Hypogonadism and Pain Perception in Androgen-Deprived Men with Prostate Cancer

描述（由申请人提供）：本提案的总体目标是评估接受雄激素剥夺治疗（ADT）的前列腺癌（PCa）患者临床和实验疼痛的变化，并将其与未接受ADT（非ADT）的前列腺癌（PCa）患者进行比较。ADT的使用与生活质量（QOL）的显著下降有关。这种下降在SF-36生活质量问卷的生理和心理组合中都很明显。身体合成的一个方面是对疼痛的感知。初步的横断面研究表明，与非ADT组和年龄匹配的健康对照组相比，接受ADT的男性报告更多的临床疼痛。即使在那些没有任何转移性疾病的雄激素缺乏的男性中也可以看到这种疼痛感的增加，这些发现暗示性腺功能减退是这些症状的主要病因。男性性腺功能减退是一种炎症状态，与IL-6和TNF-¿等促炎细胞因子的增加有关，这两种细胞因子都与临床和实验疼痛有关。雄激素剥夺疗法也与代谢异常有关，如胰岛素抵抗和高血糖症。因此，目前尚不清楚男性ADT患者疼痛发生率/严重程度的增加是由于性腺功能减退的直接影响还是这些代谢异常的继发影响。我们提出了一项前瞻性研究，其中：1)我们将比较接受ADT和非ADT的男性在6个月的时间内临床疼痛报告和心理生理疼痛反应的变化；2)我们将评估接受ADT的男性中各种代谢和炎症标志物与疼痛感知和疼痛阈值的关联。拟议的研究，除了推进我们对ADT男性疼痛发展机制的理解之外，可能对ADT患者的整体健康管理产生重大的临床影响。本研究的结果将指导医生将ADT用于适当的适应症，并筛选这些患者在ADT期间的意外疼痛。由于雄激素替代是PCa患者的禁忌症，本研究将为评估新型抗炎药、胰岛素增敏剂或选择性雄激素受体调节剂在ADT期间预防和治疗疼痛中的作用的前瞻性试验奠定基础。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to evaluate the change in clinical and experimental pain in men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT) and compare them with men with PCa not receiving ADT (non-ADT). The use of ADT is associated with a significant decrease in quality of life (QOL).This decrease is evident in both physical and mental composites of SF-36 QOL questionnaire. One of the aspects of the physical composite is the perception of pain. Preliminary cross-sectional studies have shown that men undergoing ADT report more clinical pain when compared with men in the non-ADT group and with age-matched healthy controls. As this increased pain perception is seen even in those androgen-deprived men without any metastatic disease, these findings implicate profound hypogonadism as the main etiology for these symptoms. Male hypogonadism is an inflammatory state associated with an increase in pro-inflammatory cytokines like IL-6 and TNF-¿, both of which have been associated with clinical and experimental pain. Androgen deprivation therapy is also associated with metabolic abnormalities such as insulin resistance and hyperglycemia. Hence, it is unclear whether the increased prevalence/severity of pain in men on ADT is due to direct effects of hypogonadism or secondary to these metabolic abnormalities. We propose a prospective study in which: 1) we will compare changes in clinical pain reports and psychophysical pain responses between men undergoing ADT vs. non-ADT over a 6-month time period, and 2) We will assess the associations of various metabolic and inflammatory markers with pain perception and pain threshold in men undergoing ADT. The proposed study, in addition to advancing our understanding of the mechanism of pain development in men on ADT, is likely to have a significant clinical impact on the overall health-management of patients on ADT. The results of this study will guide physicians to use ADT for appropriate indications and to screen these patients for incident pain during ADT. Since androgen replacement is contraindicated in men with PCa, this study will lay the groundwork for prospective trials assessing the role of novel anti-inflammatory agents, insulin- sensitizing agents or SARMS (selective androgen receptor modulators) in the prevention and treatment of pain during ADT.