Ageing men on TRT suffer from greater cardiovascular risk

Testosterone replacement therapy (TRT) may come with an increased risk of cardiovascular events in ageing men with low testosterone levels, a new study has found.

Accessing the UK Clinical Practice Research Datalink, researchers investigated the role of TRT on clinical outcomes in 15,041 men (mean age, 60.4±9.6 years) with low testosterone levels and no evidence of hypogonadotropic or testicular disease. The primary outcome was a composite between ischaemic stroke/transient ischaemic attacks and myocardial infarction.

TRT was prescribed to 4,485 men on at least one occasion, most of whom used testosterone gels/creams (56.8 percent); 33.6 percent received TRT via injections.

Over 71,541 person-years of follow-up, 850 cases of the composite outcome were reported, resulting in a crude incidence rate of 1.19 (95 percent CI, 1.11–1.27) per 100 persons per year. Current TRT use increased the risk of the primary outcome by 21 percent (hazard ratio [HR], 1.21, 1.00–1.46).

In absolute terms, TRT use would account for an adjusted risk difference of 2.4 events per 1,000 persons per year.

Stratified analysis found that this risk peaked in the first 6 months to 2 years of continuous TRT use (HR, 1.35, 1.01–1.79) but tapered thereafter. The effect was also strongest among those aged 45–59 years (HR, 1.44, 1.07–1.92).

Notably, current use significantly reduced the risk of all-cause mortality (HR, 0.64, 0.52–0.78) relative to nonuse of TRT, while past use had the opposite effect (HR, 1.72, 1.21–2.45).

The principal results were robust to sensitivity analyses and remained consistent even after disaggregation according to TRT formulation.