Efficacy and safety of the combination of estetrol 15 mg/drospirenone 3 mg in a cyclic regimen for the treatment of endometriosis-associated pain and objective gynecological findings: a multicenter, placebo-controlled, double-blind, randomized study

Abstract

To evaluate the efficacy and safety of 24-week cyclic administration of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg in Japanese patients with endometriosis. A 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. A total of 162 Japanese women diagnosed with endometriosis. Participants were randomly allocated to the E4/DRSP group or the placebo group. In the E4/DRSP group, participants were orally administered one tablet containing E4 15 mg and DRSP 3 mg daily for 24 days, followed by one placebo tablet for 4 days for a hormone-free interval, constituting a one-cycle regimen. One placebo tablet was administered once daily for 28 days to participants in the placebo group. The treatments were continued for six cycles (24 weeks) throughout the confirmatory period. Changes in visual analog scale scores for the most severe pelvic pain (lower abdominal and back pain) from baseline to six treatment cycles at the end of the confirmatory study period. E4/DRSP showed changes in average visual analog scale scores for the most severe pelvic pain (-33.2 mm) from baseline to the end of the six-cycle treatment. The between-group difference was significant (-8.5 mm, two-sided 95% confidence interval: -16.1 to -0.9 mm), showing superiority to placebo (p=0.028). Responder rates, ≥30% and ≥50% reduction in visual analog scale scores from baseline, were larger in the E4/DRSP group than in the placebo group: 53.2% versus 29.6% (p=0.004) and 36.4% versus 12.3% (p<0.001). Objective gynecological findings (induration of the cul-de-sac, pelvic tenderness, limited uterine mobility) were significantly improved by E4/DRSP treatment, and the proportions of stable and worsened participants were significantly lower than in the placebo group. E4/DRSP reduced the size of endometriomas and improved quality of life, based on quality of life-related questionnaires and global impression scores. No safety concerns were observed with E4/DRSP treatment. Few differences were observed in the proportion of participants with hemostasis parameters outside the reference range between the E4/DRSP and placebo groups. E4/DRSP effectively treats endometriosis-associated pain and improves gynecological findings. E4/DRSP may be a safe, new option for endometriosis treatment with a potentially reduced risk of thromboembolic events.