Cardiovascular effects of metformin and testosterone replacement therapy in older men with hormone-related cancers and cancer-free population

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.