With new testosterone data, AbbVie's AndroGel faces more questions about heart risks

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AbbVie's AndroGel is among the testosterone-replacement products under scrutiny for alleged cardiovascular risks.

AbbVie’s former blockbuster testosterone-replacement treatment AndroGel will be at the center of a class action lawsuit set to go to trial this year, alleging, in short, that previously healthy men suffered heart attacks and other side effects after taking the product.

But AndroGel is also facing a trial of a different sort—a series of scientific studies questioning whether testosterone’s benefits are worth its risks. And a collection of studies published today paint a mixed answer to that question.

One tranche of data comes from the ongoing T Trials, being conducted at 12 sites across the U.S. in 790 men age 65 or older and supported by the National Institutes of Health (NIH). The trials looked at whether AndroGel relieves anemia, strengthens bone, improves cognition—and also whether it affects the build-up of plaque in the heart, an early sign of heart disease. The answers to the first three were yes, yes and no. The data was published in the Journal of the American Medical Association (JAMA) and in JAMA Internal Medicine, according to a press release from the NIH.

Where the data gets tricky is in the cardiovascular arm. The T Trial results did show a buildup of coronary artery plaque in men taking AndroGel, which could conceivably raise their risk of heart trouble. But a separate study reviewing the records of 44,335 patients treated at Kaiser Permanente in California suggested that men receiving testosterone treatments actually faced a lower risk of cardiovascular side effects. That study was also funded by the NIH and published in JAMA Internal Medicine.

In an e-mail to Fierce, a spokesperson for AbbVie said the company supports research including the T Trial and that AndroGel has more than 10 years of clinical and safety data "with therapeutic risks well documented in the prescribing label." She added: "The Testosterone Trials are an important contribution to further increasing our understanding of the role testosterone replacement therapy plays in raising testosterone levels in men age 65 and older."

Before delving into the data, it’s worth reviewing what has happened to date in the testosterone saga. The class of products, which also includes Eli Lilly’s Axiron and other drugs, was led by AndroGel, which became a $1-billion-plus hit, driven by AbbVie’s ubiquitous ad campaign that popularized the term “low-T” and talked up the benefits of testosterone replacement in relieving fatigue, sexual function and other symptoms that many consider to be part of the normal aging process.

But sales of AndroGel started plummeting in 2014, after the FDA launched an investigation into reports that testosterone replacement resulted in an increased risk of death from heart attack or stroke. The agency mandated that AbbVie and other testosterone makers revise their labels to indicate the cardiovascular risks and to clarify that testosterone is only approved to treat hypogonadism, a serious testosterone deficiency.

Still, about 2,000 men sued AbbVie and other testosterone makers. U.S. District Judge Matthew Kennelly of the Northern District of Illinois chose AbbVie to go on trial first.

The NIH’s T Trials are a parallel effort, of sorts, to examine both the cardiovascular risks of testosterone and the oft-cited but barely studied benefits. And the most recent data does show some benefits: 54% of men with unexplained anemia, for example, had clinically significant increases in red blood cell levels, compared with 15% of men with the disease who took a placebo. After one year of treatment, men in the bone trial who were taking AndroGel showed a significant improvement in bone strength, particularly in the spine, compared with those on placebo. A larger trial of longer duration would be required to determine whether that decreases fracture risk, the investigators said in the release.

But the trial did not show any improvement in cognition in men with age-associated memory loss who were taking AndroGel. And among 170 men participating in the cardiovascular trial, the volume of noncalcified plaque “increased significantly more” in those taking testosterone.

“The results on diverse outcomes indicate the potential trade-offs between benefits and risks of testosterone treatment in older men,” said Evan Hadley, M.D., director of NIA’s Division of Geriatrics and Clinical Gerontology, in the NIH’s release. “The results also illustrate that decisions about testosterone treatment need to be individualized, taking into account each patient’s balance of risks for the various conditions that testosterone treatment could affect.”

As for the Kaiser Permanente study, it involved men diagnosed with androgen deficiency in the 10 years ended in 2010. The participants were followed for about 3 years. The authors reported that 10.2% of men who never received testosterone had a heart attack or stroke during that time, versus 8.2% of men taking testosterone.

So what’s the real risk of heart problems from testosterone? No doubt these studies will only feed the ongoing debate. The only thing that can be said with any certainty is that the data will only increase the call for further research into both the benefits and risks of testosterone. Clarifying the real effects of the hormone, said Hadley, “will require longer, larger scale trials.”