By Andrew M. Seaman
(Reuters Health) - For men with low levels of testosterone, hormone-containing gels may offer a mixed bag of benefits and risks, according to a series of five new studies.
Researchers found that for older men, hormone replacement therapy with testosterone gel might improve bone health and help avoid anemia, but it wouldn’t help with thinking skills. Two studies looking at testosterone use and heart health produced mixed results.
The new studies substantially improve the information available on testosterone treatment, said Susan Ellenberg, who co-authored four of the new studies.
“There are definitely benefits and potential risks,” said Ellenberg, a professor of biostatistics in the Perelman School of Medicine at the University of Pennsylvania in Philadelphia. “It’s not an overwhelming conclusion that every man over 65 should be on this or stay away from it.”
Testosterone levels tend to decline as men age. Doctors sometimes prescribe testosterone gel - known as androgen replacement therapy.
Four of the new studies are the last in a group of seven known as the Testosterone Trials, which evaluated the use of androgen replacement therapy in men over 65 with low testosterone unrelated to any health condition.
The three earlier Testosterone Trials, published last year in the New England Journal of Medicine, found that testosterone therapy improved sexual function but produced mixed results for physical function and vitality. (See Reuters Health story of Feb 17, 2016 here: reut.rs/2m5wYCP.)
In one of the new studies published today in JAMA, researchers compared cognitive function over 12 months in 247 men using testosterone gel and 246 men using a placebo. All the men had memory problems to start with, and there was no difference in cognitive functions at the end of the study.
Two new studies in JAMA Internal Medicine did find benefits of testosterone gel over placebo. Men with anemia - the result of too few healthy red blood cells - had their conditions improve with testosterone gel. Additionally, men using testosterone gel had increases in bone density and strength, but more studies are needed to determine if those men are also less likely to have bone fractures.
The last of the new Testosterone Trials evaluated heart health in 138 older men with low testosterone and evidence of hypogonadism, which occurs when the testes don’t produce enough of the hormone. Seventy-three participants used testosterone gel and 65 used a placebo.
At the end of that study, compared to men using the placebo, men using testosterone gel had a greater increase in coronary artery plaque, which is tied to poor heart health.
“If you’re looking for benefits, you’d like to see it in the other direction,” Ellenberg told Reuters Health.
Clouding the picture on heart health and androgen replacement therapy is a fifth study from Kaiser Permanente in JAMA Internal Medicine that linked testosterone gel to fewer cardiovascular events like strokes and heart attacks.
The researchers compared data from 8,808 men age 40 and older who received androgen replacement therapy for low testosterone and 35,527 men who never received the treatment.
The rate of cardiovascular events like heart attacks and strokes among men who received testosterone was about 17 per 1,000 people per year, compared to about 24 events per 1,000 per year among men who didn’t get the treatment.
T. Craig Cheetham, who led the new study, said previous studies suggested an increased risk of heart problems tied to testosterone use.
“We were a little surprised to find lower rates,” said Cheetham, of the Kaiser Permanente Southern California Department of Research and Evaluation in Pasadena.
The new study can’t prove testosterone treatment reduced the risk of cardiovascular problems, he told Reuters Health.
“The results suggest we didn’t find in our population that there was an increased risk,” he said. “I think that’s as far as I would go.”
In March 2015, the U.S. Food and Drug Administration (FDA) emphasized testosterone treatments are “approved only for men who have low testosterone levels caused by certain medical conditions.”
The FDA also said there is a possible increased risk of heart attacks and strokes with testosterone treatments. The agency is requiring manufacturers to conduct "a well-designed clinical trial to more clearly address the question of whether an increased risk of heart attack or stroke exists among users of these products." (bit.ly/2mjvSiu)