Is treating “low T” really safe and effective?

An ongoing pharmaceutical marketing blitz promises that treating “low T” with a daily prescription testosterone boost will make men with age-related decline in this hormone feel more alert, energetic, mentally sharp, and fully functional in the bedroom. But in an article published this week in the Perspectives section of The New England Journal of Medicine, a group of FDA scientists reiterated concerns over the widespread use of testosterone supplements in light of unresolved controversies over its effectiveness and long-term safety.

Is testosterone replacement therapy (TRT) delivering what these men expect it to? Dr. Christine P. Nguyen, one of the authors of the article, says we just don’t know yet. “The benefits of testosterone therapy have not been confirmed for the treatment of men who have low testosterone levels due to aging, even if there are symptoms that seem related to the low testosterone,” she says.

The testosterone boom

As the debate over safety and effectiveness smolders, the testosterone business is still booming. In 2013, 2.2 million American men were on prescription testosterone, and 80% of them were ages 40 to 74. Some suffer from verifiable medical problems that cause testosterone levels to plummet, like malfunctioning testes or pituitary gland tumors. No one disputes that these cases of “classical hypogonadism” warrant testosterone therapy (especially if the man starts to lose his hair and have hot flashes).

However, for most men on TRT, this is not the case. “The vast majority of men getting testosterone prescriptions today are middle-aged and older men with testosterone levels at the low end of the normal range, or just slightly below the low end of the normal range,” says Dr. Shalender Bhasin, a prominent testosterone researcher at Harvard-affiliated Brigham and Women’s Hospital. “It’s for that population that we don’t have clear evidence of either benefit or safety.”

Safety concerns

Concerns about whether testosterone supplements are safe for the heart recently moved the FDA to require stronger warning labels on these products. But overall, the evidence for long-term risks is mixed. Some studies have found that men on testosterone have fewer heart attacks, strokes, and deaths from heart disease. Other studies have found a higher cardiac risk.

Frustratingly, there has been no study to date designed to conclusively answer this basic question. “There is a hint that [men] may be at increased cardiovascular risk, but it’s not conclusive by any means,” Dr. Bhasin says.

Filling the gap

To explore the safety issue in typical TRT users, Dr. Bhasin and his colleagues studied a group of about 300 men, ages 60 and older, whose testosterone levels were either at the low end of the normal range for healthy adult men or slightly below that. The men were assigned at random to rub on either testosterone gel or a placebo gel every day. The team reported its findings August 11 in the Journal of the American Medical Association.

During and after the study, the researchers used various tests to examine the men for atherosclerosis, or hardening of the arteries — a common cause of heart attacks and other cardiovascular problems. Over three years of TRT use, the men’s arteries showed no worsening of atherosclerosis. In addition, researchers used surveys to find out if the men thought their sexual function or general quality of life improved on TRT. The surveys revealed no improvements.

Dr. Bhasin emphasizes that this study is not proof that TRT is safe for the heart; that would require a larger and longer study. But at least in this group of typical TRT users, boosting testosterone did not produce some of the key benefits promised to men.

What should men do?

It’s especially important for men experiencing possible signs of testosterone deficiency to get a thorough evaluation before opting for a supplement. The American Endocrine Society guidelines for testosterone use, which Dr. Bhasin helped to create, lay out the basics of good practice.

The guidelines, released in 2010, highlight a number of clear-cut “red flags” of hypogonadism, including low libido, erectile dysfunction, low sperm count, loss of body hair, and hot flashes. Additional, more general signs that might suggest hormone deficiency are poor concentration and memory; feeling sad or blue; insomnia; decreased energy, motivation, initiative, or self-confidence; decreased muscle mass and increased body fat; and diminished physical or work performance.

However, most of these symptoms of testosterone deficiency are also common in older men who have normal testosterone levels, so “low T” cannot be diagnosed based solely on symptoms. You also need testing to confirm that your testosterone is low. But the tests themselves can be unreliable and tricky to interpret, so testosterone blood levels need to be evaluated carefully, with tests on more than one day, as well as tests for levels of other hormones related to testosterone. “The workup is not that expensive,” Dr. Bhasin says. “It’s not like it costs thousands of dollars. Despite that, testosterone is being prescribed somewhat indiscriminately.”

Indeed, a study in the September 2015 issue of the journal Medical Care found troubling signs of improper prescribing testosterone in the VA medical system. Of nearly 112,000 new testosterone prescriptions given to men between 2009 and 2012 at VA outpatient clinics, 16.5% of men got no testosterone measurement at all. Worse, some men got testosterone prescriptions even though they had medical conditions, like prostate cancer, that would usually bar the use of hormone supplements.

“Men want a thoughtful discussion of the risks and benefits, and physicians can guide them appropriately based on the guidelines,” Dr. Bhasin says. “Patients come to you for help with their symptoms, but I’ve never had a situation in which they walked away because I declined to give them testosterone.”