TRT can increase risk of stroke, heart attack

Researchers have found that ageing men who take testosterone replacement therapy (TRT) are at a slightly greater risk of experiencing an ischemic stroke, transient ischemic attack (TIA) or myocardial infarction — especially during the first two years of use. Their study has been published in The American Journal of Medicine.

TRT is increasingly prescribed to relieve non-specific symptoms of ageing, such as fatigue and a modest decline in sexual functioning. And so while reported rates of low testosterone levels (hypogonadism) have remained stable, prescriptions for TRT have soared in the last 20 years.

With this in mind, researchers from Canada’s Jewish General Hospital and McGill University analysed a database of electronic medical records of patients enrolled in primary care practices in the UK and formed a cohort of 15,401 men, aged 45 years or older, with hypogonadism. Their study specifically aimed to study men with low testosterone levels due to ageing and not due to known secondary causes.

The study found that users of TRT had a 21% greater risk of cardiovascular events compared with non-users, corresponding to an additional 128 events. The increased risk appears to be transient, declining after two years of TRT use, which the investigators attribute to a phenomenon called ‘depletion of susceptibles’.

“Our findings show that the use of TRT was associated with an increased risk of stroke, TIAs or cardiac arrest during the first two years of use,” said Dr Christel Renoux, corresponding author on the study.

An interesting finding was that current use of TRT was associated with a decreased risk of overall mortality and past use with an increased risk. While this could indicate some protective effect on mortality, it could also be due to reverse causality, with clinicians discontinuing TRT treatment in patients with deteriorating health. The researchers did have access to the patients’ prior histories and were able to adjust for comorbidities.

Dr Renoux acknowledged that further studies should be conducted to reaffirm the results. “Until such time,” she said, “the potential cardiovascular risk of TRT should be weighed against the perceived and expected benefits among ageing men — a perspective that aligns with warnings issued by health agencies.

“There is limited evidence on the long-term clinical benefits of TRT to effectively treat the modestly declining levels of endogenous testosterone levels of ageing but healthy men. 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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