Study Suggests Testosterone Therapy Associated with Adverse Cardiovascular Outcomes among Veterans
BACKGROUND:
Annual prescriptions for testosterone increased by more than five-fold from 2000 to 2011, reaching 5.3 million prescriptions and a market of $1.6 billion in 2011. Professional society guidelines recommend testosterone therapy for patients with symptomatic testosterone deficiency; however, the effects of testosterone therapy on cardiovascular outcomes and mortality are unknown. This retrospective cohort study evaluated the association between the use of testosterone therapy and all-cause mortality, myocardial infarction (MI), and/or stroke among male Veterans who underwent coronary angiography in VA and had low testosterone levels between 2005 and 2011. Veterans were categorized as initiating testosterone therapy if they had filled a prescription for testosterone gel, patch, or injections following coronary angiography. Veterans were placed into two groups: those who received no testosterone therapy (n=7,486) and those who received testosterone therapy (n=1,223). Investigators also adjusted for the following variables: demographics; comorbidities, particularly the presence of coronary artery disease (CAD); and procedures (e.g., prior revascularization).
FINDINGS:
- The use of testosterone therapy was associated with increased risk of mortality, MI, and/or ischemic stroke. This association was consistent among patients with and without CAD.
- In 1,223 Veterans on testosterone therapy, there were 67 deaths, 23 MIs, and 33 strokes. The absolute rate of events was 26% in the testosterone therapy group and 20% in the no-testosterone therapy group at 3 years after angiography, corresponding to one additional event for every 17 Veterans begun on testosterone.
- The increased risk of adverse outcomes associated with testosterone therapy use was not related to differences in risk factor control or rates of secondary prevention medication use since patients in both groups had similar blood pressure, LDL levels, and use of secondary prevention medications.
LIMITATIONS:
- Given the observational nature of the study, unmeasured confounding or hidden bias might exist.
- Outcomes were determined using ICD-9 codes and were not validated by chart review. However, ICD-9 codes have been shown to be valid in determining outcomes including stroke and myocardial infarction in VA cohorts.
IMPLICATIONS:
- Authors suggest that while physicians should continue to discuss the symptomatic benefits of testosterone therapy with patients, it is also important to inform them that long-term risks are unknown and that there is a possibility that testosterone therapy might be harmful.
AUTHOR/FUNDING INFORMATION:
Drs. Maddox and Bradley were supported by HSR&D Career Development Awards. Dr. Ho is with HSR&D's Center for Innovation for Veteran-Centered and Value-Driven Care in Denver, and Drs. Rumsfeld, Maddox, Bradley, and Ho are part of VA/HSR&D's Ischemic Heart Disease Quality Enhancement Research Initiative (QUERI).
Vigen R, O’Donnell C, Bar?n A, Grunwald G, Maddox T, Bradley S, Barqawi A, Woning G, Wierman M, Plomondon M, Rumsfeld J, and Ho P. Association of Testosterone Therapy with Mortality, Myocardial Infarction, and Stroke in Men with Low Testosterone Levels. JAMA November 6, 2013;310(17):1829-36.
