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

This is a two-part study: Arm 1, 2, and 3: randomized, double blind \- Efficacy Study Part: designed to evaluate the frequency and severity of vasomotor symptoms \[VMS\] in both hysterectomized and non hysterectomized postmenopausal participants after treatment with two doses of E4 (15 mg or 20 mg) or placebo for 12 consecutive weeks. Thereafter, treatment proceeded for a total duration of up to 53 weeks, to continue the evaluation of secondary efficacy (effect on hemostasis, lipid and glucose metabolism, bone turnover, health-related quality of life \[HRQoL\] and treatment satisfaction \[TS\]), safety and the effect on the endometrium. For endometrial protection, all non-hysterectomized subjects received 200 mg progesterone (P4) once daily for 14 consecutive days, after completion of the E4/placebo treatment. Arm 4: open label \- Safety Study Part: designed to evaluate the general safety, secondary efficacy (lipid and glucose metabolism, HRQoL and TS) after treatment with E4 20 mg for up to 53 weeks in hysterectomized and non hysterectomized postmenopausal participants. For endometrial protection, all non-hysterectomized subjects received 200 mg progesterone (P4) once daily for 14 consecutive days, after completion of the E4 treatment.