Weight Management Plus LNG-IUS/Megestrol Acetate in Endometrial Atypical Hyperplasia

NCT ID: NCT05316493

Last Updated: 2025-08-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 172 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-13
• Study Completion Date: 2027-02-28

Brief Summary

To investigate the efficacy of weight management plus levonorgestrel intrauterine system (LNG-IUS) or megestrol acetate (MA) in obese patients with endometrial atypical hyperplasia (EAH) asking for conservative therapy.

Detailed Description

Background:

High-efficacy progesterone, such as levonorgestrel intrauterine system (LNG-IUS), megestrol acetate (MA), and medroxyprogesterone acetate(MPA), is the first-line treatment for women with endometrial atypical hyperplasia (EAH) who want to preserve fertility. About 70% to 80% of those patients can achieve complete remission (CR) with a median CR time of about 6 months, but about 20% to 30% of those patients get no response or need longer time to get CR (over one year or even longer).

Overweight or obesity is an independent risk factor for fertility-sparing treatment response and pregnancy outcomes in young females with EAH or early endometrioid cancer (EEC). Evidence showed that obesity can cause lower CR rates and longer time to get CR and lower birth rates in EAH or EEC patients asking for conservative therapy. Weight management has been proved to improve metabolic disorders, ovarian functions, and pregnancy outcomes. Metformin, as a diabetes drug, has been proved to increase CR rates in EAH or EEC patients treated with MA for fertility. Weight management has raised more and more attention and has been proved to benefit metabolic and pregnancy outcomes. Based on previous research and published studies, the hypothesise is that weight management plus progestin therapy may raise CR rates and pregnancy outcomes in young female EAH patients asking for fertility conservation.

Enhanced lifestyle management (diet control, exercise, and daily behavioral guidance) may improve metabolic conditions, increase CR rates and pregnancy outcomes in obese EAH patients who want to preserve fertility. Till now, no similar studies were found, so this study is designed to explore the efficacy of weight control in EAH fertility-sparing patients to provide new evidence for improving conservative treatment.

Objective:

To investigate whether weight management plus LNG-IUS/MA can improve the efficacy of preserving fertility in obese EAH women who want fertility conservation.

Design:

This study is designed according to Simon's Two-Stage Design. Based on BMI and treatment plans, four single-arms are designed. This study is prospective, open-label. EAH Patients requiring conservation treatment with BMI ≥ 24 kg/m2 will be recruited in this study and they will be divided into four arms, the first group recruits overweight (24kg/ m2≤BMI<28kg/m2) patients treated with LNG-IUS, the second group recruits overweight (24kg/ m2≤BMI<28kg/m2) patients treated with MA, the third group recruits obese (BMI≥28kg/m2) patients treated with LNG-IUS, and the last group recruits obese (BMI≥28kg/m2) patients treated with MA. The sample size is calculated based on Simon's Two-Stage Design and previous CR rates. All enrolled patients will receive enhanced lifestyle management to control weight and take LNG-IUS/MA for treating EAH. Hysteroscopic examination, metabolic and inflammatory indicators will be performed every 12 to16 weeks while other indexes will be evaluated every month, including weight, heart rates, blood pressure, body fat tests, and so on. For the progestin efficacy evaluation, CR is defined as the remission of EAH to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypia; no response (NR) is defined as the persistence of the disease, and progressive disease (PD) is defined as disease progression in patients. Two months' maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.

Outcomes: Primary outcome is the CR rates of the four arms. Secondary outcomes include pregnancy rates, live birth rates, weight loss, insulin resistance, chronic inflammation indicators, time to achieve CR and recurrence rates, and so on. Safety and side events during the whole trial will be monitored in two years.

Conditions

Atypical Endometrial Hyperplasia; Fertility Issues; Overweight and Obesity

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

overweight MA+ILI

enrolled overweight (24kg/m2≤BMI\<28kg/m2) patients will receive megestrol acetate 160mg po qd plus weight management

Group Type: EXPERIMENTAL

Intensive Lifestyle Intervention (ILI)

Intervention Type: BEHAVIORAL

dietary guidance, exercise guidance, lifestyle intervention

Megestrol Acetate 160 MG Oral Tablet

Intervention Type: DRUG

enrolled participants will take Megestrol Acetate 160mg daily

overweight LNG-IUS+ILI

enrolled overweight (24kg/m2≤BMI\<28kg/m2) patients will be treated with LNG-IUS plus weight management

Group Type: EXPERIMENTAL

Intensive Lifestyle Intervention (ILI)

Intervention Type: BEHAVIORAL

dietary guidance, exercise guidance, lifestyle intervention

Levonorgestrel-Releasing Intrauterine Contraceptive System (Mirena), 52 Mg

Intervention Type: DRUG

enrolled patients will be treated with LNG-IUS.

obese MA+ILI

enrolled obese (BMI≥28kg/m2) patients will receive megestrol acetate 160mg po qd plus weight management

Group Type: EXPERIMENTAL

Intensive Lifestyle Intervention (ILI)

Intervention Type: BEHAVIORAL

dietary guidance, exercise guidance, lifestyle intervention

Megestrol Acetate 160 MG Oral Tablet

Intervention Type: DRUG

enrolled participants will take Megestrol Acetate 160mg daily

obese LNG-IUS+ILI

enrolled obese (BMI≥28kg/m2) patients will be treated with LNG-IUS plus weight management

Group Type: EXPERIMENTAL

Intensive Lifestyle Intervention (ILI)

Intervention Type: BEHAVIORAL

dietary guidance, exercise guidance, lifestyle intervention

Levonorgestrel-Releasing Intrauterine Contraceptive System (Mirena), 52 Mg

Intervention Type: DRUG

enrolled patients will be treated with LNG-IUS.

Interventions

Intensive Lifestyle Intervention (ILI)

dietary guidance, exercise guidance, lifestyle intervention

Intervention Type: BEHAVIORAL

Megestrol Acetate 160 MG Oral Tablet

enrolled participants will take Megestrol Acetate 160mg daily

Intervention Type: DRUG

Levonorgestrel-Releasing Intrauterine Contraceptive System (Mirena), 52 Mg

enrolled patients will be treated with LNG-IUS.

Intervention Type: DRUG

Other Intervention Names

Weight Management; yilizhi; manyuele

Eligibility Criteria

Inclusion Criteria

1.18 years≤age≤45years 2.BMI (body mass index) ≥24kg/m2 3.Consent informed and signed 4.Pathologically confirmed as endometrial atypical hyperplasia. Patients with endometrial specimens obtained by endometrial biopsy, diagnostic curettage or hysteroscopy and diagnosed histologically as endometrial atypical hyperplasia. If specimens are from other hospitals, they must be counseled or reconfirmed by the Department of Pathology of the Obstetrics and Gynecology Hospital of Fudan University.

5.Have a strong desire to reproduce and ask for fertility preservation or those who insist on keeping the uterus despite no reproductive requirements.

6.Have good compliance and follow-up conditions, and patients are willing to follow up in Obstetrics and Gynecology Hospital of Fudan University in time.

Exclusion Criteria

1. Combined with severe medical disease or liver or kidney dysfunction: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level elevates to 3 times or more of the upper limit of normal, kidney dysfunction (creatinine clearance < 30 mL/min)

2. Patients are diagnosed with other malignant tumors of the reproductive system; patients with breast cancer or other hormone-dependent tumors that cannot be used with progesterone.

3. Those who have received high doses of high potency progestin or oral contraceptives within the last 3 months (or those on maintenance medication).

4. Those who require hysterectomy or other methods other than conservative treatment.

5. Known or suspected pregnancy.

6. Those who has contraindications to use progestin.

7. Deep vein thrombosis, stroke, myocardial infarction.

8. Severe joint lesions that prevent walking or movement.

9. untreated or recurrent pelvic inflammatory disease (PID)

10. an untreated or uncontrolled pelvic infection (vaginal, cervical, uterine);

11. Cervical dysplasia

12. Congenital or acquired uterine abnormalities, including uterine fibroid tumors or conditions that affect the shape of the uterus

13. allergic to the LNG-IUS components

14. uterine cavity is too large (average uterine diameter is over 7 cm) or have a history of LNG-IUS falling out.

Notes: the last 6 criteria are only applied for patients with LNG-IUS.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Xiaojun Chen

OTHER

Sponsor Role: lead

Responsible Party

Xiaojun Chen

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

XIAOJUN CHEN, PhD

Role: PRINCIPAL_INVESTIGATOR

Obstetrics & Gynecology Hospital of Fudan University

Locations

Obstetrics and Gynecology Hospital of Fudan University

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

WEIWEI SHAN, PhD

Role: CONTACT

danweiwei7468@fckyy.org.cn

8613817813106

XIAOJUN CHEN, PhD

Role: CONTACT

cxjlhjj@163.com

8613601680784

Facility Contacts

WEIWEI SHAN, PhD

Role: primary

fdsww1024@sina.cn

13817813106

DANDAN JU, MD

Role: backup

021-33189900-8408

Other Identifiers

53211036-02

Identifier Type: -

Identifier Source: org_study_id