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

Age

• Age ≥18 years

Other

• Negative pregnancy test at screening
• Ability to provide written informed consent and comply with study procedures
• Willingness to undergo genetic counseling and MMR/IHC tumor profiling
• 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.

• Histological Diagnosis: Histologically confirmed endometrial atypical hyperplasia or FIGO grade 1 endometrioid Endometrial Cancer
• Imaging eligibility (for patients with endometrial cancer):
  • Depth of myometrial invasion \<50% confirmed by MRI or disease limited to the endometrium
  • No evidence of extrauterine or metastatic disease on imaging.
• Treatment Rationale (at least one of the following must apply):
  • 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.
  • Medical inoperability: patients are considered a poor surgical candidate due to:
  • Class III obesity (BMI ≥40 kg/m²); or ii. ASA Physical Status Classification score ≥3.
• 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).
• Progestin washout: patients with prior progestin exposure are eligible provided the following minimum washout periods have been observed.
  • Oral progestins: 7 days
  • Injectable, short acting: 14 days
  • Injectable, long acting: 6 months
  • Contraceptive implant: 28 days
  • LNG-IUD: 7 days after removal