3. Procedures
Patients in MA group received continuous oral megestrol acetate 160 mg once daily. LNG-IUS (containing LNG 52mg) insertion was administered in patients in LNG-IUS group. Patients in MA+LNG-IUS group received MA 160 mg once daily plus LNG-IUS insertion.
All patients received complete hysteroscopic evaluation and resection of lesions before the initiation of treatment in this trial. LNG-IUS was placed during the hysteroscopic evaluation when indicated. Hysteroscopic evaluations were performed every 3 months to evaluate treatment response after initiating the treatment by two specialists (Dr. Zhang HW and Dr. Zhu CY) following standard procedure as described previously8. Suspected lesions were recorded in detail and removed completely under the principle to minimize endometrial damage. A random endometrial biopsy was performed in the area where no obvious lesion was found. All the specimens were sent separately for the pathological diagnosis.
During each hysteroscopic evaluation, the LNG-IUS was taken out, kept from contamination, and bacilli culture was performed. A new LNG-IUS was suggested to be placed in uterine cavity after each hysteroscopic evaluation. If the patient insisted on using the old one, the LNG-IUS would be swabbed by iodophor for sterilization and reinserted in the uterine cavity. The LNG-IUS would be taken out immediately if bacilli culture reported positive result.
The treatment response was categorized as follows: (1) complete response (CR), defined as no endometrial lesion. Another hysteroscope were held 3 months later for confirmation of CR; (2) partial response (PR), pathological improvement, such as endometrial hyperplasia; (3) stable disease (SD), persistence of disease as originally diagnosed; (4) progression disease (PD), any appearance of endometrial malignancy.
MA and/or LNG-IUS were administered until CR. Treatment were ceased when patients experienced unacceptable side effects. Definitive hysterectomy was suggested when patients remained SD after 7 months of treatment, or not achieving CR after 10 months of treatment, or had PD at any time of treatment 24. For those who refused hysterectomy, alternative treatment was given based on multidisciplinary consensus. Duration of treatment time to achieve CR was calculated from initiation of treatment to the first time that the patient achieved pathological CR after hysteroscopic assessment.
After achieving CR, the same regimen was administered for another 2-3 months for treatment consolidation and patients were encouraged to receive assisted reproductive treatment. Ultrasonography (every 3 months) and endometrial biopsy by Pipelle (every 6 months) were routinely used to assess the endometrium. For CR patients without recent plan to conceive, or those stopped breast breeding after delivery, cyclic oral dydrogesterone, oral contraceptive pills, or LNG-IUS was administered to prevent disease recurrence. Recurrence was defined as the presence of complex hyperplasia, AEH, or EC after achieving CR.
Data on age, height, weight, and metabolic status (fasting blood glucose (FBG), fasting insulin (FINS), and lipid panel) were collected before the initiation of treatment. Obesity was defined as body mass index (BMI)≥28 kg/m2 followed criteria for Chinese adults25, 26. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index, which was calculated as fasting blood glucose (FBG) (mmol/L) × fasting insulin (FINS) (mU/L)/22.5. HOMA-IR≥2.95 was considered insulin resistant (IR) 27. Metabolic syndrome (MS) was defined according to literature 28-30. All patients were followed up from the date of treatment initiation to July 1st, 2021.