Androgen deprivation therapy (ADT) for prostate cancer has been associated with cardiovascular morbidity, although biological mechanisms remain under investigation. This open-label randomized clinical trial published in JAMA Cardiology evaluated whether ADT accelerates coronary atherosclerosis and whether effects differ between a gonadotropin-releasing hormone (GnRH) agonist and antagonist.

Men with nonmetastatic prostate cancer without prior ADT exposure and scheduled for pelvic radiotherapy with at least 6 months of ADT were enrolled at four centers affiliated with a single academic institution in Atlanta, Georgia. Participants were randomized 1:1 to the GnRH agonist leuprolide or the GnRH antagonist relugolix. The primary endpoint was change in coronary artery total plaque volume (TPV), measured by coronary computed tomographic angiography at baseline and 12 months after ADT initiation. The secondary endpoint was change in noncalcified plaque volume (NCPV). Other outcome measures included change in calcified plaque volume (CPV) and low-attenuation plaque volume (LAPV).

Of 65 enrolled men, 62 (31 per arm) completed all procedures. Mean age was 68.5 (8.5) years; 56% were on statins. Compared with relugolix, leuprolide was associated with greater 12-month increases in TPV (+68.9 mm³; 95% CI 23.2–114.5; P=.02) and NCPV (+64.5 mm³; 95% CI 31.6–97.3; P=.004), adjusted for baseline plaque volume, age, and statin use. No significant differences were observed for CPV or LAPV.

Leuprolide was associated with greater coronary plaque progression than relugolix at 12 months. Differences were driven by increases in noncalcified plaque volume.