ABSTRACT
Objective:
To compare the effects and
safety of
dydrogesterone (DG) and
medroxyprogesterone acetate (MPA) on the
treatment in
patients with
endometrial hyperplasia without atypia (EH).
Methods:
This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021,
patients with EH admitted to the
Obstetrics and
Gynecology Hospital of Fudan
University were recruited. Enrolled
patients were stratified according to the pathological types of simple
hyperplasia (SH) or complex
hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up
time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The
secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate,
recurrence rate, and
pregnancy rate in one year after CR.
Results:
(1) A total of 292
patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH
patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH
patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292
patients, 205
patients enrolled into the primary endpoint
analysis, including 92 SH
patients and 113 CH
patients, with 100
patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI-9.9%-7.0%). Stratified by the
pathology types, the 6m-CR rate of SH
patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH
patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two
treatments had no statistical significance either (all P>0.05). A total of 194 EH
patients enrolled into the
secondary endpoint
analysis, including 88 SH
patients and 106 CH
patients, and 96
patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH
patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH
patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two
treatments both in SH and CH
patients (all P>0.05). (3) The
incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH
patients achieved CR, and the cumulative
recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH
patients achieved CR, and the cumulative
recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two
treatment groups (all P>0.05). Among the 93 SH
patients, 10
patients had
family planning but no
pregnancy happened during the follow-up period. Among the 112 CH
patients, 21 were actively preparing for
pregnancy, and the
pregnancy rate and live-
birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in
pregnancy rate and live-
birth rate between the two
treatment groups (all P>0.05).
Conclusions:
Compared with MPA, DG is of good
efficacy and
safety in treating EH. DG is a favorable alternative
treatment for EH
patients.