Ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen for the management of endometriosis-associated pelvic pain: a randomized controlled trial

Abstract

Objective: To investigate the efficacy and safety of ethinylestradiol 20 μg/drospirenone 3 mg in a flexible extended regimen (Flexible_MIB) compared with placebo to treat endometriosis-associated pelvic pain (EAPP).

Design: A phase 3, randomized, double-blind, placebo-controlled, parallel-group study, consisting of a 24-week double-blind treatment phase followed by a 28-week open-label extension phase with an unblinded reference arm.

Setting: Thirty-two centers.

Patient(s): A total of 312 patients with endometriosis.

Intervention(s): Patients were randomized to Flexible_MIB, placebo, or dienogest. The Flexible_MIB and placebo arms received 1 tablet per day continuously for 120 days, with a 4-day tablet-free interval either after 120 days or after ≥3 consecutive days of spotting and/or bleeding on days 25-120. After 24 weeks, placebo recipients were changed to Flexible_MIB. Patients randomized to dienogest received 2 mg/d for 52 weeks in an unblinded reference arm.

Main outcome measure(s): Absolute change in the most severe EAPP based on visual analog scale scores from the baseline observation phase to the end of the double-blind treatment phase.

Result(s): Compared with placebo, Flexible_MIB significantly reduced the most severe EAPP (mean difference in visual analog scale score: -26.3 mm). Flexible_MIB also improved other endometriosis-associated pain and gynecologic findings and reduced the size of endometriomas.

Conclusion(s): Flexible_MIB improved EAPP and was well tolerated, suggesting it may be a new alternative for managing endometriosis.

Clinical trials registration number: NCT01697111.

Keywords: Endometriosis; flexible extended regimen; low-dose estrogen/progestin; pain relief.