Testosterone Treatment and Coronary Artery Plaque Volume in Older Men With Low Testosterone

Abstract

IMPORTANCERecent studies have yielded conflicting results as to whether testosterone treatment increases cardiovascular risk.OBJECTIVE To test the hypothesis that testosterone treatment of older men with low testosterone slows progression of noncalcified coronary artery plaque volume.DESIGN, SETTING, AND PARTICIPANTS Double-blinded, placebo-controlled trial at 9 academic medical centers in the United States. The participants were 170 of 788 men aged 65 years or older 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 between June 24, 2010, and June 9, 2014.INTERVENTION Testosterone gel, with the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURESThe primary outcome was noncalcified coronary artery plaque volume, as determined by coronary computed tomographic angiography. 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). RESULTSOf 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 (SD) age was 71.2 (5.7) years, and 81% were white. At baseline, 70 men (50.7%) had a coronary artery calcification score higher than 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 mm 3 to 232 mm 3 vs 317 mm 3 to 325 mm 3 , respectively; estimated difference, 41 mm 3 ; 95% CI, 14 to 67 mm 3 ; P = .003). For the secondary outcomes, the median total plaque volume increased from baseline to 12 months from 272 mm 3 to 318 mm 3 in the testosterone group vs from 499 mm 3 to 541 mm 3 in the placebo group (estimated difference, 47 mm 3 ; 95% CI, 13 to 80 mm 3 ; P = .006), and the median coronary artery calcification score changed from 255 to 244 Agatston units in the testosterone group vs 494 to 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 AND RELEVANCE 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, as measured by coronary computed tomographic angiography. Larger studies are needed to understand the clinical implications of this finding.

Higher circulating androgens and higher physical activity levels are associated with less central adiposity and lower risk of cardiovascular death in older men

“…The Cardiovascular sub‐study of T‐Trials reported a greater increase in non‐calcified coronary plaque volume in men following one year of T treatment compared to placebo . At baseline, 50% of these men had severe atherosclerosis, emphasizing that the highly specific selection of men with low circulating T produced a cohort with high rates of established atherosclerosis.…”

The role of testosterone in MS risk and course

“…In the cardiovascular trial, the researchers found that the volume of arterial plaque increased significantly more in the testosterone-treated group compared to the untreated control group. 52 For the cognition trial, after a year of treatment, there was no significant change in verbal memory, visual memory, or problem solving. 53 In a pilot clinical trial in humans with MS, 10 male MS patients aged <65 years were treated with 10 g of gel containing 100 mg of testosterone in a cross-over design (6-month observation period followed by 12 months of treatment).…”

Erectile dysfunction and testosterone deficiency as cardiovascular risk factors?

“…Recently meta‐analyses have reported the positive impact of T therapy on insulin resistance and glycaemic control in men with diabetes and metabolic disease (Figure 3) . Six well‐conducted studies have evaluated patients properly diagnosed and treated to target levels for sufficient duration …”

“…Sharma et al retrospectively evaluated 83 010 male veterans with documented low TT levels. The subjects were categorised into 3 groups: T therapy with resulting normalisation of TT levels (group 1), defined as the lower limit of the laboratory reference range; T therapy without normalisation of TT levels (group 2); and did not receive T therapy (group 3).…”