The findings of plaque were not a complete surprise; many reports have tied testosterone use to an increase in heart attacks, and the Food and Drug Administration already requires testosterone products to carry warnings of an increased risk of heart attacks and stroke (men at high risk of cardiovascular disease were not allowed to participate in the latest trials). But observational studies, which are weaker, have yielded mixed results over all, with one study published last month finding that men taking testosterone actually had fewer heart problems.
Only about 15 percent of men 65 and over have the low testosterone levels studied in the recent trials. Most men experience only slight declines in testosterone as they age, so the trial results are not necessarily applicable to the general population of older men.
The findings are a follow-up to an earlier report from last year that found testosterone improved sexual function in older men with low levels of the hormone, though the bump was modest and waned over time. The researchers even noted that for erectile function, drugs like Viagra are more effective. Testosterone didn’t help older men walk farther, they found, and it didn’t temper fatigue or increase men’s sense of vitality, though it did improve mood slightly.
“Testosterone is clearly not a panacea,” said Dr. Thomas Gill, a geriatrician at Yale School of Medicine who was one of the study’s authors and ran one of the clinical trial sites. “It’s not an agent that’s going to restore the fountain of youth. The benefits are modest, even when they are favorable.”
Dr. David J. Handelsman, director of the Anzac Research Institute in Sydney, Australia, who wrote an editorial accompanying the publication of the latest trials and who was not involved in them, was more somber in his assessment.
“What you see in these testosterone trials is an ominous portent of cardiovascular disease, although it remains a prediction, not a fact,” Dr. Handelsman said in an interview. He noted that older men with low testosterone levels often have other chronic health conditions, like obesity, that can affect hormone levels but that can be managed by lifestyle factors like diet and exercise.
Testosterone has been available as a drug for so long that it was never subjected to clinical trials of safety and efficacy as most new drugs are today. Nor has it been tested in large government-sponsored trials lasting many years, like the one of hormone replacement therapy for older women that found hormones did not prevent heart disease in postmenopausal women and actually posed serious risks.
Larger and longer-term studies would be needed to further assess testosterone’s safety, because the latest studies, called the T trials, followed men for only a year, too short a time to determine whether testosterone increases the risk of problems like heart disease or prostate cancer.
The T trials “didn’t answer the question of risk,” said Dr. Evan Hadley, director of the division of geriatrics and clinical gerontology at the National Institute on Aging. “We’ve gotten a lot more data on benefits, but benefit trials alone would not answer all the questions about use of testosterone therapy. It’s very important to get definitive data on risk so we have the whole picture of risk and benefit.”
But the results do not support the promise implied by advertisements for testosterone that using it “will make you stronger and fitter,” he said, though many men said they simply “felt better” while on the drug, and some improvements in walking could be seen when the findings were analyzed differently.
Testosterone prescriptions in the United States nearly doubled in recent years to 2.2 million in 2013, up from 1.2 million three years earlier, as more and more healthy middle-aged and older men started taking it. Many of them did not have the kind of medical conditions, like genetic defects, chemotherapy or problems with the hypothalamus and pituitary glands in the brain, that make men unable to produce sufficient hormone on their own. Many younger men also take the hormone for bodybuilding purposes.
Using testosterone for bodybuilding or for normal age-related declines in hormones is not approved by the F.D.A., but physicians are allowed to prescribe drugs for nonapproved reasons, a practice called “off-label use.”
The F.D.A. has told drug manufacturers that sell testosterone that any larger studies must be carried out at their own expense. A spokeswoman for AbbVie, which makes AndroGel and provided the testosterone gel for the latest trials, said manufacturers are working with the agency to design such a trial.
“I think these results are more than sufficient to warrant a longer trial,” said Dr. Peter Snyder, an endocrinologist and professor of medicine in the Perelman School of Medicine at the University of Pennsylvania and principal investigator of the T trials.