INTRODUCTION: In this article we advance a potential explanation for the incidence of cardiovascular (CV) and cardiometabolic risk in patients undergoing androgen deprivation therapy (ADT) for prostate cancer. Our conceptual model involves the differential impact of gonadotropin-releasing hormone (GnRH) agonists and antagonists on the follicle-stimulating hormone (FSH) system. MATERIALS AND METHODS: Authors searched online repositories and meeting abstract databases for relevant materials. RESULTS: Mounting evidence links FSH with development and progression of prostate cancer. What is also becoming clear is that the differential effects of GnRH agonists and antagonists on FSH may at least partially explain the differing effects these agents have on CV risk during ADT. While GnRH antagonists immediately suppress FSH, GnRH agonists provoke a transient surge in FSH that may contribute to the higher CV risk observed with these agents. Additionally, recent studies suggest that GnRH antagonists may significantly reduce CV risk compared to GnRH agonists, particularly in men with pre-existing CV disease. CONCLUSIONS: Patients with cardiovascular risk factors who require ADT may benefit from the better control of FSH provided by GnRH antagonists. ADT itself appears to heighten CV risk, and data suggest that FSH may at least partly drive this risk by promoting inflammation, atherosclerosis, insulin resistance, adipocyte rearrangement and plaque instability.
INTRODUCTION: In this article we advance a potential explanation for the incidence of cardiovascular (CV) and cardiometabolic risk in patients undergoing androgen deprivation therapy (ADT) for prostate cancer. Our conceptual model involves the differential impact of gonadotropin-releasing hormone (GnRH) agonists and antagonists on the follicle-stimulating hormone (FSH) system. MATERIALS AND METHODS: Authors searched online repositories and meeting abstract databases for relevant materials. RESULTS: Mounting evidence links FSH with development and progression of prostate cancer. What is also becoming clear is that the differential effects of GnRH agonists and antagonists on FSH may at least partially explain the differing effects these agents have on CV risk during ADT. While GnRH antagonists immediately suppress FSH, GnRH agonists provoke a transient surge in FSH that may contribute to the higher CV risk observed with these agents. Additionally, recent studies suggest that GnRH antagonists may significantly reduce CV risk compared to GnRH agonists, particularly in men with pre-existing CV disease. CONCLUSIONS:Patients with cardiovascular risk factors who require ADT may benefit from the better control of FSH provided by GnRH antagonists. ADT itself appears to heighten CV risk, and data suggest that FSH may at least partly drive this risk by promoting inflammation, atherosclerosis, insulin resistance, adipocyte rearrangement and plaque instability.
Authors: Herjan J T Coelingh Bennink; Jeroen A van Moorselaar; E David Crawford; Erik P M Roos; Diederik M Somford; Ton A Roeleveld; Tjard D de Haan; Harm H E van Melick; Yacov Reisman; Yvette Zimmerman; Gonnie van Osta; Jan Krijgh; Neal D Shore; Fred Saad; Andrew V Schally; Frans M J Debruyne Journal: Eur Urol Open Sci Date: 2021-05-06