Mechanism of Action of Ulipristal Acetate (Ella)
Ulipristal acetate works primarily by inhibiting or delaying ovulation through its action as a selective progesterone receptor modulator, and this mechanism remains effective even when administered shortly before ovulation when other emergency contraceptives fail. 1
Primary Mechanism
Ulipristal acetate is a selective progesterone receptor modulator with both antagonistic and partial agonistic effects at the progesterone receptor, preventing progesterone from occupying its receptor. 1
The drug postpones follicular rupture when taken immediately before ovulation is to occur, which is the likely primary mechanism of action for emergency contraception. 1
When administered in the mid-follicular phase, ulipristal acetate causes inhibition of folliculogenesis and reduction of estradiol concentration. 1
Timing-Dependent Effects on Ovulation
The effectiveness of ulipristal acetate's mechanism depends critically on when it is administered during the menstrual cycle:
When taken before the LH surge begins, ulipristal acetate postponed follicular rupture for at least 5 days in 100% of subjects. 1
When taken immediately before ovulation (when LH has already started to rise), it postponed follicular rupture in 79% of subjects. 1
However, treatment was not effective in postponing follicular rupture when administered on the day of LH peak. 1
Advantage Over Levonorgestrel
Ulipristal acetate can delay ovulation even 24 to 48 hours prior to expected ovulation, a time when levonorgestrel is no longer effective. 2
This represents a critical clinical advantage, as ulipristal acetate has a direct inhibitory effect on follicular rupture that allows it to work even when administered shortly before ovulation. 3
The "window of effect" for ulipristal acetate is broader than levonorgestrel, which only works after selection of the dominant follicle and before the LH peak begins to rise. 3
Secondary Mechanism
Alterations to the endometrium that may affect implantation may also contribute to efficacy, though this is considered a secondary mechanism. 1
When dosed in the early luteal phase, ulipristal acetate does not significantly delay endometrial maturation but decreases endometrial thickness by 0.6 ± 2.2 mm. 1
Clinical Implications
Ulipristal acetate (30 mg single dose) is effective throughout the entire 120-hour window after unprotected intercourse, unlike levonorgestrel which shows decreased effectiveness after 72 hours. 4
The drug should be taken as soon as possible within 5 days of unprotected sexual intercourse for maximum effectiveness. 5, 4
If a woman wishes to initiate or resume hormonal contraception after using ulipristal acetate, she should wait no sooner than 5 days after intake and use a reliable barrier method until the next menstrual period. 1