Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia

Study Overview
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Brief Summary
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To see if megestrol acetate plus rosuvastatin will be superior to reversing the endometrial lesion to a normal endometrium than megestrol acetate alone in patients with atypical endometrial hyperplasia (AEH). Considering the large sample size in RCT, we used Simon two-stage design.

Detailed Description
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After diagnosed of AEH by hysteroscopy, patients will be enrolled. Age, height, weight, waist circumstances, blood pressure, basic history of infertility and blood pressure will be collected. Blood tests, including fasting blood glucose (FBG), fasting insulin (FINS), OGTT 2h blood glucose and insulin, blood lipids, SHBG, sex hormone levels, anti-müllerian hormone(AMH), creatine kinase(CK) and renal/liver function tests will be performed before treatment to evacuate their basic conditions. Each subject will receive body fat testing by Inbody 520. Patients are randomized to 1 of 2 treatment groups. Patients will receive MA 160 mg plus rosuvastatin 10mg by mouth daily for at least 6 months. Then hysteroscopy will be used to evaluate the endometrial condition every 3 months, and intra-operative findings will be recorded. Complete response (CR) is defined as the reversion of endometrial atypical hyperplasia to proliferative or secretory endometrium; partial response (PR) is defined as regression to simple or complex hyperplasia without atypic; stable disease (SD) is defined as the persistence of the disease; and progressive disease (PD) is defined as the appearance of endometrial cancer in patients. Continuous therapies will be needed in PR or NR. Patients with PD will be recommended for hysterectomy. Two months of maintenance treatment will be recommended for patients with CR, and participants will be followed up for 2 years.

Official Title
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Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia

Conditions
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Atypical Endometrial Hyperplasia

Intervention / Treatment
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* Drug: Megestrol Acetate
* Drug: Rosuvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a confirmed pathological diagnosis based upon hysteroscopy Have a desire for remaining reproductive function or uterus Good compliance with adjunctive treatment and follow-up Abnormal blood lipid. At least meet one of the following five items: Total cholesterol (TC) ≥ 5.2mmol/L (200mg/dL) Low-density lipoprotein cholesterol (LDL-C) ≥ 3.4mmol/L (130mg/dL) Fasting triglycerides (TG) ≥ 1.7mmol/L (150mg/dL) High-density lipoprotein cholesterol (HDL-C) <1.03mmol/L (40mg/dL) Apo-lipoprotein-A (Apo-A) ≥ 1.0g/L Exclusion Criteria: Acute liver disease or liver tumor (benign or malignant) or renal dysfunction Pregnancy or potential pregnancy Under treatment of high-dose progestin therapy more than 1 months in recent 6 months Confirmed diagnosis of any cancer in reproductive system Acute severe disease such as stroke or heart infarction or a history of thrombosis disease Hypersensitivity or contradiction for using MA or statins Already diagnosed with hyperlipidemia and using lipid-lowering drugs With other factors of reproductive dysfunction; Strong request for uterine removal or other conservative treatment Smoker (>15 cigarettes a day) Drinker (>20 grams a day)

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

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MA + Rosuvastatin<br>Patients will receive MA 160 mg and rosuvastatin 10 mg by mouth daily for at least 6 months.Then every 3 months, hysteroscopy will be used to evaluate the endometrial condition, and findings will be recorded. Due to personal reasons, it may not be possible to accept hysteroscopic evaluation every three months, then the longest duration will be 8 months. | Drug: Megestrol Acetate<br>* At a dosage of 160 mg/day<br>Drug: Rosuvastatin<br>* At a dosage of 10 mg/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 16 weeks. | 12 to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | From date of randomization or initial therapy until the date of CR or date of hysterectomy, whichever come first, assessed up to 32 weeks. | 28 to 32 weeks | 
| Pathological response duration | Pathological response duration | Up to 2 years | 
| Pathological response rate classified by different blood lipid level | Pathological response rate classified by different blood lipid level | Up to 32 weeks | 
| Toxicity evaluation | Toxicity evaluation according to CTCAE 5.0 version. | Up to 32 weeks | 
| Relapse rate |  | up to 2 years after the therapy for each patient | 
| Pregnancy rate |  | up to 2 years after the therapy for each patient | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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megestrol acetate, rosuvastatin, atypical endometrial hyperplasia, conservative treatment