BACKGROUND Androgen deprivation therapy (ADT) is the backbone of systemic therapy for men with prostate cancer (PC); almost one-half of patients receive treatment during their disease course. However, a range of cognitive and other central nervous system (CNS) changes have been associated with ADT. In this review, we discuss extant data describing these complications and the mechanisms through which medications used to deliver ADT may affect them. METHODS We performed a MEDLINE search for appropriate papers published between January 2000 and December 2018. Relevant papers were selected and reviewed; additional publications were identified by manually assessing references from included papers, and recent congress abstracts. RESULTS Of ~230 search outputs, 33 were selected for inclusion. Some studies suggested a clear association between ADT and CNS effects in men with PC, whereas others did not. Accurate assessment is limited by test instrument variability, inadequate sample sizes, short follow-up duration, and limited prospective longitudinal studies. The approved second-generation androgen receptor (AR) inhibitors enzalutamide and apalutamide were associated with some CNS-related adverse events (AEs) in clinical studies, including fatigue (which can interfere with cognitive function). The androgen synthesis inhibitor abiraterone acetate was associated with a low CNS AE profile when compared with enzalutamide. The AR antagonist darolutamide demonstrated a comparable incidence of cognitive disorder in clinical trials to that of ADT alone. CONCLUSIONS Adequately caring for men receiving ADT requires an understanding of the symptoms, incidence and magnitude of cognitive effects, and a feasible approach to cognitive assessment and management in clinical settings. Some CNS effects could relate to blood-brain barrier penetration and direct AR inhibitor activity; drug safety profiles may differ by the degree of blood-brain barrier penetration of particular agents. Ongoing clinical trials seek to define the CNS tolerability of newer AR pathway-targeted therapy options more clearly.

中文翻译：

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前列腺癌治疗对中枢神经系统和认知功能影响的综述。

背景雄激素剥夺疗法（ADT）是男性前列腺癌（PC）全身治疗的支柱。几乎一半的患者在病程中接受治疗。然而，一系列认知和其他中枢神经系统 (CNS) 变化与 ADT 相关。在这篇综述中，我们讨论了描述这些并发症的现有数据以及用于 ADT 的药物可能影响这些并发症的机制。方法 我们对 2000 年 1 月至 2018 年 12 月期间发表的适当论文进行了 MEDLINE 检索。选择并审查了相关论文；通过手动评估所包含论文和最近的大会摘要中的参考文献，确定了其他出版物。结果 在约 230 个搜索输出中，选择包含 33 个。一些研究表明 ADT 与 PC 男性中枢神经系统的影响之间存在明显关联，而其他研究则不然。准确的评估受到测试仪器变异性、样本量不足、随访时间短和前瞻性纵向研究有限的限制。临床研究中，已批准的第二代雄激素受体（AR）抑制剂恩杂鲁胺和阿帕鲁胺与一些中枢神经系统相关不良事件（AE）相关，包括疲劳（可能干扰认知功能）。与恩杂鲁胺相比，雄激素合成抑制剂醋酸阿比特龙与较低的 CNS AE 相关。AR 拮抗剂达洛鲁胺在临床试验中表现出与单独使用 ADT 相当的认知障碍发生率。结论 充分护理接受 ADT 的男性需要了解认知影响的症状、发生率和程度，以及临床环境中认知评估和管理的可行方法。一些中枢神经系统效应可能与血脑屏障渗透和直接 AR 抑制剂活性有关；药物安全性可能因特定药物的血脑屏障渗透程度而异。正在进行的临床试验旨在更清楚地定义新的 AR 通路靶向治疗方案的中枢神经系统耐受性。