Could you have low testosterone?
That's the question Abbott Laboratories (now AbbVie) has been urging men to consider with its "Is It Low T?" awareness campaign, a highly effective effort to change how doctors and the public think about managing aging in men.
Since 2008, this massive marketing endeavor has targeted middle-aged men who have put on some weight, sometimes feel grumpy or get sleepy after meals, encouraging them to have their testosterone levels tested and to consider treatment if levels are low. It has helped persuade legions of men to take a drug that may not help and may actually do harm for a condition they probably don't have.
In a recent article in JAMA Internal Medicine, we described the tactics such campaigns use to sell disease. Since the start of the campaign, testosterone sales, which had been stable for years, have risen more than 1,800%, exceeding $1.9 billion in 2012.
By targeting men worried about weight, muscle tone, energy levels, mood and sexual satisfaction, the campaigns imply that treatment will help them become thinner, more muscular, more energetic, less grumpy and more sexually satisfied. But there's a big problem: We really don't know if diagnosing and treating "low T" does any good. More important, there is some evidence it may cause harm. Last month, a new study of men found that older men taking the drug were more likely to have heart attacks. Shortly after the study's release, the Food and Drug Administration announced a new investigation into the possible harms of testosterone.
Testosterone drugs were initially developed for a narrow use: treating men with a reduced ability to produce testosterone because of such things as trauma, chemotherapy, genetic abnormalities or undescended testicles. For these men, testosterone replacement provides a clear quality-of-life benefit, permitting normal sexual development or restoring male appearance and sexual function. In the years since the drug was first developed, the FDA has approved a whole medicine cabinet of testosterone products — gels, pills, patches and even an underarm roll-on.
But who should be getting the drug? Drug information approved by the FDA is ambiguous about which conditions testosterone drugs are approved to treat. This matters because pharmaceutical companies can promote drugs only for "on-label" FDA-approved uses. Years ago, the Institute of Medicine, the nation's premier medical advisory group, described prescribing testosterone for low T as an off-label use. Last month, the FDA seemed to agree. In announcing its new investigation, the agency specifically mentioned that testosterone is approved only to treat hormonal problems caused by medical problems. So why has the FDA tolerated six years of aggressive marketing of the drug to a much wider range of potential patients?
One reason is that the FDA only regulates advertisements that mention drugs by name. Strictly speaking, the disease awareness campaign does not mention any brand names. But this seems like sophistry since the campaign does specifically mention testosterone and lists the variety of ways it is available — patches, injections, tablets, etc.
And the "Is It Low T?" website links to a direct-to-consumer website for the testosterone gel Androgel. Websites for the gel and other testosterone products use tactics very similar to the "Is It Low T?" website — except they explicitly mention the brand-name drug. Doesn't this bump up against FDA regulations about off-label promotion?
It's time for the FDA to rein in these kinds of "disease awareness" campaigns and branded advertising, because they are misleading: They imply unproven benefits and ignore possible harms.
The proven benefits of treating low T are small: subtle increases in lean body mass, libido or sexual satisfaction. Studies have found no improvement or inconsistent results when it comes to effects on weight, depression or strength; effects on energy and irritability are unknown. Even campaigns promoting low T as a diagnosis are careful not to suggest directly that treatment will address the symptoms that bring men to their websites.
Moreover, any benefits need to be weighed against the possibility of serious harm. The FDA's new investigation was prompted by two recent studies. In the first, older men and men with heart disease filling new prescriptions for testosterone had more heart attacks than similar men filling prescriptions for erectile dysfunction drugs. In the second, among veterans who had undergone cardiac catheterization, the use of testosterone drugs was associated with a higher risk of heart attack, stroke or death. Because neither study was a randomized trial, it's not possible to know whether the findings were due to testosterone or something else about the men who happened to take it.
A randomized trial published in the New England Journal of Medicine in 2010 raised concerns about giving the drug to frail, elderly men. The trial was stopped early because 7% of the men in the testosterone gel group versus 1% in the placebo group experienced serious heart problems (although some criticize this evidence because the trial had not set out to look for heart problems). Other testosterone trials have been too small and brief, even when combined, to confidently exclude an important increase in heart attacks.
As physicians who study communication about prescription drugs, we find the marketing of low T eerily reminiscent of another campaign: the hyper-promotion of hormone replacement for post-menopausal women. While these drugs can have an important quality-of-life benefit for women with severe menopausal symptoms, a gold-standard randomized trial showed that for most women the hormones did more harm than good.
For men with severe hormone deficiency from a medical problem, testosterone replacement is a major advance. But for the aging men targeted by the low T campaign, the balance of benefits and harms is unknown. And there is good reason to worry about heart attacks, especially in men with heart disease and in the frail and elderly.
When it comes to testosterone, the pharmaceutical industry has gone too far — and the FDA not far enough. Maybe the problem isn't low T; maybe instead it is low R — low regulation.