There's new evidence that widely prescribed testosterone drugs touted for men with flagging libidos and general listlessness might increase the risk of heart attacks.
A study of more than 55,000 men found a doubling of heart attack risk among testosterone users older than 65, compared with men who didn't take the drug.
The research was inspired by a smaller study published in 2010 that hinted at an elevated risk among frail, older men who were on testosterone replacement therapy. The earlier study was halted ahead of schedule because of a higher rate of heart attacks, strokes and other cardiovascular problems.
What's new, says William Finkle, lead author of a study published Wednesday by PLOS ONE, is that in men younger than 65 with known heart disease, "we also found a twofold increase in risk of nonfatal heart attack shortly after initiation of testosterone therapy."
Nonusers had a risk of heart attack of 5 per 1,000 men followed for 1 year, while testosterone users older than 65, and those under 65 with known heart disease, had an absolute risk of 10 per 1,000 patient years. These numbers were adjusted to account for other health issues, including high blood pressure, diabetes and smoking.
As men age, their production of testosterone falls. For some, testosterone drops so low that it becomes a medical problem. But millions of U.S. men use testosterone drugs as lifestyle drugs, resorting to replacements to reverse a natural decline. In a sign of the drugs' popularity, sales of AbbVie's Androgel, the leading testosterone replacement, surpassed Viagra's in 2012.
In one frequently aired TV ad, a youthful-looking 50-something man owns up to having "low T," which his doctor discovered after he complained of sagging energy and irritability. After taking Androgel, he's back in the swing of things, the ad suggests, riding around in a convertible with a younger-looking woman.
With such inducements (and common symptoms), some specialists worry that many men are being prescribed testosterone drugs even if they have normal levels of the male sex hormone. The drugs cost around $300 to $400 a month, but companies are offering to cover patients' insurance copayments or are giving away the first month's supply.
In addition to the new study and the one in 2010, a Veterans Affairs study last November found a higher rate of heart attacks, strokes and deaths among 1,223 men taking testosterone therapy, compared with 7,486 who didn't get the hormone treatment.
Finkle, who's with a California firm called Consolidated Research, tells Shots that "the risk of heart attack should be added to the discussion between patients and physicians" before anyone starts testosterone treatment.
He also says the Food and Drug Administration should require a warning on the labels of testosterone drugs such as Androgel and Axiron. "We have a 2010 study that was canceled because of unexpected cardiovascular risk," he tells Shots. "I think that was sufficient to justify a warning. Why withhold that from the patient?"
Dr. Sidney Wolfe, of the Health Research Group, tells Shots that his consumer advocacy organization plans to petition the FDA, asking for a strong warning on the instructions for testosterone drugs. The group also intends to ask the FDA to hold off on a long-acting, injectable form of testosterone called Aveed. The agency is expected to make a decision on the drug in February.
But at least one advocate of testosterone therapy says the evidence of risks is overblown and poorly founded. "It feels almost like it's open season on testosterone," Boston urologist Abraham Morgentaler tells Shots. "None of the studies is very impressive."
Morgentaler, author of Testosterone for Life, published by Harvard Health Books, says authors of the latest study "have made the classic mistake of confusing treatment for a condition with the condition. There's a rich literature spanning more than 20 years that shows low testosterone itself is a risk factor for cardiovascular events."
He also criticizes the new study for not following patients long enough, and notes that the rate of heart attacks among testosterone users was low.
It's "high time" for a study of testosterone therapy involving a large number of men who are followed for years, Morgentaler says, similar to the Women's Health Initiative study on postmenopausal estrogen supplements.
"There is potential for testosterone to be important for general health and longevity," Morgentaler says. "There's strong evidence it increases muscle strength and decreases fat things we would associate with improved health."
But large, lengthy studies cost hundreds of millions of dollars. And in the case of estrogen replacement, that sort of research ultimately discredited the long-held belief that taking hormone supplements lowers the risk of heart attacks.