Effects of the progesterone receptor modulator VA2914 in a continuous low dose on the hypothalamic-pituitary-ovarian axis and endometrium in normal women: a prospective, randomized, placebo-controlled trial.
BACKGROUND
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 can inhibit ovulation, alter endometrial receptivity, and improve cycle control.


OBJECTIVE
We evaluated the effects of a new progesterone receptor modulator, VA2914, administered continuously for 3 months, on ovulation and endometrial maturation.


METHODS
Forty-six normal women were included in a prospective, placebo-controlled, randomized trial, conducted in four referral centers.


METHODS
VA2914 (2.5, 5, or 10 mg/d) was administered continuously for 84 d. Pelvic ultrasound (treatment d 67 and 77), hormonal monitoring (FSH, LH, estradiol, and progesterone on treatment d 59, 63, 67, 70, 74, 77, 80, and 84), and endometrial biopsy (treatment d 77) were performed.


METHODS
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, and 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.
Chabbert-Buffet
Nathalie
N
Department of Obstetrics and Gynecology, Hospital Tenon, 4 Rue de la Chine, 75020 Paris, France. nathalie.chabbert-buffet@tnn.aphp.fr
Pintiaux-Kairis
Axelle
A
Bouchard
Philippe
P
D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000187:drug effects; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004717:Endometrium / Q000187:drug effects*; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D009649:Norpregnadienes / Q000008:administration & dosage* / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects*; D010865:Pilot Projects; D010919:Placebos; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*
D003271:Contraceptive Agents, Female; D009649:Norpregnadienes; D010919:Placebos; D011980:Receptors, Progesterone; C094854:ulipristal