Bipolar Androgen Therapy: When Excess Fuel Extinguishes the Fire

• Published in: Biomedicines Vol. 11; no. 7; p. 2084
• Main Authors: Nabavi, Nima, Mahdavi, Seied Rabi, Ardalan, Mohammad Afshar, Chamanara, Mohsen, Mosaed, Reza, Lara, Aline, Bastos, Diogo, Harsini, Sara, Askari, Emran, Velho, Pedro Isaacsson, Bagheri, Hamed
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2023; MDPI
• Subjects: Acetic acid; Androgen receptors; Androgens; bipolar androgen therapy (BAT); Cancer; Cancer therapies; Care and treatment; Castration; Cell cycle; Cell growth; Clinical trials; Development and progression; Gene amplification; Ligands; Metastasis; metastatic castration-resistant prostate cancer; positron emission tomography (PET); Prostate cancer; prostate-specific membrane antigen; Quality of life; Review; Steroids; supraphysiologic testosterone; Testosterone; Iran; novel hormonal agents (NHAs); prostate cancer; positron emission tomography (PET); metastatic castration-resistant prostate cancer; bipolar androgen therapy (BAT); supraphysiologic testosterone; prostate-specific membrane antigen
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11072084

Androgen deprivation therapy (ADT) remains the cornerstone of advanced prostate cancer treatment. However, the progression towards castration-resistant prostate cancer is inevitable, as the cancer cells reactivate androgen receptor signaling and adapt to the castrate state through autoregulation of the androgen receptor. Additionally, the upfront use of novel hormonal agents such as enzalutamide and abiraterone acetate may result in long-term toxicities and may trigger the selection of AR-independent cells through "Darwinian" treatment-induced pressure. Therefore, it is crucial to develop new strategies to overcome these challenges. Bipolar androgen therapy (BAT) is one such approach that has been devised based on studies demonstrating the paradoxical inhibitory effects of supraphysiologic testosterone on prostate cancer growth, achieved through a variety of mechanisms acting in concert. BAT involves rapidly alternating testosterone levels between supraphysiological and near-castrate levels over a period of a month, achieved through monthly intramuscular injections of testosterone plus concurrent ADT. BAT is effective and well-tolerated, improving quality of life and potentially re-sensitizing patients to previous hormonal therapies after progression. By exploring the mechanisms and clinical evidence for BAT, this review seeks to shed light on its potential as a promising new approach to prostate cancer treatment.