Staff scientists at the US Food and Drug Administration (FDA) have concluded that there's no "convincing evidence" linking testosterone replacement therapy with adverse cardiovascular events.
Staff scientists at the US Food and Drug Administration (FDA) have concluded that there’s no “convincing evidence” linking testosterone replacement therapy with adverse cardiovascular events.
Agency officials published this conclusion online after reviewing existing research on the subject and finding “major limitations” in two much-publicized studies that warn against testosterone along with a number of conflicting studies that suggest testosterone may protect the heart.
The lengthy review was intended to help members of two FDA advisory committees weigh the apparent risks and benefits of the drug, question witnesses who will address the topic at a public meeting on September 17 and consider what response, if any, the data warrant.
The committee could advocate anything from adding new safety warnings to testosterone products to narrowing the indication for the entire class of drugs to mandating post-market studies from all manufacturers. Or it could endorse the status quo.
“Given the limitations of the available data and the conflicting study results,” the review authors write, “the FDA has decided to seek advisory committee input on the potential risk of major adverse cardiac events attributable to testosterone therapy and how best to further evaluate such cardiovascular risk, should the advisory committee panel determine that one exists.”
The advisory committees will also consider whether existing research demonstrates that testosterone therapy provides any meaningful benefits for patients with age-related hypogonadism rather than specific problems in the testicles, hypothalamus or pituitary glands.
The FDA’s staff reviewed dozens of studies that associate testosterone replacement therapy with a wide range of benefits for older men: increased libido, improved sexual function, greater energy, fat loss, muscle gain, metabolic improvements and others.
On the other hand, the staff also found conflicting studies that found no significant association between testosterone use and some of those same benefits.
All the studies on both sides, moreover, suffered significant limitations. The large ones were retrospective and observational, often with many potential confounders. The randomized trials tended to be small, short and — in some cases — poorly structured.
“Aging men often experience many of the signs and symptoms that are associated with hypogonadism, including decreases in energy level, sexual function, bone mineral density, muscle mass and strength, and increases in fat mass. Whether these symptoms are a clinical consequence of the age-related decline in endogenous testosterone has not been established, and therefore, the need to replace testosterone in these older men remains debatable.”
Overall, the review authors write, “treatment benefits with testosterone replacement therapy for ‘age-related hypogonadism’ remain questionable, and there are no reliable data on the benefit in such a population.”
A separate review, conducted by a dozen firms that make testosterone replacement therapies and submitted to the FDA advisory committees, reached a considerably different conclusion.
“The data consistently support testosterone replacement therapy benefits on measures of lean mass, fat mass, and bone mineral density and architecture. Less consistently, data also suggest benefit with sexual function. Additionally, there is some evidence that suggests benefit with mood and fatigue.”
Still, the industry review acknowledges, “there are limitations to these data sets… One limitation is the relative absence of large controlled long-term studies, which makes it difficult to interpret the long-term clinical impact of testosterone replacement therapy.”