Clinical Co-Leader: Andrea Hagemann, MD
Basic Co-Leader: Kimberly Leslie, MD, University of New Mexico
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. 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 bariatric surgery 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 a randomized controlled trial 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. Our aim 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. Our exploratory aim 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.
Clinical Trials
UPLifT-Endo: Uterine Preservation via Lifestyle Transformation: This trial is enrolling women between the ages of 18-45 with BMI ≥ 30 kg/m2 who have been diagnosed with AEH/EIN or grade 1 endometrial cancer. All participants will have a levonorgestrel IUD placed. Participants will be randomized to a psychologist-led telemedicine weight loss intervention or enhanced usual care. The primary objective is to determine the efficacy of progestin IUD plus a behavioral weight loss intervention in allowing uterine preservation at 1 year. Download the IRB-approved recruitment flyer (PDF).
Semaglutide/Wegovy Trial: This trial is enrolling women between the ages of 18-45 with BMI ≥ 30 kg/m2 who have been diagnosed with non-atypical/benign endometrial hyperplasia or AEH/EIN. All participants will have a levonorgestrel IUD placed. Participants will be randomized to receive Wegovy or placebo for up to two years. The primary objective is to determine the efficacy of the combination of semaglutide 2.4 mg and IUD in allowing uterine preservation at 2 years or study exit. Download the IRB-approved recruitment flyer (PDF).