Higher Circulating Testosterone Linked to Higher Coronary Artery Disease (CAD) Risk in Men: Mendelian Randomization and Survival Analyses
Authors' conclusion
These data suggest that increased testosterone may increase the risk of cardiovascular disease and that this safety concern should be a focus in future clinical trials for testosterone supplementation.
Study context
- Population
- European ancestry adults from the UK Biobank (testosterone genetic instrument) and 1,165,690 individuals in CARDIoGRAMplusC4D (CAD summary statistics); longitudinal cohort of men aged 40 to 69UK Biobank
- Participants
- 425,097 adults
- Exposure
- Higher vs lower genetically predicted circulating testosterone
- Outcome
- CAD as defined in CARDIoGRAMplusC4D
Methodological detailslongitudinal observational analyses
- Longitudinal observational analyses
Main finding
As reported in the abstract
CAD risk per higher genetically predicted circulating testosterone
Odds ratio (95% CI)P value
Men
1.17(1.07–1.27)
P = 3.32 × 10-4Womenno evidence of an effect
1.01(0.94–1.10)
P = 0.73Per higher genetically predicted circulating testosterone, as printed
Observational data: associations, not effects.
Further findings
Mediation in men
- The genetic association in men appeared to be mediated by higher blood pressure
Measured circulating testosterone and CAD in men (longitudinal observational)
- Directionally opposite association observed in men, likely due to confounding by T2D and BMI
Original publication
Higher Circulating Testosterone Linked to Higher CAD Risk in Men: Mendelian Randomization and Survival Analyses. J Clin Endocrinol Metab. Published 24 October 2025. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →