1941年，去势治疗前列腺癌的好处被发现，导致雄激素剥夺疗法，它仍然是治疗晚期前列腺癌男性的重要策略。然而，早在这项最初的研究中，去势耐药性前列腺癌的不可避免发展就被认识到了。抵抗首先表现为雄激素反应基因PSA的持续升高，这与雄激素受体通路的重新激活一致。临床样本的评估表明，去势耐药前列腺癌细胞仍然依赖于雄激素信号，并适应慢性低睾酮状态。与此相矛盾的是，几项研究的结果表明，超生理水平的睾酮治疗可以减缓前列腺癌的生长。从这些研究中得出的启示被用于研究给前列腺癌患者施以超生理水平的睾酮，以获得临床益处，这被称为双向雄激素疗法（BAT）。BAT涉及从超生理睾酮水平迅速循环回接近去势睾酮水平的4周周期。了解BAT在分子和细胞水平的作用可能有助于合理地将BAT与其他药物结合起来，以实现更高的功效和肿瘤反应。© 2022. Springer Nature Limited.

The discovery of the benefits of castration for prostate cancer treatment in 1941 led to androgen deprivation therapy, which remains a mainstay of the treatment of men with advanced prostate cancer. However, as early as this original publication, the inevitable development of castration-resistant prostate cancer was recognized. Resistance first manifests as a sustained rise in the androgen-responsive gene, PSA, consistent with reactivation of the androgen receptor axis. Evaluation of clinical specimens demonstrates that castration-resistant prostate cancer cells remain addicted to androgen signalling and adapt to chronic low-testosterone states. Paradoxically, results of several studies have suggested that treatment with supraphysiological levels of testosterone can retard prostate cancer growth. Insights from these studies have been used to investigate administration of supraphysiological testosterone to patients with prostate cancer for clinical benefits, a strategy that is termed bipolar androgen therapy (BAT). BAT involves rapid cycling from supraphysiological back to near-castration testosterone levels over a 4-week cycle. Understanding how BAT works at the molecular and cellular levels might help to rationalize combining BAT with other agents to achieve increased efficacy and tumour responses.© 2022. Springer Nature Limited.