Drospirenone found to ease menstrual symptoms

Drospirenone found to ease menstrual symptoms | Image Credit: © Towfiqu Barbhuiya - © Towfiqu Barbhuiya - stock.adobe.com.

Drospirenone linked to symptom improvement

The oral contraceptive drospirenone (NEXTSTELLIS; Mayne Pharma) has been linked to significant improvements in physical and emotional premenstrual and menstrual symptoms among US women, according to a recent study published in Contraception.¹

The drug received a New Drug Application approval from the FDA on April 16, 2021. It is the first contraceptive pill containing estetrol, the first new estrogen introduced to the United States in 50 years.² Safety and efficacy toward pregnancy prevention were proven in 2 phase 3 clinical trials including 3725 women.

Predictable bleeding profile encourages further study

“Whereas products that contain estradiol tend to cause unpredictable irregular bleeding, the bleeding profile with estetrol 15mg/drospirenone 3 mg is predictable,” wrote investigators.¹ With this in mind, the multicenter, open-label, single arm trial was conducted to determine the impact of drospirenone on menstrual symptoms.

These symptoms were evaluated using the Menstrual Distress Questionnaire (MDQ), a self-reported questionnaire containing 48 symptoms across 8 domains. Participants included healthy, heterosexually active, pre-menopausal women aged 16 to 50 years with regular menstrual cycles and a body mass index of 35 kg/m² or under.

The study drug included estetrol 15 mg/DRSP tablets and 4 inactive tablets, with a regimen of daily use for 28 days. This regimen lasted for up to 13 menstrual cycles, and follow-up assessments occurred at cycles 2, 4, 7, 10, and within 3 weeks after completing cycle 13.

MDQ scoring and domains of focus

MDQ assessments were completed at baseline and end of treatment (EOT). Symptoms throughout the premenstrual, menstrual, and intermenstrual phases were rated by participants on a scale ranging from 0 to 4, with higher scores indicating more severe symptoms.

Investigators focused on the 4 domains containing the most bothersome menstrual symptoms in the current analysis. These included the Pain and Water Retention physical domains and the Negative Affect and Impaired Concentration emotional domains.

Participants with at least 1 dose of drospirenone completing the MDQ at baseline and EoT were included in the analysis. Scores with more than 2 domain items missing were excluded.

There were 1308 patients included in the final analysis, 82% of whom completed most EoT assessments. Mean t-scores for MDQ domains significantly decreased between baseline and EoT. For menstrual Pain, premenstrual Water Retention, menstrual Water Retention, and premenstrual Negative Affect, these declines were -2.3, -1.3, -1.2, and -1.1, respectively.

Starters vs. switchers: Differences in symptom improvement

Starters, defined as patients with no hormonal contraception use in the 3 months prior to enrollment, displayed significantly higher average t-scores for all premenstrual and menstrual domains compared to switchers. These patients had significant reductions for menstrual Pain, premenstrual and menstrual Water Retention, and premenstrual Negative Affect.

These reductions were -3.3, -1.5, -2, and -1.2, respectively. However, switchers did not display significant changes in t-scores. Shift analyses were also performed for Cramps, Backache, Fatigue, and General Aches and Pains.

Symptoms with significant improvements in starters included cramps, backache, general aches and pains, skin blemish or disorder, breast tenderness, swelling, and irritability. However, these domains were not significantly influenced in switchers.

Implications for clinical practice

The largest t-score change was observed for starters in the Cramps item, with a reduction of -3.3. Improvements had more pronounced changes overall compared to worsening symptoms, highlighting the efficacy of drospirenone for improving premenstrual and menstrual symptoms.

“Although MDQ t-score comparison showed benefits occurred primarily in participants not using hormones before enrollment, shift table analysis showed improved outcomes in a significant proportion of all participants,” wrote investigators. “This information should be helpful for patients and clinicians during contraceptive counseling.”

References

1. 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
2. Mayne Pharma and Mithra announce FDA approval of new oral contraceptive NEXTSTELLIS. Mayne Pharma. April 16, 2021. Accessed April 10, 2025. https://www.maynepharma.com/wp-content/uploads/2022/04/fda-approval-of-novel-oral-contraceptive-nextstellis.pdf.