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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. [ABSTRACT FROM AUTHOR]

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.

In 1941, Dr. Huggins discovered the effectiveness of castration for prostate cancer, and this then became the main treatment for the management of prostate cancer. Although many new drugs have since been developed, they need to be used in combination with androgen deprivation therapy (ADT). In recent years, prospective randomized trials have evaluated the effectiveness of ADT combination. A comparison of 96 cases of castration-resistant prostate cancer treated with docetaxel + ADT and 102 cases treated with docetaxel alone, showed no significant difference in overall survival. Another phase II randomized trial of hormone-sensitive prostate cancer compared three treatment groups: (1) abiraterone (AAP) + ADT, (2) apalutamide (APA) alone, and (3) AAP + APA. Most patients treated with APA plus AAP (97.4%) and APA (90.0%) had a PSA decline of 80%, similar to the 100% treated with ADT plus AAP. Moreover, several studies have confirmed the clinical benefit of bipolar androgen therapy (BAT), in which the serum testosterone levels are rapidly driven to a supraphysiologic range followed by a return to near-castrate levels over a 28-day cycle. These reports suggest that continuous use of ADT may not be necessary in certain situations. Further research regarding the continuous use of ADT is warranted in the future since this therapy may not be necessary in certain situations. [ABSTRACT FROM AUTHOR]