Efficacy and safety of desogestrel/ethinylestradiol 150/20 flexible extended regimen (FREEDOM 150/20) in dysmenorrhea: phase 3 study in Japan.

OBJECTIVE: To evaluate the efficacy and long-term safety of a user-driven flexible extended regimen of desogestrel 150 μg/ethinylestradiol 20 μg (DSG/EE 150/20) for the treatment of primary or secondary dysmenorrhea in women from Japan. DESIGN: Phase 3, randomized, placebo-controlled, parallel-group, double-blind study with an open-label extension period. SUBJECTS: Two hundred and eleven women with regular menstrual cycles and primary or secondary dysmenorrhea in 21 centres across Japan. INTERVENTION: Participants were randomly assigned (3:1) to receive DSG/EE 150/20 μg or placebo once daily for 24-80 consecutive days, with each treatment period followed by a 4-day tablet-free interval. After the double-blind phase (three 28-day cycles), participants entered an open-label phase (≤10 cycles); participants initially receiving placebo were switched to DSG/EE. MAIN OUTCOME MEASURES: Primary endpoint was change from baseline through day 84 in total dysmenorrhea score (TDS). Secondary endpoints included number of days with dysmenorrheic pain, patient global impression of change (PGI-C), treatment satisfaction questionnaire for medication (TSQM-9), quality of life (QoL) measured by the 36-item short form health survey version 2.0 (SF-36v2), and safety outcomes. RESULTS: In the 211 participants randomized to DSG/EE (n = 159) and placebo (n = 52), the mean (SD) age was 32.3 (7.56) years, and body mass index was 21.94 (3.18). A significant reduction in TDS from baseline through day 84 was observed in the DSG/EE group vs. placebo (least squares mean: -2.50 vs. -0.84; treatment difference [95% confidence interval: -1.67 [-2.08, -1.26]). The number of days with mild, moderate, and severe pain were 12.9 vs. 12.1, 4.8 vs. 6.5, and 0.8 vs. 1.1 days in the DSG/EE vs. placebo group. Over 80% of DSG/EE-treated participants reported improvement in PGI-C scores compared with <30% on placebo. TSQM-9 global satisfaction and effectiveness least squares mean scores were higher with DSG/EE (63.69 vs. 36.62 and 62.86 vs. 35.5) compared with placebo. DSG/EE improved SF-36v2 scores, particularly in the physical component summary, bodily pain, and role-physical domains. Overall, the most frequent treatment-emergent adverse events were intermenstrual bleeding, nasopharyngitis, and nausea. No deaths were reported during the entire study period. CONCLUSION: DSG/EE 150/20 effectively reduced dysmenorrhea severity, improved SF-36v2 scores and treatment satisfaction, offered dosing flexibility, and was well-tolerated with a safety profile consistent with combined oral contraceptives. TRIAL REGISTRATION: jRCT2031230276 (https://jrct.mhlw.go.jp/en-latest-detail/jRCT2031230276).