Prescribing Testosterone Therapy May Increase Risk of Cardiovascular Complications

APRIL 08, 2014
Deviney Chaponis, MS IV, and Frank J. Domino, MD


Vigen R, O’Donnell C, Baron A, Grunwald G, Maddox T, Bradley S, Barqawi A, Woning G, Wierman M, Plomondon M, Rumsfeld J, Ho M. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310(17):1829-36.

Study Methods

This retrospective cohort study examined the medical records of 8,709 male patients with low testosterone who underwent cardiac catheterization at hospitals in the US Veterans Affairs (VA) system between 2005 and 2011.
The investigators used the VA Clinical Assessment Reporting and Tracking (CART) program to compare outcomes between patients who initiated testosterone supplementation after their initial catheterizations with those who did not take the drug after catheterization.
Patient outcomes defined by the ICD-9 codes for myocardial infarction (MI), stroke, or any other cause of death were compared between the 2 groups and used to estimate percent survival at 500, 1,000, 1,500, and 2000 days after testosterone treatment initiation.

Patient Demographics

Participants were male veterans with a mean age between 60 and 63 years who underwent coronary angiography, had low levels of serum testosterone (<300 ng/dL), and had never previously used any form of testosterone treatment. Patients were excluded if they had taken testosterone after MI or had hematocrit >50% or a prostate-specific antigen (PSA) level >4 ng/mL.
With the exception of lower mean diastolic blood pressure in the testosterone-treated group compared to control subjects after 2 years of testosterone supplementation, the authors found age, presence of coronary artery disease (CAD), blood pressure, and cholesterol levels were not significantly different between the 2 groups. Of the 8,709 men studied, 20% had a history of MI, 50% had diabetes, and >80% had CAD, which was defined as >20% stenosis of one or more epicardial vessels. 

Intervention and Control

Using data from the VA pharmacy dispensary, patients were assigned to the intervention group if they filled at least one prescription for testosterone gel, patch, or injection after a median of 531 days post-coronary catheterization. Of the 1,223 patients in the intervention group, 13 (1.1%) were prescribed the gel, 436 (35.7%) received the injections, and 774 (63.3%) used a testosterone patch. However, there was no significant difference in risk of adverse outcomes between the formulations.
The study’s primary combined endpoint was time to all-cause death or hospitalization for MI or stroke. 

Results and Outcomes

After 3 years, 25.7% of those receiving testosterone therapies had an adverse cardiovascular (CV) outcome compared to 19.9% of those who did not receive testosterone. Testosterone use was also associated with increased risk of adverse outcomes, including all-cause mortality, MI, and ischemic stroke. The findings remained unchanged after adjusting for the presence of CVD.


Men with known CVD who receive testosterone therapy experience an increased risk of death, stroke, and heart attack.

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