Research Needed to Evaluate Cardiovascular Risks and Testosterone Replacement Therapy

While effects of testosterone replacement therapy on cardiovascular risks and mortality remain controversial, there may be potential benefits of the hormone.

Researchers have called for a large, prospective, long-term study of testosterone replacement therapy (TRT) to accurately assess its effects on cardiovascular (CV) disease and risk.

In a state-of-the-art review published in the Journal of the American College of Cardiology, authors describe how low testosterone levels have been associated with atherosclerosis, coronary artery disease, and other CV events. Interestingly, the hormone may also play a vital role in treating heart failure, myocardial ischemia, and angina.

In heart failure, intravenously administered testosterone will increase cardiac input and reduce peripheral vascular resistance. Circulating levels of inflammatory markers, including tumor necrosis factor alpha and interlekin-1 beta, may also be reduced, which could lead to a reduction of left ventricular muscle fibrosis.

In myocardial ischemia, testosterone may be able to reduce infarct size. “Larger studies are needed to determine whether testosterone has future potential as an anti-ischemic, antianginal therapy,” researchers wrote.

The proposed study should include men who have symptomatic hypogonadism (the condition of low testosterone), verified by low T (total, free, bioavailable) levels obtained on at least 2 separate morning blood draws. The primary end point would be defined as major adverse CV/cerebrovascular events (myocardial infarction, stroke, CV death), and secondary end points should include hospitalization for acute coronary syndrome and/or heart failure, patient vital signs (heart rate and blood pressure), electrocardiogram, and any prostate abnormalities.

“Whereas most epidemiological studies have suggested that low T is associated with increased atherosclerotic disease,” the authors wrote, “there is a raging controversy about the effects of TRT on CV events and mortality. Meta-analyses published between 2005 and 2010 show that TRT, in general, had neutral effects on the occurrence of major, adverse CV events; testosterone did increase hematocrit and hemoglobin, and various small effects on lipid levels.”

In March 2015, the US Food and Drug Administration (FDA) stated that TRT should only be used for men with “documented low testosterone caused by specific medical conditions. They also wrote that the benefits and safety of TRT are not clear for the aging male with low testosterone, even if symptomatic.” The FDA later required label changes to include additional warnings and called for additional studies to determine TRT’s safety.

The authors concluded that in their opinion, “patients with recent MI, revascularization, poorly controlled HF, or stroke within the last 6 months are not good candidates for the initiation or maintenance of TRT, given the uncertainty of CV risk.”

Disclosures: The authors report various ties to the pharmaceutical industry, including consulting for Abbvie and Teso-Rx.


Kloner RA, Carson C, Dobs A, Kopecky S, Mohler ER. Testosterone and cardiovascular disease. J Am Coll Cardiol. 2016;67(5):545-557. doi: 10.1016/j.jacc.2015.12.005.