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，并且症状非特异性，导致大多数（85%）卵巢癌妇女被诊断为晚期（局部或远处癌症）疾病。晚期诊断为卵巢癌的妇女预后相对较差（局部癌症的5年生存率为72%，远处癌症的5年生存率为27%），疾病和由此产生的治疗对生活质量（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紊乱的昼夜皮质醇模式。正常情况下，皮质醇水平在一天中下降，也就是说，皮质醇水平在醒来时最高，在晚上最低；昼夜节律紊乱的人在一天中皮质醇水平的下降比预期的要少（即斜率更平坦）。受干扰的皮质醇谱与卵巢癌幸存者的疲劳、植物性抑郁和更大的功能残疾以及晚期乳腺癌幸存者的较差生存率有关。最近，一项针对II-IV期乳腺癌幸存者的小型随机研究表明，瑜伽对皮质醇模式和疲劳都有有益的影响。耶鲁大学公共卫生学院正在进行一项大型随机试验，该试验正在测试以家庭为基础的6个月运动干预的有效性，以改善卵巢癌幸存者的生活质量并减少疲劳，这为我们探索运动是否影响皮质醇模式提供了一个独特的成本效益机会。在入组时，女性相对不爱运动，在6个月的干预期间，被随机分配到运动组的女性每周的运动时间增加到150分钟（主要是步行）。参与研究的所有女性每周都有一位运动教练（锻炼组）或一位健康教育者（对照组）与她们联系一次。两组受试者与研究人员的接触时间相同，这是有效探索运动效果的重要组成部分，因为注意力本身会影响生活质量的某些方面。在这项拟议的研究中，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日皮质醇模式，与对照组的类似幸存者相比ii)探索日皮质醇模式与卵巢癌幸存者的生活质量、抑郁和疲劳之间的关系。由于受干扰的皮质醇模式与乳腺癌幸存者较差的生存率有关，探索运动如何影响皮质醇可以为运动影响癌症幸存者预后的机制提供重要信息。尚未研究皮质醇对卵巢癌幸存者生存的影响。如果我们发现运动有益地改变卵巢癌幸存者的日常皮质醇模式，这将证明进一步的研究可以调查其影响

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.