Ann Epidemiol. 2025 Dec 5:S1047-2797(25)00352-7. doi: 10.1016/j.annepidem.2025.12.004. Online ahead of print.
ABSTRACT
PURPOSE: This study examines the association between use of metformin and testosterone replacement therapy (TTh) with risk of cardiovascular disease (CVD) and its subcategories in the overall population, hormone-related cancer (HRC) survivors, and cancer-free population.
METHODS: A retrospective cohort of 58,028 men ≥65 years was identified using SEER-Medicare 2007-2015 data. Metformin and TTh prescriptions were ascertained for this analysis. The primary outcome was incident composite CVD and CVD subcategories (heart failure [HF], ischemic heart disease [IHD], peripheral arterial disease [PAD], and stroke). Multivariable time-dependent Cox proportional hazard models were conducted.
RESULTS: Metformin use was inversely associated with CVD in the overall population (Hazard Ratio [HR] = 0.72, 95% CI, 0.68 - 0.76), cancer-free population (HR = 0.72, 95% CI, 0.68 - 0.76), and HRC survivors (HR = 0.67, 95% CI, 0.64 - 0.73). Likewise, TTh use was inversely associated with CVD in overall population (HR = 0.82, 95% CI, 0.67 - 0.99), cancer-free population (HR = 0.80, 95% CI, 0.64 - 0.99), and HRC survivors (HR = 0.64, 95% CI, 0.48 - 86).
CONCLUSIONS: Metformin and TTh were inversely associated with CVD among older men in the overall population, HRC survivors, and cancer-free populations. Metformin users showed the greatest CVD risk reduction. Further studies are warranted to confirm these associations.
PMID:41354168 | DOI:10.1016/j.annepidem.2025.12.004