Inhibition of ovulation by administration of estetrol in combination with drospirenone or levonorgestrel: Results of a phase II dose-finding pilot study

Objectives The aim of the study was to evaluate the efficacy of different dosages of estetrol (E<inf>4</inf>) combined with one of two progestins in suppressing the pituitary-ovarian axis and ovulation in healthy premenopausal women.Methods This was an open, parallel, phase II, dose-finding, pilot study performed in healthy women aged 18 to 35 years with a documented ovulatory cycle before treatment. For three consecutive cycles in a 24/4-day regimen, participants received 5 mg or 10 mg E<inf>4</inf>/3 mg drospirenone (DRSP); 5 mg, 10 mg or 20 mg E<inf>4</inf>/150 g levonorgestrel; or 20 g ethinylestradiol (EE)/3 mg DRSP as comparator. Pituitary-ovarian axis activity and the occurrence of ovulation were evaluated by monitoring follicular size, serum levels of follicle-stimulating hormone, luteinising hormone, estradiol and progesterone during treatment cycles 1 and 3. Endometrial thickness was evaluated throughout the trial, and the return of ovulation was evaluated after the last intake of medication.Results A total of 109 women were included in the trial. No ovulation occurred in any treatment group. Ovarian activity inhibition seemed proportional to the E<inf>4</inf> dosage: the highest suppression was observed in the 20 mg E<inf>4</inf> group and was very similar to that observed with EE/DRSP. Endometrial thickness was suppressed to the same extent in all groups. Post-treatment ovulation occurred in all participants between 17 and 21 days after the last active treatment. The study combinations were well tolerated and safe.Conclusions Combined with a progestin, E<inf>4</inf> adequately suppresses ovarian activity, particularly when given at a dosage above 10 mg/day. © 2015 The European Society of Contraception and Reproductive Health.