Semaglutide, Weight Loss, and LNG-IUD for Conservative Treatment of Endometrial Atypical Hyperplasia and Grade 1 Endometrial Cancer

Who can take part

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 acknowledgment that fertility-sparing treatment is not standard of care for endometrial cancer. 2. Medical inoperability: patients are considered a poor surgical candidate due to: i. Class III obesity (BMI ≥40 kg/m²); or ii. ASA Physical Status Classification score ≥3. 4. Metabolic Profile: BMI ≥ 30 kg/m², or BMI 27-29.9 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes mellitus, dyslipidemia, obstructive sleep apnea, or non-alcoholic fatty liver disease). 5. Progestin washout: patients with prior progestin exposure are eligible provided the following minimum washout periods have been observed. 1. Oral progestins: 7 days 2. Injectable, short acting: 14 days 3. Injectable, long acting: 6 months 4. Contraceptive implant: 28 days 5. LNG-IUD: 7 days after removal Exclusion Criteria: 1. Age ≥18 years 2. Negative pregnancy test at screening 3. Ability to provide written informed consent and comply with study procedures 4. Willingness to undergo genetic counseling and MMR/IHC tumor profiling 5. Willingness and ability to participate in a structured weight loss program, including attendance at counseling sessions (in person or virtual) and adherence to dietary and physical activity goals.

Registry changes

No changes recorded since the trial was added.