Association between Long-term Testosterone Exposure and Major Adverse Cardiovascular Events in Ageing Men

Context Hypogonadism is a common endocrine disorder in ageing men, associated with adverse cardiometabolic outcomes. Concerns about the cardiovascular safety of testosterone, an important therapy option for the condition, may be disproportionately influencing treatment decisions. Objective To investigate the association between long-term testosterone therapy and major adverse cardiovascular events (MACE) in men 51 years and older. Methods This retrospective cohort study used linked health data from the NHS Greater Glasgow and Clyde (GGC) population, accessed via the West of Scotland Safe Haven. Men aged 51 years and older as of 1 January 2012 were included. Testosterone exposure was defined as having at least a two-year interval between the first and last prescription during a five-year exposure window (2012–2016). Individuals were followed from 1 January 2017 to 31 December 2022. The primary outcome was time to first MACE, defined as a composite of acute myocardial infarction, unstable angina, stroke, heart failure, or cardiovascular death. Cox’s 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 (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). Conclusions In this real-world cohort, long-term testosterone therapy was associated with increased cardiovascular risk. While recent trials inform short- to medium-term cardiovascular safety, this study underscores the need for more longer-term data to fully ascertain the impact of testosterone therapy.