Context: Progestin-only pills, the main hormonal alternative to ethinyl estradiol containing pills in women bearing vascular risk factors, are poorly tolerated due to irregular bleeding. In contrast, progesterone receptor modulators (PRMs) can inhibit ovulation, alter endometrial receptivity, and improve cycle control.

Objective: We evaluated the effects of a new PRM, VA2914, administered continuously for three months, on ovulation and endometrial maturation.

Design, Settings and patients: 46 normal women were included in a prospective placebo controlled randomized trial, conducted in 4 referral centers.

Intervention: 2.5, 5, or 10 mg/d were administered continuously for 84 days. Pelvic ultrasound (treatment day 67 and 77), hormonal monitoring (FSH, LH, estradiol and progesterone on treatment day 59, 63, 67, 70, 74, 77, 80 and 84) and endometrial biopsy (treatment day 77) were performed.

Main outcome measure: Ovulation inhibition was assessed by the absence of progesterone values above 3 ng/ml at any time during treatment month 3.

Results: Anovulation was observed in 81.8% women in the 5 mg group and 80% in the 10 mg group, amenorrhea occurred in 81.2% and 90% of cases in the 5 and 10 mg groups. We did not detect any cases of endometrial hyperplasia, despite estradiol levels that remained in the physiological follicular phase range throughout treatment cycle 3.

Conclusions: Continuous low dose VA2914 can induce amenorrhea and inhibit ovulation without down regulating estradiol levels or inducing endometrial hyperplasia in normal women. Long term studies with a larger population are required to confirm the contraceptive efficacy of this regimen.