Association Between Long-Term Testosterone Exposure and Major Adverse Cardiovascular Events in Aging Men

CONTEXT: Hypogonadism is a common endocrine disorder in aging men, associated with adverse cardiometabolic outcomes. Concerns about the cardiovascular (CV) safety of testosterone, an important therapy option for the condition, may be disproportionately influencing treatment decisions. OBJECTIVE: This work aimed to investigate the association between long-term testosterone therapy and major adverse CV events (MACE) in men aged 51 years and older. METHODS: This retrospective cohort study used linked health data from the National Health Service Greater Glasgow and Clyde population, accessed via the West of Scotland Safe Haven. Men aged 51 years and older as of January 1, 2012, were included. Testosterone exposure was defined as having at least a 2-year interval between the first and last prescription during a 5-year exposure window (2012-2016). Individuals were followed from January 1, 2017, to December 31, 2022. The primary outcome was time to first MACE, defined as a composite of acute myocardial infarction, unstable angina, stroke, heart failure, or CV death. Cox proportional hazards models were used to estimate associations, adjusting for age, ethnicity, socioeconomic deprivation, and comorbidities. RESULTS: The study included 440 testosterone-exposed and 136 051 unexposed men. Testosterone exposure was associated with a 54% increased risk of MACE in the unadjusted analysis (hazard ratio [HR]: 1.54; 95% CI, 1.18-2.00), and a 55% increased risk after adjustment (HR: 1.55; 95% CI, 1.19-2.01). CONCLUSION: In this real-world cohort, long-term testosterone therapy was associated with increased CV risk. While recent trials inform short- to medium-term CV safety, this study underscores the need for more longer-term data to fully ascertain the effect of testosterone therapy.