Association Of Sex Hormone-binding Globulin Research Articles

Association of sex hormones with non-alcoholic fatty liver disease: An observational and Mendelian randomization study.

Sex-specific associations of sex hormone-binding globulin (SHBG) and bioavailable testosterone (BAT) with NAFLD remain indeterminate. We aimed to explore observational and genetically determined relationships between each hormone and NAFLD. We included 187 395 men and 170 193 women from the UK Biobank. Linear and nonlinear Cox regression models and Mendelian randomization (MR) analysis were used to test the associations. During 12.49 years of follow-up, 2209 male and 1886 female NAFLD cases were documented. Elevated SHBG levels were linearly associated with a lower risk of NAFLD in women (HR (95% CI), .71 (.63, .79)), but not in men (a "U" shape, pnon-linear < .001). Higher BAT levels were associated with a lower NAFLD risk in men (HR (95% CI), .81 (.71, .93)) but a higher risk in women (HR (95% CI): 1.25 (1.15, 1.36)). Genetically determined SHBG and BAT levels were linearly associated with NAFLD risk in women (OR (95% CI): .57 (.38, .87) and 2.21 (1.41, 3.26) respectively); in men, an "L-shaped" MR association between SHBG levels and NAFLD risk was found (pnon-linear = .016). The bidirectional MR analysis further revealed the effect of NAFLD on SHBG and BAT levels in both sexes. Consistently, linear associations of lower SHBG and higher BAT levels with increased NAFLD risk were both conventionally and genetically found in women, while in men, SHBG acts in a nonlinear manner. In addition, NAFLD may affect SHBG and BAT levels.

Sex hormones and the risk of myocardial infarction in women and men: a prospective cohort study in the UK Biobank

ObjectivesThere is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank.MethodsThe UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40–69 years) women and men between 2006 and 2010.Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone–binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men.ResultsData were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women.ConclusionsA higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI.

Associations of Sex Hormone-binding Globulin with Bone Mineral Density Among US Adults, NHANES 2013-2016.

BackgroundBone metabolism can be influenced by sex steroid hormones. However, the relationship between sex steroid hormones and bone mineral density (BMD) remains inconsistent. Our study explored existing evidence of the association between sex hormones, blood glucose and BMD.MethodsWe conducted a cross-sectional study of 6434 participants aged 18–80 years in the National Health and Nutrition Examination Survey (NHANES) 2013–2016 to assess the association between SHBG and BMD. The multivariable linear regression models were performed to evaluate the associations between testosterone, estrogen, sex hormone-binding globulin (SHBG) and BMD.ResultsOn adjustment for traditional risk factors (age, BMI, ALB, ALK, ASP, calcium, cholesterol, potassium, sodium, total protein, uric acid), SHBG could be regarded as an independent predictor for BMD, while fasting blood glucose did not. SHBG levels were significant associated with BMD in the multivariate model; however, it will be a different effect between the genders. On comparative analysis, high level SHBG was predictive of lumbar BMD irrespective of other two sex steroid hormones.ConclusionThis study indicated that SHBG may improve the predictive value for bone loss in adults.

485Prospective associations between sex hormone-binding globulin and risk of type 2 diabetes

Abstract Background Circulating sex hormone–binding globulin levels are inversely associated with insulin resistance. However, epidemiologic evidence on the association of sex hormone-binding globulin (SHBG) and the risk of developing diabetes is limited. This study aimed to evaluate the prospective associations between serum SHBG level and risk of type 2 diabetes (T2D) among adults ≥ 40 years old in the Yangpyeong and Namwon cohort. Methods A total of 4,383 (1,651 men and 2,732 women) participants who did not have T2D were enrolled. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During follow-up (27,146 person-years), 284 T2D cases were newly diagnosed. Results Significant dose-response inverse associations were observed between serum SHBG (tertiles) and T2D in women, even after controlling for baseline fasting glucose (incidence rate ratio, IRR=0.42, 95% CI = 0.26–0.68, P for trend = &amp;lt;.001 in the highest tertile). Similar significant linear trends were found among menopausal women, and the inverse associations persisted across participant subgroups with diabetes risk profiles. However, there were no significant associations with serum SHBG in men. When we examined the association, except for men with higher levels of hs-CRP (≥ 3 mg/L) and HOMA-IR (≥ 2.5) at baseline, the non-significant associations did not change (IRR=1.45, 95% CI = 0.78–2.70, P for trend=0.167 in the highest tertile). The sex-specific differences in associations between serum SHBG and T2D risk were statistically significant (P for interaction=0.005). Conclusions Serum SHBG may be inversely associated with T2D in women, but not in men. Key messages Circulating SHBG may play different roles in the development of T2D in men and women.

Association of sex hormone binding globulin with gestational age and parity in gestational diabetes mellitus

Objective Recent research on sex hormone binding globulin (SHBG) has emphasized its role in the prediction of gestational diabetes mellitus (GDM) development. SHBG is associated with glucose tolerance status, and its level is regulated by prenatal and perinatal factors during pregnancy. This study aimed to determine the levels of SHBG in pregnant women with normal glucose tolerance and those with GDM in association with parity and gestational age (weeks). Materials and methods This cross-sectional study enrolled 218 pregnant women (165 controls and 53 women with GDM). Serum SHBG levels were analyzed using enzyme-linked immunosorbent assay. The association of SHBG with gestational age was assessed using multivariate regression analysis after adjustment for GDM-related risk factors. Results Parity sub-group analyses indicated the presence of significant differences in the SHBG levels between nulliparous women in the GDM and control groups (p = .04). Moreover, in the GDM group, SHBG was significantly associated with gestational age beyond the risk factors of GDM. Conclusion This study demonstrated a strong association between SHBG and gestational age in women with GDM. Our findings suggest that parity and gestational age should be considered in the analysis of SHBG as a marker for GDM diagnosis.

Associations of sex hormone-binding globulin and testosterone with genome-wide DNA methylation

BackgroundLevels of sex hormone-binding globulin (SHBG) and the androgen testosterone have been associated with risk of diseases throughout the lifecourse. Although both SHBG and testosterone have been shown to be highly heritable, only a fraction of that heritability has been explained by genetic studies. Epigenetic modifications such as DNA methylation may explain some of the missing heritability and could potentially inform biological knowledge of endocrine disease mechanisms involved in development of later life disease. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we explored cross-sectional associations of SHBG, total testosterone and bioavailable testosterone in childhood (males only) and adolescence (both males and females) with genome-wide DNA methylation. We also report associations of a SHBG polymorphism (rs12150660) with DNA methylation, which leads to differential levels of SHBG in carriers, as a genetic proxy of circulating SHBG levels.ResultsWe identified several novel sites and genomic regions where levels of SHBG, total testosterone, and bioavailable testosterone were associated with DNA methylation, including one region associated with total testosterone in males (annotated to the KLHL31 gene) in both childhood and adolescence and a second region associated with bioavailable testosterone (annotated to the CMYA5 gene) at both time-points. We also identified one region where both SHBG and bioavailable testosterone in males in childhood (annotated to the ZNF718 gene) was associated with DNA methylation.ConclusionOur findings have important implications in the understanding of the biological processes of SHBG and testosterone, with the potential for future work to determine the molecular mechanisms that could underpin these associations.

Association of sex hormone-binding globulin with nonalcoholic fatty liver disease in Chinese adults

BackgroundSex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults.MethodsWe conducted a community-based, cross-sectional study in China involving 2912 participants aged 40–75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations. The association of serum SHBG with the presence of NAFLD was reported by adjusted odds ratio after applying logistic regression models. To further explore the relationship between SHBG and NAFLD, mRNA expression of SHBG and hepatocyte nuclear factor 4-α (HNF4α), as well as intrahepatic triglycerides, were determined from the liver tissues of 32 subjects with different degrees of steatosis.ResultsSerum SHBG levels in patients with NAFLD (median, 43.8 nmol/L; interquartile range, 33.4–56.8 nmol/L) were significantly lower than those in non-NAFLD subjects (median, 63.4 nmol/L; interquartile range, 47.6–83.1 nmol/L). Serum SHBG levels were inversely correlated with WHR, trunk fat percentage, glucose, HOMA-IR, TG, UA and DHEAS, and were positively correlated with HDL-C levels (all p < 0.001). Logistic regression analysis indicated that serum SHBG levels were negatively associated with the presence of NAFLD in all subjects, as well as the subgroups stratified by sex, BMI and HOMA-IR (all p < 0.05). In human liver tissues, SHBG and HNF4α mRNA expression decreased along with the elevated grade of hepatic steatosis. Both SHBG and HNF4α mRNA expression levels were negatively correlated with intrahepatic triglycerides.ConclusionsThese results demonstrate that SHBG levels were negatively associated with the presence of NAFLD in middle-aged and elderly Chinese adults.

The association of sex hormone-binding globulin with mortality is mediated by age and testosterone in men with type 2 diabetes.

Serum sex hormone-binding globulin levels have been associated with mortality in adult men with type 2 diabetes (T2DM). To confirm the association of serum sex hormone-binding globulin with mortality and then determine whether this association is mediated by age and total testosterone concentration. We studied 364 men (median age: 66years) with T2DM over a median follow-up of 4.3years using the Cox regression to study associations between sex hormone-binding globulin, age, total testosterone, and mortality. Mortality was significantly and independently associated with sex hormone-binding globulin, age, and total testosterone. In pairwise combinations of age and sex hormone-binding globulin dichotomized by median values, the association of sex hormone-binding globulin with mortality was age-dependent. Relative to the combination of age >66years/SHBG >35nmol/L (mortality 22.5%), the other combinations were associated with significantly less mortality (mortality in men ≤66years/SHBG≤35nmol/L was 3.23%). In men >66years, SHBG≤35nmol/L was associated with decreased mortality (HR: 0.41, p=0.037) compared with SHBG>35nmol/L. In men ≤66years, there was no significant difference between those with sex hormone-binding globulin above or below the median (HR: 1.73, p=0.56, reference: SHBG≤35nmol/L). TT<12nmol/L was associated with increased mortality in both age categories. Men >66years with the reference combination of SHBG>35nmol/L and TT<12nmol/L (36.84%) nmol/L had significantly higher mortality than those with SHBG>35nmol/L and TT≥12 (18.06%) and those with SHBG≤35nmol/L and TT<12nmol/L (13.79%). Our data suggest sex hormone-binding globulin and total testosterone have particular impact on mortality in men aged over 66years. Further, in older men, the combination of high sex hormone-binding globulin levels and low total testosterone is associated with greater risk than either high sex hormone-binding globulin or low total testosterone individually. Our findings are compatible with data suggesting the importance of sex hormone-binding globulin lies in mediating free testosterone levels.

Sex Hormone–Binding Globulin, Cardiometabolic Biomarkers, and Gestational Diabetes—A Longitudinal Pregnancy Cohort Study and a Meta-analysis

Background: Sex hormone-binding globulin (SHBG) has been implicated in glucose metabolism and the development of type 2 diabetes. However, its role in glucose metabolism during pregnancy is unclear. Objectives: This study investigated the prospective associations of SHBG with cardiometabolic biomarkers during pregnancy and gestational diabetes (GDM) risk. Methods: We conducted a nested case-control study of 107 GDM cases and 214 matched controls without GDM in the NICHD Fetal Growth Studies-Singleton Cohort. GDM was ascertained by medical record review. Blood samples were drawn at 10-14, 15-26, 23-31 and 33-39 gestational weeks (GW). Prospective associations of SHBG with cardiometabolic biomarkers were estimated using Spearman’s correlation coefficient adjusting for potential confounders. Difference in SHBG levels between GDM and non-GDM women was estimated in the present study cohort and a meta-analysis of existing prospective evidence. Odds ratios (OR) for GDM by SHBG quartiles were estimated using conditional logistic regression. Results: SHBG at GW 10-14 was significantly and inversely related to fasting glucose, fasting insulin, insulin resistance and HbA1c levels, and positively related to high-density lipoprotein and cholesterol levels at GW 15-26. Cases had lower SHBG levels compared to controls at GW 10-14 (mean ± SD: 204.0 ± 97.6 vs. 220.9 ± 102.5 nmol/L) and 15-26 (305.6 ± 124.3 vs. 322.7 ± 105.1 nmol/L), yet the differences were not significant. Meta-analysis of 11 prospective studies, including ours, estimated SHBG levels to be 0.50 SD (95% CI: 0.36-0.65) lower among women with than without GDM. Conclusions: Higher SHBG levels in early pregnancy was associated with a favorable glucose metabolic profile among pregnant women. Synthesis of prospective studies supports an inverse association between SHBG levels and GDM risk. Disclosure M. Li: None. S. Rawal: None. S. Hinkle: None. S. Liu: None. F. Tekola-Ayele: None. C. Zhang: None.

Sex Hormone-Binding Globulin Levels During the First Trimester May Predict Gestational Diabetes Mellitus Development

To investigate the association of sex hormone-binding globulin (SHBG) levels of early pregnancy with gestational diabetes mellitus (GDM) development. A total of 443 pregnant women during the first trimester (<12 weeks) were enrolled. SHBG levels were measured. SHBG level was lower in women with GDM than in women without GDM (93.9±34.4nmol/l vs 128.1±60.3nmol/l; p =0.001). Among the four quartiles (Q1-Q4) according to SHBG levels, GDM incidences were 17.5, 27.8, 5.1 and 2.6%, respectively. No differences were found between Q1 and Q2, and Q3 and Q4. The risk of developing GDM among women in Q1 + Q2 compared with Q3 + Q4 was 5.7. Decreased SHBG concentrations during the first trimester may predict GDM development.

Associations of Steroid Sex Hormones and Sex Hormone-Binding Globulin With the Risk of Type 2 Diabetes in Women: A Population-Based Cohort Study and Meta-analysis.

It remains unclear whether endogenous sex hormones (ESH) are associated with risk of type 2 diabetes (T2D) in women. Data of 3,117 postmenopausal women participants of the Rotterdam Study were analyzed to examine whether ESH and sex hormone-binding globulin (SHBG) were associated with the risk of incident T2D. Additionally, we performed a systematic review and meta-analysis of studies assessing the prospective association of ESH and SHBG with T2D in women. During a median follow-up of 11.1 years, we identified 384 incident cases of T2D in the Rotterdam Study. No association was observed between total testosterone (TT) or bioavailable testosterone (BT) with T2D. SHBG was inversely associated with the risk of T2D, whereas total estradiol (TE) was associated with increased risk of T2D. Similarly, in the meta-analysis of 13 population-based prospective studies involving more than 1,912 incident T2D cases, low levels of SHBG and high levels of TE were associated with increased risk of T2D, whereas no associations were found for other hormones. The association of SHBG with T2D did not change by menopause status, whereas the associations of ESH and T2D were based only in postmenopausal women. SHBG and TE are independent risk factors for the development of T2D in women.

Low Sex Hormone-Binding Globulin Levels Associate with Prediabetes in Chinese Men Independent of Total Testosterone

ObjectiveThe association ns between prediabetes and androgens have been rarely reported, especially in Chinese men. We aimed to investigate whether androgens were associated with the prevalence of prediabetes diagnosed with new American Diabetes Association criteria in Chinese men and then to assess which androgen value was the most relevant factor.MethodsA total of 2654 men (52.6±13.4 years old) were selected. Serum total testosterone (TT), sex hormone-binding globulin (SHBG) and free testosterone (FT) were measured. Covariance analysis of different androgen values were performed in age subgroups. Multinomial logistic regression was used for the association of TT, SHBG and FT with prediabetes and diabetes, as well as prediabetes in age subgroups.ResultsAccording to ADA new criteria, normoglycemia, prediabetes, and diabetes were diagnosed in 1405, 907 and 342 men, respectively. In covariance analysis, SHBG of prediabetes were found lower than that of normoglycemia but higher than that of diabetes (P <0.05). In multinomial logistic regression, serum TT and SHBG were inversely associated with prediabetes and diabetes. While, after full adjustment for age, residence area, economic status, waist circumference, metabolic factors, other two androgen values and HOMA-IR, only the associations of SHBG with prevalence of prediabetes and diabetes persisted statistically significant, especially in the elderly with prediabetes (all P for trend <0.05).ConclusionsSerum androgen was inversely associated with prediabetes and diabetes in Chinese men. Low serum SHBG was the most relevant factor for prediabetes and diabetes. Whether it is an independent predictor for incident prediabetes in Chinese men needs further explorations.

Association of sex hormone-binding globulin and free testosterone with mortality in men with type 2 diabetes mellitus

Low circulating testosterone levels have been associated with increased mortality in men. We hypothesized that the prognostic role of testosterone in men with type 2 diabetes mellitus (T2DM) is influenced by its carrier protein sex hormone-binding globulin (SHBG). We conducted a prospective cohort study at a tertiary referral centre. In total, 531 men with T2DM presenting to a diabetes clinic in 2004-2005 were followed prospectively until death, or July 31, 2014, and a survival analysis was performed. The main outcome measure was all cause mortality. Over a mean (S.D.) follow up of 7.6 years (2.6) 175 men (33%) died. In Cox proportional hazard models both higher SHBG (Hazard Ratio (HR) 1.012 (95% CI 1.002-1.022), P=0.02) and lower calculated free testosterone (cFT) (HR 0.995 (95% CI 0.993-0.998), P=0.001) were risk factors for all cause mortality independently of age, BMI, presence of macro- and microvascular disease, duration of T2DM, hemoglobin, renal function, insulin use, C-reactive protein and homeostatic model of insulin resistance. By contrast, the inverse association of total testosterone (TT) with mortality weakened after these adjustments (P=0.11). SHBG remained associated with mortality (P<0.001) both if substituted for or added to TT in the multivariable model. In the fully adjusted model, an increase of SHBG by 17.3 nmol/l (1 S.D.) increased mortality by 22% and a decrease in cFT by 81 pmol/l (1 S.D.) increased mortality by 45%. The association of SHBG with mortality in men with T2DM is novel. Whether SHBG acts via regulation of testosterone, has intrinsic biological roles, or is a marker of poor health requires further study.

Levels of adipokines and some steroids during the menstrual cycle.

The cyclical effects of hormones during the menstrual cycle (MC) are not just responsible for driving ovulation, but also have significant influence on dietary intake and appetite, as well as psychological and behavioral changes. The aim of our study was to describe changes and relationships between the MC and selected steroids, adipokines and food intake-related hormones. Twenty-seven women with regular menstrual cycles were included in the study, and their hormonal spectrum was measured in regular intervals starting from the first day of their cycle. Classical changes in gonadotropins, estrogens and progesterone during the menstrual cycle are accompanied by less striking but significant changes in 17-hydroxyprogesterone and testosterone. No significant changes show dehydroepiandrosterone and its 7-oxygenated metabolites. Adipokines show a tendency to increase during ovulation, while ghrelin and resistin decrease. There is also a remarkable association of sex hormone-binding globulin on the day of the cycle. Our results demonstrate that changes to adipokines during the menstrual cycle are not substantial, but nonetheless can play a role in the changes of food intake described in the literature. Precise descriptions of physiological changes in healthy women are important in helping us understand the significance of the changes accompanying various pathological states.

Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: observational and causal effect estimates.

The causal role of circulating sex hormone-binding globulin (SHBG) for type 2 diabetes is controversial. Information on the relations between SHBG and new biomarkers of cardiometabolic risk is scarce. We applied quantitative nuclear magnetic resonance metabolomics in three Finnish population-based cohorts to comprehensively profile circulating lipids and metabolites and study their associations with SHBG. Mendelian randomization was used to examine potential causality of SHBG on the metabolic measures and insulin resistance. Prospective associations and causal effect estimates of SHBG on type 2 diabetes were assessed via meta-analysis including summary statistics from the DIAGRAM consortium. In cross-sectional analysis in 6475 young adults (mean age 31, 57% men), higher SHBG was linked with a more favourable cardiometabolic risk profile, including associations with lipoprotein subclasses, fatty acid composition, amino acids, ketone bodies and inflammation-linked glycoproteins. Prospective analysis of 1377 young adults with 6-year follow-up indicated that SHBG is also associated with future insulin resistance. Mendelian randomization suggested only minor, if any, causal effects of SHBG on lipid and metabolite measures and insulin resistance(n = 10,895).Causal effect estimates on type 2 diabetes for 41,439 cases and 103,870 controls indicated a causative protective role of SHBG (OR = 0.83 per 1-SD, 95% CI: 0.76, 0.91); however, effects were considerably weaker than observed in meta-analysis of prospective studies [hazard ratio (HR) = 0.47 per 1-SD, 95% CI: 0.41, 0.53]. Circulating SHBG is strongly associated with systemic metabolism and predictive for insulin resistance and diabetes. The weaker causal estimates suggest that the observational associations are partly confounded rather than conferred directly via circulating SHBG.

A Possible Association of Sex Hormone-Binding Globulin with Weight Gain in the Valproic Acid-Treated Female Patients with Epilepsy

Weight gain is a common adverse consequence of treatment with valproic acid. Although a low sex hormone-binding globulin (SHBG) level was shown to be an independent risk factor for the development of metabolic syndrome and type 2 diabetes in the general popu- lation, there is presently no data available regarding the association between the SHBG level and valproic acid-induced weight gain. The association between the plasma SHBG level and being overweight was retrospectively investigated in 46 valproic acid-treated and 59 carbamazepine-treated patients with epilepsy. Among the female patients treated with valproic acid, the plasma SHBG levels tended to be negatively correlated with the gap between the body mass index value for each patient and the upper limit of the normal range (adjusted partial regression coefficient = -6.86, P = 0.041), and the SHBG levels were significantly lower in the overweight subjects than in the normal weight subjects (P = 0.001). These associations were not observed among the valproic acid-treated male patients or the carbamazepine-treated male and female patients. The plasma SHBG levels may be therefore associated with being overweight in the valproic acid-treated female patients.

Maternal Testosterone Levels are Associated with C-Peptide Levels in the Mexican American Subset of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cohort

Altered sex hormone levels are thought to play an important role in adult-onset diseases including obesity, cardiovascular disease, and diabetes. They contribute to these complex diseases through changes in their availability, which is influenced, in part, by binding proteins. Insulin resistance, which is characteristic of these diseases, along with increased insulin secretion, is a physiologic change that occurs normally during pregnancy. To determine the relationship between insulin resistance and sex hormone levels, we examined the associations of sex hormone-binding globulin (SHBG) and testosterone with measures of glycemia and insulinemia in a healthy pregnant population. We measured fasting serum SHBG and testosterone levels in 215 Hispanic mothers of Mexican ancestry from the HAPO Study cohort and tested for associations between SHBG and testosterone levels and maternal plasma glucose and C-peptide. After adjusting for confounding variables, serum total testosterone (TT) was positively associated with fasting C-peptide (0.18 μg/l higher for TT higher by 1 SD, p=0.001) and 1-h C-peptide (0.79 μg/l higher for TT higher by 1 SD, p<0.001). Free testosterone (FT) was also positively associated with fasting C-peptide (0.19 μg/l higher for FT higher by 1 SD, p<0.001), and 1-h C-peptide (0.83 μg/l higher for FT higher by 1 SD, p<0.001). Although these findings are from a single cohort, this study provides evidence for an association between testosterone and C-peptide during pregnancy in a nondiabetic Hispanic obstetric population.

Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population

BackgroundThe aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population.MethodsThe study is based on a random sample of a Swedish population of men and women aged 30–74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7.ResultsIn men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: β=−0.143 p<0.001) and systolic blood pressure (systolic blood pressure β=−0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: β=−0.113 p<0.001; systolic blood pressure β=−0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=−0.024 p<0.001) and women (B=−0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=−0.014, p=0.008).ConclusionIn conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure.

Associations of sex hormone-binding globulin and testosterone with diabetes among men and women (the Saku Diabetes study): a case control study

BackgroundSex hormone-binding globulin (SHBG) levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. As fatty liver has been suggested to be a major determinant of SHBG levels, we examined whether the associations of SHBG and testosterone with diabetes were independent of fatty liver.MethodsWe conducted a case–control study that included 300 diabetes cases (215 men and 85 women) and 300 matched controls from the Saku cohort study. Diabetes was defined by either fasting plasma glucose levels ≥126 mg/dL, 2-h post-load glucose levels ≥200 mg/dL after a 75 g oral glucose tolerance test, or diabetes diagnosed by physicians. We fitted conditional logistic regression models to examine the associations between SHBG and total testosterone levels with diabetes by sex. To evaluate the impact of fatty liver, we used the fatty liver index (FLI), a validated measure derived from serum triglyceride levels, body mass index (BMI), waist circumference, and γ-glutamyltransferase levels.ResultsAfter adjusting for age, family history of diabetes, smoking, physical activity, BMI, and FLI, SHBG levels were inversely associated with diabetes among women (odds ratio [OR] comparing the highest with the lowest quartiles, 0.13 [95% confidence interval {CI}, 0.02–0.96]), but not among men. Similar patterns were observed in a subgroup analysis restricted to postmenopausal women"(OR, 0.12 [95% CI, 0.01–1.17]). In contrast, testosterone levels were inversely associated with diabetes among men (OR, 0.45 [95% CI, 0.23–0.89]), but not among women.ConclusionsOur findings suggest that SHBG in women and testosterone in men may be inversely associated with diabetes.

Sex Hormone-Binding Globulin is an Independent Predictor of Biochemical Recurrence After Radical Prostatectomy

We studied the association of serum sex hormone levels with clinicopathological variables and biochemical recurrence in men with prostate cancer treated with radical prostatectomy. We prospectively studied preoperative serum sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone, and free and total testosterone in 372 patients undergoing radical prostatectomy. Biochemical recurrence was analyzed in 285 patients and defined as prostate specific antigen 0.2 ng/ml or higher at least 30 days after radical prostatectomy. Median followup was 43.6 months. Median sex hormone-binding globulin was 37.4 nmol/l, luteinizing hormone 4.1 mU/ml, follicle-stimulating hormone 5.9 mU/ml, and free and total testosterone 0.069 and 3.7 ng/ml, respectively. There was no significant association of sex hormone-binding globulin, luteinizing hormone, follicle-stimulating hormone or total testosterone with T and N stage, and margin status. Luteinizing hormone, follicle-stimulating hormone, and free and total testosterone were not associated with biochemical recurrence. In contrast, for each 10 U increase in sex hormone-binding globulin the risk of biochemical recurrence increased by 12% (p = 0.045). On multivariable analysis sex hormone-binding globulin achieved independent predictor status after adjusting for standard clinicopathological variables. After stepwise regression a model containing T and N stage, Gleason score, margin status, prostate weight and sex hormone-binding globulin improved the accuracy of a base model by 1.3% (79.0% vs 77.7%). Preoperative serum sex hormone-binding globulin is independently associated with biochemical recurrence after radical prostatectomy and increases the predictive accuracy of a standard multivariable model. Routine assessment of sex hormone-binding globulin sex hormone-binding globulin may be a helpful adjunct to identify patients who need early adjuvant therapy.