Post Hoc Analysis of a Previous Study of Estetrol 15 mg/Drospirenone 3 mg Combination for Dysmenorrhea and Uterine Bleeding in Adenomyosis Patients

ABSTRACT Purpose To clarify the efficacy and safety of the estetrol 15 mg/drospirenone 3 mg combination among Japanese women with adenomyosis by post hoc analyses of a previous randomized clinical study. Methods Post hoc analyses were performed using data from a 16‐week, multi‐center, randomized, double‐blinded, placebo‐controlled, parallel‐group study, followed by a 36‐week, open‐label extension study involving 162 Japanese women with dysmenorrhea. Participants received cyclic estetrol/drospirenone or placebo. The primary endpoint was the absolute change in total dysmenorrhea score from baseline to the end of the 16‐week double‐blinded period. Results Among participants with adenomyosis, estetrol/drospirenone reduced the change from baseline of the total dysmenorrhea score at Week 16 by 2.5. The between‐treatment difference was estimated as −1.8 (two‐sided 95% confidence interval: −2.5 to −1.0), showing a significant difference from placebo ( p < 0.001). Responder rate, as the proportion of participants who achieved a ≥ 2.0‐point reduction in total dysmenorrhea score from baseline, was 66.7% following 16‐week estetrol/drospirenone treatment, significantly greater than with placebo (20.0%; p < 0.001). Fewer safety concerns were reported with estetrol/drospirenone treatment, including the occurrence of venous thromboembolism. Conclusions Estetrol/drospirenone ameliorates adenomyosis‐associated symptoms, offering safer treatment with potentially reduced thromboembolic risk. Trial Registration jRCT registration number: jRCT2011210023