Purpose To describe the effects of estetrol (E4) 15 mg/drospirenone (DRSP) 3 mg on physical and emotional premenstrual and menstrual symptoms. Materials and Methods We used Menstrual Distress Questionnaire (MDQ) data from a phase-3 trial (NCT02817828) in Europe and Russia with participants (18 − 50 years) using E4/DRSP for up to 13 cycles. We assessed mean changes in MDQ-t-scores from baseline to end of treatment in premenstrual (4 days before most recent flow) and menstrual (most recent flow) scores for 4 MDQ domains in starters and switchers (use of hormonal contraception in prior 3 months) and performed a shift analysis on individual symptoms within each domain. Results Of 1,553 treated participants, 1,398(90.0%), including 531(38%) starters, completed both MDQs. Starters reported improvements for premenstrual Pain (−1.4), Water Retention (−3.3) and Negative Affect (−2.5); and for menstrual Pain (−3.5), Water Retention (−3.4), and Negative Affect (−2.7) (all p < 0.01). For switchers, no changes were significant except an increase in premenstrual (+1.0, p = 0.02) and menstrual (+1.5, p = 0.003) Water Retention. We observed a change in symptom intensity in >40% of participants for Cramps, Backache and Fatigue (domain Pain), Painful or Tender Breast and Swelling (domain Water Retention) and Mood Swings and Irritability (domain Negative Affect). Conclusion E4/DRSP starters experienced significant improvements in the domains Pain, Water Retention and Negative Affect particularly benefiting those with more severe baseline symptoms. Switchers showed minimal changes.