This heightened risk seems to peak in the first two years of use, reports a study due to be published in The American Journal of Medicine.

The findings confirm concerns voiced by many health agencies about the potential risks associated with the treatment. 

The study analysed a large 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 low testosterone levels (hypogonadism).

Users of TRT had a 21 per cent greater risk of cardiovascular events compared with nonusers, 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.” 

Dr. Christel Renoux of McGill University in Canada said: “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. 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. We strongly recommend that clinicians proceed with caution when considering prescribing TRT and first discuss both the potential benefits and risks with patients.”

The study specifically aimed to study men with low testosterone levels due to aging and not due to known secondary causes.

While reported rates of hypogonadism have remained stable, prescriptions for TRT have soared in the last 20 years, TRT is increasingly prescribed to relieve nonspecific symptoms of aging, such as fatigue and a modest decline in sexual functioning.

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 analysis did have access to the patients’ prior histories and was able to adjust for comorbidities. 

“Further large and methodologically sound observational studies should be conducted to reaffirm these results. Until such time, the potential cardiovascular risk of TRT should be weighed against the perceived and expected benefits among aging men, a perspective that aligns with warnings issued by health agencies,” advised Dr. Renoux.

This study will be published in the September 2019 issue of the American Journal of Medicine.