Chronic Stress and Reproductive Function in Female Cancer Survivors

女性癌症幸存者的慢性压力和生殖功能

• 批准号: 9258744
• 负责人: Theresa Hardy
• 金额: $ 3.54万
• 依托单位: MARQUETTE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-30 至 2018-06-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9258744
• 关键词: Acute; Adrenal Glands; Adult; Affect; Aftercare; Age; Aging; American Society of Clinical Oncology; Anti-Inflammatory Agents; Anti-inflammatory; Biological; Biological Markers; Biological Preservation; Cancer Center; Cancer Patient; Cancer Survivor; Characteristics; Child; Childhood; Chronic stress; Clinical; Cohort Studies; Complex; Data; Enrollment; Enzyme-Linked Immunosorbent Assay; Etiology; Female; Fertility; Follicle Stimulating Hormone; Functional disorder; Future; Glucocorticoids; Goals; Gonadotropins; Growing Follicle; Guidelines; Hair; Health Personnel; Hormonal; Hospitals; Hydrocortisone; Hypothalamic structure; Individual; Infertility; Inflammatory; Interleukin-6; Knowledge; Laboratories; Late Effects; Linear Regressions; Luteinizing Hormone; Malignant Childhood Neoplasm; Measures; Medical Research; Menstrual cycle; Menstruation; Mentors; Modeling; Non-linear Models; Ovarian; Ovarian Follicle; Ovary; Patients; Periodicity; Pituitary Gland; Population; Predictive Value; Premature Ovarian Failure; Procedures; Process; Psychological Stress; Quality of life; Reporting; Reproductive Physiology; Research; Research Institute; Research Project Grants; Risk; Salivary; Sampling; Serum; Stress; Survival Rate; Survivors; Testing; The Sun; Training Programs; Treatment/Psychosocial Effects; Visit; biobehavior; biological adaptation to stress; cancer therapy; childhood cancer survivor; clinical practice; cytokine; experience; follow-up; gonad function; hypothalamic-pituitary-adrenal axis; improved; mullerian-inhibiting hormone; ovarian failure; programs; reproductive; reproductive function; treatment effect

PROJECT SUMMARY Due to significant advances in the treatment of pediatric cancer patients, the five year survival rate now exceeds 80% in the USA. Among the myriad long-term physical and psychosocial effects of treatment, reproductive dysfunction is reported as a major concern and is highly correlated with quality of life in this population. The etiology of reproductive dysfunction in childhood cancer survivors (CCS) is complex and few predictors of this effect of treatment have been identified. High levels of psychological stress have also been observed in CCS; psychological stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which can suppress hypothalamic-pituitary gonadal function and disrupt reproductive function. The proposed research project will examine ovarian function in survivors of childhood cancer, a population at increased risk of reproductive dysfunction due to late effects of cancer treatment and psychological stress. The specific aims are (aim 1) to explore the relationship between perceived stress, biomarkers of HPA activity, gonadotropin levels, and anti-Müllerian hormone (AMH); and (aim 2) to determine the model that best explains the relationship between the most salient variables identified in aim 1. This cross-sectional cohort study will enroll 50 female patients between the ages of 16 and 35 who were treated for childhood cancer at the Edinburgh Children’s Cancer Centre, Royal Hospital for Sick Children. Perceived stress will be measured using the Perceived Stress Scale-10. HPA activity will be measured using salivary and hair cortisol and salivary IL-6. Ovarian function will be measured using serum gonadotropin levels, serum AMH levels, and menstrual cycle characteristics, which are collected routinely during the subject’s annual follow-up visit. Biological samples will be analyzed using commercially available ELISA kits in the Queen’s Medical Research Institute. For aim 1, data will be analyzed using linear regression models using a best-subset variable selection procedure and aim 2 will employ nonlinear models to determine the model that best explains the relationship between variables identified from the analysis of aim 1.The findings from this study will increase our understanding of AMH as a biomarker of reproductive function, especially ovarian function. The sponsors are experienced mentors and experts in ovarian function (Anderson) and laboratory assessment of biomarkers (McCarthy). While conducting this study, the applicant will attend weekly seminars on reproductive physiology. This training program will prepare the applicicant to conduct cutting edge research on biobehavioral processes affecting ovarian aging.

项目概要 由于儿科癌症患者治疗的显着进步，五年生存率 在美国，这一比例现已超过 80%。 据报道，生殖功能障碍是一个主要问题，并且与治疗高度相关 该人群的生活质量。儿童癌症幸存者生殖功能障碍的病因。 (CCS) 很复杂，并且几乎没有确定这种治疗效果的预测因素。 CCS 中也观察到心理压力；心理压力会激活 下丘脑-垂体-肾上腺 (HPA) 轴，可抑制下丘脑-垂体性腺 拟议的研究项目将检查卵巢。 儿童癌症幸存者的功能，这是生殖功能障碍风险增加的人群 由于癌症治疗的后期影响和心理压力。具体目标是（目标 1）： 探索感知压力、HPA 活性生物标志物、促性腺激素水平、 和抗苗勒氏管激素 (AMH)；以及（目标 2）确定最能解释这一现象的模型 目标 1 中确定的最显着变量之间的关系。这项横断面队列研究 将招募 50 名年龄在 16 岁至 35 岁之间的女性患者，她们在 爱丁堡儿童癌症中心、皇家病童医院将感受到压力。 使用感知压力量表 10 测量 HPA 活性将使用唾液和头发进行测量。 使用血清促性腺激素水平、血清测量皮质醇和唾液 IL-6。 AMH 水平和月经周期特征，在受试者的月经期间定期收集 每年一次的随访将使用市售的 ELISA 试剂盒进行分析。 女王医学研究所对于目标 1，将使用线性回归分析数据。 使用最佳子集变量选择程序的模型，目标 2 将采用非线性模型 确定最能解释分析中确定的变量之间关系的模型 目标 1.本研究的结果将加深我们对 AMH 作为生物标志物的理解 生殖功能，尤其是卵巢功能的资助者是经验丰富的导师和 卵巢功能专家（安德森）和生物标志物实验室评估专家（麦卡锡）。 进行这项研究时，申请人将参加每周一次的生殖生理学研讨会。 培训计划将使申请人做好准备进行生物行为的前沿研究 影响卵巢衰老的过程。