LHRH Agonist Therapy and Cognitive Functioning in Men with Prostate Cancer

LHRH 激动剂治疗和男性前列腺癌患者的认知功能

• 批准号: 7628543
• 负责人: PAUL B JACOBSEN
• 金额: $ 40.49万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7628543
• 关键词: Address; Adverse effects; Age; Alleles; Cancer Patient; Cessation of life; Characteristics; Clinical; Cognitive; Data; Diagnosis; Disease; Education; Elderly; Elderly man; Estradiol; Fatigue; Future; Genetic Status; Genetic Variation; Goals; Gonadal Steroid Hormones; Gonadotropin Hormone Releasing Hormone; Hormonal; Hot flushes; Individual; Learning; Luteinizing Hormone-releasing Hormone Agonist; Malignant Neoplasms; Malignant neoplasm of prostate; Mind; National Cancer Institute; Patients; Population; Production; Quality of life; Recording of previous events; Recruitment Activity; Reporting; Research; Research Design; Rest; Sample Size; Sampling; Supplementation; Survivors; Symptoms; Testosterone; Time; Variant; cancer therapy; cognitive function; comparison group; depression; depressive symptoms; experience; follow up assessment; genetic variant; hormone therapy; improved; men; older men; public health relevance; time interval

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.

描述（由申请人提供）： 越来越多的证据表明，全身癌症治疗可能会导致认知问题。尽管在理解这些问题方面已经取得了进展，但仍然存在一些重要的差距。一个显着的差距是缺乏对患有前列腺癌的男性的研究，前列腺癌是美国男性中最常见的癌症。人们主要担心的是每年估计有 50,000 名男性适合接受黄体生成素释放激素 (LHRH) 激动剂治疗。这种担忧反映了这样一个事实：这些药物通过阻断睾酮的产生来对抗前列腺癌。除了产生干扰认知功能的副作用（例如疲劳、抑郁和潮热）外，LHRH 激动剂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，健康老年男性的睾酮水平较低与认知功能较差有关，而男性补充睾酮与认知功能的改善有关。其他证据包括少数研究显示接受 LHRH 激动剂的前列腺癌患者存在认知功能问题。然而，大多数这些研究都存在方法学局限性（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，几乎没有人努力检查 LHRH 激动剂对认知功能影响的机制，或确定可能减轻其对认知功能影响的患者特征。考虑到这些问题，本研究的目的是：1）确定 LHRH 激动剂治疗前列腺癌引起的认知功能变化的程度和特征； 2) 检查LHRH激动剂治疗期间睾酮和雌二醇的变化与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遗传变异是否可以预测与接受 LHRH 激动剂治疗相关的认知功能变化； 4) 确定 LHRH 激动剂治疗期间的认知困难是否是与睾酮下降相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男性的研究以及未接受 LHRH 激动剂治疗的前列腺癌男性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。这一目标与美国国家癌症研究所 2015 年消除癌症痛苦和死亡挑战目标中概述的改善癌症患者和幸存者生活质量的战略目标一致。