Megestrol Acetate Plus Rosuvastatin in Young Women With Atypical Endometrial Hyperplasia

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.

Study Overview

• Status: Completed
• Conditions: Atypical Endometrial Hyperplasia
• Intervention / Treatment: Drug: Megestrol Acetate; Drug: Rosuvastatin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Obstetrics and Gynecology Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. Total cholesterol (TC) ≥ 5.2mmol/L (200mg/dL)
  2. Low-density lipoprotein cholesterol (LDL-C) ≥ 3.4mmol/L (130mg/dL)
  3. Fasting triglycerides (TG) ≥ 1.7mmol/L (150mg/dL)
  4. High-density lipoprotein cholesterol (HDL-C) < 1.03mmol/L (40mg/dL)
  5. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MA + Rosuvastatin; 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; At a dosage of 160 mg/day; Drug: Rosuvastatin; At a dosage of 10 mg/day

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Xiaojun Chen, Obstetrics and Gynecology Hospital, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2020
• Primary Completion (Actual): June 20, 2022
• Study Completion (Actual): June 20, 2022

Study Registration Dates

• First Submitted: June 21, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 26, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: rosuvastatin; conservative treatment; megestrol acetate; atypical endometrial hyperplasia
• Additional Relevant MeSH Terms: Pathologic Processes; Uterine Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Hyperplasia; Endometrial Hyperplasia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Central Nervous System Stimulants; Appetite Stimulants; Rosuvastatin Calcium; Megestrol; Megestrol Acetate
• Other Study ID Numbers: 53211029-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No