FDA Issues Warning About Blood Clot Risks Associated with Testosterone Replacement

The US Food and Drug Administration (FDA) recently announced it will now require the makers of testosterone replacement therapies to add general warnings about venous blood clots to product labels.

Such products had warned about the risk of clots arising from polycythernia, an overabundance of red blood cells that sometimes occurs in patients who take testosterone.

Now, thanks to post-market reports of venous clots unrelated to polycythemia, the wording must be enhanced to provide a broader warning about the possible risk of venous thromboembolisms.

Most cases of deep vein thrombosis develop in the legs and cause nothing more than swelling and pain, but if the clot — or part of the clot — breaks loose and gets into the blood stream, it can block the flow of blood to the lungs. Research suggests that venous clots may kill 180,000 Americans a year, more than breast cancer and prostate cancer combined.

The FDA’s public announcement did not say how many reports of deep vein thrombosis or pulmonary embolisms it had received or how severe the clots had been.

The agency did, however, note that the new warning requirement is not related to an ongoing evaluation of evidence that testosterone products may increase the risk of stroke, heart attack and death in some user groups.

The FDA began that review in response to a pair of recent studies. The first, which was published last November in the Journal of the American Medical Association, reviewed health records for veterans who used testosterone and concluded that it significantly increased the risk of stroke, heart attack, and death. The second, which was published early this year in PLOS One, found an increased risk of heart attack for all older men who received testosterone prescriptions and also for younger men with a history of heart disease.

The FDA’s conduct of that investigation has drawn fire both from those who think the agency isn’t acting quickly enough to restrict usage — or at least dissuade potential users — and also from those who think that neither study provided enough information to merit an investigation.

On the one side, advocacy groups are demanding that the agency require that black-box warning labels be added to testosterone drug packages. Public Citizen, for example, has petitioned the FDA for a warning that specifically mentions heart attacks, strokes and other cardiovascular risks.

On the other side, many researchers who were not affiliated with either of the studies mentioned above — some with ties to the testosterone industry, others with none — say that both papers have serious flaws.

In a letter to JAMA’s editor, a group of more than a dozen researchers headed by Abraham Morgentaler, an associate clinical professor of urology at Harvard Medical School, called for a full retraction on grounds that the study was riddled with errors.

Actual trials of testosterone — as opposed to retrospective analyses — have come to many contradictory findings on its effects on everything from heart health to diabetes.

Still the FDA’s decision to mandate enhanced blood-clot warnings is just one more sign of the serious scrutiny that testosterone replacement therapy has come under.