Comparison of the effect of levonorgestrel-intrauterine system with or
without oral megestrol acetate on fertility-preserving treatment in
patients with atypical endometrial hyperplasia: a prospective,
open-label, randomized controlled phase II study
Abstract
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 Obstetrics & Gynecology Hospital of Fudan University,
Shanghai, China Population A total of 180 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), respectively. Main outcomes and measures The primary
endpoint was the complete response (CR) rate at 16 weeks of treatment.
The secondary endpoints were the CR rate at 32 weeks of treatment,
adverse events, recurrent rate, and pregnancy rate. Results LNG-IUS
group yielded a higher 16-week CR rate than MA group (P=0.049; Odds
ratio [OR], 2.44; 95% confidence interval [95%CI], 1.00-6.00).
However, 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). Meanwhile, less side-effects were found in LNG-IUS group
compared with the other two groups. No significant difference was seen
in recurrence rates and pregnancy rates among all three groups.
Conclusions LNG-IUS might be considered as the first-line choice of
fertility-sparing treatment in AEH patients with proper size of uterine
cavity. LNG-IUS combined with MA might not provide better treatment
effect than MA or LNG-IUS alone.