Effect of exercise on cortisol dysregulation in ovarian cancer survivors

描述（由申请人提供）：没有有效的卵巢癌筛查试验，症状是非特异性的，导致大多数（85%）卵巢癌女性被诊断为晚期（区域或远处癌症）疾病。晚期诊断为卵巢癌的女性预后相对较差（5年生存率：区域性癌症为72%，远处癌症为27%），疾病和治疗对生活质量（QOL）产生负面影响。被诊断为晚期疾病的卵巢癌幸存者经常被发现有昼夜皮质醇模式紊乱。正常情况下，皮质醇水平在一天中会下降，也就是说，水平在醒来时最高，晚上最低;有昼夜模式干扰的人在一天中皮质醇水平的下降幅度小于预期（即斜率较平缓）。皮质醇谱紊乱与卵巢癌幸存者的疲劳、植物性抑郁和更大的功能障碍以及晚期乳腺癌幸存者的生存率降低有关。最近，一项针对II-IV期乳腺癌幸存者的小型随机研究表明，瑜伽有益于影响皮质醇模式和疲劳。耶鲁大学公共卫生学院正在进行的一项大型随机试验正在测试为期6个月的家庭运动干预对改善卵巢癌幸存者生活质量和减少疲劳的有效性，这为我们提供了一个独特的成本效益机会来探索运动是否影响皮质醇模式。在登记时，女性相对不活跃，那些随机分配到运动组的女性在6个月的干预期间每周增加运动150分钟（主要是步行）。研究中的所有妇女每周与运动教练（运动组）或健康教育家（对照组）联系一次。这两组人从研究人员那里获得相同的接触时间，这是有效探索运动效果的重要组成部分，因为注意力本身可以影响生活质量的某些方面。在拟议的研究中，我们计划i）探索6个月的家庭运动干预是否会改变卵巢癌幸存者的昼夜皮质醇模式，与对照组中的类似幸存者相比，ii）探索昼夜皮质醇模式与卵巢癌幸存者的QOL，抑郁和疲劳之间的关联。由于扰动的皮质醇模式与乳腺癌幸存者的生存率较差有关，因此探索运动如何影响皮质醇可以提供有关运动可能影响癌症幸存者预后的机制的重要信息。皮质醇对卵巢癌幸存者生存的影响尚未研究。如果我们发现运动有益地改变了卵巢癌幸存者的昼夜皮质醇模式，这将需要进一步的研究来调查其影响。 运动对卵巢癌妇女生存率的影响;一组未充分研究的癌症幸存者。

DESCRIPTION (provided by applicant): There is no effective screening test for ovarian cancer and the symptoms are non-specific resulting in the majority (85%) of women with ovarian cancer being diagnosed with late stage (regional or distant cancer) disease. Women diagnosed with ovarian cancer at a late stage have a relatively poor prognosis (5-year survival: 72% for regional cancer, 27% for distant cancer), with the disease and resulting treatment negatively impacting quality of life (QOL). Ovarian cancer survivors diagnosed with late stage disease have frequently been found to have perturbed diurnal cortisol patterns. Normally, cortisol levels decline over the course of the day, that is levels are highest upon waking and lowest in the evening; people who have a perturbed diurnal pattern show a less than expected decline in cortisol level over the course of the day (i.e. a flatter slope). Perturbed cortisol profiles have been associated with fatigue, vegetative depression and greater functional disability in ovarian cancer survivors and poorer survival in later stage breast cancer survivors. Recently a small randomized study in Stage II-IV breast cancer survivors has shown that yoga beneficially affects both cortisol patterns and fatigue. A large ongoing randomized trial at the Yale School of Public Health, which is testing the efficacy of a home-based 6-month exercise intervention to improve QOL and reduce fatigue in ovarian cancer survivors, gives us a unique cost effective opportunity to explore whether exercise effects cortisol patterns. At enrollment women are relatively inactive, and those randomized to the exercise group increase their exercise to150 minutes per week (primarily walking) during the 6-month intervention. All women in the study are contacted once a week by an exercise trainer (exercise group) or a health educator (control group). The two groups receive equal contact time from study personnel, an essential component to effectively explore the effect of exercise, as attention itself can affect some aspects of QOL. In the proposed study we plan to i) explore whether a 6-month home-based exercise intervention will alter the diurnal cortisol patterns in ovarian cancer survivors compared to similar survivors n the control group and ii) explore the association between diurnal cortisol patterns and QOL, depression and fatigue in ovarian cancer survivors. Since perturbed cortisol patterns have been associated with poorer survival in breast cancer survivors, exploring how exercise affects cortisol could provide important information on the mechanisms through which exercise may impact prognosis for cancer survivors. The impact of cortisol on survival among ovarian cancer survivors has not been studied. If we find that exercise beneficially alters diurnal cortisol patterns in ovarian cancer survivors, this would warrant further research to investigate the effect of exercise on survival in women diagnosed with ovarian cancer; a group of understudied cancer survivors.