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Sex-specific impact of serum testosterone on the risk of atherosclerotic cardiovascular disease

Year: 2025

Type: article

Abstract: BACKGROUND: Testosterone plays multifaceted roles in cardiovascular health. However, the prospective sex-specific impact of serum testosterone on atherosclerotic cardiovascular disease (ASCVD) risk remains unclear. METHODS: This prospective study included 2978 participants (1184 men and 1794 women) with a followed-up 10.66 years. The Cox proportional hazards model was employed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for ASCVD events according to testosterone tertiles. Additionally, structural equation modeling was used to investigate whether hypertension and metabolic factors mediate the association between serum testosterone levels and ASCVD risk. RESULTS: During follow-up, 142 and 203 ASCVD events occurred in men and women, respectively. Compared with participants in the lowest serum testosterone tertile, men in the highest tertile exhibited a reduced ASCVD risk (HR: 0.59, 95% CI: 0.38-0.90), while women in the highest tertile showed an increased risk of ASCVD (HR: 1.79, 95% CI:1.26-2.55). Structural equation modeling revealed that in men, the association between testosterone and ASCVD risk was indirectly mediated by metabolic factors (β = -0.119). Among women, the results indicated a total effect of testosterone on ASCVD risk (β = 0.051), comprising a significant direct positive effect (β = 0.056) and a negative indirect effect mediated by hypertension and metabolic factors (β = -0.005). CONCLUSIONS: Elevated serum testosterone levels are associated with a reduced risk of ASCVD in men but an increased risk in women.

Source: Endocrine Research

DOI: 10.1080/07435800.2025.2606082