Ulipristal Acetate and Uterine Fibroids and Fibroid-Related Bleeding

Results of a randomized, double-blind, placebo-controlled, phase 3 study [N Engl J Med. 2012;366(5):409-420] show that oral ulipristal acetate at a dose of 5 or 10 mg/day given for 13 weeks is effective in controlling excessive bleeding and shrinking fibroids in women with symptomatic fibroids.

Medical therapies currently used to treat fibroids are limited. Gonadotropin-releasing hormone agonists are effective in shrinking fibroids and correcting anemia, but are limited by side effects such as hot flashes that interfere with compliance. Preliminary evidence from a pilot study and 2 small phase 2 trials has suggested a benefit with selective progesterone-receptor modulators, such as ulipristal acetate, to reduce the size and abnormal bleeding from fibroids.

To further evaluate the efficacy and safety of ulipristal acetate in this setting, investigators randomized 242 women with symptomatic fibroids to oral ulipristal acetate at a dose of 5 mg/day (n=96) or 10 mg/day (n=98) or placebo (n=48) for up to 13 weeks. Iron supplementation (80 mg) once daily was also given to all patients. Patients were eligible for surgery after 13 weeks but no further medical therapy was given.

All patients enrolled in the study were 18 to 50 years of age, had excessive uterine bleeding as indicated by a pictorial blood-loss assessment chart [PBAC] score of >100 during days 1 to 8 of menstruation, fibroid-related anemia as indicated by a hemoglobin level of <10.2 g/dL, a myomatous uterus that was the same size as a uterus at ≤16 weeks of gestation, had at least 1 fibroid that was ≥3 cm in diameter, and a body mass index of 18 to 40.

The primary outcomes of the study were control of uterine bleeding (PBAC score of <75) and reduction of fibroid volume at 13 weeks.

Based on a modified intent-to-treat analysis, uterine bleeding was controlled in significantly more women treated with ulipristal acetate at 5 mg and 10 mg compared with placebo (91% and 92% vs 19%; P<.001 for each comparison). Compared with placebo, median changes in total fibroid volume were also significantly reduced in patients treated by ulipristal acetate at 5 mg (+3% vs −21%; P=.002) and at 10 mg (+3% vs −12%; P=.006).

Among the other outcomes of the study assessed were amenorrhea rates, reductions in fibroid and uterine size of at least 25%, and side effects.

The study found that the rates of amenorrhea were 73%, 82%, and 6% for patients treated with ulipristal acetate at 5 mg and 10 mg and placebo. Amenorrhea occurred within 10 days in most patients receiving ulipristal acetate. Compared with placebo, significantly more patients treated with ulipristal acetate at 5 mg and 10 mg also had a reduction in fibroid volume of at least 25% (18% vs 41% and 41%; P=.01 for both comparisons) and a reduction in uterine volume of at least 25% (6% vs 34% for 5 mg, P<.001; and 6% vs 28% for 10 mg; P=.006).

No significant differences were found in adverse events among the 3 groups, with headache and pain, discomfort, or breast tenderness reported as the most common adverse events in patients treated with ulipristal acetate. A low rate (<3%) of hot flashes was reported by all groups.

Serious adverse effects were reported in 1 patient treated with 10 mg ulipristal acetate who had a uterine hemorrhage and in 1 patient treated with placebo who had a fibroid that protruded through the cervix.

The study was limited by its short duration of 13 weeks, and the investigators state that the need for more data to assess the benefits and risks of long-term treatment with ulipristal acetate. The investigators also emphasize that the study was focused only on perioperative treatment and was not designed to evaluate any potential treatment-related differences in surgical outcomes.