By Kathleen Doheny
WebMD Health News
Reviewed by Brunilda Nazario, MD
Sept. 4, 2014 -- Testosterone replacement therapy has tripled in the past decade. Nearly 3% of U.S. men 40 and over use it, and that percentage rises with age. Sales now top $2 billion annually.
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But is it safe for your heart? Opinions differ.
Researchers from the University of Texas Medical Branch reported on July 2 that they found no link between testosterone therapy and heart attack risk.
Their findings are directly opposite those from a study in January. Researchers from the University of California Los Angeles and other institutions said the therapy can double the risk of heart attack in men with existing heart disease.
The FDA, in a review published Sept. 3, said it could find no evidence of either risk or benefit in men prescribed testosterone therapy. It hasn't been shown that symptoms such as a decrease in energy level and sexual function stem from an age-related decline in testosterone, the review said, and "the need to replace testosterone in these older men remains debatable."
Because of their limitations, studies on the issue have not provided "convincing evidence" that testosterone therapy is associated with cardiovascular problems, the FDA said. But the agency also noted the increasing popularity of testosterone therapy. In 2010, 1.3 million patients received a prescription for testosterone; by 2013, this had risen to 2.3 million patients.
WebMD asked the experts to sort out the debate.
What have the major studies found about testosterone therapy and heart attack?
"We have many studies now showing different results that conflict," says Bradley Anawalt, MD, chief of medicine at the University of Washington Medical Center, Seattle. He is familiar with the research but was not involved in the two recent studies.
Some researchers have found a higher risk of heart attacks, while others haven't. In those that have found some risk, the degree varies. Some studies consider whether the men had pre-existing heart disease.
In the UCLA study, researchers looked at the medical records of nearly 56,000 men using testosterone therapy. Ninety days after starting the therapy, the risk of a heart attack doubled -- compared to a year before starting treatment -- for men 65 and above and for younger men with heart disease.
In the University of Texas study, researchers looked at more than 6,000 men ages 66 and older who were treated with testosterone. The researchers compared them to more than 19,000 men 66 and older who did not get testosterone.
They found no difference in the risk of heart attack in the two groups, says study leader Jacques Baillargeon, PhD, director of research in the division of epidemiology and outcomes at the University of Texas Medical Branch, Galveston. Baillargeon says he even found testosterone may offer some protection for men at the highest risk of heart attack. But he says that finding should be duplicated by other researchers to see if it holds up.
Why are the findings at odds?
"The studies are quite different in the way they are being conducted," Anawalt says.
The studies look at men of different ages and at different time periods. The Texas study focused only on men 66 or older who were on Medicare. The UCLA study looked at a wider age range of men.
Researchers have looked at different time periods to see if testosterone raises heart attack risk, says Sander Greenland, PhD, professor emeritus of epidemiology and statistics at UCLA. He was a researcher on the UCLA study and reports consultant work in various testosterone lawsuits.
His team tracked heart attacks soon after beginning the treatment. "We were looking at the first 90 days," he says.
The Texas researchers followed men between 1997 and 2005.
The men who are studied may differ in health habits, and that could affect results, Baillargeon says.
How might testosterone raise or lower heart attack risk?
The link between testosterone therapy and heart attack is complicated, Baillargeon says. Testosterone may help the heart by improving cholesterol and decreasing body fat and inflammation.
It could also raise heart disease risk in a number of ways, Baillargeon says. Men on testosterone therapy might retain more salt and water while using it, which could lead to high blood pressure and other problems, he says.
Does the research so far tip the balance one way or the other?
Experts disagree. "I think if you look at all the data in summary, there is not a clear trend towards increased risk of cardiovascular events -- stroke and heart attack, and early death -- or a clear trend toward blood clot formation [with testosterone use]," Anawalt says.
In June, the FDA added a general warning label to testosterone products, describing the risk of blood clots in the veins. The blood clot warning is not related to the FDA's ongoing evaluation of the possible link between testosterone and heart attack, according to the agency.
Greenland says the studies, overall, do show a risk. "More studies have found an association than have not," he says.
Experts do agree that, if needed, testosterone therapy can be helpful.
How is low testosterone defined, and how many men have it?
About 5 million American men have low testosterone, according to the National Institutes of Health.
Testosterone helps make sperm and maintains muscles and bones. Low testosterone can affect a man's sex drive and mood.
"Low testosterone by itself is not a disease," Anawalt says. "It is the combination of having symptoms and side effects associated with too little testosterone, plus a low blood testosterone level that you have confirmed on two or more occasions on early-morning blood tests."
Blood levels of testosterone change throughout the day.
Who needs testosterone therapy?
The FDA has approved testosterone in a patch, gel, and other forms. The approval is for men with low blood levels and an associated medical condition, such as a problem with the hypothalamus and pituitary gland, which control the making of testosterone.
According to guidelines from the Endocrine Society, testosterone can be considered for men with confirmed low blood levels (usually below 300 nanograms per deciliter) and consistent symptoms, including low libido.
Until more research is in, what's the best advice for men?
Getting a blood-level test of testosterone is crucial, experts agree. But they suspect many doctors don't check that before prescribing the testosterone.
"I don't think men should be fearful of it," Anawalt says of testosterone replacement therapy. "If they go to their doctor and it is truly low, the benefit exceeds any potential risk."
A man's health history should also factor into the decision about the therapy, Greenland says. "If I had had a heart attack, no, I wouldn't touch this."
If a man has low testosterone, with no family history of heart attacks and no risk factors, "I would say proceed with caution," Greenland says. "Certainly you would want to be monitored by a doctor."
SOURCES: Bradley Anawalt, MD, chief of medicine, University of Washington Medical Center, Seattle. Sander Greenland, PhD, professor emeritus of epidemiology and statistics, University of California Los Angeles Fielding School of Public Health. Jacques Baillargeon, PhD, director of research, division of epidemiology and outcomes, correctional managed care, University of Texas Medical Branch, GalvestonFinkle, W. PLoS One, Jan. 29, 2014. Baillargeon, J. Annals of Pharmacotherapy, July 9, 2014. The Endocrine Society: "Testosterone Therapy in Adult Men With Androgen Deficiency Syndromes." Baillargeon, J. JAMA Internal Medicine, Aug. 12-26, 2013. FDA: "Testosterone Information." FDA: "FDA adding general warning to testosterone products about potential for venous blood clots."
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