LHRH Agonist Therapy and Cognitive Functioning in Men with Prostate Cancer

描述(由申请人提供)： 越来越多的证据表明，系统性癌症治疗可能会导致认知问题。尽管在理解这些问题方面取得了进展，但仍存在几个重要差距。一个值得注意的差距是缺乏对前列腺癌男性的研究，前列腺癌是美国男性最常见的癌症。据估计，每年有50,000名男性接受促黄体激素释放激素(LHRH)激动剂的治疗，这主要是令人担忧的。这种担忧反映了这样一个事实，即这些药物通过阻止睾丸素的产生来对抗前列腺癌。LHRH激动剂除了会引起干扰认知功能的副作用(如疲劳、抑郁和潮热)外，还可能对认知功能产生直接影响。这方面的证据包括研究表明，在健康的老年男性中，睾丸素水平较低与认知功能较差有关，而男性补充睾丸素与认知功能的改善有关。其他证据包括少量研究表明，接受LHRH激动剂治疗的前列腺癌患者存在认知功能问题。然而，大多数这些研究的特点是方法上的局限性(即样本量小，使用横断面研究设计，以及缺乏适当的比较组)。此外，很少有人研究LHRH激动剂对认知功能影响的可能机制，或者确定可能缓和其对认知功能影响的患者特征。考虑到这些问题，目前这项研究的目的是：1)确定可归因于LHRH激动剂治疗前列腺癌的认知功能变化的幅度和特征；2)检查睾酮和雌二醇的变化与LHRH激动剂治疗期间认知功能变化的关系；3)确定其他人群中与认知功能相关的基因变异是否预测与接受LHRH激动剂治疗有关的认知功能变化；以及4)确定LHRH激动剂治疗期间的认知困难是否是与睾酮下降有关的一系列症状的一部分，这些症状还包括潮热、疲劳、抑郁症状和性欲丧失。这些目标将通过对接受LHRH激动剂治疗的前列腺癌患者的研究，以及没有接受LHRH激动剂治疗的前列腺癌患者和没有癌症病史的男性的匹配比较样本来实现。 公共卫生相关段落：通过更多地了解接受前列腺癌激素治疗的男性所经历的认知问题，我们希望为未来改善这些人的生活质量的努力奠定基础。这一目标与国家癌症研究所2015年消除癌症带来的痛苦和死亡的挑战目标中概述的提高癌症患者和幸存者的生活质量的战略目标是一致的。

DESCRIPTION (provided by applicant): A growing body of evidence suggests cognitive problems can occur as a consequence of systemic cancer treatment. Although progress has been made in understanding these problems, several important gaps remain. One notable gap is the lack of research on men with prostate cancer, the most common cancer in U.S. men. Concern rests primarily with the estimated 50,000 men per year who are candidates for treatment with luteinizing hormone- releasing hormone (LHRH) agonists. The concern reflects the fact that these agents act against prostate cancer by blocking testosterone production. In addition to giving rise to side effects that can interfere with cognitive functioning (e.g., fatigue, depression, and hot flashes), LHRH agonists may have a direct effect on cognitive functioning. Evidence for this includes studies showing that lower levels of testosterone are associated with poorer cognitive functioning in healthy older men and that testosterone supplementation in men is associated with improvements in cognitive functioning. Additional evidence includes a small number of studies showing problems with cognitive functioning among prostate cancer patients receiving LHRH agonists. Most of these studies, however, have been characterized by methodological limitations (i.e., small sample sizes, use of cross-sectional research designs, and absence of appropriate comparison groups). In addition, there has been little effort to examine mechanisms that may underlie the impact of LHRH agonists on cognitive functioning or to identify patient characteristics that may moderate their impact on cognitive functioning. With these issues in mind, the aims of the current study are: 1) to identify the magnitude and features of changes in cognitive functioning attributable to treatment of prostate cancer with LHRH agonist therapy; 2) to examine the relationship of changes in testosterone and estradiol to changes in cognitive functioning during treatment with LHRH agonist therapy; 3) to identify whether genetic variations associated with cognitive functioning in other populations are predictive of changes in cognitive functioning related to receipt of LHRH agonist therapy; and 4) to identify whether cognitive difficulties during LHRH agonist therapy are part of a cluster of symptoms related to declines in testosterone that also includes hot flashes, fatigue, depressive symptoms, and loss of sexual desire. These aims will be addressed through the study of men with prostate cancer receiving LHRH agonist therapy and matched comparison samples of men with prostate cancer not receiving LHRH agonist therapy and men with no history of cancer. Public Health Relevance Paragraph: By learning more about the cognitive problems experienced by men receiving hormonal therapy for prostate cancer, we hope to lay the groundwork for future efforts to improve the quality of life of these individuals. This aim is consistent with the strategic objective of improving the quality of life of cancer patients and survivors outlined in the National Cancer Institute's 2015 Challenge Goal of Eliminating the Suffering and Death Due to Cancer.