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

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:

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

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.