Multicentre Trial Evaluating the Safety and Tolerability of Estetrol-Drospirenone Combined Oral Contraceptive in Postmenarchal Female Adolescents

Abstract

Objectives: This study aims to evaluate the safety and tolerability of estetrol/drospirenone in adolescents. Methods: In this Phase 3 open-label study, postmenarchal adolescents (12–17 years) received estetrol (E4)/drospirenone (DRSP) 15 mg/3 mg orally for six cycles (24 active/4 placebo regimen). Safety was evaluated through adverse event (AE) reporting. Participants also recorded daily pill intake, bleeding/spotting, dysmenorrhea, and pain medication use in e-diaries. Descriptive statistics were used. Results: Of 112 enrolled participants, 105 received treatment (mean age: 15.2 years), and 84.8% were completers. No serious treatment-related AEs or safety concerns were observed. Nausea and dysmenorrhea (each 1.9%) were the most common treatment-related AEs. Over 71% of participants took all tablets in each cycle. The percentage of participants with unscheduled bleeding and/or spotting decreased from 45.8% (Cycle 1) to 14.5% (Cycle 5), and the number of days with unscheduled bleeding and/or spotting decreased from nine to six days per cycle. The scheduled bleeding and/or spotting rate ranged between 77.4% and 90.5%, with a duration decreasing from six to four days in Cycle 1 to Cycle 5. Absence of scheduled bleeding increased from 9.5% in Cycle 3 to 22.6% in Cycle 5. The proportion of participants reporting dysmenorrhea decreased by 34.8%, with a median visual analogue scale score dropping from 5.0 at baseline to 3.7 at Cycle 6. Pain medication use decreased from 63.9% to 31.6% in Cycle 6. Conclusions: The use of E4/DRSP in adolescents raised no safety concerns, was well tolerated, resulted in a clear and stable cyclic bleeding pattern, and reduced pain associated with dysmenorrhea.