Androgen deprivation therapy and cardiovascular risk in prostate cancer

Androgen-deprivation therapy (ADT), with or without palliative local treatments, is the standard of care for many patients with locally-advanced and/or metastatic prostate cancer. However, the possible cardiovascular (CV) risks associated with gonadotropin-releasing hormone (GnRH) antagonists and agonists continue to be the subject of concern, especially in a patient population that may already be at increased CV risk. The present review provides a narrative summary of the evidence regarding the CV risks associated with GnRH antagonists and agonists from randomized clinical trials (RCTs), real-world evidence, and meta-analyses. From RCTs, it appears clear that there is a direct class effect for CV risk in patients with prostate cancer being administered GnRH agonists and antagonists, with the latter being associated with reduced CV risk. Real-world data and the available meta-analyses largely indicate that CV risk is lower with GnRH antagonists than with GnRH agonists. A review of the pathophysiological mechanisms of gives further support to the possibility that GnRH antagonists are associated with lower CV risk than agonists. It can be highlighted that when treating patients with advanced or metastatic prostate cancer it is important to screen for underlying comorbidities prior to choosing the most appropriate therapy; moreover, patients should be closely monitored for factors associated with CV risk in order to optimize outcomes. Further studies are needed to define the most appropriate treatment according to the individual patient characteristics.