Testosterone treatment raises levels of heart plaque detected on Coronary CT Angiography scans

Testosterone treatment raises levels of heart plaque

By Eric Barnes, AuntMinnie.com staff writer

February 22, 2017 — A new study using coronary CT angiography (CCTA) reveals that testosterone treatments may increase the risk of heart disease by raising the volume of arterial plaque by 20% among men 65 years and older. More research is needed to assess actual risk, according to a February 21 paper in the Journal of the American Medical Association.

The multicenter trial, which followed 138 men in the U.S. National Institutes of Health (NIH)-funded Testosterone Trials (TTrials), aimed to determine if testosterone treatment could help improve a series of end points in older men, including walking ability, vitality, balance, mood, bone health, and blood counts. The results showed that men who received testosterone treatments for a year had significant increases in total coronary and noncalcified plaque volumes at CCTA — while the increase was negligible in patients who had been given a placebo.

“It showed there was a 20% increase in plaque in those taking testosterone and just a couple percent increase in plaque in those taking a placebo,” said lead author Dr. Matthew Budoff, a cardiologist and researcher from the Los Angeles Biomedical Research Institute, in an interview with AuntMinnie.com. “There was much more atherosclerosis progression in those taking testosterone therapy.”

The results were the opposite of what the endocrinologists involved in the study had predicted — that testosterone would somehow have a protective effect.

“Clearly that was incorrect,” Budoff said.

Budoff’s co-authors from several U.S. institutions included Susan Ellenberg, PhD; Dr. Cora Lewis; Dr. Emile Mohler III; Dr. Nanette Wenger; Dr. Shalender Bhasin; and Dr. Peter Snyder (JAMA, February 21, 2017, Vol. 317:7, pp. 708-716).

Supplement’s inconclusive results

Testosterone replacement is being used with increasing frequency in aging men. Nevertheless, the cardiovascular benefits and risks of such supplementation have yielded conflicting results, the authors noted. Meta-analysis of several clinical trials showed no association between testosterone treatment and adverse events, but a clinical study of men with mobility limitations showed an excess of cardiovascular events with testosterone supplementation versus a placebo.

The Cardiovascular Trial of the TTrials aimed to test the hypothesis that testosterone treatment of older men with low testosterone actually slows progression of noncalcified coronary artery plaque volume. The 170 patients in the prospective trial were a subset of patients in the TTrials, which aimed to determine the efficacy of testosterone management of men 65 years and older with low testosterone.

While the TTrials looked at several end points for measuring the effects of testosterone supplementation, “there was no cardiovascular end point,” Budoff said. “So I went to the NIH and I was able to get funding for our study that looked at about 170 men.”

The participants had an average of two serum testosterone levels lower than 275 ng/dL. In all, 82 men were randomized to placebo and 88 to testosterone, applying either testosterone gel or a placebo gel for 12 months. The primary study outcome was noncalcified coronary artery plaque volume, as determined by CCTA acquired at baseline and again after the 12-month study period.

Of the 170 men enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) actually completed the study with results analyzed. At baseline, 70 men (50.7%) had Agatston scores of 300 or higher, indicating severe atherosclerosis.

Rapid plaque growth

Testosterone treatment versus the placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (p = 0.003), the authors concluded. In secondary outcomes, median total plaque volume again increased significantly from baseline to 12 months in the testosterone group but rose little in the placebo group (p = 0.003).