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

Conditions

• Endometrial Atypical Hyperplasia
• Endometrial Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia
• Endometrial Cancer
• Endometrial Cancer Stage I
• Fertility-Sparing Treatment (FST)
• Obesity & Overweight

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Semaglutide (Wegovy) weekly injection — DRUG
  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.
• LNG-IUD (Progestin) — DEVICE
  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.
• Structured Weight Loss Program — BEHAVIORAL
  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.

Study Details

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

Key Dates

First listed

Sep 15, 2026

Start date

Jan 1, 2027

Status verified

Aug 2026

Primary completion

Dec 31, 2028

Completion

Dec 31, 2031

Study Design

Enrollment

48 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Combination Fertility-Sparing Treatment
  Participants will receive a three-component combination intervention consisting of: (1) a levonorgestrel-releasing intrauterine device (LNG-IUD), inserted at baseline; (2) semaglutide 2.4 mg, administered per standard dosing schedule; and (3) a structured weight loss program. Participants will undergo hysteroscopy with endometrial sampling to assess pathological response. Treatment will be administered for 6 months of active intervention, followed by a 6-month follow-up period.

Primary Outcome Measure

Pathological Response Rate [ Time Frame: 6 months ]

Locations (4)

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