New Concern About Testosterone and Heart Risks

Stuart Bradford

A large new study found that prescription testosterone raised the risk of heart attacks in older men and in middle-aged men with a history of heart disease, prompting some experts on Wednesday to call for more extensive warning labels on the drugs.

The new study is one of several in recent years that have highlighted cardiac problems as a potential side effect of testosterone gels, patches, pellets and injections. The hormone is approved for low testosterone levels and is widely marketed for symptoms of 'low T,' including fatigue, low libido and loss of energy. Sales in the last decade have soared.

By itself, the new study, which was not a randomized trial, the gold standard in medical research, 'may not tell us very much,' said Dr. Michael Lauer, the director of cardiovascular sciences at the National Heart, Lung and Blood Institute, who was not involved in the study. 'But when you put this together with the rest of the medical literature, this tells us that we potentially have a problem.'

The drugs carry no mention of an increased risk on their labels or in their advertising materials, said Dr. Sidney M. Wolfe, a senior adviser to the Washington advocacy group Public Citizen. 'Given that there have been several studies now, I don't see how the Food and Drug Administration can justify having no warnings of heart attacks at all,' he said.

In a statement, Andrea Fischer, an F.D.A. spokeswoman, said the agency was reviewing the new findings. 'We will communicate any new safety information on testosterone products when our reviews of all new information have been completed,' she said.

The new study, published on Wednesday in the journal PLoS ONE and funded by the National Institutes of Health, tracked about 56,000 older and middle-aged men around the country who were prescribed testosterone between 2008 and 2010. The study looked specifically at their rate of heart attacks in the year before receiving their new prescriptions, and in the three months after.

Men 65 and older had double the rate of heart attacks in the months after starting the drug, as did those younger than 65 with a previous diagnosis of heart disease. There was no evidence of greater risk in the younger men without a history of heart problems.

One question surrounding testosterone is whether any potential increase in cardiac risk is caused directly by the drug, or by its impact on behavior. Testosterone boosts libido, for example, which may spur older men to engage in strenuous sexual activity.

The new study sought to address this question by comparing the men using testosterone to a separate group of 170,000 older and middle-aged men who filled prescriptions for Viagra and Cialis. Those men did not experience more heart attacks. The new research was led by a team at the National Cancer Institute, the University of California, Los Angeles, and Consolidated Research, an independent research firm specializing in epidemiology.

In November, a study in The Journal of the American Medical Association found that older men, many with a history of heart disease, had a nearly 30 percent increase in mortality, heart attacks and stroke after using testosterone. And in 2009, a federally financed, randomized study that was intended to test whether testosterone gel could help elderly men build muscle and strength was halted early because of heart attacks and other cardiac problems in men using the drug.

Testosterone increases the production of red blood cells, which can clump together or coagulate, essentially making blood thicker, said Mary Schooling, a professor of public health at Hunter College who published a large study linking testosterone use to cardiovascular events last year. That may be especially hazardous in men who have narrowed arteries because of aging and disease. 'There is a potential for harm, and people should know about this,' she said.

Although testosterone levels naturally decline with age, testosterone therapy is approved for use only in men with hypogonadism, an underlying endocrine disorder that typically results in a severe testosterone deficiency. Making that diagnosis requires doing a blood test. But studies show that nearly a quarter of men prescribed the drug do not have their levels tested.

Dr. Peter J. Snyder of the University of Pennsylvania School of Medicine, who is leading a $50 million series of trials looking at testosterone treatment in men 65 and older with documented low levels, cautioned against drawing conclusions based on the new study.

'We don't know if these findings apply to men who have low testosterone and meet the criteria for a prescription, or if it applies only to men who have normal levels and then take testosterone in addition,' he said.

Dr. Snyder said he and his colleagues found it plausible that testosterone might actually protect against heart disease, in part by reducing body fat and improving blood sugar metabolism.

But, he added, the sharp rise in such prescriptions in the last decade was evidence that many men without testosterone deficiencies were receiving them. 'In those cases, there is no medical reason for it,' he said, 'and that runs counter to all guidelines for physicians.'