Objective: Variation in circulating sex hormone binding globulin (SHBG) levels are subject to regulation from a variety of hormonal, metabolic, nutritional, and genetic factors. Data on the regulation of male SHBG levels have largely been derived from epidemiological studies, with notable design limitations (e.g. smaller, non-representative samples, age ranges, limited control of related covariates, and cross-sectional design).
Material and Methods: SHBG (measured by chemiluminescent immunoassay) was examined in relation to body composition (DEXA), metabolic state (glucose, insulin, triglycerides), thyroid hormones (thyroxine (fT4)), sex steroids (testosterone (T), oestradiol(E2)), pro-inflammatory cytokines (Il-6, TNF-α, MPO & eSel), and socio-demographic, lifestyle, and other health-related factors at baseline and after 5 years in a randomly-selected cohort of community-dwelling men aged 35-80 at enrolment (n=2563). After excluding men with illness or on medications known to affect SHBG (n=220), data from 1738 men were available at baseline and 1428 at follow-up. Multiple stepwise linear regression models were used to estimate the cross-sectional and longitudinal determinants of SHBG.
Results: At baseline, there were independent positive associations between SHBG and age (β=.220, p=.000), T (β=.434, p=.000) and inverse associations between SHBG and triglycerides (β=-.099, p=.023) and E2 (β=-.119, p=.003), with no significant relationships, observed for smoking, physical activity, abdominal fat mass, insulin, glucose, ALT, fT4, IL6, TNF-α, MPO or eSel. Longitudinal multi-adjusted analyses revealed an inverse association of change in SHBG levels with baseline triglycerides (β=-.125, p=.000), abdominal fat mass (β=-.103, p=.006), and positive associations between SHBG and age (β=.404, p=.000), physical activity (β=.065, p=.043), fT4 (β=.091, p=.005) and T (β=.567, p=.000), with no significant effect observed for smoking, insulin, glucose, ALT, E2, IL6, TNF-α, MPO or eSel.
Conclusion: SHBG has an inverse relationship with triglycerides and a positive relationship with serum testosterone in community-dwelling men. SHBG levels reflects the metabolic state, in particular factors relating to lipid metabolism.