The role of sex hormone-binding globulin and testosterone in the risk of incident metabolic syndrome

Aim: The aim of this study was to further evaluate the suggested independent association of sex hormone-binding globulin (SHBG) with incident metabolic syndrome (MetS) in men. Research design and methods: We used data from 1906 men aged 20-79 years from the population-based Study of Health in Pomerania (SHIP). Multivariable logistic regression models were implemented to analyse cross-sectional and longitudinal associations of total testosterone (TT), SHBG, and free testosterone (free T) concentrations with MetS. Furthermore, we associated changes between baseline and follow-up concentrations of TT, SHBG, and free T with incident MetS. Results: Cross-sectional logistic regression models revealed a significant inverse association of TT (odds ratio [OR] per standard deviation [SD] decrease: 1.28; 95% confidence interval (CI): 1.10-1.50), and free T (OR per SD decrease: 1.29; 95% CI: 1.11-1.51), but not SHBG (OR per SD decrease: 1.13; 95% CI: 0.98-1.30) with prevalent MetS. At the 5-year follow-up 1435 men were repeatedly examined and of the 956 men without baseline MetS, 328 men (34.3%) had incident MetS. Longitudinal analyses showed, after adjustment for the respective sex hormone, that lower baseline SHBG (OR per SD decrease: 1.30; 95% CI: 1.03-1.65), but not TT (OR per SD decrease: 1.14; 95% CI: 0.93-1.39) was associated with incident MetS. Change analyses revealed an inverse association between TT change and incident MetS (OR per SD decrease between baseline and follow-up: 1.19; 95% CI: 1.01-1.39), independent of SHBG; whereas SHBG change was not associated with incident MetS until adjustment for TT. Conclusions: Although baseline SHBG predicts incident MetS independent of testosterone, change analyses suggest the testosterone decline as the main driver of the association between sex hormones and MetS.