Men taking testosterone replacement therapy (TRT) for age-related hypogonadism are at an increased risk for ischemic stroke, transient ischemic attack (TIA) and myocardial infarction, especially during their first two years of use, researchers report in the American Journal of Medicine.
Christel Renoux, MD, PhD, of McGill University and the Jewish General Hospital in Montreal, Canada, and colleagues noted that while reported rates of hypogonadism—or low testosterone levels—in men have remained steady for the past 20 years, TRT is increasingly prescribed today to relieve “nonspecific symptoms of aging,” like fatigue and decreased sexual function.
“In addition to the unclear benefits of TRT among aging men with testosterone decline, concerns have emerged as to the cardiovascular and cerebrovascular safety of these medications,” Renoux and co-authors wrote in the journal. “While randomized controlled trials have not been sufficiently powered to detect differences in the rates of adverse vascular events comparing testosterone with placebo, observational studies have generated conflicting findings.”
For their own research, the authors analyzed a database of electronic medical records of patients enrolled in primary care practices throughout the U.K., eventually forming a study cohort of 15,401 men aged 45 and up with hypogonadism. During a combined 71,541 person-years of follow-up, 850 patients experienced an ischemic stroke, TIA or MI.
Compared with men who didn’t use TRT, those who did saw a 21% greater risk of cardiovascular events, corresponding to an additional 128 events. Odds of a CV event were greatest during the first six months of use and declined after around two years.
Renoux et al. also reported that current use of TRT was associated with a decreased risk of mortality in users, while past use was associated with an increased risk. The finding, which the authors called “surprising” given the concurrent increased risk of vascular events, suggests TRT’s protective effect on mortality was likely due to reverse causality.
“The protective effect may 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,” they wrote. “Moreover, TRT may be less frequently initiated among men with a higher baseline risk of mortality, particularly in the elderly, and those who did not receive TRT may have been overall healthier compared with their untreated counterparts.”
The study was limited in that it specifically targeted men with hypogonadism due to aging and not due to known secondary causes.
“Further large and methodologically sound observational studies should be conducted to reaffirm these results,” Renoux and colleagues wrote. “Until such a time, the potential harms of TRT should be critically weighed against its perceived and expected benefits, and caution is warranted when prescribing these medications to aging but otherwise healthy men.”