The role of androgen therapy in prostate cancer: from testosterone replacement therapy to bipolar androgen therapy

• Published in: Drug discovery today Vol. 26; no. 5; pp. 1293 - 1301
• Main Authors: Xie, Tao, Song, Xian-Lu, Wang, Chong, Yu, Yu-Zhong, Wang, Jing-Quan, Chen, Zhe-Sheng, Zhao, Shan-Chao
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2021
• Subjects: Androgens - administration & dosage; Androgens - metabolism; Animals; Hormone Replacement Therapy - adverse effects; Hormone Replacement Therapy - methods; Humans; Male; Prostatic Neoplasms - etiology; Prostatic Neoplasms - therapy; Prostatic Neoplasms, Castration-Resistant - etiology; Prostatic Neoplasms, Castration-Resistant - therapy; Testosterone - administration & dosage; Testosterone - adverse effects; Testosterone - deficiency
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2021.01.034

•An overview of the re-evaluation of the relationship between androgen and PC in the historical development.•Paradoxical view of androgen saturation model outlines a critical role that the effect of androgens on PC cell proliferation is biphasic.•TRT can improve TD symptoms and confers significant health benefits in patients with non-cancer or early stage PC without stimulating cancer progression or recurrence.•New clinical trials data suggests there may even be a therapeutic role for BAT in men with advanced PC and potential mechanisms are emphasized. Testosterone replacement therapy (TRT) is the primary treatment for male testosterone deficiency. This therapy raises concerns over the risk of prostate cancer (PC), because testosterone has historically been considered the fuel for PC. We discuss the re-evaluation of the relationship between androgen and PC, and highlight the safety of TRT in the treatment of symptomatic men with testosterone deficiency who have low-risk disease after treatment for localized PC with surgery or radiation. Furthermore, we review the clinical application and potential mechanisms of bipolar androgen therapy (BAT) in the treatment of castration-resistant PC, emphasizing that much remains to be done before BAT can be broadly applied.