For aging men with low testosterone levels, testosterone replacement therapy (TRT) may increase the risk of cardiovascular events, especially in the first two years of use, according to a study published in the September issue of The American Journal of Medicine.

Simone Y. Loo, from the Lady Davis Institute for Medical Research at Jewish General Hospital in Montreal, and colleagues formed a cohort of 15,401 men, aged 45 years or older, with low testosterone levels and no evidence of hypogonadotropic or testicular disease between 1995 and 2017. Hazard ratios were assessed for a composite of ischemic stroke/transient ischemic attack and myocardial infarction for those with TRT use versus nonuse.

The researchers found that 850 patients experienced an ischemic stroke/transient ischemic attack/myocardial infarction during 71,541 person-years of follow-up (crude incidence ratio, 1.19 per 100 persons per year). Current TRT use correlated with increased risk of the composite outcome compared with nonuse (hazard ratio, 1.21; 95 percent confidence interval, 1.00 to 1.46). The highest risk was seen in the first six months to two years of continuous TRT use and among men aged 45 to 59 years (hazard ratios, 1.35 [95 percent confidence interval, 1.01 to 1.79] and 1.44 [95 percent confidence interval, 1.07 to 1.92], respectively).

"There is limited evidence on the long-term clinical benefits of TRT to effectively treat the modestly declining levels of endogenous testosterone levels of aging but healthy men," a coauthor said in a statement. "We strongly recommend that clinicians proceed with caution when considering prescribing TRT, and first discuss both the potential benefits and risks with patients."

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