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，由于全身性癌症治疗，可能发生认知问题。尽管在理解这些问题方面取得了进展，但仍然存在一些重要差距。一个值得注意的差距是缺乏对前列腺癌男性的研究，这是美国男性最常见的癌症。关注主要是每年估计有50,000名男性，他们是叶酸激素 - 释放激素（LHRH）激动剂治疗的候选者。问题反映了这些药物通过阻止睾丸激素的产生来抵抗前列腺癌的事实。除了产生可能干扰认知功能的副作用（例如疲劳，抑郁和潮热）外，LHRH激动剂可能对认知功能有直接影响。这包括研究表明，睾丸激素水平较低与健康老年男性的认知功能较差有关，而男性补充睾丸激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激动剂的前列腺癌患者的认知功能问题。但是，这些研究大多数的特征是方法论上的局限性（即，样本量，横断面研究设计的使用以及没有适当的比较组）的特征。此外，几乎没有努力检查可能是LHRH激动剂对认知功能的影响或确定可能减轻对认知功能影响的患者特征的影响的机制。考虑到这些问题，当前研究的目的是：1）确定归因于通过LHRH激动剂疗法治疗前列腺癌的认知功能变化的大小和特征； 2）检查睾丸激素和雌二醇与LHRH激动剂治疗期间认知功能变化的变化； 3）确定在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激动剂疗法有关的认知功能的变化； 4）确定LHRH激动剂疗法期间的认知困难是否是与睾丸激素下降有关的一系列症状的一部分，睾丸激素还包括潮热，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来解决，并匹配前列腺癌男性未接受LHRH激动剂疗法和没有癌症史的男性的比较样本。 公共卫生相关性段落：通过更多地了解接受荷尔蒙治疗前列腺癌所遇到的认知问题，我们希望为未来的努力奠定基础，以改善这些人的生活质量。该目标与改善国家癌症研究所2015年癌症患者的生活质量和幸存者的战略目标是一致的，该研究所在2015年国家癌症研究所（National Cancer Institute）的挑战目标中，消除了由于癌症而导致的痛苦和死亡。