Testosterone, sex hormone-binding globulin and the metabolic syndrome: A systematic review and meta-analysis of observational studies

Background: Accumulating evidence suggests a sex-dependent role of circulating testosterone in the metabolic syndrome (MetS). Methods:: We conducted a meta-analysis of observational studies (PubMed and EMBASE-1 May 2010) relating MetS to determinants of testosterone status [total testosterone (TT), free testosterone (FT) and sex hormone-binding globulin (SHBG)]. Results: A total of 52 studies were identified, comprising 22 043 men and 7839 women and presenting relative risk (RR) estimates or hormone levels for subjects with and without MetS. Endogenous TT and FT levels were lower in men with MetS [TT mean difference =-2.64 nmol/l, 95% confidence interval (CI) -2.95 to -2.32; FT standardized mean difference=-0.26 pmol/l, 95% CI -0.39 to -0.13] and higher in women with MetS (TT mean difference =0.14 nmol/l, 95% CI 0.07-0.20; FT standardized mean difference =0.52 pmol/l, 95% CI 0.33-0.71) compared with those without. Similarly, men with higher TT levels had a lower MetS risk (RR estimate=0.38, 95% CI 0.28-0.50) whereas higher TT levels increased the risk of MetS in women (RR estimate=1.68, 95% CI 1.15-2.45). In both sexes, higher SHBG levels were associated with a reduced risk (men: RR estimate=0.29, 95% CI 0.21-0.41; women: RR estimate=0.30, 95% CI 0.21-0.42). Conclusion: This meta-analysis supports the presence of a sex-dependent association between testosterone and MetS: TT and FT levels are lower in men with MetS, whereas they are higher in women with MetS. There are no indications for a sex-specific association between SHBG and MetS. In both men and women, MetS is associated with lower SHBG levels.