Is Testosterone Therapy Safe in Older Men?

Older men without a history of myocardial infarction or stroke who have symptoms of hypogonadism and evidence of low testosterone levels may benefit from testosterone replacement therapy (TRT), suggested new research.

The study’s investigators assessed the records of approximately 83,000 male patients who received treatment at Veterans Health Administration (VHA) facilities between December 1999 and May 2014. Men who achieved normalized testosterone levels after TRT had lower mortality rates and were less likely to suffer heart attacks or strokes than men who did not receive TRT or did not reach normal testosterone levels with the therapy. There was no difference in risks of heart attack and stroke in men who did not achieve normalized testosterone levels or who did not undergo TRT.

Low testosterone is a growing problem that affects an estimated 2.4 million older men in the United States, according to the researchers. Although the FDA has warned against the use of TRT based on age alone, its use has skyrocketed in recent years, raising concerns about its negative impact on mortality rates and cardiovascular health.

Four recent studies that suggested testosterone therapy increased the risk of cardiovascular events contradicted previous research, according to study co-author Dr. Rajat Barua, a practicing cardiologist in the VHA health system and an assistant professor of medicine in the division of cardiovascular diseases at the University of Kansas Medical Center.

“Our study was born out of our own dilemma,” he said. “What do we say to patients who hear this conflicting news and ask about the risks?”

The current findings are consistent with the majority of previous studies, which found that normalization of testosterone levels is associated with lower all-cause mortality and fewer heart attacks and strokes in patients without history of either, said Dr. Barua. “We also showed that simply prescribing TRT is not good enough,” he said. “To achieve mortality and cardiovascular benefits, the patients’ testosterone levels must achieve normal therapeutic range.”

Dr. Barua said health-system pharmacists who ask patients about side-effect-related issues and alert prescribing physicians would “be a great help” to improving care.

“Additionally,” he continued, “if pharmacists have access to patients’ post-treatment testosterone levels, they could alert physicians about low or supra-therapeutic testosterone levels.”

According to FDA estimates, only half of men on TRT need it to treat low testosterone levels and approximately a quarter of men do not have testosterone concentrations tested before initiating the therapy or anytime during the course of treatment. The FDA now mandates that the labeling of TRT warn of increased risks of heart attack and stroke, noted the researchers.

The current findings suggested that the risks and benefits of testosterone replacement therapy depend on the risk profile of the patient rather than the therapy itself, according to Dr. Barua, who said there is a need for appropriate screening, selection, dosing, and follow-up to maximize the benefit of TRT.

“Testosterone therapy is not a fountain youth,” commented Dr. Barua. “Like any other medication, its benefit must be weighed against its side effects and toxicity.”

He said TRT should be reserved for patients with signs and symptoms of androgen deficiency and persistently low testosterone levels.

The authors report no support from industry.

The study was published in the European Heart Journal.

—Dan Cook

Reference:

1. Sharma R, Oni OA, Gupta K, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015 Aug 6. [Epub ahead of print]