GnRH Agonists Linked to Accelerated Coronary Plaque Progression Compared to Antagonists in Prostate Cancer Patients

Introduction: The Cardiovascular Paradox of Androgen Deprivation Therapy

Androgen deprivation therapy (ADT) has remained the cornerstone of management for men with intermediate-risk and high-risk localized, as well as metastatic, prostate cancer (PCa) for decades. By suppressing testosterone to castrate levels, ADT effectively inhibits tumor growth and improves oncological outcomes. However, this therapeutic benefit comes at a significant metabolic and cardiovascular cost. Clinicians have long observed that men undergoing ADT experience an increased risk of cardiovascular (CV) morbidity, including myocardial infarction, stroke, and sudden cardiac death.

Recent years have seen a shift in the pharmacological landscape of ADT, moving from traditional gonadotropin-releasing hormone (GnRH) agonists (like leuprolide) to GnRH antagonists (like relugolix). The landmark HERO trial previously demonstrated that relugolix was associated with a 54% lower risk of major adverse cardiovascular events (MACE) compared with leuprolide. Despite these clinical findings, the underlying biological mechanism—specifically how these two classes of drugs differentially affect the coronary vasculature—has remained elusive. A new randomized clinical trial by Patel et al., published in JAMA Cardiology, provides critical insights into this mystery by examining coronary plaque progression through advanced imaging.