Division of Urology, University of California San Diego, La Jolla, California, USA.
Can J Urol. 2020 Apr;27(2):10167-10173.
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.
Authors searched online repositories and meeting abstract databases for relevant materials.
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.
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.
本文提出了一种可能的解释，即接受雄激素剥夺疗法（ADT）治疗前列腺癌的患者会出现心血管（CV）和心脏代谢风险。我们的概念模型涉及促性腺激素释放激素（GnRH）激动剂和拮抗剂对卵泡刺激素（FSH）系统的不同影响。
作者搜索了在线知识库和会议摘要数据库，以获取相关材料。
越来越多的证据将 FSH 与前列腺癌的发展和进展联系起来。同样清楚的是，GnRH 激动剂和拮抗剂对 FSH 的不同作用至少部分解释了这些药物在 ADT 期间对 CV 风险的不同影响。虽然 GnRH 拮抗剂立即抑制 FSH，但 GnRH 激动剂会引起 FSH 的短暂激增，这可能导致这些药物引起的更高 CV 风险。此外，最近的研究表明，与 GnRH 激动剂相比，GnRH 拮抗剂可能会显著降低 CV 风险，尤其是在患有预先存在的 CV 疾病的男性中。
需要 ADT 的有心血管危险因素的患者可能会从 GnRH 拮抗剂提供的更好的 FSH 控制中受益。ADT 本身似乎会增加 CV 风险，并且数据表明，FSH 至少部分通过促进炎症、动脉粥样硬化、胰岛素抵抗、脂肪细胞重排和斑块不稳定来驱动这种风险。
