Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with nonmetastatic advanced prostate cancer, as well as frankly metastatic disease. Today’s standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g., leuprolide), second-generation nonsteroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today’s standard of care will require an accounting of an individual’s androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.

中文翻译：

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前列腺癌的激素疗法


Huggins和Hodges在20世纪40年代证明了性腺睾酮剥夺的治疗效果，因此牢固地确立了前列腺癌是一种高度雄激素依赖性疾病的概念。从那时起，激素疗法经历了迭代发展，从性腺睾酮剥夺的类型到阻止肾上腺和其他性腺外雄激素生成的方式，再到直接结合和抑制雄激素受体（AR）的方式。前列腺癌的临床状态是这些疗法与非转移性晚期前列腺癌以及坦率地说转移性疾病叠加的产物。当今晚期前列腺癌的标准治疗包括促性腺激素释放激素激动剂（例如亮丙瑞林）、第二代非甾体 AR 拮抗剂（恩杂鲁胺、阿帕鲁胺和达洛鲁胺）和雄激素生物合成抑制剂阿比特龙。本综述的目的是对前列腺癌各种临床状态的激素疗法进行评估。当今护理标准的进步将需要对个体的雄激素生理学进行核算，该生理学最近还认识到外周雄激素代谢的种系决定因素，其中包括HSD3B1遗传。