Metformin Plus Megestrol Acetate as a Fertility-sparing Treatment in Patients With Atypical Endometrial Hyperplasia

Study Overview
=================
Brief Summary
-----------------
To verify whether metformin could improve the effect of progestin as fertility-sparing treatment in patients with atypical endometrial hyperplasia(AEH).

Detailed Description
-----------------
Whether metformin could improve the effect of progestin as fertility-sparing treatment in patients with atypical endometrial hyperplasia(AEH) is still not clear. Our previous finding from subgroup analysis in a phase II randomized controlled trial showed that 39.6% of AEH patients in metformin plus megestrol acetate group achieved complete response, compared with 20.4% in group of megestrol acetate alone. This trial aim to fully testify the effect of metformin in fertility-sparing treatment for AEH patients with adequate sample size.

Official Title
-----------------
Comparing Metformin Plus Megestrol Acetate With Megestrol Acetate Alone as a Fertility-sparing Treatment in Patients With Atypical Endometrial Hyperplasia

Conditions
-----------------
Atypical Endometrial Hyperplasia

Intervention / Treatment
-----------------
* Drug: Metformin plus Megestrol acetate
* Drug: Megestrol Acetate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-45 years old; pathologically diagnosed with AEH for the first time; desire to preserve their fertility; no signs of suspicious myometrial invasion or extrauterine metastasis by enhanced magnetic resonance imaging (MRI), enhanced computed tomography (CT) or transvaginal ultrasonography (TVUS); no contraindication for metformin, megestrol acetate or pregnancy; no hormone or metformin treatment within 6 months before entering the trial; not pregnant when participating in the trial; willing to follow the trial arrangement after being fully informed of all the risks and inconveniences caused by the trial. Exclusion Criteria: Patients who had one or more of the following conditions: allergy history or contraindications for megestrol acetate or metformin; pregnant when initiating the study; alcoholism, severe infection, severe chronical diseases (dysfunction of heart, liver, lung or kidney); high risk of thrombosis; recurrent AEH; endometrial cancer; other malignancy history.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin plus megestrol acetate<br>Metformin 1500mg per day plus megestrol acetate 160mg per day. | Drug: Metformin plus Megestrol acetate<br>* metformin 1500mg, per day, oral; megestrol acetate 160mg per day, oral<br>|
| Active Comparator: Megestrol acetate<br>Megestrol acetate 160mg per day. | Drug: Megestrol Acetate<br>* megestrol acetate 160mg per day, oral<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response within 16 weeks of treatment | reversion of AEH The reversion of AEH to proliferative or secretory endometrium | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response within 32 weeks of treatment | The reversion of AEH to proliferative or secretory endometrium | 32 weeks | 
| Adverse events | Adverse events during the treatment of metformin plus megestrol acetate or megestrol acetate alone | 32 weeks | 
| 2-year recurrence rate | recurrence rate within 2 years after the treatment | 2 years | 
| 2-year pregnancy rate | Pregnancy rate within 2 years after the treatment | 2 years | 
| 2-year live-birth rate | Live-birth rate within 2 years after the treatment | 2 years |