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Testosterone therapy under fire for possible link to CV events
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After the publication of several studies and analyses linking testosterone therapy to elevated risk for CV events, the FDA announced Jan. 31 that it will re-evaluate the possible link to increased stroke, MI and death in men who use approved testosterone products.
The risk for CV events appears most pronounced in men aged at least 65 years and in men younger than 65 years who have a history of CVD.
Culley C. Carson III
In an interview with Cardiology Today, Culley C. Carson III, MD, FACS, said the recent data crystallize what health care professionals have known for a while.
“Testosterone is safe in the right patients, but it has to be the ‘right’ patients. And the right patients are those who are otherwise healthy and have measureable low testosterone,” said Carson, who is Rhodes distinguished professor of urology at the University of North Carolina, Chapel Hill.
Cardiology Today reviewed available evidence and interviewed experts on how to navigate the recent data while awaiting the FDA determination about the CV safety of approved testosterone therapies.
Data suggest elevated risks
The FDA’s decision to re-evaluate the safety of testosterone therapy follows results from two observational studies, according to a press release.
In late January, William D. Finkle, PhD, of Consolidated Research Inc., Los Angeles, and colleagues published in PLoS One findings from a retrospective cohort study suggesting an elevated risk for nonfatal acute MI in the 90 days after initial testosterone therapy prescription.
Finkle and colleagues reviewed records of 55,593 men prescribed testosterone therapy and 167,279 men prescribed a phosphodiesterase type 5 (PDE5) inhibitor such as sildenafil (Viagra/Revatio, Pfizer) or tadalafil (Cialis, Lilly). They compared the incidence rate of MI in the 90 days after initial prescription with the incidence rate of MI in the year before initial prescription. For men aged at least 65 years, the post/pre-prescription rate ratio for those prescribed testosterone was 2.19 (95% CI, 1.27-3.77) compared with 1.15 (95% CI, 0.83-1.59) for those prescribed PDE5 inhibitors. For men younger than 65 years with a history of CVD, the post/pre-prescription rate ratio for testosterone therapy was 2.9 (95% CI, 1.49-5.62) compared with 1.4 (95% CI, 0.91-2.14) for PDE5 inhibitors. Of note, the researchers observed no risk increase among younger men without a history of CVD.
The second study, published in JAMA in November by Rebecca Vigen, MD, MSCS, of the University of Texas at Southwestern Medical Center in Dallas, and colleagues, demonstrated greater risk for all-cause mortality, MI and ischemic stroke among men in the Veterans Affairs health care system prescribed testosterone therapy compared with those who did not use testosterone (HR=1.29; 95% CI, 1.04-1.58). In this study, the effect was similar regardless of the presence of CAD.
Other recent studies have suggested mixed results. A meta-analysis published in April of 27 trials covering 2,994 mostly elderly men found that testosterone therapy was associated with increased risk for a CV-related event (OR=1.54; 95% CI, 1.09-2.18), according to data from Lin Xu, BMed, MPH, MPhil, PhD, and colleagues. Carson and fellow researchers performed a review published in 2011 that demonstrated no link between testosterone therapy and elevated risk for CV events; however, the populations studied included a higher proportion of middle-aged men than those included in the more recent studies.
A call for evaluation of CV risk
In discussing results of the recent studies, Ravi Dave, MD, said one concern is that participants using testosterone therapy who had the higher risk for CV events had underlying CVD to begin with.
Ravi Dave
“Many patients are not aware of underlying CVD. They’re not getting proper checkups to evaluate their risks and have risk factors that are not fully treated,” said Dave, director of interventional cardiology at UCLA Medical Center.
The experts Cardiology Today interviewed said it is important to evaluate CV risk before prescribing testosterone therapy to any patient. Dave first suggested obtaining the patient’s medical history and determining whether he has any risk factors for CVD. A good method to assess a patient’s risk is the new 10-year risk calculator that was described in the American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk. “The patients who should definitely avoid using testosterone supplementation are those with documented heart disease of any kind, including a previous MI, stent or CABG,” Dave said.
Future concerns
As of press time, the FDA has not yet come to any conclusions regarding the risk for CV events with use of testosterone therapy. Until then, patients should not stop taking testosterone products without first consulting with a physician, and physicians should weigh the benefits and risks of testosterone when counseling patients, according to the press release.
The approved formulations under re-evaluation include topical gel, transdermal patch, buccal system and injection.
Although it is difficult to predict what the FDA will recommend after the re-evaluation of CV risks associated with approved testosterone therapies, Carson said a warning may be added to alert physicians of such risks. The ultimate goal should be to “bring it to the attention of prescribing physicians, where it may not be in the front of their brain when they’re prescribing testosterone.”
Dave suspects that, in the future, “the ease with which physicians were prescribing testosterone for patients is going to be significantly limited,” and there may be dose alterations or preparation changes.
“One of the bad messages that can come out of things like this is that people may become afraid to use testosterone,” Carson said. “It’s very safe, as long as it’s used in the right patients, controlled well and followed appropriately. It can help many men, but it’s not for everyone.” – by Erik Swain
Disclosure: Carson and Dave report no relevant financial disclosures.