Mitchell Creinin, MD, reports estetrol pill eases menstrual symptoms

In a recent interview with Contemporary OB/GYN, Mitchell Creinin, MD, professor at University of California Davis Health, discussed a study evaluating the impact of estetrol (E4) combined with drospirenone, a novel oral contraceptive, on premenstrual and menstrual symptoms.

This was a planned secondary analysis of a phase 3 trial conducted in the United States and Canada, designed to assess not only contraceptive effectiveness but also the impact on menstrual complaints using the Menstrual Distress Questionnaire (MDQ). A similar study had already been conducted and published in Europe and Russia. Due to demographic and clinical differences in the participant populations, the results were not pooled but analyzed separately.

Participants completed the MDQ at the start and end of the study, and were categorized as either "starters" (those not using hormonal contraception prior to the study) or "switchers" (those transitioning from another hormonal contraceptive). This differentiation allowed for more accurate interpretation, as baseline symptom profiles varied between the groups.

The results showed that switchers generally reported low levels of menstrual distress at baseline, and those levels remained stable, indicating that switching to estetrol/drospirenone maintained their symptom relief. In contrast, starters showed a significant decrease in symptom intensity across key domains, particularly pain, water retention, and negative affect. Symptoms such as cramps, headaches, back pain, fatigue, swelling, tender breasts, anxiety, and irritability notably improved, with many showing at least a 40% reduction in severity.

A unique aspect of this study was the use of "shift tables," a tool designed to translate average score changes into more practical clinical information. Rather than relying solely on mean symptom score reductions, shift tables tracked individual symptom progression, allowing clinicians to see how patients with varying symptom severities at baseline were likely to respond. For example, many participants with severe cramping experienced moderate or even no symptoms by the study’s end, making the data directly applicable for patient counseling.

In switchers, although overall scores remained consistent, individual improvements were still observed, especially among those with more severe initial symptoms. This suggested that estetrol/drospirenone can enhance symptom management even in those already on hormonal contraception.

Creinin emphasized that while the results are promising, further research is needed, particularly randomized controlled trials comparing estetrol/drospirenone with other contraceptive options in the same population. This would allow for definitive comparisons of efficacy in managing menstrual symptoms across different contraceptive methods.

Disclosures: Mayne Pharma Commercial LLC

Reference

Bouchard C, Bitzer J, Chen MJ, et al. Effects of estetrol/drospirenone on self-reported physical and emotional premenstrual and menstrual symptoms: Data from the phase 3 clinical trial in the United States and Canada. Contraception. 2025. doi:10.1016/j.contraception.2025.110889