June 10, 2022 -- Men with low levels of testosterone who received testosterone replacement therapy for three months to a year did not develop more heart-related problems than similar men who received a placebo, a new study shows.

The researchers say the findings – which come from an analysis that combined data from lots of smaller studies -- offer some reassurance that testosterone replacement therapies are safe for the heart when taken for a short time by men who qualify for this therapy.

Testosterone levels fall as men get older, and some individuals diagnosed as officially having low testosterone levels (hypogonadism) might qualify for testosterone replacement therapy.

But some experts caution that this new ‘meta-analysis’ did not follow the men for long enough, and doctors and patients should wait for the results of a very large study currently underway -- which is comparing five years of treatment with testosterone gel versus a dummy gel in more than 5,000 men -- before drawing any firm conclusions on whether testosterone is indeed safe for the heart.

This is because a few previous studies have found that testosterone replacement therapy is associated with an increased risk of a heart attack or stroke. But other studies did not come to this same conclusion.

Still, since 2014, the FDA has required that companies put a warning label on testosterone products about possible heart-related risks.

And the agency stresses that testosterone products are only approved for use in men who lack or have low testosterone levels in conjunction with an associated medical condition.

For Some Older Men Only?

"If your doctor thinks you need testosterone, be reassured that the chance of having serious side effects including heart problems is very low," says researcher Channa N. Jayasena, MD, PhD, from Imperial College, London, in the United Kingdom.

"However, all drugs including testosterone are hazardous if taken when not needed," he says, adding that "older men may still benefit from testosterone, but only if they have…low testosterone levels."

Cardiologist Erin D. Michos, MD, says that "Testosterone levels normally go down with age in men and [guidelines say] we don’t need to put someone on testosterone replacement just to treat age-related testosterone decline."

"If you are a man who has lower testosterone…and have symptoms — decreased sexual desire, decreased energy, decreased muscle mass, decreased facial body hair, you might discuss with your doctor whether you are a candidate for testosterone replacement therapy," said Michos, who is from Johns Hopkins University School of Medicine in Baltimore, MD.

But if men "had a strong family history of heart disease in their family or if they had high blood pressure or high cholesterol, I would still be cautious about using testosterone therapy in them," she says.

However, "if men are otherwise low risk for cardiovascular disease and they really are symptomatic — we're not just treating a number — what we know now is that it seems to be reasonably safe in the short term, but we really are lacking data about long-term safety."

Best Study to Date

In their new analysis -- to be presented at The Endocrine Society meeting in Atlanta on Monday June 13 and recently published in The Lancet Healthy Longevity -- researchers combined data from 35 studies conducted from 1992 to 2018 with a total of 5,601 men who had clinically low testosterone levels and an average age of 65.

The men received either atestosterone or a placebo for 3 months to a year (except for one study of 3 years), with average treatment lasting 9.5 months.

Using this data, the rate of any heart-related event during the study was not significantly different in men who received testosterone therapy (7.5%) versus men who received a placebo (7.2%).

There were also no significantly increased risks of death, stroke, abnormal heart rhythms, coronary heart disease, heart failure, or heart attack, between men who received testosterone versus a placebo.

This is "the most comprehensive study to date investigating the safety of testosterone treatment of hypogonadism," the researchers write in their study.

“Men with hypogonadism should be counselled that there is no current evidence that testosterone treatment increases cardiovascular risk in the short to medium term. Long-term safety of testosterone is not yet established” they conclude.

Michos agrees. "We should wait for the results of [the long-term study] to be published before widespread use of testosterone replacement therapy is considered," she writes in an editorial in the Lancet.

The longer study "is specifically designed to determine risk of heart attack, stroke, or death from cardiovascular causes, during five years of testosterone therapy, versus placebo, and the results are expected to be reported later this year."

Show Sources

National Library of Medicine: "A Study to Evaluate the Effect of Testosterone Replacement Therapy (TRT) on the Incidence of Major Adverse Cardiovascular Events (MACE) and Efficacy Measures in Hypogonadal Men (TRAVERSE)."

The Lancet: "Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis." "Testosterone: therapeutic or toxic for the cardiovascular health of men?"

FDA: "FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use." "Testosterone Information."

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