Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort II)

Phase 3 Completed 1015 enrolled Estetra ICON Clinical Research · collab

RandomizedParallel-groupQuadruple-blindTreatment

Summary

A two-part study designed to evaluate the effect of Estetrol (E4) 15 mg, 20 mg, or placebo on the severity and frequency of vasomotor symptoms (VMS) in the Efficacy Study Part and the safety of E4 20 mg in the Safety Study Part.

Timeline

Start: 2019-09-27
Primary completion: 2022-08-18
Completion: 2022-08-18

Outcome

Mixed primary results

registry Estetrol 15 mg - Efficacy Study Part vs Placebo - Efficacy Study Part; p = 0.0436; Least square mean difference -8.42 NCT04090957 ↗

registry Estetrol 15 mg - Efficacy Study Part vs Placebo - Efficacy Study Part; p = 0.7786; Least square mean difference -0.04 NCT04090957 ↗

Publications

Panay N, Simoncini T, Taziaux M, Bouchard C, Black A, Kapoor E, Utian W, Foidart JM, Lobo RA. Estetrol for the treatment of moderate to severe vasomotor symptoms in postmenopausal women: The design of the E4COMFORT I and II trials. Maturitas. 2026 Jan;204:108781. doi: 10.1016/j.maturitas.2025.108781. Epub 2025 Nov 17.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Estetrol	Other / unclassified	15 mg	Oral
Subject	Estetrol	Other / unclassified	20 mg	Oral

Indications

No indication recorded.