Current intervention strategies for management of uterine fibroids in women of reproductive age are primarily surgical or radiological. There are limited options for medical therapy. Two small placebo-controlled trials showed that ulipristal acetate, a selective progesterone-receptor modulator (SPRM), reduced fibroid and uterine sizes in women with symptomatic fibroids.
The aim of this randomized, double-blind, controlled noninferiority trial was to determine whether ulipristal acetate was noninferior to leuprolide acetate in controlling bleeding before planned surgery in premenopausal women with symptomatic fibroids. Another aim was to compare the adverse effect profile of the 2 drugs. The participants, 307 patients with heavy uterine bleeding, were randomized to receive 3 months of daily therapy with oral ulipristal acetate (either 5 or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (3.75 mg). The primary study outcome was the proportion of patients with controlled uterine bleeding at week 13. A prespecified noninferiority margin of −20% was used.
Bleeding was controlled at 13 weeks in all 3 treatment groups; there was 90% control with the 5-mg dose of ulipristal acetate: 98% with the 10-mg dose versus 89% with the leuprolide acetate injection; the difference between ulipristal acetate and leuprolide acetate was 1.2 percentage points (95% confidence interval, −9.3 to 11.8) for the 5-mg dose and 8.8 percentage points (95% confidence interval, 0.4 to 18.3) for the 10-mg dose. Bleeding was attenuated more rapidly with ulipristal acetate than leuprolide acetate: median times to amenorrhea were 7 days in patients receiving 5 mg of ulipristal acetate and 5 days in those receiving 10 mg versus 21 days in those receiving leuprolide acetate. Moderate-to-severe hot flashes occurred less frequently in patients treated with ulipristal acetate than in those treated with leuprolide acetate: 11% with the 5-mg dose of ulipristal acetate and 10% with the 10-mg dose compared with 40% in those treated with leuprolide acetate (P < 0.001 for both comparisons).
These findings show that daily doses of oral ulipristal acetate of both 5 and 10 mg were noninferior to once-monthly injections of leuprolide acetate in controlling bleeding in patients with fibroids and were less likely to cause hot flashes.