Abstract
Objective:
Assess the effect of estetrol/drospirenone 15 mg/3 mg (E4/DRSP) on menstrual symptoms and health-related quality of life (HRQoL) in adolescents aged 12–17 years.
Methods:
This was a phase 3, open-label, six-cycle trial. We measured menstrual symptoms using the Menstrual Distress Questionnaire–Short Form (MDQ), focusing on bothersome symptom domains. We assessed HRQoL with KIDSCREEN-27. Participants completed both instruments at baseline, Cycles 1, 3, and 6. We compared Cycle 6 outcomes versus baseline using the Wilcoxon signed-rank test.
Results:
Eighty-nine adolescents completed treatment; 51 completed both MDQ and KIDSCREEN-27. E4/DRSP reduced MDQ t-scores for menstrual Pain and Negative Affect, and premenstrual and menstrual Water Retention (p<0.05). Impaired Concentration did not change. Overall, shift analysis revealed that most adolescents improved to milder categories, often to no symptoms, with minimal worsening. Largest shifts occurred for menstrual cramps, backache, general aches and pains, painful or tender breasts, mood swings, crying, tension, and feeling sad or blue. Baseline KIDSCREEN-27 t-scores indicated reduced HRQoL in Physical Well-being, Psychological Well-being, Social Support & Peers, and School Environment compared to European norms, while Autonomy & Parent Relations was within the normal range. Following treatment, all domains improved, with significant gains in Physical Well-being and Autonomy & Parent Relations (p<0.05). By Cycle 6, all domains initially below the normative range had reached the normative range.
Conclusions:
E4/DRSP reduced menstrual symptom burden and improved health-related quality of life in adolescents. Its native estrogen and progesterone-like progestin profile may support acceptability and adherence in this population.
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Copyright (c) 2026 Lali Pkhaladze, Angelica Lindén Hirschberg, Kristina Gemzell-Danielsson, Kai Haldre, Nino Davidova, Nina Flerin, Guillaume Chatel, Dan Apter