Key Advisory Panel Member Concedes It Is Medically Plausible That Testosterone Replacement Therapy Can Be Associated With Heart Attacks / Strokes Side Effects
On September 17, 2014 members of the FDA's Bone, Reproductive and Urologic Drugs and Drug Safety and Risk Management advisory panels considered the issue of whether the popular testosterone products Axiron, AndroGel, and Testim, as well as other so-called "Low-T" drugs, are safe. Not surprising -- but certainly unsettling -- was the outcome of their discussions, which was essentially that for most current users of testosterone replacement therapy (TRT) medications we do not know and cannot know, because no safety study has been done, yet.
From a September 18, 2014 Healio EndocrineToday report, "FDA committees near-unanimous on need to investigate testosterone therapies":
A key presentation by Shalender Bhasin, MD, of Harvard Medical School, with advisory board seats for two of the sponsors, broached the biggest topic of concern in the room during a presentation on cardiovascular events and testosterone therapies.
“Testosterone’s effects in preclinical and clinical models are diverse,” Bhasin said. “Some effects are beneficial, and some may be potentially deleterious.”
Bhasin conceded biologic plausibility for the association of testosterone with cardiovascular events. He presented data from a meta-analysis demonstrating lower testosterone levels were associated with higher all-cause mortality, epidemiologic studies showing mixed results and a small randomized placebo-controlled trial showing increased cardiovascular events with therapy.
“It’s important to distinguish between classical hypogonadism and age-related decline,” Bhasin said. “In young men with classical hypogonadism, testosterone replacement therapy improves symptoms with low adverse event frequency. In older men, with age related decline or frailty, neither benefits nor risks have been clearly demonstrated.”
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And from a September 18 Medscape Medical News article, "FDA Advisory Panel Urges Restrictions on Testosterone Use":
Regarding the safety question, Tobias Gerhard, PhD, from the Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey, said: "The evidence regarding cardiovascular safety is obviously very insufficient. We need more data. At this point, I don't think there's evidence for a clear causal association, but I believe we do have a signal of reasonable strength."
Given the magnitude of off-label use "and lack of strong data on effectiveness in this population, I think it's important to include something about cardiovascular safety in the label. Maybe not to the level of black box, but certainly that there are serious concerns that have not yet been adequately addressed," he added....
Toby C. Chai, MD, professor and vice chair of the department of urology at Yale University School of Medicine, New Haven, Connecticut, said, "For a population it was not originally intended to be used [in]…if we want to look at reality we have to do safety studies....Whether it should be randomized or observational, I think we'll be prospectively looking at those cardiovascular risks."
We have to wait to see what regulatory action the FDA will take, if any, concerning the possible increased risks of heart attacks and strokes that some link to Axiron, AndroGel, Testim, and other "Low-T" drugs.
One can say, however, that despite this September FDA Advisory Committee meeting, many questions about the safety of these testosterone drugs remain unanswered, still.