Hormonal Therapy for Prostate Cancer

Abstract 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 t...

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Bibliographic Details
Published in:Endocrine reviews 2021-06, Vol.42 (3), p.354-373
Main Authors: Desai, Kunal, McManus, Jeffrey M, Sharifi, Nima
Format: Article
Language:English
Subjects:
Androgen Antagonists - therapeutic use
Androgen Receptor Antagonists - therapeutic use
Androgen receptors
Androgens
Androgens - therapeutic use
Antagonists
Antimitotic agents
Antineoplastic agents
Biosynthesis
Cancer
Care and treatment
Corticosteroids
Deprivation
Endocrine therapy
Gonadotropin-releasing hormone
Gonadotropins
Health aspects
Humans
Male
Metabolism
Metastases
Metastasis
Physiological aspects
Pituitary (anterior)
Pituitary hormones
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Prostatic Neoplasms, Castration-Resistant - drug therapy
Prostatic Neoplasms, Castration-Resistant - pathology
Receptors, Androgen - therapeutic use
Review
Testosterone
Testosterone - therapeutic use
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Summary:Abstract 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. Graphical Abstract Graphical Abstract
ISSN:0163-769X
1945-7189
1945-7189
DOI:10.1210/endrev/bnab002