Testosterone and CV Risk? No Quick Answers

Shelley Wood

April 28, 2014

SEATTLE, WA — Another prestigious voice is joining the chorus of debate over the cardiovascular risks of testosterone prescriptions in older men. Wading into the fray, Lancet Diabetes & Endocrinology has published a Comment online today by Dr Stephanie Page (University of Washington, Seattle) that appraises the recent headline-generating studies linking testosterone to cardiovascular events but warns that definitive answers aren't just around the corner[1].

Page is an endocrinologist focused on male hormones and their link with chronic diseases. She points to the recent observational studies by Vigen and Finkle, noting that both "should serve to galvanize both the public and medical communities to fund an appropriate clinical study."

But both have important flaws, she continues. In the case of the Vigen et al analysis, conducted in 8000 male veterans, she observes that the highly significant increased risk of cardiovascular events reported with testosterone treatment in the adjusted primary analysis actually goes in the other direction prior to adjustment. Moreover, testosterone treatment in that analysis was based on a single filled prescription but not verified biologically or tracked for duration of use.

Likewise, the Finkle et al study, which also investigated a large healthcare database, relied solely on a testosterone prescription without verifying usage and lacked information on whether the men actually had low serum T at baseline.

By contrast, she notes, and compounding the confusion, a 2012 study by Shores and colleagues showed that testosterone treatment decreased mortality.

At issue is the lack of randomized controlled trial data addressing the question of testosterone treatment in older men. Completed studies were either stopped early due to excess CV events or showed no increased events, but in a lower-risk population. What physicians need to know, says Page, is that the much-anticipated, US National Institutes of Health Testosterone Trial in Older Men (the T Trial), at 800 patients, is not large enough to deliver a clear answer on risks of prostate cancer or cardiovascular events—a point also acknowledged by the trial's lead investigator.

Both US and European regulators have announced reviews of testosterone-containing medications, and the US Endocrine Society has called for a larger, more comprehensive trial. But as Page points out, this is of little use to physicians treating patients today.

"What, then, can older patients be told about the risks associated with testosterone, and in particular about cardiovascular risk?" she asks. "Testosterone is a billion-dollar industry, probably fueled partly by direct-to-consumer advertising and, undoubtedly, some degree of overprescription. Physicians need to admit they simply do not know and use conservative treatment guidelines to guide therapeutic decisions."

A sobering thought, Page reminds readers, is that a trial powered for safety, even if launched today, would take at least a decade to deliver conclusive answers.

In the meantime, she cautions, "observational data should fuel the scientific and clinical imperative to do appropriate large randomized trials to provide evidence-based guidelines for testosterone treatment."

Page declared she has no conflicts of interest.

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