Ulipristal acetate is a selective progesterone receptor modulator with antagonistic and partial agonistic effects (a progesterone agonist/antagonist) at the progesterone receptor. It binds the human progesterone receptor and prevents progesterone from occupying its receptor.

The pharmacodynamics of ulipristal acetate depend on the timing of administration in the menstrual cycle. Administration in the mid-follicular phase causes inhibition of folliculogenesis and reduction of estradiol concentration. 

Pharmacodynamic data showed that administration of ella to 34 women in the late follicular phase postponed follicular rupture for at least 5 days in all (100%) of 8 subjects who took ella before the luteinizing hormone (LH) surge and 11 (79%) of 14 subjects who took ella immediately before ovulation (when LH has already started to rise). However, treatment was not effective in postponing follicular rupture when administered on the day of LH peak.

Dosing in the early luteal phase does not significantly delay endometrial maturation but decreases endometrial thickness by 0.6 ± 2.2 mm (mean ± SD).

Hormonal Contraceptives after ella intake:

In women initiating hormonal contraception (quickstart scenario):

When a combined oral contraceptive pill (COC) containing ethinyl estradiol 30 µg + levonorgestrel 150 µg was started the day after ella intake during the follicular phase, ella did not interfere with the COC’s ability to suppress ovarian activity, as assessed by measurement of follicle size via transvaginal ultrasound, combined with serum progesterone and estradiol levels: ovarian activity was suppressed in 61.5% (24/39) of subjects receiving ella plus COC and 62.2% (23/37) of subjects receiving a placebo plus the COC. The incidence of ovulation was similar between the group that received ella plus the COC [33.3% (13/39)] and the group that received a placebo plus the COC [32.4% (12/37)]. [see Dosage and Administration (2.2), Warnings and Precautions (5.5) and Drug Interactions (7.3)].

The initiation of a desogestrel 75 µg progestin-only pill (POP) the day after ella intake during the follicular phase was associated with a higher incidence of ovulation in the six days following ella intake compared to an ella-only treatment group, and a relatively slower onset (3 to 4 days) of thickened cervical mucus compared to a group given desogestrel without prior ella intake (2 days), suggesting an effect of prior use of ella on the ability of desogestrel to inhibit mucus permeability. [See Dosage and Administration (2.2), Warnings and Precautions (5.5) and Drug Interactions (7.1; 7.3)].

When a COC containing ethinyl estradiol 30 µg + levonorgestrel 150 µg was started 2 days after ella intake, ella's ability to delay ovulation, as assessed by transvaginal ultrasound, was reduced: follicular rupture occurred in 9/33 subjects (27%) in less than 5 days, compared to 1/33 subjects after ella alone (3%). [See Dosage and Administration (2.2), Warnings and Precautions (5.5) and Drug Interactions (7.1)].

In women resuming combined hormonal contraception (missed pills scenario): 

The effects on ovarian activity of delaying versus immediately resuming COCs after ella intake were investigated in 49 women who had been using COCs containing ethinyl estradiol 30 µg + levonorgestrel 150 µg once daily for 21 days followed by 7 days of placebo pills for at least one cycle. All subjects missed three consecutive pills (Days 5-7) during the first week of pills in the subsequent cycle and took ella on the following day (Day 8). These subjects were randomized to resume their COCs either on the same day as ella intake versus five days later. No ovulations with potential risk of pregnancy occurred in either group in the five days following ella intake. However, in the group that waited five days to resume taking COCs, 4/23 (17.4%) women did ovulate later in the cycle (Days 18-26) whereas no ovulations (0/26) occurred in the group that resumed COC intake on the same day as ella intake. Whether similar results can be expected with other COC products containing different progestins or missed active pills during different weeks in a treatment cycle is unknown.