Cross-sectional association between testosterone, sex hormone-binding globulin and metabolic syndrome: The Healthy Twin Study

Objectives: This study evaluated an association between testosterone, sex hormone-binding globulin (SHBG) and metabolic syndrome (MetS). We also evaluated the genetic and environmental influences on the association. Design: Cross-sectional. Setting: Community-based study. Participants: A total of 1098 Korean adult men including 139 monozygotic twin pairs. Main Outcome Measure: MetS was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (NCEP ATP III) and International Diabetes Federation (IDF) criteria. The associations between MetS and sex hormones were evaluated using linear mixed model and generalized estimating equation model. Results: After considering covariates such as smoking, alcohol consumption and physical exercises as well as SHBG or testosterone, the risk of MetS defined by NCEP ATP III criteria decreased by 31%, 29%, and 48%, respectively, with 1-standard deviation increase in total testosterone (TT), free testosterone (cFT) and SHBG. Similar findings were revealed with IDF criteria. Metabolic component specific analysis showed that sex hormones were inversely associated with several components of MetS: TT with abdominal obesity, low high-density lipoprotein cholesterol (HDL-C) and high blood pressure; cFT with abdominal obesity and high blood pressure; SHBG with all components except high blood pressure. Cotwin control analysis found an inverse correlation between within-pair differences in testosterone and SHBG levels and within-pair differences in waist circumference only. Conclusion: Both testosterone and SHBG were inversely associated with MetS although the inverse associations with the sex hormones were not consistently found across individual metabolic components. Findings from cotwin analysis suggest a significant contribution of unshared unique environmental effect to the association between testosterone and SHBG and abdominal obesity.