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: 8105510
• 负责人: CLARISA R. GRACIA
• 金额: $ 50.92万
• 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/8105510
• 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

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）：肿瘤学的近期诊断和治疗进展导致儿童和年轻人恶性肿瘤的存活率更高。但是，在女性中，尽管癌症疗法可以改善长期生存，但这种治疗通常会导致与早期卵巢衰老有关的早产卵巢衰竭和不育。随着越来越多的年轻妇女能够生存癌症并过着生产力，这些担忧变得越来越重要。然而，很难预测是否以及何时出现此类问题以及严重性和持续时间。确实，卵巢功能障碍降低，即使在治疗后保持环状月经的年轻女性也没有早期的临床迹象，其不孕症，更年期早期和与早期卵巢衰竭有关的长期健康问题的风险很高。虽然最近已经观察到，长期癌症幸存者的激素和超声措施受到损害，但尚不清楚这些措施是否反映了该人群中生育能力的潜力和更年期的时间。我们有有趣的初步数据，以表明20年代中期暴露于高风险癌症疗法的童年和年轻的成年癌症幸存者具有激素和超声措施，类似于40年代中期的卵巢储备类似于自然老化的妇女。当前的提案是对青少年和年轻妇女癌症治疗的急性和长期生殖后果的首次全面且适当的动力研究。 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暴露于高剂量烷基化剂治疗的受试者和2个未暴露女性种群之间的循环。该提案的发现将有助于确认我们的初步发现，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作用的了解，并有助于建立一种预测治疗前化学疗法影响的方法。最终，这些数据对于确定这些措施是否有助于预测该人群中卵巢功能障碍的时间和程度以及生育潜力，并且对生存癌症的女孩和女性的生活质量产生重大影响。 公共卫生相关性：肿瘤学的近期诊断和治疗进展导致儿童和年轻人恶性肿瘤的存活率更高。但是，尽管癌症疗法，尤其是烷基化剂，改善了长期生存，但这种治疗通常会导致早产卵巢衰竭和与早期卵巢衰老有关的生殖功能障碍。该建议将评估暴露于化学疗法的年轻女性生殖功能的立即和长期变化。这项研究的发现将对患者咨询和定位生育力的工作产生重大影响。