusions. The results obtained suggest that only at high-normal level of testosterone in the blood it can have a stimulating effect on spermatogenesis. As a result of the accumulation of cases of androgenic deficiency in the population, the direct positive effect of serum testosterone on spermatogenesis is becomes insufficient for normal regulation, and the negative effect of testosterone deficiency on spermatogenesis, mediated through the accumulation of overweight and obesity comes to the fore.

Effects of 8-week strength training on basal hormone levels, sex hormone binding globulin, insulin-like growth factor binding protein-3, oxidative stress markers, and IL-6 levels in adolescent athletes.

The aim of the study was to investigate how 8-week strength training affects adolescent athletes' basal hormone concentrations, sex hormone binding globulin (SHBG), insulin-like growth factor binding protein-3 (IGFBP-3), cytokine, and oxidative stress markers. Twenty adolescent handball players participated in this study. The participants were randomly divided into the strength training group (ST, n = 10) and the control group (C, n = 10). ST participates in strength training 3 sessions a week for 8 weeks and C participates only in handball training. We quantified serum basal hormone concentration, SHBG, IGFBP3, oxidative stress markers, and IL-6 in each subject's blood samples before and after 8 weeks of strength training. Interestingly, while insulin-like growth factor-1 (IGF-1) concentration declined in group C (p < 0.05), it did not in ST (p > 0.05). Furthermore, the basal concentration of growth hormone (GH), total testosterone (T), cortisol (Cor), total antioxidant status (TAS), and serum-free androgen index (FAI) basal concentration did not change in ST and C. Basal IGFBP-3 and SHBG concentrations decreased only in ST (p < 0.05), but not in C (p > 0.05). Serum-free testosterone (FT) levels increased in ST and C (p > 0.05). Total oxidant status (TOS) and oxidative stress index (OSI) reduced ST and C (p < 0.05). Serum interleukin-6 (IL-6) levels did not alter groups ST and C. Strength training did not affect basal serum concentrations of T, GH, IGF-1, COR, IL-6, and TAS, but it caused a decrease in SHBG and IGFBP3 concentrations in ST. Increased basal FT concentration and improved serum TOS may not depend on strength training.

Impact of Smoking and Obesity on the Selected Peptide Hormones and Metabolic Parameters in the Blood of Women with Polycystic Ovary Syndrome-Preliminary Study.

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

The association between low sex hormone binding globulin and increased risk of type 2 diabetes is mediated by increased visceral and liver fat: results from observational and Mendelian randomization analyses.

The aim of this study was to investigate the associations between sex hormone binding globulin (SHBG), visceral fat (VAT), liver fat content, and risk of type 2 diabetes. In the Netherlands Epidemiology of Obesity study 5690 women (53%) and men without pre-existing diabetes were included and followed for incident type 2 diabetes. SHBG concentrations were measured in all, VAT with MRI, and liver fat content with proton-MR spectroscopy in n=1822. We examined associations between SHBG and liver fat with linear regression and bidirectional Mendelian randomization analyses, and between SHBG and type 2 diabetes with Cox regression adjusted for confounding, and additionally for VAT and liver fat to examine mediation. The mean(SD) age was 56(6) years, BMI 30(4) kg/m2, median(IQR) SHBG was 47 (34,65) nmol/L in women and 34 (26,43) nmol/L in men, median(IQR) liver fat was 3.4(1.6,8.2)% in women and 6.0 (2.9,13.5)% in men. Compared with the highest SHBG quartile, liver fat was 2.9-fold (95%CI: 2.4,3.4) increased in women and 1.6-fold (95%CI: 1.3,1.8) in men, and the hazard ratio (95%CI) of type 2 diabetes was 4.9 (2.4,9.9) in women and 1.8 (1.1,2.9) in men. Genetically predicted SHBG was associated with liver fat content (women: SD (95%CI) -0.45(-0.55,-0.35), men: ln(95%CI) -0.25 (-0.34,-0.16)). VAT and liver fat together mediated 43% (women) and 60% (men) of the SHBG-type 2 diabetes association. To conclude, in a middle-aged population with overweight, the association between low SHBG and increased risk of type 2 diabetes was for a large part mediated by increased VAT and liver fat.

Exploring Resveratrol Intervention in Managing Menopausal Symptoms: A Comprehensive Systematic Review of Clinical Trials

Introduction: Menopause, a significant event in a woman's reproductive lifespan, entails hormonal changes and a range of symptoms affecting various bodily systems. Conventional treatments like hormone replacement therapy (HRT) have limitations and associated risks, prompting interest in alternative therapies such as resveratrol. Materials/Methods: The literature search was conducted in six databases. The outcome of interest measures the mean changes in bone mineral density (BMD), Quality of Life (QoL), bone biomarkers, menopause symptoms, and cognitive and mood functions pre- and post-interventions. Resveratrol was administered in various forms and doses, including trans-resveratrol 75 mg twice or once daily, 250/500/1000 mg resveratrol tablets, and a combination of fermented soy containing 10 mg equol and 25 mg resveratrol. Quality appraisal was done using the Cochrane Risk of Bias Tool 2. Results: Resveratrol supplementation in post-menopausal women, involving 745 participants across various studies, has shown remarkable health benefits. These include improved cerebral vasoreactivity (CVR) to hypercapnia, a 10% decrease in overall pain, and enhanced quality of life. Additionally, resveratrol boosts flow-mediated dilation (FMD) by 23% and increases serum sex hormone-binding globulin (SHBG) concentrations by 10%, benefiting bone mineral density (BMD). Over the long term, it leads to a significant 35% increase in FMD and a substantial 33% enhancement in overall cognitive performance, highlighting its diverse benefits. Conclusion: For women in the post-menopausal stage, resveratrol supplementation shows potential for improving cardiovascular health, relieving pain, enhancing quality of life, supporting bone health, boosting cognitive function, and promoting overall mental well-being.

Genetically predicted high sex hormone binding globulin was associated with decreased risk of polycystic ovary syndrome

BackgroundPrevious observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary syndrome (PCOS). Nevertheless, conventional observational studies may be susceptible to bias. Consequently, we conducted a two-sample Mendelian randomization (MR) investigation to delve deeper into the connection between SHBG levels and the risk of PCOS.MethodsWe employed single-nucleotide polymorphisms (SNPs) linked to serum SHBG levels as instrumental variables (IVs). Genetic associations with PCOS were derived from a meta-analysis of GWAS data. Our primary analytical approach relied on the inverse-variance weighted (IVW) method, complemented by alternative MR techniques, including simple-median, weighted-median, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) testing. Additionally, sensitivity analyses were conducted to assess the robustness of the association.ResultsWe utilized 289 SNPs associated with serum SHBG levels, achieving genome-wide significance, as instrumental variables (IVs). Our MR analyses revealed that genetically predicted elevated circulating SHBG concentrations were linked to a reduced risk of PCOS (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.39–0.78, P = 8.30 × 10–4) using the IVW method. MR-Egger regression did not detect any directional pleiotropic effects (P intercept = 0.626). Sensitivity analyses, employing alternative MR methods and IV sets, consistently reaffirmed our results, underscoring the robustness of our findings.ConclusionsThrough a genetic epidemiological approach, we have substantiated prior observational literature, indicating a potential causal inverse relationship between serum SHBG concentrations and PCOS risk. Nevertheless, further research is needed to elucidate the underlying mechanism of SHBG in the development of PCOS.

Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses.

Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. To clarify associations of sex hormones with these outcomes. Systematic literature review to July 2019, with bridge searches to March 2024. Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. Observational study design, heterogeneity among studies, and imputation of missing data. Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).

SHBG gene polymorphisms and their influence on serum SHBG, total and free testosterone concentrations in men.

Genetic variation in sex hormone-binding globulin (SHBG) structure may affect estimates of sex steroid exposure by altering the affinity of the protein for its ligand. Consequently, free hormone calculations assuming constant binding affinity may, for certain genetic variations, lead to incorrect diagnoses if genetic variation is not taken into consideration. To investigate the effects of genetic variation in SHBG on calculated and measured serum free testosterone (T) in men. Population-based sibling-pair study in 999 healthy men aged 25 to 45 (mean: 34.5) years. Genotyping using microarray (Illumina®) for SNPs suggested to affect binding affinity and/or concentration of SHBG or T. SHBG concentrations were measured using immunoassay and in a subset (n = 32) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Total T was measured using LC-MS/MS. Free T was calculated and in a subset (n = 314) measured directly using LC-MS/MS after equilibrium dialysis. Allelic frequencies of analyzed SNPs ranged from 0.5% to 58.2%. Compared to wild-type, SHBG concentrations were lower in rs6258 heterozygotes (-24.7%; p < 0.05) and higher in rs6259 heterozygotes, rs727428 homozygotes, and carriers of rs1799941 (+10.8 to 23.1%; all p < 0.05). Total T was higher in rs727428 homozygotes and carriers of rs5934505, rs1799941and rs6259 (+3.9 to 21.4%; all p < 0.05). No clear effects on measured free T were found, except for a trend towards higher values in rs6259 homozygotes, significant for calculated free T (+18.7%; p < 0.05) in the larger global study population. In these men, analyzed SNPs were relatively prevalent and affected serum concentrations of total T and SHBG but not calculated or measured free T except for a higher trend in rs6259 homozygotes.

Polygenic Scores for Adult Testosterone and SHBG Levels Are Associated With Reproductive Hormone Levels in Male Infants.

The hypothalamic-pituitary-gonadal axis's transient activity in infancy, i.e, minipuberty, is considered crucial for male reproductive function. Historically, minipuberty has been considered a passive response triggered by the withdrawal of placental steroids at birth. However, given its potential link to adult reproductive function, we hypothesize that minipuberty is a partially genetically regulated process, suggesting a link between the genetic architecture of reproductive hormone concentrations across lifespan. To investigate the association of UK Biobank Study-based polygenic scores (PGS) of adult total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations with trajectories of reproductive hormones concentrations in male infants. Prospective, longitudinal birth cohort (The COPENHAGEN Minipuberty Study, 2016-2018, ClinTrial: NCT02784184). Individual PGSs in male infants derived from published literature were calculated for total T and SHBG. The associations with mean SD scores (SDS) of reproductive hormone concentrations in infancy were tested. Population-based. Healthy, male, term, singleton newborns were followed with repeated clinical examinations including blood sampling during a 1-year follow-up (n = 109). Circulating reproductive hormone concentrations. T-PGSadult were significant associated with mean T-SDSinfancy, mean SHBG-SDSinfancy, and mean LH-SDSinfancy (P = .02, <.001 and .03, with r2 = 0.05, 0.21 and 0.04, respectively). SHBG-PGSadult was significantly associated with mean SHBG-SDSinfancy (P < .001, r2 = 0.18). T-PGSadult explained 5% and 21% of the phenotypic variation in infancy of mean T-SDSinfancy and SHBG-SDSinfancy, respectively. Our findings suggest that the genetic architecture underlying total T and SHBG in adults also associates with hormone concentrations and their trajectories during infancy.

Sex-steroid hormones and risk of postmenopausal estrogen receptor-positive breast cancer: a case-cohort analysis.

Sex-steroid hormones are associated with postmenopausal breast cancer but potential confounding from other biological pathways is rarely considered. We estimated risk ratios for sex-steroid hormone biomarkers in relation to postmenopausal estrogen receptor (ER)-positive breast cancer, while accounting for biomarkers from insulin/insulin-like growth factor-signaling and inflammatory pathways. This analysis included 1208 women from a case-cohort study of postmenopausal breast cancer within the Melbourne Collaborative Cohort Study. Weighted Poisson regression with a robust variance estimator was used to estimate risk ratios (RRs) and 95% confidence intervals (CIs) of postmenopausal ER-positive breast cancer, per doubling plasma concentration of progesterone, estrogens, androgens, and sex-hormone binding globulin (SHBG). Analyses included sociodemographic and lifestyle confounders, and other biomarkers identified as potential confounders. Increased risks of postmenopausal ER-positive breast cancer were observed per doubling plasma concentration of progesterone (RR: 1.22, 95% CI 1.03 to 1.44), androstenedione (RR 1.20, 95% CI 0.99 to 1.45), dehydroepiandrosterone (RR: 1.15, 95% CI 1.00 to 1.34), total testosterone (RR: 1.11, 95% CI 0.96 to 1.29), free testosterone (RR: 1.12, 95% CI 0.98 to 1.28), estrone (RR 1.21, 95% CI 0.99 to 1.48), total estradiol (RR 1.19, 95% CI 1.02 to 1.39) and free estradiol (RR 1.22, 95% CI 1.05 to 1.41). A possible decreased risk was observed for SHBG (RR 0.83, 95% CI 0.66 to 1.05). Progesterone, estrogens and androgens likely increase postmenopausal ER-positive breast cancer risk, whereas SHBG may decrease risk. These findings strengthen the causal evidence surrounding the sex-hormone-driven nature of postmenopausal breast cancer.