Testosterone, Sex Hormone-Binding Globulin and Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

Endogenous sex hormones are associated with the risk of diabetes and metabolic syndrome. Recent studies suggested the role of these hormones in nonalcoholic fatty liver disease (NAFLD). We conducted a systematic review and meta-analysis of observational studies investigating the association between sex hormones and NAFLD. A comprehensive search of the databases of the MEDLINE and EMBASE was performed from inception through April 2016. The inclusion criterion was the observational studies that assessed the association of serum total testosterone (TT) and sex-hormone binding globulin (SHBG) and NAFLD. We calculated pooled effect estimates of TT and SHBG with 95% confidence intervals (CI) comparing between subjects with and without NAFLD by using random-effects model. Sixteen trials comprising 13,721 men and 5,840 women met the inclusion criteria. TT levels were lower in men with NAFLD (MD = -2.78 nmol/l, 95%CI -3.40 to -2.15, I2 = 99%) than in those without. Men with higher TT levels had lower odds of NAFLD whereas higher TT levels increased the odds of NAFLD in women. In both sexes, SHBG levels were lower in patients with NAFLD than controls and this inverse association was stronger in women than men and higher SHBG levels were associated with reduced odds of NAFLD. Our meta-anal-ysis demonstrated a sex-dependent association between TT and NAFLD. Lower TT levels are associated with men with NAFLD and inversely associated with women with NAFLD, whereas higher SHBG levels are associated with lower NAFLD odds in both men and women.