Ovarian Reserve After Cancer: Longitudinal Effects (The ORACLE Study)

癌症后的卵巢储备：纵向影响（ORACLE 研究）

• 批准号: 8301493
• 负责人: CLARISA R. GRACIA
• 金额: $ 50.83万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8301493
• 关键词: Acute; Adolescent; Aftercare; Age; Age-Years; Aging; Alkylating Agents; Alkylating Antineoplastic Agents; Amenorrhea; Biological Preservation; Cancer Patient; Cancer Survivor; Characteristics; Child; Childhood; Clinical; Clinical Trials; Cohort Studies; Counseling; Data; Diagnostic; Dose; Endocrine; Estrone; Failure; Female; Fertile Period; Fertility; Functional disorder; Glucuronides; Health; High-Risk Cancer; Hormones; Hypothalamic structure; Infertility; Investigation; Knowledge; Lead; Long-Term Survivors; Luteal Phase; Malignant Neoplasms; Measures; Menopause; Menstrual cycle; Menstruation; Methods; Newly Diagnosed; Ovarian; Ovarian Follicle; Patients; Pituitary Gland; Population; Pregnanediol; Premature Ovarian Failure; Prior Chemotherapy; Quality of life; Radiation therapy; Research; Research Design; Risk Factors; Severities; Survival Rate; Survivors; Testing; Therapeutic; Time; Ultrasonography; Woman; aged; base; cancer therapy; chemotherapy; girls; high risk; improved; oncology; prospective; public health relevance; reproductive; reproductive function; time interval; urinary; young adult; young woman

DESCRIPTION (provided by applicant): Recent diagnostic and therapeutic advances in oncology have led to greater survival rates in children and young adults with malignancies. However, in women, while cancer therapies improve long-term survival, such treatments often lead to premature ovarian failure and infertility related to early ovarian aging. As more young women survive cancer and lead productive lives, these concerns are becoming increasingly important. Nevertheless, it is difficult to predict if and when such problems will arise and what the severity and duration will be. Indeed, there are no early clinical signs of decreased ovarian dysfunction and even young women who maintain cyclic menses after therapy are at high risk of infertility, early menopause, and long-term health problems related to early ovarian failure. While it has recently been observed that hormone and ultrasound measures of ovarian reserve are impaired in long term survivors of cancer, it is not clear whether these measures reflect fertility potential and time to menopause in this population. We have intriguing preliminary data to suggest that childhood and young adult cancer survivors exposed to high risk cancer therapies in their mid 20's have hormone and ultrasound measures of ovarian reserve similar to naturally aging women in their mid 40's. The current proposal represents the first comprehensive and appropriately powered investigation of the acute and long-term reproductive consequences of cancer treatment in adolescent and young women. The proposed aims are 1) to assess acute changes in reproductive function during and after chemotherapy in cancer patients, 2) to assess the long-term reproductive function of women exposed to cancer therapies and make comparisons to similarly aged and late reproductive aged unexposed females and 3) assess for the presence of follicular and luteal dysfunction in cancer survivors by comparing daily urinary hormone metabolites over 2 menstrual cycles between subjects exposed to high dose alkylating agent therapy and 2 unexposed populations of females. The findings of this proposal will help confirm our preliminary findings, and will be critical in estimating the reproductive window in cancer survivors. In addition, this research will expand our knowledge of the effects of cancer therapy and will help to establish a method to predict the impact of chemotherapy prior to treatment. Ultimately, this data will be critical to determine if these measures are useful in predicting the timing and extent of ovarian dysfunction as well as fertility potential in this population and will have a major impact on the quality of life of girls and women who survive cancer. PUBLIC HEALTH RELEVANCE: Recent diagnostic and therapeutic advances in oncology have led to greater survival rates in children and young adults with malignancies. However, while cancer therapies, especially alkylating agents, improve long- term survival, such treatments often lead to premature ovarian failure and reproductive dysfunction related to early ovarian aging. This proposal will assess the immediate and long-term changes in reproductive function in young females exposed to chemotherapy. The findings of this research will have a major impact on patient counseling and targeting fertility preservation efforts.

描述（由申请人提供）：肿瘤学的最新诊断和治疗进展提高了患有恶性肿瘤的儿童和年轻人的生存率。然而，对于女性来说，虽然癌症治疗可以提高长期生存率，但这种治疗通常会导致卵巢早衰和与卵巢早期衰老相关的不孕。随着越来越多的年轻女性战胜癌症并过上富有成效的生活，这些担忧变得越来越重要。然而，很难预测此类问题是否会出现、何时出现以及严重程度和持续时间。事实上，没有卵巢功能下降的早期临床迹象，即使是治疗后保持周期性月经的年轻女性也面临着不孕、提前绝经和与早期卵巢功能衰竭相关的长期健康问题的高风险。虽然最近观察到癌症长期幸存者的卵巢储备激素和超声测量受到损害，但尚不清楚这些测量是否反映了该人群的生育潜力和绝经时间。我们有有趣的初步数据表明，在 20 多岁接受高风险癌症治疗的儿童和年轻成年癌症幸存者的卵巢储备激素和超声波测量结果与 40 多岁自然衰老的女性相似。目前的提案代表了对青少年和年轻女性癌症治疗的急性和长期生殖后果的首次全面且适当的调查。拟议的目标是 1) 评估癌症患者化疗期间和化疗后生殖功能的急性变化，2) 评估接受癌症治疗的女性的长期生殖功能，并与年龄相仿和晚育龄未接受癌症治疗的女性进行比较3) 通过比较暴露于高剂量烷化剂治疗的受试者和 2 个未暴露的女性群体之间 2 个月经周期内的每日尿激素代谢物，评估癌症幸存者是否存在卵泡和黄体功能障碍。该提案的结果将有助于证实我们的初步发现，并且对于估计癌症幸存者的生殖窗口至关重要。此外，这项研究将扩大我们对癌症治疗效果的了解，并将有助于建立一种在治疗前预测化疗影响的方法。最终，这些数据对于确定这些措施是否有助于预测该人群卵巢功能障碍的时间和程度以及生育潜力至关重要，并将对癌症幸存者的生活质量产生重大影响。 公共卫生相关性：肿瘤学的最新诊断和治疗进展提高了患有恶性肿瘤的儿童和年轻人的生存率。然而，虽然癌症治疗，尤其是烷化剂，可以改善长期生存，但此类治疗常常导致卵巢早衰和与卵巢早期衰老相关的生殖功能障碍。该提案将评估接受化疗的年轻女性生殖功能的即时和长期变化。这项研究的结果将对患者咨询和针对生育力保存的努力产生重大影响。