Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia

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

This phase II trial studies whether adding tirzepatide injections to a levonorgestrel intrauterine device (LNG-IUD) improves pathologic response (absence of cancer cells in tissue samples after treatment) in women with endometrial atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) or grade 1 endometrial cancer who are overweight or obese. Endometrial cancer occurrence has continued to rise in the United States. Over half of endometrial cancer cases are thought to be attributable to being overweight and obese, and the risk relationship appears to be weight dependent. AH/EIN is a precancerous condition of the endometrium (the uterus or womb) where the lining of the uterus grows abnormally thick, and the cells become abnormal. Women with this thickening have a higher-than-average risk of developing endometrial cancer if left untreated. The usual approach for patients who have AH/EIN and grade 1 endometrial cancer is the removal of the uterus. While surgical treatment is generally safe and effective, it may not be the best approach for some patients. The LNG-IUD is a small, T-shaped device inserted into the uterus that releases the hormone levonorgestrel, a progestin, which counteracts the effects of estrogen in the endometrium. Tirzepatide is a dual glucagon-like peptide 1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) agonist which has been shown to drive weight loss. Adding tirzepatide injections to LNG-IUD may help overweight or obese women with AH-EIN or grade 1 endometrial cancer lose weight, which may improve pathologic response.