From the Journals

Increased cardiovascular risk seen early on with testosterone replacement therapy



Testosterone replacement therapy is associated with an increased risk of cardiovascular and cerebrovascular events in older men, particularly during the first 2 years of use, a study in the American Journal of Medicine has found.

Simone Y. Loo of the Lady Davis Institute for Medical Research at the Jewish General Hospital in Montreal and colleagues looked at a cohort of 15,401 men aged 45 years or older with low testosterone levels, of whom 4,485 (29.1%) were prescribed testosterone replacement therapy on at least one occasion during a mean follow-up of 4.7 years. They saw that individuals who were currently using testosterone replacement therapy had a 21% increase in the risk of the composite outcome of ischemic stroke, transient ischemic attack, or myocardial infarction, compared with those who had not had hormone therapy.

In the first 6 months to 2 years after initiation of continuous treatment, the risk was even higher – at 35% – and was particularly high in individuals aged 45-59 years (at 44%).

However, the study also noted a significant 36% reduction in the risk of all-cause mortality in individuals currently using testosterone replacement therapy and a significant 28% higher risk of all-cause mortality in past users, compared with nonusers.

Concerns about the safety of testosterone replacement therapy had previously been kindled by the outcomes of the Testosterone in Older Men trial, which was stopped early because of the higher number of cardiovascular events in the treatment group. However, other randomized controlled trials have not seen that effect, the authors said.

They noted that the protective effect of current hormone replacement use on mortality was surprising, but suggested it could be the result of reverse causality, “in which physicians may discontinue TRT based on perceived deterioration of health or imminent death, because TRT is not a vital medication.”

“Moreover, TRT may be less frequently initiated among men with a higher baseline risk of mortality, particularly in the elderly, and those who received TRT may have been healthier overall, compared with their untreated counterparts,” the authors wrote.

Despite this, they suggested that larger observational studies were still needed to investigate the potential harms of testosterone replacement therapy. In the meantime, they advised that potential harms should be weighed against perceived benefits and caution be applied to prescribing.

The study was supported by the Canadian Institutes of Health Research. No conflicts of interest were reported.

SOURCE: Loo S et al. Am J Med 2019 Apr 3. doi: 10.1016/j.amjmed.2019.03.022.

Next Article: