Project 3: Primary Prevention and Uterine Preservation in Premenopausal Women with Obesity and Endometrial Hyperplasia/Cancer

项目3：绝经前妇女肥胖和子宫内膜增生/癌症的一级预防和子宫保留

基本信息

批准号：
10711638
负责人：
Andrea Hagemann
金额：
$ 59.7万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-23 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10711638
关键词：
Address Aftercare Agonist Atypia Atypical Endometrial Hyperplasias Behavior Therapy Behavioral Biopsy Body Weight decreased Combined Modality Therapy Development Diagnosis Early Diagnosis Endometrial Endometrial Carcinoma Endometrial Hyperplasia Enrollment Ensure Equity Estrogen Receptors Estrogens FDA approved Fertility Funding Future GLP-I receptor Genetic Transcription Hyperplasia Hysterectomy Impairment Injections Institution Insulin Resistance Intrauterine Devices Levonorgestrel Live Birth Malignant Neoplasms Measures Metabolism Obesity Overweight Pathology Patients Persons Pharmaceutical Preparations Placebos Plasma Population Sciences Pregnancy Rate Premenopause Prevention Primary Prevention Progesterone Progesterone Receptors Progestin Therapy Progestins Proliferation Marker Psychologist Randomized Randomized, Controlled Trials Relapse Route Serum Standardization Telemedicine Testing Therapeutic Time Tissues Universities Uterus Washington Weight Weight Gain Woman Work bariatric surgery biomarker identification cancer prevention efficacy evaluation experience improved outcome insulin secretion metabolomics predicting response premalignant preservation prevent randomized, clinical trials recruit response secondary endpoint treatment as usual weight loss intervention

项目摘要

PROJECT SUMMARY/ ABSTRACT Up to 90% of the ~65,000 women diagnosed with endometrial cancer each year in the U.S. are overweight or obese, and up to 60% of endometrial cancer cases are attributed to obesity. This is, in large part, because obesity promotes development of atypical endometrial hyperplasia (AEH), a precursor of grade 1 endometrial cancer. If diagnosed at one of these stages, a patient can be treated with hysterectomy, which is 100% effective in preventing/curing endometrial cancer. However, hysterectomy is often unacceptable to premenopausal women who would like to retain fertility. Instead, such patients are commonly treated with progestin, most commonly via a levonorgestrel-releasing intrauterine device (IUD). However, up to 41% of women on progestin eventually experience relapse and require a hysterectomy. Moreover, fewer than 12% of women who choose this option go on to have a live birth, likely because obesity and the commonly co- occurring insulin resistance impair fertility. As weight loss alone can also reverse AEH and grade 1 endometrial cancer, an ideal treatment for premenopausal women desiring future fertility would be to simultaneously provide a progestin IUD along with an effective weight loss strategy. This Early detection, Prevention and Population Science project includes two randomized controlled trials testing the overall hypothesis that combined treatment with progestin and either therapeutic or behavioral weight loss interventions leads to greater uterine preservation than progestin use alone. Aim 1 is to determine the efficacy of progestin plus a behavioral weight loss intervention to allow uterine preservation and cancer prevention in premenopausal women with AEH or grade 1 endometrial cancer. Aim 2 is to determine the efficacy of a glucagon-like peptide 1 receptor agonist plus progestin plus a behavioral weight loss intervention to allow uterine preservation and cancer prevention in premenopausal women with AEH. The therapeutic drug in this trial is approved by the FDA for treating obesity. Exploratory Aim 3 is to identify biomarkers that reflect response to progestin plus weight loss. If this project identifies effective strategies, they can be widely implemented to allow premenopausal women with AEH or grade 1 endometrial cancer to both avoid cancer and preserve their uterus for future fertility.

项目摘要/摘要在美国，在美国诊断出患有子宫内膜癌的约65,000名妇女中，多达90％是超重或肥胖，最多60％的子宫内膜癌病例归因于肥胖。这在很大程度上是因为肥胖促进非典型子宫内膜增生（AEH）的发展，这是1级子宫内膜的前体癌症。如果在其中一个阶段进行诊断，可以用子宫切除术治疗患者，为100％有效预防/固化子宫内膜癌。但是，子宫切除术通常是不可接受的希望保留生育能力的绝经前妇女。相反，此类患者通常接受孕激素，最常见的是通过左旋肺癌释放宫内装置（IUD）。但是，多达41％孕妇的妇女最终会经历复发，需要进行子宫切除术。而且，不到不到12％选择这种选择的妇女继续出生，这可能是因为肥胖和通常共同发生胰岛素抵抗会损害生育能力。因为仅减肥也会逆转AEH和1级子宫内膜癌症，这是对未来生育能力的绝经前妇女的理想疗法提供孕激素宫内节育器以及有效的减肥策略。早期发现，预防和人口科学项目包括两个随机对照试验，测试了总体假设与孕激素和治疗或行为减肥干预措施结合治疗导致与仅孕激素的使用更大的子宫保存更大。目标1是确定孕激素和A的功效行为减肥干预措施以允许绝经前的子宫保存和预防癌症患有AEH或1级子宫内膜癌的妇女。 AIM 2是确定胰高血糖素样肽1的功效受体激动剂加孕激素加上行为减肥干预措施，以允许子宫保存和 AEH绝经前妇女的预防癌症。该试验中的治疗药已由 FDA治疗肥胖症。探索目的3是识别反映孕激素加反应的生物标志物减肥。如果该项目确定了有效的策略，则可以广泛实施绝经前女性患有AEH或1级子宫内膜癌以避免癌症并保留子宫未来的生育能力。