Background:
The role of testosterone in metabolic syndrome (MetS) etiology is receiving increasing attention, given the overlap of testosterone deficiency and MetS in ageing men. We conducted an individual participant data (IPD) meta-analysis to examine this association in a uniform way and to produce more precise estimates of risk overall and in certain subgroups.
Methods:
Individual participant data of 20 observational studies including 12,811 men (mean age: 58.6 ± 15.6 years) were pooled and cross-sectional as well as prospective associations between total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (FT) and MetS were assessed. We calculated odds ratios (ORs) and hazard ratios (HRs) by study-specific quartiles of sex hormones using mixed effects models (with random effects at the study level) and tested for effect modification by age and body mass index (BMI).
Results:
Cross-sectional analyses revealed that men with low concentrations of TT, SHBG or FT were more likely to have MetS. ORs for the lowest versus highest quartile were 4.56 (95% CI 4.02-5.16) for TT, 5.26 (95% CI 4.49-6.17) for SHBG and 2.18 (95% CI 1.88-2.53) for FT. Associations were attenuated but remained significant after adjustment for BMI and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)). Prospective analyses yielded similar results, but of smaller magnitude (HRs for the lowest versus highest quartile were 2.00 (95% CI 1.57-2.56) for TT, 2.71 (95% CI 1.99-3.70) for SHBG and 1.41 (95% CI 1.04-1.92) for FT). Stratified analyses revealed significant interactions by age and BMI, such that associations were strongest in young and nonobese men. Sex hormone concentrations decreased gradually with increasing number of MetS components and, for single components, were most strongly associated with abdominal obesity and hypertriglyceridemia.
Conclusion:
This meta-analysis of pooled individual data shows a robust, dose-response relationship of testosterone and SHBG concentrations with prevalent and incident MetS in men. The strong associations with abdominal obesity and hypertriglyceridemia provide insight into the underlying biological mechanisms.
Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies
