European Panel Says There Is Little Evidence Showing Testosterone Replacement Therapy Increases Heart Disease Risk

Another comprehensive review of all the research on testosterone replacement therapy finds no consistent evidence that such treatment increases the risk of cardiovascular problems.

The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) began its analysis in April, soon after the US Food and Drug Administration (FDA) launched an investigation of its own.

The FDA concluded about a month ago that “major limitations” in 2 studies that warned against testosterone replacement‑‑along with a number of conflicting studies that suggest testosterone may actually protect the heart‑‑undermine the case against the hormone.

Now, the PRAC has issued a similar statement, one that says the evidence is “inconsistent” and goes on to note both the limitations in studies that found serious risks and a significant number of unrelated studies that found no risks.

Overall, the report concludes, “The committee considered that the benefits of testosterone continue to outweigh its risks but recommended that testosterone-containing medicines should only be used where lack of testosterone has been confirmed by signs and symptoms as well as laboratory tests.”

Unlike some FDA officials, who have recommended efforts to greatly reduce the overall use of testosterone therapy, the European committee advocated only minor changes to existing product labeling.

The first of those changes would stress the point of treating only those patients who have both low levels of testosterone and actual symptoms associated with hypogonadism. The second would warn against use in men with severe heart, liver or kidney problems. The third would note the limited data on safety and value in men who are over the age of 65, along with the fact that testosterone levels typically decline with age and that research has yet to determine normal testosterone levels in older men.

The PRAC report represents another significant boost for testosterone therapy producers who are defending themselves against claims that their products are dangerous and for nervous users who benefit from treatment.

Safety concerns peaked early this year, after the publication of a pair of large retrospective analyses found significant positive correlation between testosterone replacement and the likelihood of stroke, myocardial infarction and death.

Critics attacked both studies almost immediately, but consumer health advocates demanded that regulators systematically review the evidence, and both the FDA and the EMA soon complied.

Shortly after those reviews began, researchers published a number of new studies that indicated testosterone replacement might actually help the heart. The largest of those, which appeared in the Annals of Pharmacotherapy this summer, analyzed tens of thousands of records from Medicare and found that testosterone therapy was associated with lower risk of myocardial infarction for some men and no change in risk for others.

Still, despite the large number of studies that have already investigated the effect of testosterone replacement on cardiovascular health, both European and American regulators advocate far more research.

A pair of the FDA’s expert panels have recommended that the agency force companies that sell testosterone replacement therapies to undertake large studies that would settle a number of issues conclusively.

PRAC members believe that several ongoing projects may also provide valuable additional information.

“The safety of testosterone medicines should continue to be monitored,” the committee wrote. “In particular, a number of studies are still ongoing and their results will be considered in future regular benefit-risk assessments for these medicines.”