Abstract
Despite its widespread clinical use, there is little data available from population-based studies on the determinants of serum sex hormone binding globulin (SHBG). We aimed to examine multifactorial determinants of circulating SHBG levels in community-dwelling men. Study participants comprised randomly selected 35–80 y.o. men (n = 2563) prospectively-followed for 5 years (n = 2038) in the Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. After excluding men with illness or medications known to affect SHBG (n = 172), data from 1786 men were available at baseline, and 1476 at follow-up. The relationship between baseline body composition (DXA), serum glucose, insulin, triglycerides, thyroxine (fT4), sex steroids (total testosterone (TT), oestradiol (E2)), and pro-inflammatory cytokines and serum SHBG level at both baseline & follow-up was determined by linear and penalized logistic regression models adjusting for age, lifestyle & demographic, body composition, metabolic, and hormonal factors. Restricted cubic spline analyses was also conducted to capture possible non-linear relationships. At baseline there were positive cross-sectional associations between age (β = 0.409, p<0.001), TT (β = 0.560, p<0.001), fT4 (β = 0.067, p = 0.019) and SHBG, and negative associations between triglycerides (β = -0.112, p<0.001), abdominal fat mass (β = -0.068, p = 0.032) and E2 (β = -0.058, p = 0.050) and SHBG. In longitudinal analysis the positive determinants of SHBG at 4.9 years were age (β = 0.406, p = <0.001), TT (β = 0.461, p = <0.001), and fT4 (β = 0.040, p = 0.034) and negative determinants were triglycerides (β = -0.065, p = 0.027) and abdominal fat mass (β = -0.078, p = 0.032). Taken together these data suggest low SHBG is a marker of abdominal obesity and increased serum triglycerides, conditions which are known to have been associated with low testosterone and low T4.
Highlights
Sex hormone binding globulin (SHBG) is a circulating homodimeric glycoprotein, primarily synthesised in the liver, that binds circulating sex steroids with high affinity [1, 2]
sex hormone binding globulin (SHBG) was positively associated with age, fT4, TT and E2, and inversely associated with alcohol consumption, smoking, abdominal total fat mass, triglycerides, glucose, insulin, alanine transaminases (ALT) activity, and eSel levels
After adjustment for age, SHBG remained positively associated with fT4, TT and E2 and inversely associated with smoking, abdominal total fat mass, triglycerides, glucose, insulin, ALT activity, interleukin 6 (IL-6), MPO activity and eSel levels
Summary
Sex hormone binding globulin (SHBG) is a circulating homodimeric glycoprotein, primarily synthesised in the liver, that binds circulating sex steroids with high affinity [1, 2]. SHBG has been positively associated with testosterone [11, 15], follicle stimulating hormone [11], serum thyroxine [15], adiponectin [26], olive oil [27], red wine (resveratrol) [28], increasing age [29], physical activity [25] and resistance training [20, 30] These data are derived largely from cross-sectional studies with a variety of limitations including small sample size, non-representative samples, restricted age ranges, limited biochemistry, non-concurrent variables [12, 15, 18, 22, 31] generally leading to inconclusive and inconsistent findings. Recent longitudinal data from the Boston Area Community Health/Bone Survey examining changes in anthropometric measures and sex steroids demonstrated that SHBG at baseline was not associated with changes in any of the included measures of body composition [32] Another recent study (n = 1316) [33] undertook a secondary analysis of serum SHBG determinants. The follow-up period was relatively short, men were all older, and adjustment for confounders was limited [33]
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