Evidence on Testosterone Therapy Does Not Support Cardiac Risk

Recent articles in the scientific literature and mass media that question the use of testosterone therapy to treat testosterone deficiency, or "low T," and assert the cardiovascular risks of testosterone therapy are flawed, according to a new, provocative editorial.

The public judgment of the overselling of testosterone therapy demands a response, stated the lead author, Martin Miner, MD, Clinical Associate Professor of Family Medicine and Urology, Warren Alpert Medical School of Brown University.

“As researchers and clinicians with extensive experience with testosterone deficiency and its treatment, we do not find any credible evidence that testosterone prescriptions increase health risks. We find the assertion that testosterone is prescribed to men ‘who are simply reluctant to accept the fact that they are getting older’ is without foundation, and we object to comments that question the reality of testosterone deficiency, regardless of whether it is called hypogonadism or, as in advertisements, ‘low T,’” Dr Miner stated.

“In addition, in our opinion, the idea that physicians prescribe testosterone due to pressure from drug companies is irresponsible and not supported by scientific evidence."

Over-the-top comments tend to scare both patients and physicians. “The FDA announcement that it is investigating the reports of increased cardiovascular risks has only added to the impression that a major study has determined serious problems with testosterone therapy,” he stated.

A case in point is a recent report¹ published in PLoS ONE that investigated the risk of acute nonfatal myocardial infarction (MI) in a retrospective cohort study of a health-claims database. The authors compared the rates of MI within the first 90 days of an initial prescription for testosterone with the rates of MI for the 12 prior months in nearly 56 000 men. They also examined pre- and post-prescription incidence rates for nonfatal MI in another large cohort of more than 167 000 men for whom only phosphodiesterase-5 inhibitor (PDE5i) medications were prescribed, and after adjusting for potential confounders, compared these results to those of men who received testosterone prescriptions.

The authors concluded that the risk of MI following testosterone prescription was “substantially” increased (at least twofold) in older men and younger men with preexisting, diagnosed heart disease.

“A close examination reveals that this study is too flawed to provide meaningful information on the cardiovascular risk of testosterone therapy,” stated Dr Miner. “First, the overall rate of nonfatal MI in the testosterone-treated group increased in all ages from 3.48 to 4.75 per 1,000 person-years. This amounts to just greater than one additional MI in 1,000 years of exposure to testosterone. It is misleading to characterize this increase as ‘substantial’ based on relative risk when the absolute risk is so small and clinically meaningless.”

Also, the study duration (90 days) was short, and a true control group would have consisted of men with untreated testosterone deficiency, not those who received PDE5i medications. The overall risk was low, and the number of events in subgroups was remarkably few, he noted.

More data from larger, longer term studies are needed to assess the potential effects of testosterone therapy on cardiovascular events in men. Based on the current evidence, he stated, "we can find no foundation for suggesting new restrictions on testosterone therapy in men with cardiac disease."

The researchers reported their results² in the April 8, 2014 issue of Journal of Men's Health.

Disclosures:

References:

1. Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE. 2014;9: e85805. doi: 10.1371/journal.pone.0085805. (Full text PDF)

2. Miner M, Heidelbaugh JJ, Morgentaler A. Testosterone therapy and cardiovascular riks: a cautionary tale. J Men’s Health. 2014;11. doi: 10.1089/jomh.2014.3504 (Full text PDF)