12-week ulipristal acetate course fails to suppress ovulation

A 12-week course of daily oral contraception with ulipristal acetate does not appear to be reliable, with a recent study showing that women who have received daily oral ulipristal acetate have progesterone concentrations that indicate ovulation during treatment.

The phase I/II 84-day study randomized 180 women to use either oral ulipristal 10 or 5 mg daily or a three-cycle regimen of 5 mg for 24 days, followed by 4 placebo days (cyclic). Randomization was stratified by body mass index (BMI) <32 or 32–40 kg/m².

The primary outcome of ovulation inhibition was estimated by performing transvaginal ultrasound and blood sampling twice weekly. Safety was analysed using three endometrial biopsies and liver chemistry tests.

Of the 180 women enrolled, 137 were included in the ovulation inhibition analyses. Consistent ovulation inhibition, defined as progesterone values remaining <3 ng/mL throughout treatment, was achieved in 52 (38 percent) women overall: 25 out of 47 (53 percent) in the 10-mg group, 20 out of 44 (45 percent) in the 5-mg group, and seven out of 46 (15 percent) in the cyclic treatment group (p<0.01).

Consistent ovulation inhibition was more common among women with a BMI >32 kg/m² (25 out of 50 [50 percent] vs 27 out of 87 [31 percent]; p=0.01).

Of note, average ulipristal concentrations were higher among women with low progesterone concentrations (p<0.01).

Based on endometrial biopsies, progesterone-receptor-modulator-associated endometrial changes occurred during treatment in 52 women overall: 22 (40 percent) in the 10-mg group, 16 (29 percent) in the 5-mg group, and 14 (26 percent) in the cyclic treatment group (p=0.07 for trend). These endometrial changes were resolved following treatment cessation. Liver transaminase changes were rare.