What are the long-term consequences of testosterone replacement therapy? Based on results from a three-year study, researchers say testosterone has no effect on the progression of hardening of the arteries in older men with low to low normal testosterone levels. Unfortunately, these same men are unlikely to derive any benefits in terms of sexual function or quality of life from testosterone either, the Brigham and Women's Hospital researchers note. Win, lose?

From $324 million in 2002, pharmaceutical sales of testosterone skyrocketed to $2 billion in 2012, the Journal of the American Geriatric Society reported earlier this year, and these figures do not include the contributions made by Internet and direct-to-patient clinic transactions. By all accounts, the testosterone replacement drug business has grown substantially over the past decade and will likely continue to do so as the population ages. The risks and benefits of long-term use, though, have never been completely understood.

A natural hormone secreted by the testicles, testosterone is necessary for the development of male sexual characteristics. The hormone also contributes to muscle growth, bone mass, and sexual function. With age, men’s testosterone levels naturally decline by one percent a year, on average, after age 40.

Past studies have raised concerns about cardiovascular risks in men prescribed testosterone replacement therapy. Earlier this year, the Food and Drug Administration required manufacturers of approved pharmaceutical testosterone products change their labeling to add information about a possible increased risk of heart attacks and strokes in patients taking testosterone. Could T, as it is known, be bad for men?

The research team enrolled more than 300 men over the age of 60 with low to low normal range testosterone levels in a three-year, double-blind study. The researchers measured in each man two separate indicators of atherosclerosis or hardening of the arteries, which can trigger a life-threatening blood clot. To measure sexual function and quality of life, the research team asked participants to complete a 15-item questionnaire.

For three years, participants applied either a testosterone gel or a placebo gel daily.

At study’s end, the two groups of men did not differ significantly or meaningfully in terms of rates of hardening of the arteries. Yet, the testosterone gel also did not “significantly improve erectile or ejaculatory function, sexual desire, partner intimacy, or health-related quality of life,” wrote the researchers. They warn that more long-term data from large trials is needed to determine whether testosterone might have other major cardiovascular effects.

“These findings should not be interpreted as establishing cardiovascular safety of testosterone use in older men,” they concluded, adding the results suggest testosterone should never be used indiscriminately by any man.

Source: Basaria S, Harman SM, Travison TG, et al. Effects of Testosterone Administration for 3 Years on Subclinical Atherosclerosis Progression in Older Men With Low or Low-Normal Testosterone LevelsA Randomized Clinical Trial. JAMA. 2015.