Ulipristal acetate versus leuprolide acetate for uterine fibroids

N Engl J Med. 2012 Feb 2;366(5):421-32. doi: 10.1056/NEJMoa1103180.

Abstract

Background: The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear.

Methods: In this double-blind noninferiority trial, we randomly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate (at a dose of either 5 mg or 10 mg) or once-monthly intramuscular injections of leuprolide acetate (at a dose of 3.75 mg). The primary outcome was the proportion of patients with controlled bleeding at week 13, with a prespecified noninferiority margin of -20%.

Results: Uterine bleeding was controlled in 90% of patients receiving 5 mg of ulipristal acetate, in 98% of those receiving 10 mg of ulipristal acetate, and in 89% of those receiving leuprolide acetate, for differences (as compared with leuprolide acetate) of 1.2 percentage points (95% confidence interval [CI], -9.3 to 11.8) for 5 mg of ulipristal acetate and 8.8 percentage points (95% CI, 0.4 to 18.3) for 10 mg of ulipristal acetate. Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate, 5 days for those receiving 10 mg of ulipristal acetate, and 21 days for those receiving leuprolide acetate. Moderate-to-severe hot flashes were reported for 11% of patients receiving 5 mg of ulipristal acetate, for 10% of those receiving 10 mg of ulipristal acetate, and for 40% of those receiving leuprolide acetate (P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate).

Conclusions: Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes. (Funded by PregLem; ClinicalTrials.gov number, NCT00740831.).

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Endometrium / drug effects
  • Endometrium / pathology
  • Female
  • Humans
  • Injections, Intramuscular
  • Intention to Treat Analysis
  • Leiomyoma / complications
  • Leiomyoma / drug therapy*
  • Leiomyoma / surgery
  • Leuprolide / adverse effects
  • Leuprolide / therapeutic use*
  • Menorrhagia / drug therapy*
  • Menorrhagia / etiology
  • Middle Aged
  • Norpregnadienes / administration & dosage
  • Norpregnadienes / adverse effects
  • Norpregnadienes / therapeutic use*
  • Uterine Neoplasms / complications
  • Uterine Neoplasms / drug therapy*
  • Uterine Neoplasms / surgery
  • Young Adult

Substances

  • Norpregnadienes
  • Leuprolide
  • ulipristal acetate

Associated data

  • ClinicalTrials.gov/NCT00740831