Advertisements for treatments for “low T,” or low testosterone levels in middle-aged and older men, have led to spikes in demand. But the safety and legitimacy of those testosterone therapies hasn’t been clear.
In a new study published in the New England Journal of Medicine and presented at the Endocrine Society’s annual meeting, researchers provide the most conclusive evidence yet that testosterone treatments appear to be safe for the heart and are not associated with an increased risk of certain heart-related events.
In the study, led by researchers at the Cleveland Clinic, more than 5,200 men ages 45 to 80 were randomly assigned to apply a daily gel containing testosterone, called AndroGel and made at the time by Abbvie (now marketed by Ascend Therapeutics of Besins Healthcare), or a placebo. All of the men had low blood levels of testosterone and reported symptoms as a consequence, including fatigue, low libido, depression, reduced pubic hair, or reduced hair under the arms.
To join the trial, the men also had to have either a history of previous heart disease or at least three risk factors that put them at higher risk of heart disease. That’s because the study was designed to measure any increased risk of heart problems among men using testosterone, and researchers hoped that testing in a more vulnerable population would reveal the strongest potential risk.
After nearly two years of treatment and almost three years of follow up, the men in the testosterone-treated group did not show any increased risk of heart attack, stroke, or death from heart disease.
Read More: The Truth About Low Testosterone
“It was reassuring to see that those patients who we felt like were most likely to have problems did not,” says Dr. A. Michael Lincoff, vice chair of research in cardiovascular medicine at the Cleveland Clinic and first author on the paper. “What we got is what I believe is the definitive answer in this population of patients and this therapy.”
While that’s good news, the study’s senior author, Dr. Steve Nissen, professor of cardiology at Cleveland Clinic, says he’s concerned about how the findings will be interpreted. “I do not want the results of this trial to be used as justification for a large number of men to be treated with testosterone,” he says. “We studied a very specific group of patients with documented low testosterone levels—measured twice, in the morning—and who had symptoms associated with their low testosterone. My take-home message is that for this select group of men, testosterone appears to be safe.”
What concerns Nissen are the large numbers of so-called “low T” clinics that prescribe testosterone, often without even measuring blood levels to determine if the men actually have low testosterone levels or not. These clinics, along with prescriptions for testosterone or androgen replacement, began proliferating in the mid 2000s and early 2010s as a generation of men born in the baby boom of the late 1940s and 1950s reached middle age saw their testosterone levels start to wane. Eager to recapture the muscle mass and energy they had when they were younger, they turned to testosterone as a way to restore their dwindling hormone levels. According to a 2013 study, prescriptions for androgen replacement in the form of gels, patches, or injections among men 40 and older increased more than three times from 2001 to 2011. About 25% of men received these prescriptions without having their testosterone levels checked.
As more men used the hormone therapy, however, reports of side effects, specifically involving the heart, began accumulating. A National Institutes of Health-sponsored study in 2010 found that men with limited mobility who were treated with daily testosterone gel for low blood levels of the hormone had a significantly higher risk of developing heart-related events compared to those receiving a placebo gel. A study involving veterans also found increased risk of heart problems among testosterone users, but another study involving veterans found no increased heart risks associated with the treatments.
Concerned, the U.S. Food and Drug Administration (FDA) convened a panel of experts in 2014 to review the conflicting and available data, and the committee required that testosterone makers conduct a proper clinical trial—which resulted in the new study, funded by a consortium of those manufacturers. The trial needed to compare heart events among men receiving testosterone therapy to those getting a placebo, when neither group knew what they were getting.
The FDA will now take the results and consider whether to modify the label for AndroGel along with other testosterone treatments, which currently carry a warning about the possible risk of heart-related harms.
Modifying that warning may open the door for further abuse of the drug, Nissen fears, especially among those who prescribe it without first measuring testosterone levels. Even if the study did not find an overall increased risk for the heart, the trial did raise questions about possible higher risks of arrhythmias, blood clots, and kidney problems that need further study.
Nissen is also concerned that men taking testosterone may not have their blood levels of the hormone monitored and adjusted properly throughout the course of their treatment. During the study, he said the researchers tested levels regularly and made changes to keep the men from developing excessive levels of testosterone, which can contribute to high cholesterol and increase the risk of heart problems. “There was a considerable amount of dose adjustment that went on in the trial,” he says. “The men didn’t just get a fire-and-forget strategy where they all got the same doses.”
Nissen feels that despite the reassuring results of the study, doctors and their patients, should remember that testosterone should still be prescribed carefully and monitored vigilantly. “Testosterone is a drug that has been misused,” says Nissen. “And I do not want our study to lead to greater misuse.”
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