Quartile Of Sex Hormone-binding Globulin Research Articles

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

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

Physical Activity and Sex Hormone–Binding Globulin in Older Adults

Besides its known function as a transport protein for testosterone and other steroid hormones, sex hormone-binding globulin (SHBG) is a biomarker associated with many adverse health effects. The aim of this study was to investigate the association of physical activity with SHBG serum levels in older adults. The physical activity and SHBG values for 1,259 older adults (43.4% female; 56.6% male) with a mean age of 75.6 ± 6.5 years were included in the analysis. The average daily walking duration was 104.2 ± 40.4 (mean ± SD) min. A positive dose-response relationship of daily walking duration with quartiles of SHBG was seen after adjustment for age, sex, history of cardiovascular diseases, diabetes, smoking, γ-glutamyl transferase, and C-reactive protein (p for trend = .010). However, this relationship disappeared after adjustment for body mass index (p for trend = .977). Body mass index seems to be an important determinant of SHBG and a possible confounding factor in the relationship of physical activity and SHBG.

Association of total testosterone, free testosterone, bioavailable testosterone, sex hormone-binding globulin, and hypertension.

Low testosterone has been inversely associated with hypertension. Our objective was to determine the associations between total testosterone (TT), free testosterone (FT), bioavailable testosterone (BioT), sex hormone–binding globulin (SHBG), and hypertension. Two hundred fifty-three men were enrolled in this study. TT and SHBG were measured by chemiluminescent immunoassay, and FT and BioT were calculated. Hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg and/or diastolic blood pressure (DBP) ≥90 mm Hg. Our results showed that hypertensive men had higher SHBG levels, and lower FT and BioT, compared to normotensive men. FT and BioT were inversely associated with SBP and DBP after adjusting for covariates (age, smoking, alcohol consumption, and physical activity). Furthermore, there was a significant decrease in the odds ratios for hypertension in the third and fourth quartiles of BioT and FT, compared to the lowest quartile before and after adjusting for covariates. In contrast, the OR for hypertension in the third quartile of SHBG was lower than the highest quartile. Our data show that FT and BioT are inversely correlated with SBP, DBP, and hypertension in men.

Are thyroid nodules associated with sex-related hormones? A cross-sectional SPECT-China study

ObjectiveLittle is known about the association between thyroid nodules (TNs) and endogenous sex hormones. We aimed to investigate the relationship between TNs and sex-related hormones among men in China.SettingThe data...

Correlation of serum sex hormone levels with metabolic syndrome in elderly men

To investigate the relationship between sex hormones and metabolic syndrome (MS), as well as its components in elderly men. 1 505 elderly men (≥60 years old, mean age 75.4±9.7 years old) who participated in a routine health screening examination in PLA general hospital from May to June in 2012 were enrolled in this cross-sectional study. Serum lipids, glucose and sex hormones were measured along with body height, weight and blood pressure. Free testosterone (FT) and bioavailable testosterone (BT) were calculated. The correlation of serum sex hormones with the presence of MS and its components were analyzed. The prevalence of MS was 21.7% (326/1 505) in this study. Elderly men with MS had lower levels of sex hormone-binding globulin (SHBG), total testosterone (TT), FT and BT than those without MS. The levels of SHBG, TT, FT and BT were significantly lower in the overweight/obesity group, hyperglycemia group and dyslipidemia group than those in the respective control groups (P<0.05). Logistic regression analysis showed that the SHBG level was an independent risk factor for MS in elderly men(OR=0.977, 95%CI: 0.964-0.989, P<0.001), while the levels of TT, FT and BT were not associated with MS. The prevalence of MS gradually increased with decreasing of SHBG values (P<0.001). When comparing subjects in the lowest and highest quartile of SHBG, the former group demonstrated a 2.13-fold increase in the odds ratio for MS after adjusting for age, smoking, drinking and other sex hormone indices. In elderly men, lower SHBG level, not TT, FT or BT may be an independent predictor for the prevalence of MS, in which the mechanism requires further studies.

Sex Hormone–Binding Globulin and Risk of Clinical Diabetes in American Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women

Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) concentrations and risk of clinical diabetes in white individuals. However, it remains unclear whether this relationship extends to other racial/ethnic populations. We evaluated the association between baseline concentrations of SHBG and clinical diabetes risk in the Women's Health Initiative Observational Study. Over a median follow-up of 5.9 years, we identified 642 postmenopausal women who developed clinical diabetes (380 blacks, 157 Hispanics, 105 Asians) and 1286 matched controls (777 blacks, 307 Hispanics, 202 Asians). Higher concentrations of SHBG at baseline were associated with a significantly lower risk of clinical diabetes [relative risk (RR), 0.15; 95% CI, 0.09-0.26 for highest vs lowest quartile of SHBG, adjusted for BMI and known diabetes risk factors]. The associations remained consistent within ethnic groups [RR, 0.19 (95% CI, 0.10-0.38) for blacks; RR, 0.17 (95% CI, 0.05-0.57) for Hispanics; and 0.13 (95% CI, 0.03-0.48) for Asians]. Adjustment for potential confounders, such as total testosterone (RR, 0.11; 95% CI, 0.07-0.19) or HOMA-IR (RR, 0.26; 95% CI, 0.14-0.48) did not alter the RR substantially. In addition, SHBG concentrations were significantly associated with risk of clinical diabetes across categories of hormone therapy use (never users: RR(per SD) = 0.42, 95% CI, 0.34-0.51; past users: RR(per SD) = 0.53;, 95% CI, 0.37-0.77; current users: RR(per SD) = 0.57; 95% CI, 0.46-0.69; P-interaction = 0.10). In this prospective study of postmenopausal women, we observed a robust, inverse relationship between serum concentrations of SHBG and risk of clinical diabetes in American blacks, Hispanics, and Asians/Pacific Islanders. These associations appeared to be independent of sex hormone concentrations, adiposity, or insulin resistance.

Abstract 011: Sex Hormone-Binding Globulin (SHBG) and Risk of Clinical Diabetes in American Black, Hispanic, and Asian/Pacific Islander Postmenopausal Women.

BACKGROUND: Recent prospective studies have shown a strong inverse association between sex hormone-binding globulin (SHBG) levels and risk of clinical diabetes in Whites. However, it remains unknown whether this relation extends to other racial/ethnic populations. METHODS: We evaluated the association between baseline levels of SHBG and risk of clinical diabetes in the Women’s Health Initiative Observational Study. Over a median follow-up of 5.9 years, 542 postmenopausal women developed clinical diabetes (338 Blacks, 128 Hispanics, 76 Asians) and were matched to 1,110 controls (707 Blacks, 249 Hispanics, 154 Asians). To complement our protein-level findings, we also genotyped 5 SHBG polymorphisms. We performed Mendelian randomization analysis to assess the potential causal relation between SHBG levels and risk of clinical diabetes. RESULTS: Overall, higher levels of SHBG at baseline were associated with a significantly lower risk of clinical diabetes (Relative risk [RR]=0.24, 95% confidence interval [CI]=0.15-0.39 for highest versus lowest quartile of SHBG, adjusted for BMI and other known diabetes risk factors). The associations remained consistent across ethnic groups (p-for-heterogeneity=0.72): RR=0.29 (95%CI=0.16-0.54) for Blacks, RR=0.26 (95%CI=0.09-0.74) for Hispanics, and RR=0.32 (95%CI=0.06-1.73) for Asians, comparing highest to lowest quartiles of SHBG. In addition, SHBG polymorphisms affected diabetes risk proportional to serum SHBG levels. Mendelian randomization analysis confirmed the significant direct effect of SHBG on diabetes development (p=0.03). CONCLUSIONS: In this prospective cohort of postmenopausal women, we observed a robust, inverse relation between serum levels of SHBG and clinical diabetes risk in American Blacks, Hispanics, and Asian/Pacific Islanders. Genetic variants associated with SHBG levels demonstrated a similar relationship, providing support for a causal role of SHBG in the pathogenesis of type 2 diabetes.

Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis

To assess the relation between moderate iron overload on sex hormone binding globulin (SHBG) levels and gonadotroph function in men with dysmetabolic iron overload syndrome and the effects of phlebotomy. The relationship between magnetic resonance imaging assessed liver iron concentration (LIC) and plasma ferritin levels with total testosterone, bioavailable testosterone (BT), SHBG and LH levels, were studied in 50 men with moderate dysmetabolic iron excess, in the absence of genetic haemochromatosis, who were randomised to phlebotomy therapy or to normal care. Four patients (8%) had low total testosterone (<10.4 nmol/l) and 13 patients (26%) had low BT (<2.5 nmol/l). In the entire population, those with LIC above the median (90 μmol/l) had a higher mean SHBG (P=0.028), lower LH (P=0.039) than those with LIC below the median. In multivariable analysis (adjusted for age, and fasting insulin) LIC was significantly associated with SHBG (positively) and LH (negatively). Patients in the highest quartile of SHBG had higher LIC (P=0.010) and higher ferritinaemia (P=0.012) than those in the three other quartiles. Iron depletion by venesection did not significantly improve any hormonal levels. Hypogonadism is not infrequent in men with dysmetabolic iron overload syndrome. Liver iron excess is associated with increased plasma SHBG and moderate hypogonadotrophic hypogonadism. Phlebotomy therapy needs further investigation in symptomatic hypogonadal men with dysmetabolic iron excess.

Sex steroids and bone health in older Chinese men

This study examines the association between sex steroids, bone mineral density (BMD), and incident fractures in 1,489 community-living Chinese men aged 65 and over. Chinese men with low serum estradiol levels display elevated bone loss and increased risk of fractures similar to findings in Caucasians. This study examines the association between serum total testosterone (TT), free testosterone (free T), estradiol (E(2)), bioavailable estradiol (bioE(2)), sex hormone binding globulin (SHBG), BMD, and incident fractures. This is a cohort study with 4-year follow-up in the community in Hong Kong SAR, China. One thousand four hundred eighty-nine community-living Chinese men aged 65 and over participated. Sex steroid levels and BMD were measured at baseline; BMD was repeated after 4 years of follow-up, and fracture incidence from ascertainment from hospital databases was determined over 4 years of follow-up. The strongest age-adjusted positive association with total hip and femoral neck BMD was with bioE(2), followed by E(2). Greater bone loss occurred in the lowest quartile of E(2) and bioE(2). The lowest quartile of free T and bioE(2) and the two highest quartile of SHBG were associated with the highest percentage of participants with incident fractures. Those in the lowest quartile of E(2) and bioE(2) had approximately a 50% increased risk of incident fractures compared with the other three quartiles. This relationship remains significant for nonvertebral incident fractures (hip, radius, pelvis, and humerus) for E(2) only, but not bioE(2). Compared with the group with the three highest quartiles of TT and E(2), the group with the lowest quartile of both had approximately twice the risk of nonvertebral osteoporosis-related incident fractures. Chinese men with low serum estradiol levels display elevated bone loss and increased risk of fractures similar to findings in Caucasians.

Association of Testosterone and Sex Hormone–Binding Globulin With Metabolic Syndrome and Insulin Resistance in Men

OBJECTIVEWe sought to assess the associations of testosterones and sex hormone–binding globulin (SHBG) with metabolic syndrome and insulin resistance in men.RESEARCH DESIGN AND METHODSWe defined metabolic syndrome according to the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Among men aged ≥20 years who participated in the Third National Health and Nutrition Examination Survey (n = 1,226), the Cox proportional hazards model was used to estimate the prevalence ratio and 95% CI of metabolic syndrome according to circulating concentrations of testosterones and SHBG.RESULTSAfter adjustment for age, race/ethnicity, smoking status, alcohol intake, physical activity level, LDL cholesterol, C-reactive protein, and insulin resistance, men in the first quartile (lowest) (prevalence ratio 2.16 [95% CI 1.53–3.06]) and second quartile of total testosterone (2.51 [1.86–3.37]) were more likely to have metabolic syndrome than men in the fourth quartile (highest, referent group) (P < 0.001 for linear trend). Similarly, men in the first quartile of SHBG (2.17 [1.32–3.56]) were more likely to have metabolic syndrome than men in the fourth quartile (P = 0.02 for linear trend). No significant associations of calculated free testosterone (P = 0.31 for linear trend) and bioavailable testosterone (P = 0.11 for linear trend) with metabolic syndrome were detected after adjustment for all possible confounders.CONCLUSIONSLow concentrations of total testosterone and SHBG were strongly associated with increased likelihood of having metabolic syndrome, independent of traditional cardiovascular risk factors and insulin resistance.

Interrelation Between Sex Hormones and Plasma Sex Hormone-Binding Globulin and Hemoglobin A1c in Healthy Postmenopausal Women

Androgenicity, as measured by low sex hormone-binding globulin (SHBG) and elevations in testosterone and free androgen index (FAI), is associated with adverse cardiovascular (CV) outcomes, possibly due to effects on insulin resistance and glycemia. Glycosylated hemoglobin (HbA1c) concentration, SHBG, and sex hormones were available in 200 nondiabetic postmenopausal women who were not using hormone therapy (HT) in the Women's Health Study. Of these, 98 were cardiovascular disease (CVD) cases; the remainders were matched controls. To achieve normality, continuous values were log transformed and geometric means were calculated. Associations between sex hormones and HbA1c were examined using general linear models (GLM), partial correlations, and multiple linear regression analyses. Lower SHBG levels and higher FAI and HbA1c values were found among the CVD cases, and all analyses were adjusted for this factor. In GLM, higher values of HbA1c were observed in the highest quartiles of FAI and the lowest quartiles of SHBG. However, the correlation between SHBG and HbA1c across quartiles was eliminated after adjusting for body mass index (BMI). In partial correlations, HbA1c values were inversely associated with SHBG (r = -0.19, P = 0.008) and positively associated with FAI (r = 0.19, P = 0.01), even after adjusting for age, CVD case-control status, and BMI. In multivariate models, a significant inverse association between SHBG and HbA1c persisted, as well as a significant positive association between FAI and HbA1c. Androgenicity, as measured by low SHBG and high FAI, is associated with glycemia, and thereby may contribute to CVD risk in postmenopausal women.

Endogenous sex steroids, weight change and rates of hip bone loss in older men: the MrOS study

Lower levels of endogenous sex steroids or declines in these hormones may contribute to the increased rates of bone loss observed in older adults experiencing weight loss. We hypothesized that among older men with weight loss, higher rates of bone loss at the hip would be observed in men with lower baseline bioavailable sex steroids or those with greater declines in these hormones. To test this hypothesis, body weight, hip bone mineral density (BMD) using dual energy x-ray absorptiometry and endogenous sex steroids in paired serum samples by sensitive immunoassays were measured at a baseline and at a second examination that was held an average of 1.8 years later in 1267 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study. Men experiencing weight loss had higher rates of hip bone loss than those with stable weight or weight gain within each quartile of baseline sex steroid level [p values for test of trend across weight change categories <0.010 within each quartile of bioavailable estradiol and testosterone and <0.060 within each quartile of sex hormone-binding globulin (SHBG)]. Results were similar when a change in sex steroids was substituted for baseline sex steroids in the analyses. Among men with weight loss, the rate of decline in total hip BMD showed a stepwise increase in magnitude with decreasing baseline bioavailable estradiol (p value for trend <0.040), with increasing baseline SHBG (p value for trend<0.030) and with greater decreases in bioavailable testosterone from baseline (p value for trend <0.001). These findings support the hypothesis that the impact of weight loss in older men on rates of hip bone loss may be increased by the presence of a sex steroid insufficiency.

Cross-Sectional Association between Markers of Inflammation and Serum Sex Steroid Levels in the Postmenopausal Estrogen/Progestin Interventions Trial

Standard risk factors do not adequately capture cardiovascular risk in postmenopausal women. We sought to determine the associations between levels of sex steroids and levels of inflammatory markers in postmenopausal women. We analyzed baseline data from a subset of postmenopausal women aged 45-64 years who had stored samples during a randomized controlled trial. We measured levels of C-reactive protein (CRP), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), soluble intercellular adhesion molecule (sICAM), and circulating sex steroids. Multiple linear regression models were created with each of the following hormone levels as the primary exposure variable: estrone, total estradiol, bioavailable estradiol, total testosterone, bioavailable testosterone, progesterone, and sex hormone-binding globulin (SHBG). Sociodemographic and lifestyle covariates were derived from standardized self-report questionnaires and direct measurement (weight, height). Mean age of the 623 women was 56 years. After adjustment for age, body mass index (BMI), physical activity, alcohol consumption, and smoking, the bioavailable testosterone level (p = 0.03) was positively and the SHBG level (p < 0.001) was negatively associated with the logCRP level. The increment in CRP level between the highest and lowest quartile of bioavailable testosterone was 1.28 microg/mL. The increment in CRP level between the lowest and highest quartile of SHBG was 2.62 microg/mL. Compared with SHBG or bioavailable testosterone as predictors of logCRP in separate regression models, when both SHBG and bioavailable testosterone were included in the same multivariate linear regression model, only SHBG remained a statistically significant predictor of logCRP. Progesterone level was positively associated with the logMMP-9 level (p < 0.001); no other sex steroid level was associated with the logMMP-9 level. In multiply adjusted models, no association was found between levels of any sex steroid and IL-6 or sICAM level.

Serum levels of sex hormones and breast cancer risk in premenopausal women: a case-control study (USA).

High levels of serum estrogens and androgens have been convincingly linked with an increased risk of breast cancer among postmenopausal women. By contrast, the role of blood levels of these hormones in the etiology of premenopausal breast cancer is not well understood. In a case-control study, we sought to examine associations between levels of serum estradiol, sex-hormone binding globulin (SHBG), dehydroepiandrosterone (DHEA), testosterone, androstenedione and progesterone and risk of premenopausal breast cancer. Cases of breast cancer under age 45 were identified using rapid ascertainment systems in Seattle/Puget Sound, Washington and control subjects were identified from the same area through random digit dialing methods. A total of 169 eligible breast cancer cases and 195 control subjects donated blood (either before or six or more weeks after surgery) and were interviewed using a standardized questionnaire. The fully adjusted risk ratios and 95% confidence intervals for the highest versus lowest tertiles of estradiol, according to menstrual cycle phase, were 3.10 (0.8-12.7) for early follicular, 0.54 (0.2-1.7) for late follicular and 0.60 (0.3-1.4) for luteal. Risks for highest versus lowest quartiles of SHBG and androgens were 0.81 (0.4-1.6) for SHBG, 2.42 (1.1-5.2) for DHEA, 1.12 (0.6-2.5) for testosterone, and 1.33 (0.6-2.8) for androstenedione. For luteal progesterone, the RR for the highest versus lowest tertile was 0.55 (0.2-1.4). In summary, we did not find a convincing association between serum SHBG, estradiol, testosterone or androstenedione and premenopausal breast cancer risk. Observed differences between cases and controls subjects in serum levels of DHEA and luteal phase progesterone should be investigated further in large prospective studies.

Endogenous postmenopausal hormones and carotid atherosclerosis: a case-control study of the atherosclerosis risk in communities cohort.

Studies examining the relation between endogenous postmenopausal hormone levels and cardiovascular disease have yielded conflicting results. After excluding women with a history of hormone replacement therapy (HRT) use, the authors conducted a US case-control study in 1987-1992 comparing endogenous postmenopausal hormone levels in women with and without significant carotid atherosclerosis in the Atherosclerosis Risk in Communities (ARIC) cohort. Atherosclerosis was assessed by using B-mode ultrasound to measure carotid artery intimal-medial thickness (IMT). Cases (n = 182) were postmenopausal women with average IMT measurements greater-than-or-equal the 95th percentile. Controls (n = 182) were frequency matched to cases on age and ARIC center and had IMT measurements < the 75th percentile. After adjustment for cardiovascular risk factors, no association was found between the odds of atherosclerosis and increasing quartiles of estrone, dehydroepiandrosterone sulfate, or androstenedione. Compared with participants in the lowest quartile of sex hormone-binding globulin (SHBG), those in the highest quartile had a significantly lower odds of atherosclerosis (odds ratio = 0.48, 95% confidence interval: 0.24, 0.97). Similarly, participants in the highest quartile of total testosterone had a lower odds of atherosclerosis (odds ratio = 0.38, 95% confidence interval: 0.20, 0.74). The authors found higher total testosterone and SHBG to be inversely related to carotid atherosclerosis, suggesting their potential importance in reducing atherosclerotic risk in postmenopausal women not using HRT.

Serum steroid hormone levels, sex hormone-binding globulin, and body mass index in the etiology of postmenopausal breast cancer.

Serum concentrations of estrone, androstenedione, testosterone, and sex hormone-binding globulin (SHBG) were measured postoperatively in 122 postmenopausal women with incident breast cancer and 122 age-matched population controls. After mutual adjustment, through conditional logistic regression, between the hormonal variables and body mass index (BMI), the odds ratios for increasing control-defined quartiles of estrone and androstenedione, respectively, were 1.00, 1.44, 1.76, 1.94 and 1.00, 0.83, 0.97, 2.43; there was no association of testosterone with breast cancer risk. Moreover, the odds ratios for increasing quartiles of SHBG and BMI were 1.00, 0.72, 0.28, 0.25 and 1.00, 0.39, 0.28, 0.19, respectively. This study reveals sharp contrasts in breast cancer risk between women with high estrone and low BMI and SHBG, vs women with low estrone and high BMI and SHBG.