More than a million men have smeared testosterone gels on their bodies in recent years, hoping it will rejuvenate them, energize them, and increase their libido. But until now, there has never been a rigorous study asking if there were any real benefits to testosterone therapy for healthy men with so-called “low T.”
The first results of such research were published Wednesday in The New England Journal of Medicine. Although it found at best modest benefits, mostly in sexual functioning, it is a said Dr. Eric S. Orwoll, a professor of medicine at Oregon Health and Science University, because it provides the first credible data on testosterone’s effects on some of the problems it is thought to resolve.
Some doctors said they hoped the modest results might bring some sanity to the testosterone frenzy of recent years. “Frankly,” said Dr. Sundeep Khosla, a dean at the Mayo Clinic College of Medicine, “there is a lot of abuse.” Men lured by advertisements seek the drug, and Dr. Khosla said he had heard of doctors who prescribed it without first measuring the man’s testosterone levels to see if they were low.
“What I hope is that this will bring a more conservative approach,” Dr. Orwoll said. “There is a lot of prescribing out there, and it doesn’t look like, for the average man, it will have a big effect.”
The study, led by the Perelman School of Medicine at the University of Pennsylvania and funded by the National Institutes of Health and AbbVie, the maker of the testosterone gel AndroGel, nvolved 790 men 65 and older with low testosterone levels for their age.
Testosterone levels normally fall as men age, but these men had levels on the low end — below 275 nanograms per deciliter of blood. Some of the men said they had lost their sexual drive, others said they were walking much slower than they used to, and others said they just felt blah, as if they had lost their zest for life. The men were randomly assigned to use AndroGel or a placebo for a year.
As expected, the men who used AndroGel ended up with markedly higher testosterone levels — those of men 19 to 40. But the question the researchers wanted to know was: Did they feel or act any differently?
Men who had said their sexual functioning had been flagging reported moderate increases in their interest in sex and in their performance, although when it came to erections, a drug like Viagra or Cialis would be more effective, the researchers reported. Those who said they felt blue reported a small improvement in mood. But the drug had no discernible effect on vitality or walking speed in men with those complaints.
The study was too small and short-term to address another longstanding question about testosterone gels: whether using them increases the risk of heart disease and prostate cancer and other conditions. And that, said Dr. Richard J. Hodes, the director of the National Institute on Aging, was deliberate.
About 15 years ago, worried about soaring numbers of men using testosterone gels, Dr. Hodes and administrators at the Department of Veterans Affairs suggested a huge clinical trial that would involve thousands of men, go on for years and find out definitively what the risks and benefits of testosterone treatment were. But the plan ran into resistance.
There were real hazards to men participating, critics said. Not just risk of cancer and, it later emerged, the possibility of heart disease, but an issue with P.S.A. tests, the blood examinations used to screen for prostate cancer. Testosterone increases P.S.A. levels. Men with high levels usually get biopsies of their prostates to look for cancer. But in a large clinical trial, investigators do not know who is getting the drug and who is getting a placebo. So thousands of men taking testosterone could end up with biopsies resulting solely from P.S.A. levels that were raised by the drug, not by cancer.
Dr. Hodes turned to the Institute of Medicine for guidance. A group of medical experts there advised starting small. Do a study, they said, that first asks if there is any benefit to testosterone in older healthy men with low levels of the hormone. If there is no benefit, why do a trial?
The new study is the result. It also had a few additional outcomes for which data is still being analyzed, including whether testosterone would help with anemia by increasing production of red blood cells, and whether it increased or stabilized bone density and strength, as measured by a scan. Researchers are also asking if it has an effect on mental functioning. And they are asking if it has an effect on plaque in coronary arteries as measured by a heart scan.
The testosterone gels used by the men in the study are not as powerful as the very high doses of testosterone and similar hormones that some bodybuilders and athletes have injected to grow muscle and improve performance.
Some men with serious medical conditions that deplete their bodies of testosterone use the hormone as therapy and that practice is not in question, researchers said. At issue is the men whose testosterone levels dropped simply because they grew older.
For David Bostick, a 71-year-old Pittsburgh man who participated in the study, the appeal of testosterone was that it might help with his sluggish feeling and reduced libido. After a few weeks of smearing a gel — he did not know if it was AndroGel or a placebo — on his stomach, he began to feel different, with more sexual desire and more energy. He guessed he must be receiving testosterone. When the study ended, he saw his primary care doctor and obtained a prescription for AndroGel. He knew there were possible risks but, he said, “I made an informed decision to take it.” On Saturday, he received a letter from the study finally telling him what was in the gel he had used. It was testosterone.
But concern over risks persists. Last summer, the Food and Drug Administration announced that it asked makers of testosterone gels to conduct a large clinical trial to assess whether there were heart risks with the drugs. The companies are working on designing it, said Morry Smulevitz, a spokesman for AbbVie.
For now, doctors are divided on whether to stress the study’s finding that the gel has some benefits or to stress the fact that the benefit is small and the risks unknown.
Dr. William Bremner, a professor of medicine at the University of Washington, said that now, armed with solid, if short-term data, he can say to men who have demonstrably low testosterone levels that treatment, “is a reasonable thing to think about doing.”
Dr. Joel Finkelstein, a professor of medicine at Harvard, was less sanguine. “Testosterone is clearly not a panacea,” he said. He worries about the lack of data on long-term risks and worries about encouraging large numbers of men to take a drug without knowing answers. For now, he would like to know more about who might respond in order to avoid exposing huge numbers of men to potential risks.
But he wants that large clinical trial to go forward, even if it means dealing with the P.S.A. problem.
“I think it’s necessary,” Dr. Finkelstein said.