ArticleEndocrine2025
Total and free testosterone as independent predictors of metabolic syndrome in U.S. Men: evidence from NHANES.
Article in Endocrine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeTestosterone deficiency has been linked to cardiometabolic dysfunction, yet the extent to which circulating testosterone is independently associated with metabolic syndrome (MetS) remains debated. We examined the relationship between total testosterone (TT), calculated free testosterone (cFT), and MetS in a nationally representative cohort of U.S. men, and explored clinically relevant threshold values.
methodsWe analyzed data from 2,934 men aged ≥ 18 years across five NHANES cycles (1999–2016). TT was measured by isotope dilution liquid chromatography–tandem mass spectrometry; cFT was calculated using the Vermeulen equation. MetS was defined according to ATP III criteria. Multivariate logistic regression models adjusted for demographic and lifestyle factors, physical activity, and body mass index (BMI) were applied. Receiver operating characteristic (ROC) curves were used to identify discriminatory thresholds.
resultsThe prevalence of MetS was 20.2%. Men with MetS had significantly lower TT, cFT, and SHBG (all p < 0.0001). In fully adjusted models, each 1 nmol/L decrease in TT was associated with higher odds of MetS (OR 1.10; 95% CI 1.08–1.13; p < 0.001), as was each 10 pmol/L decrease in cFT (OR 1.05; 95% CI 1.04–1.07; p < 0.001). ROC analysis suggested TT < 12.6 nmol/L (AUC 0.72; 95% CI 0.70–0.74) and cFT < 293 pmol/L (AUC 0.67; 95% CI 0.64–0.69) as potential thresholds.
conclusionBoth TT and cFT are inversely associated with MetS in U.S. men, independent of obesity and lifestyle factors. Thresholds above conventional hypogonadism cut-offs indicate that testosterone decline within the low-normal range may already be associated with increased cardiometabolic risk.
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