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

> **NIH NIH P50** · WASHINGTON UNIVERSITY · 2024 · $528,932

## Abstract

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.

## Key facts

- **NIH application ID:** 10912620
- **Project number:** 5P50CA265793-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Andrea Hagemann
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $528,932
- **Award type:** 5
- **Project period:** 2023-08-23 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912620

## Citation

> US National Institutes of Health, RePORTER application 10912620, Project 3: Primary Prevention and Uterine Preservation in Premenopausal Women with Obesity and Endometrial Hyperplasia/Cancer (5P50CA265793-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10912620. Licensed CC0.

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