Middle-age American men have been aggressively marketed treatments for low testosterone, despite risks and skepticism about benefits. Now insurers have another reason to strictly control coverage.
The Food & Drug Administration is directing prescription testosterone manufacturers like AbbVie to change the product labels to include warnings about risks of heart attack and stroke, to clarify the approved uses and conduct clinical trials.
"The benefit and safety of these medications have not been established for the treatment of low testosterone levels due to aging, even if a man's symptoms seem related to low testosterone," the agency wrote in a notice referring to products including AndroGel, Testim, Testopel, Axiron and Androderm. "FDA has become aware that testosterone is being used extensively in attempts to relieve symptoms in men who have low testosterone for no apparent reason other than aging."
Artificial testosterone is approved by the FDA as replacement therapy only for men who have hypogonadism, difficulty producing the hormone naturally because of genetic, pituitary gland or brain disorders or damage from chemotherapy or infections.
Aside from those approved uses, the nation's aging men have fueled demand for testosterone treatments, with higher rates of diabetes and obesity than their fathers' generation and thus perhaps less natural testosterone, which declines with age and excess abdominal weight.
"Low-T" is now a $2 billion industry and could double by 2017, thanks to the likes of Chicago drugmaker AbbVie and specialized clinics pitching the hormone therapy as a rejuvenation for men suffering from reduced labido, lethargy or mood swings. An AbbVie-supported website called IsItLowT? asks men to take a quiz to probe likely symptoms and then explore treatment options.
In the decade between 2001 and 2011, the proportion of men over 40 being treated for Low T is estimated to have tripled from less than 1 percent to 2.8 percent, according to a JAMA Internal Medicine study. Among men over 60--those particularly at risk of cardiovascular events-- 3.75 percent were taking testosterone products. Only about half of the men in the study actually had hypogonadism
"This trend has been driven, in large part, by direct-to-consumer marketing campaigns that have targeted middle-aged men and the expansion of clinics specializing in the treatment of low testosterone," said lead researcher Jacques Baillargeon, a professor in preventive medicine and community health at the University of Texas Medical Branch. (Texas is home to a number of Low-T clinic chains.)
Testosterone treatment is a "lifetime commitment," as Kentucky physician Stephen Dreisbach, MD, of Norton Healthcare, told USA Today in 2013. "Once you start on it, you are going to suppress your own production of testosterone."
That, along the rise of lifestyle-related usage, may have been a factor in the FDA warning. Last year the FDA started evaluating the issue, after two studies found an associated increased risk of heart attack and strokes.
In a 55,000 person Plos One study, men over 65 taking Low T prescriptions had double the risk of a heart attack in the course of three months compared to men not using the products. For younger men with pre-existing heart disease, the risk of a heart attack was associated with two- to three-fold increase when taking testosterone.
In a JAMA study of 8,700 veterans who received coronary angiographies and had lower-than-average testosterone levels, 26 percent of those with a testosterone prescription suffered a heart attack or stroke after three years, compared to 20 percent of those not taking the hormone.
A more recent research review in the Mayo Clinic Proceedings concluded that the evidence is not established enough to prove a link between testosterone treatments and cardiovascular events. Still, the FDA believes the "possible increased risk of heart attacks and strokes associated with testosterone use" warrant labeling changes, and the treatments are also leading to legal disputes, with men who took the products complaining of harms.
"Requiring warning label changes that specifically reference increased risks of heart attacks and strokes will be pivotal in the already existing testosterone litigation nationwide," lawyer Matthew Casey, whose firm has 230 clients suing testosterone drug makers, told the Philadelphia Inquirer.
Health insurers are also ending up in the thick of litigation. Last November, Medical Mutual of Ohio sued Abbvie, Abbott Laboratories, Solvay, Eli Lilly, Auxilium and Actavis, alleging that their their Low T awareness and promotional activities constitute racketeering. The testosterone drugs have been "marketed as part of a decade-long deceptive marketing scheme to transform the male aging process into a curable disease state," the complaint reads.