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Purpose <p>Testosterone 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.</p> Methods <p>We 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.</p> Results <p>The prevalence of MetS was 20.2%. Men with MetS had significantly lower TT, cFT, and SHBG (all <i>p</i> &lt; 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; <i>p</i> &lt; 0.001), as was each 10 pmol/L decrease in cFT (OR 1.05; 95% CI 1.04–1.07; <i>p</i> &lt; 0.001). ROC analysis suggested TT &lt; 12.6 nmol/L (AUC 0.72; 95% CI 0.70–0.74) and cFT &lt; 293 pmol/L (AUC 0.67; 95% CI 0.64–0.69) as potential thresholds.</p> Conclusion <p>Both 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.</p>

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Total and free testosterone as independent predictors of metabolic syndrome in U.S. Men: evidence from NHANES

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Daniele Tienforti,
  • Federica Antolini,
  • Luca Spagnolo,
  • Claudio Capuano,
  • Elisabetta Perfetto,
  • Marco Giorgio Baroni,
  • Arcangelo Barbonetti

摘要

Purpose

Testosterone 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.

Methods

We 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.

Results

The 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.

Conclusion

Both 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.