Cardiovascular and Cerebrovascular Safety of Testosterone Replacement Therapy Among Aging Men with Low Testosterone Levels: A Cohort Study.

PURPOSE

We assessed the risk of ischemic stroke, transient ischemic attack, and myocardial infarction associated with testosterone replacement therapy (TRT) among aging men with low testosterone levels.

METHODS

Using the UK Clinical Practice Research Datalink, we formed a cohort of men aged 45 years or older with low testosterone levels and no evidence of hypogonadotropic or testicular disease, between 1995 and 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) of a composite of ischemic stroke/transient ischemic attack and myocardial infarction were estimated using time-dependent Cox proportional hazards models, comparing current use of TRT with nonuse.

RESULTS

The cohort included 15,401 men. During 71,541 person-years of follow-up, 850 patients experienced an ischemic stroke/transient ischemic attack/myocardial infarction (crude incidence rate 1.19 [95% confidence interval (CI), 1.11-1.27] per 100 persons per year). Compared with nonuse, current use of TRT was associated with an increased risk of the composite outcome (HR 1.21; 95% CI, 1.00-1.46). This risk was highest in the first 6 months to 2 years of continuous TRT use (HR 1.35; 95% CI, 1.01-1.79), as well as among men aged 45-59 years (HR 1.44; 95% CI, 1.07-1.92).

CONCLUSIONS

TRT may increase the risk of cardiovascular events in aging men with low testosterone levels, particularly in the first 2 years of use. In the absence of identifiable causes of hypogonadism, TRT should be initiated with caution among aging men with low testosterone levels.