The Reproductive Window in Young Adult Cancer Survivors

年轻癌症幸存者的生殖窗口

• 批准号: 8926238
• 负责人: Hui-Chun Irene Su
• 金额: $ 51.68万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-16 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8926238
• 关键词: Address; Age; Aging; Automobile Driving; Biological Markers; Biological Preservation; Blood; Breast Sarcoma; Cancer Survivor; Cardiovascular system; Characteristics; Climacteric; Clinical; Collection; Colon Carcinoma; Counseling; Data; Decision Making; Diagnosis; Distress; Endocrine; Enrollment; Estradiol; Female; Fertility; Follicle Stimulating Hormone; Future; Heterogeneity; Hydrocortisone; Hypothalamic structure; Infertility; Intervention; Intervention Studies; Life Style; Light; Longevity; Luteinizing Hormone; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Measures; Metabolic; Modeling; Modification; National Institute of Child Health and Human Development; Outcome; Ovarian; Ovarian Ablation; Participant; Patients; Pattern; Population; Pregnancy; Quality of life; Recovery; Reporting; Reproductive Health; Research; Residual state; Risk; Saliva; Salivary; Sampling; Skin Cancer; Spottings; Stress; Survivors; Symptoms; Testing; Time; Toxic effect; Uterine Cancer; Woman; base; cancer therapy; clinical risk; cohort; experience; follow-up; hypothalamic pituitary ovarian axis; innovation; leukemia/lymphoma; minimally invasive; mullerian-inhibiting hormone; novel strategies; premature; primary ovarian insufficiency; programs; psychological distress; public health relevance; reproductive; reproductive senescence; social; young adult; young cancer survivor; young woman

DESCRIPTION (provided by applicant): Infertility and premature ovarian senescence are life-changing consequences of cancer in young women. Yet, the reproductive window after cancer treatment in young adult cancer survivors (YA survivors) is not known. In light of growing numbers of YA survivors and emergence of promising interventions on fertility after cancer treatment, there is a clear need to identify and categorize patterns of ovarian aging after cancer and the clinical profiles associated with them to assist in patient counseling and decision making. 1000 female YA survivors who are between ages 18-35 will be enrolled at varying durations after cancer treatment and followed for 18 months. First, the study will test the hypothesis that patterns of anti-mullerian hormone (AMH), follicle stimulating hormone (FSH) and estradiol (E2) after cancer treatment will differ among three broad treatment toxicity groups. Ovarian function biomarker levels will be measured from serial self-collected dried blood spot (DBS) samples in each participant. Data from the entire cohort will then be modeled by time after cancer treatment, and patterns (including time to peak, duration at peak and time to decline of ovarian function) will be compared among minimal, moderate and severe treatment toxicity groups. The aim will demonstrate that these biomarkers can depict differential durations of the reproductive window. Second, spurred by exciting preliminary data, the study will test the hypothesis that disproportionate psychological distress experienced by this population is associated with hypothalamic suppression of ovarian function. The aim will determine the association between distress (measured by patient-reported symptoms and salivary cortisol) and luteinizing hormone (LH), FSH, E2 and AMH. Hypothalamic-pituitary-ovarian axis suppression has never been studied in the context of cancer, and discovery of an association between distress and ovarian function would be critical to future intervention studies on distress to modify reproductive health outcomes. Third, the study will generate clinical risk profiles for te window of ovarian function for the moderate toxicity group, which encompasses the majority of YA survivors. Due to heterogeneity, there are no data on predicting variability in the course of ovarian aging within this group. This aim will identify subpopulations in patterns of ovarian function within the moderate toxicity group, followed by the clinical factors that are associated with them. Building on the PI's K23 data, this proposal directly responds to priorities of the NICHD Fertility Preservation Program to develop biomarkers and clinical parameters to better predict gonadal reserve, and optimize and expand options for fertility preservation. The significance lies in estimating the reproductive lifespan in the context of cancer in order to guid patient counseling, individualize risks and preserve opportunities for biologic parenthood. Through innovative use of social media for recruitment and non-clinic- based, minimally invasive DBS and saliva collection for biosample accrual, the proposal overcomes longstanding, critical barriers to studying young adults with cancer. 1

描述（由申请人提供）：不孕症和卵巢早衰是癌症对年轻女性生活的改变。然而，年轻成年癌症幸存者（YA 幸存者）接受癌症治疗后的生殖窗口尚不清楚。鉴于 YA 幸存者数量不断增加以及癌症治疗后生育力干预措施的出现，显然需要对癌症后卵巢衰老模式以及与之相关的临床特征进行识别和分类，以协助患者咨询和决策。 1000 名年龄在 18 至 35 岁之间的女性 YA 幸存者将在癌症治疗后的不同时期入组，并进行为期 18 个月的随访。首先，该研究将检验以下假设：癌症治疗后抗苗勒氏管激素 (AMH)、卵泡刺激素 (FSH) 和雌二醇 (E2) 的模式在三大治疗毒性组之间会有所不同。卵巢功能生物标志物水平将通过每个参与者连续收集的干血点（DBS）样本进行测量。然后，将根据癌症治疗后的时间对整个队列的数据进行建模，并在轻度、中度和重度治疗毒性组之间比较模式（包括卵巢功能达到峰值的时间、峰值持续时间和卵巢功能衰退的时间）。目的将证明这些生物标志物可以描述生殖窗口的不同持续时间。其次，在令人兴奋的初步数据的推动下，该研究将检验这一假设：该人群经历的不成比例的心理困扰与下丘脑对卵巢功能的抑制有关。目的是确定痛苦（通过患者报告的症状和唾液皮质醇来衡量）与黄体生成素 (LH)、FSH、E2 和 AMH 之间的关联。下丘脑-垂体-卵巢轴抑制从未在癌症背景下进行过研究，发现痛苦与卵巢功能之间的关联对于未来通过痛苦干预研究来改变生殖健康结果至关重要。第三，该研究将为中度毒性组（包括大多数 YA 幸存者）的卵巢功能窗口期生成临床风险概况。由于异质性，没有预测该组卵巢衰老过程变异性的数据。这一目标将确定中度毒性组内卵巢功能模式的亚群，然后是与其相关的临床因素。该提案以 PI 的 K23 数据为基础，直接响应了 NICHD 生育力保存计划的优先事项，即开发生物标志物和临床参数，以更好地预测性腺储备，并优化和扩大生育力保存的选择。其意义在于估计癌症背景下的生殖寿命，以指导患者咨询、个体化风险并保留亲生父母的机会。通过创新地使用社交媒体进行招募以及非临床、微创 DBS 和唾液采集来采集生物样本，该提案克服了研究年轻癌症患者长期存在的关键障碍。 1