Testosterone Treatment and Coronary Artery Plaque Volume

Study Questions:

What is the impact of testosterone treatment of older men with low testosterone on progression of noncalcified coronary artery plaque volume?

Methods:

This was a double-blinded, placebo-controlled trial at nine academic medical centers in the United States. The participants were 170 of 788 men aged ≥65 years with an average of 2 serum testosterone levels lower than 275 ng/dl (82 men assigned to placebo, 88 to testosterone) and symptoms suggestive of hypogonadism, who were enrolled in the Testosterone Trials. Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months was administered. The primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography (CCTA). Secondary outcomes included total coronary artery plaque volume and coronary artery calcium score (range of 0 to >400 Agatston units, with higher values indicating more severe atherosclerosis).

Results:

Of 170 men who were enrolled, 138 (73 receiving testosterone treatment and 65 receiving placebo) completed the study and were available for the primary analysis. Among the 138 men, the mean (standard deviation) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score >300 Agatston units, reflecting severe atherosclerosis. For the primary outcome, testosterone treatment compared with placebo was associated with a significantly greater increase in noncalcified plaque volume from baseline to 12 months (from median values of 204-232 mm3 vs. 317-325 mm3, respectively; estimated difference, 41 mm3; 95% confidence interval [CI], 14-67 mm3; p = 0.003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272-318 mm3 in the testosterone group versus from 499-541 mm3 in the placebo group (estimated difference, 47 mm3; 95% CI, 13-80 mm3; p = 0.006), and the median coronary artery calcification score changed from 255-244 Agatston units in the testosterone group versus 494-503 Agatston units in the placebo group (estimated difference, −27 Agatston units; 95% CI, −80 to 26 Agatston units). No major adverse cardiovascular events occurred in either group.

Conclusions:

The authors concluded that among older men with symptomatic hypogonadism, treatment with testosterone gel for 1 year compared with placebo was associated with a significantly greater increase in coronary artery noncalcified plaque volume.

Perspective:

This study reports that a year of testosterone treatment in men aged ≥65 years with low testosterone was associated with an increase in noncalcified coronary artery plaque volume, as determined by CCTA. Furthermore, testosterone treatment was also associated with increased total plaque volume, but not with changes in coronary artery calcium score. This trial was not powered to assess impact of testosterone treatment on major adverse cardiovascular events, and additional larger studies are indicated to assess hard clinical outcomes given the concerning finding of increased plaque volume. Clinicians should factor in the adverse effects of testosterone on plaque volume when prescribing these medications.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging

Keywords: Angiography, Atherosclerosis, Coronary Artery Disease, Diagnostic Imaging, Hypogonadism, Plaque, Atherosclerotic, Primary Prevention, Testosterone, Tomography, X-Ray Computed


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