Objective To compare the effect of levonorgestrel-intrauterine system (LNG-IUS) with or without oral megestrol acetate (MA) versus MA alone on fertility preserving treatment in patients with atypical endometrial hyperplasia (AEH).

Design Single-center phase II study with open-label, randomized and controlled trial conducted between July 2017 and June 2020.

Setting Shanghai OBGYN Hospital of Fudan University, China

Population A total of 132 patients (18–45 years) with primary AEH were randomly assigned (1:1:1) to MA group (N=60), LNG-IUS group (N=60), or MA+LNG-IUS group (N=60).

Methods Patients received MA (160 mg orally daily), LNG-IUS, or MA+LNG-IUS (MA 160 mg orally daily plus LNG-IUS).

Main outcomes and measures

The primary endpoint was complete response (CR) rate at 16 weeks of treatment. The secondary endpoints were CR rate at 32 weeks of treatment, adverse events, recurrent rate, and pregnancy rate.

Results LNG-IUS group yielded higher 16-week CR rate than MA group (P=0.048; Odds ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00–6.00). MA+LNG-IUS group did not yield better 16-week or 32-week CR rates than MA group (P=0.245; P=0.915) or LNG-IUS group (P=0.419; P=0.653). LNG-IUS group achieved less weight gain, nocturnal urine, night sweats, insomnia, or edema face compared with the other two groups. Recurrence rates and pregnancy rates showed no difference among the three groups.

Conclusion Our data support the usage of LNG-IUS as first line choice for fertility sparing treatment in AEH patients with proper uterine cavity size. LNG-IUS combined with MA did not provide better treatment effect than either LNG-IUS alone or MA alone.

This study was supported by the National Key Research and Development Program of China (Grant No 2019YFC1005200 and 2019YFC1005204), Shanghai Medical Centre of Key Programs for Female Reproductive Diseases (Grant No. 2017ZZ010616) and sponsored by Shanghai sailing program (Grant No.19YF1404200).