Men taking testosterone therapy had a 29 percent greater risk of death, heart attack and stroke according to a study of a "real world" population of men. An accompanying editorial in JAMA by an endocrinologist with the Perelman School of Medicine at the University of Pennsylvania notes that the mounting evidence of a signal of cardiovascular risk warrants cautious testosterone prescribing and additional investigation.

An estimated 2.9 percent of US men over 40 years old are prescribed testosterone therapy, yet there are limited randomized trial data examining the long term benefits and risks.

A study of patients in the VA system compared 1,223 men taking testosterone with 7,489 men not using testosterone and found a greater percentage of deaths, heart attacks and strokes in the testosterone group. Approximately 1 in 5 men not taking the therapy had such an event, whereas more than 1 in 4 men taking testosterone had a heart attack, stroke, or died over a three year period.

"We do not know if this risk extends to men who are taking testosterone for 'low T syndrome' or younger men taking it for physical enhancement, as there is a lack of long term safety data of testosterone therapy in men," said Anne Cappola, MD, ScM, associate professor of Medicine in the Division of Endocrinology, Diabetes, and Metabolism in the Perelman School of Medicine at the University of Pennsylvania. "But the men who were taking testosterone in this study were slightly healthier to begin with, and surprisingly had a higher risk of catastrophic events."

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