The Methodist Hospital Research Institute
The goal of this clinical trial is to learn if a combination treatment of a hormonal intrauterine device (LNG-IUD), semaglutide, and a structured weight loss program can treat endometrial atypical hyperplasia or grade 1 endometrioid endometrial cancer while preserving fertility in women of reproductive age with endometrial atypical hyperplasia (EAH) or FIGO grade 1 endometrioid endometrial cancer who wish to preserve their fertility. The main questions it aims to answer are: * What proportion of participants achieve a complete pathological response after treatment? * How durable is the response at 12 months? * What effect does the treatment have on metabolic outcomes (weight, BMI, HbA1c) and quality of life? Participants will: * Receive an LNG-IUD * Receive semaglutide 2.4mg * Participate in a structured weight loss program * Undergo hysteroscopy with endometrial sampling to assess treatment response * Complete quality-of-life assessments at baseline, 6 months, and 12 months
Inclusion Criteria: 1. Histological Diagnosis: Histologically confirmed endometrial atypical hyperplasia or FIGO grade 1 endometrioid Endometrial Cancer 2. Imaging eligibility (for patients with endometrial cancer): 1. Depth of myometrial invasion \<50% confirmed by MRI or disease limited to the endometrium 2. No evidence of extrauterine or metastatic disease on imaging. 3. Treatment Rationale (at least one of the following must apply): 1. Desire for future fertility: Patient expresses a documented desire to preserve the uterus and future reproductive function, with explicit acknow…
Semaglutide 2.4 mg administered subcutaneously once weekly, following standard dose-escalation protocol, for the duration of the 6-month active treatment period. Used off-label in this trial for its metabolic effects in combination with LNG-IUD, rather than as monotherapy for weight loss.
Levonorgestrel-releasing intrauterine device inserted at study baseline and maintained through the active treatment and follow-up periods, providing continuous local progestin delivery to the endometrium in combination with systemic semaglutide.
A structured, protocol-defined weight loss program combining dietary counseling and physical activity guidance, delivered concurrently with pharmacologic and device-based treatment to support metabolic response, distinct from weight loss achieved through semaglutide alone.