002 Cross-Sectional and Longitudinal Determinants of Serum Sex Hormone Binding Globulin (Shbg) in Community-Dwelling Men: The Men Androgen Inflammation Lifestyle Environment and Stress (Mailes) Study

BackgroundReduced circulating testosterone and sex hormone-binding globulin (SHBG) are implicated as risk factors for metabolic syndrome. As SHBG increases with age while testosterone declines, we examined the relative contributions of SHBG and testosterone to the risk of metabolic syndrome in older men.MethodsWe conducted a cross-sectional study of 2502 community-dwelling men aged ≥70 years without known diabetes. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP-ATPIII) criteria. Early morning fasting sera were assayed for total testosterone, SHBG and LH. Free testosterone was calculated using mass action equations.ResultsThere were 602 men with metabolic syndrome (24.1%). The risk of metabolic syndrome increased for total testosterone <20 nmol/l, SHBG <50 nmol/l and free testosterone <300 pmol/l. In univariate analyses SHBG was associated with all five components of metabolic syndrome, total testosterone was associated with all except hypertension, and free testosterone was associated only with waist circumference and triglycerides. In multivariate analysis, both total testosterone and especially SHBG remained associated with metabolic syndrome, with odds ratios of 1.34 (95% confidence interval (CI): 1.18–1.52) and 1.77 (95% CI: 1.53–2.06) respectively. Men with hypogonadotrophic hypogonadism (total testosterone <8 nmol/l, LH ≤12 IU/l) had the highest prevalence of metabolic syndrome (53%,P<0.001).ConclusionsLower SHBG is more strongly associated with metabolic syndrome than lower total testosterone in community-dwelling older men. SHBG may be the primary driver of these relationships, possibly reflecting its relationship with insulin sensitivity. Further studies should examine whether measures that raise SHBG protect against the development of metabolic syndrome in older men.

Download Full-text

Serum Testosterone is Inversely and Sex Hormone-binding Globulin is Directly Associated with All-cause Mortality in Men

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa743 ◽

2020 ◽

Author(s):

Bu B Yeap ◽

Ross J Marriott ◽

Leen Antonio ◽

Yi X Chan ◽

Suchitra Raj ◽

...

Keyword(s):

Mortality Rate ◽

Serum Testosterone ◽

Cox Proportional Hazards ◽

Community Dwelling ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Atherosclerotic Cardiovascular Disease ◽

Hormone Binding ◽

Baseline Serum ◽

Related Mortality

Abstract Context Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase. Objective To analyze associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men. Design, Setting, and Participants The UK Biobank prospective cohort study of community-dwelling men aged 40–69 years old, followed for 11 years. Main Outcome Measures All-cause, atherosclerotic cardiovascular disease (CVD) and cancer-related mortality. Cox proportional hazards regression was performed, adjusting for age, waist circumference, medical conditions, and other covariates. Models for testosterone included SHBG and vice versa. Results In a complete case analysis of 149 436 men with 10 053 deaths (1925 CVD and 4927 cancer-related), men with lower testosterone had a higher mortality rate from any cause (lowest vs highest quintile, Q1 vs Q5, fully-adjusted hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.06–1.22, overall trend P < 0.001), and cancer (HR = 1.20, CI = 1.09–1.33, P < 0.001), with no association for CVD deaths. Similar results were seen for cFT. Men with lower SHBG had a lower mortality rate from any cause (Q1 vs Q5, HR = 0.68, CI = 0.63–0.73, P < 0.001), CVD (HR = 0.70, CI = 0.59–0.83, P < 0.001), and cancer (HR = 0.80, CI = 0.72–0.89, P < 0.001). A multiply imputed dataset (N = 208 425, 15 914 deaths, 3128 CVD-related and 7468 cancer-related) and analysis excluding deaths within the first 2 years (9261, 1734, and 4534 events) yielded similar results. Conclusions Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related, and cancer-related mortality. Confirmation and determination of causality requires mechanistic studies and prospective trials.

Download Full-text

Cross-sectional association between testosterone, sex hormone-binding globulin and metabolic syndrome: The Healthy Twin Study

Clinical Endocrinology ◽

10.1111/cen.13390 ◽

2017 ◽

Vol 87 (5) ◽

pp. 523-531 ◽

Cited By ~ 9

Author(s):

Heesun Moon ◽

Inyoung Choi ◽

Somi Kim ◽

Hyeonyoung Ko ◽

Jinyoung Shin ◽

...

Keyword(s):

Metabolic Syndrome ◽

Twin Study ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding ◽

Cross Sectional

Download Full-text

Establishment of sex difference in circulating uric acid is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys

Scientific Reports ◽

10.1038/s41598-021-96959-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yutang Wang ◽

Fadi J. Charchar

Keyword(s):

Uric Acid ◽

Sex Difference ◽

Weighted Least Squares ◽

Cross Sectional Study ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Least Squares Regression ◽

Hormone Binding ◽

Adolescent Boys ◽

Cross Sectional

AbstractMen have higher circulating levels of uric acid than women. This sex difference is suspected to be a result of suppressive effects of estradiol on uric acid. If so, estradiol would be inversely associated with circulating uric acid. This study aimed to test this hypothesis. This cross-sectional study included 9472 participants (weighted sample size of 184,342,210) aged 12–80 years from the 2013 to 2016 US National Health and Nutrition Examination Survey. Associations of sex hormones with uric acid were analyzed using weighted least squares regression, adjusting for demographic characteristics, lifestyle risk factors, and comorbidities. Neither free nor bioavailable estradiol was inversely associated with circulating uric acid in adolescent boys or girls, or adult men or women, or perimenopausal women after full adjustment. The sex difference in uric acid was established during adolescence as a result of a dramatic increase in uric acid in adolescent boys. During adolescence, the increase in estradiol in girls over time was accompanied by a relatively unchanged level of uric acid. All three fractions of estradiol (free, bioavailable, and total) were positively associated with uric acid in adolescent boys and girls after full adjustment. In adolescent boys, all three fractions of testosterone were positively associated with serum uric acid, and sex hormone-binding globulin was inversely associated with uric acid after full adjustment. These results suggest that estradiol is not inversely associated with circulating uric acid in adolescents and the establishment of sex difference in circulating uric acid during adolescence is associated with higher testosterone and lower sex hormone-binding globulin in adolescent boys.

Download Full-text

The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men. The Tromsø Study

Diabetes & Metabolism ◽

10.1016/s1262-3636(07)70086-1 ◽

2004 ◽

Vol 30 (1) ◽

pp. 29-34 ◽

Cited By ~ 46

Author(s):

J Svartberg ◽

T Jenssen ◽

J Sundsfjord ◽

R Jorde

Keyword(s):

Glycosylated Hemoglobin ◽

Community Dwelling ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Hormone Binding

Download Full-text

Sex hormone-binding globulin as a marker for hyperinsulinemia and/or insulin resistance in obese children

Acta Endocrinologica ◽

10.1530/eje.0.1430085 ◽

2000 ◽

pp. 85-89 ◽

Cited By ~ 33

Author(s):

F Gascon ◽

M Valle ◽

R Martos ◽

FJ Ruz ◽

R Rios ◽

...

Keyword(s):

Insulin Resistance ◽

Sex Hormone ◽

Obese Group ◽

Sex Hormone Binding Globulin ◽

Control Group ◽

Hormone Binding ◽

Obese Children ◽

Anthropometric Measures ◽

Cross Sectional ◽

Glucose Ratio

OBJECTIVE: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globulin (SHBG) has been described in adults. We evaluated the usefulness of SHBG as an index of hyperinsulinemia and/or insulin resistance in obese children (aged 6-9 years) of both sexes and its possible influence on the androgenic status. DESIGN: We carried out a cross-sectional study of cases and controls. We studied 61 obese children (22 males, 39 females) with body mass index (BMI) superior to the 90(th) percentile and a control group of age- and sex-matched non-obese children. We measured serum glucose, insulin, TSH, free thyroxine, 17beta-estradiol, testosterone and SHBG. Also, we correlated these parameters with anthropometric measures. RESULTS: The obese group presented significantly elevated levels of insulin (P=0.001) and insulin/glucose ratio (P=0.0012) compared with the control group. SHBG (P=0.0001) and testosterone (P=0.0169) levels were significantly lower than those in the non-obese group. We did not find any difference in the free androgen index (FAI). Fasting insulin (r=-0.4512; P<0.001), BMI (r=-0.3185; P<0.05) and testosterone (r=-0.3705; P<0.01) were inversely correlated with SHBG concentration. According to multivariate analyses, insulin was the only independent predictor factor for serum SHBG concentration in the obese group (r partial=0.1280; P=0.0171). CONCLUSIONS: In summary, at this age there is a strong relationship between insulin and SHBG. The changes in SHBG levels of the obese group did not affect FAI and, therefore, they did not cause changes in the androgenic status. Our data support the role of insulin in the regulation of serum SHBG levels.

Download Full-text

Plasma Sex Hormone-binding Globulin, Corticosteroid-binding Globulin, Cortisol, and Free Cortisol Levels in Outpatients Attending a Lipid Disorders Clinic: A Cross-sectional Study of 1137 Subjects

Hormone and Metabolic Research ◽

10.1055/s-0029-1243260 ◽

2010 ◽

Vol 42 (04) ◽

pp. 274-279 ◽

Cited By ~ 9

Author(s):

J. G. Lewis ◽

K. K. Borowski ◽

B. I. Shand ◽

P. M. George ◽

R. S. Scott

Keyword(s):

Cross Sectional Study ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Sectional Study ◽

Hormone Binding ◽

Cross Sectional ◽

Lipid Disorders ◽

Free Cortisol ◽

Corticosteroid Binding Globulin ◽

Cortisol Levels

Download Full-text

Testosterone but not estradiol level is positively related to muscle strength and physical performance independent of muscle mass: a cross-sectional study in 1489 older men

Acta Endocrinologica ◽

10.1530/eje-10-0952 ◽

2011 ◽

Vol 164 (5) ◽

pp. 811-817 ◽

Cited By ~ 55

Author(s):

Tung Wai Auyeung ◽

Jenny Shun Wah Lee ◽

Timothy Kwok ◽

Jason Leung ◽

Claes Ohlsson ◽

...

Keyword(s):

Muscle Strength ◽

Grip Strength ◽

Muscle Mass ◽

Physical Performance ◽

Older Men ◽

Community Dwelling ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Cross Sectional ◽

Skeletal Mass

ObjectiveTo examine the relationship between different measures of testosterone and estradiol (E2), muscle mass, muscle strength, and physical performance; and to test whether the association of sex hormone level with muscle strength and physical performance was independent of muscle mass.Design and methodsA cross-sectional survey on 1489 community-dwelling men older than 64 years of age. Serum levels of testosterone and E2were measured by mass spectrometry, and sex hormone-binding globulin (SHBG) levels were measured by immunoradioassay. Muscle mass was examined by dual-energy X-ray absorptiometry and physical performance was assessed by hand-grip strength, gait speed, step length and chair-stand test.ResultsAppendicular skeletal mass (ASM) was positively associated with total testosterone (TT;P<0.001), free testosterone (FT;P<0.001), and total E2(P<0.001) but not with free E2(P=0.102). After adjustment for age, serum SHBG and relative ASM, both TT and FT were significantly associated with grip strength, narrow-walk speed and the composite neuromuscular score. Higher total E2, but not free E2was associated with lower grip strength (P<0.05) after adjustment for age, FT, SHBG and relative ASM.ConclusionsTestosterone level was related to both muscle mass, strength and physical performance. Total E2level, though related to muscle mass positively, affected muscle strength adversely in older men.

Download Full-text