Elagolix for Heavy Menstrual Bleeding in Women with Uterine Fibroids

N Engl J Med. 2020 Jan 23;382(4):328-340. doi: 10.1056/NEJMoa1904351.


Background: Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding.

Methods: We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation.

Results: A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy.

Conclusions: Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).

Publication types

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

MeSH terms

  • Adult
  • Bone Density / drug effects
  • Double-Blind Method
  • Drug Therapy, Combination
  • Estradiol / therapeutic use*
  • Estrogens / therapeutic use*
  • Female
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Hot Flashes / chemically induced
  • Humans
  • Hydrocarbons, Fluorinated / adverse effects
  • Hydrocarbons, Fluorinated / therapeutic use*
  • Leiomyoma / complications*
  • Menorrhagia / drug therapy*
  • Menorrhagia / etiology
  • Middle Aged
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Quality of Life
  • Severity of Illness Index
  • Surveys and Questionnaires


  • Estrogens
  • Hydrocarbons, Fluorinated
  • Pyrimidines
  • Gonadotropin-Releasing Hormone
  • Estradiol
  • elagolix

Associated data

  • ClinicalTrials.gov/NCT02654054
  • ClinicalTrials.gov/NCT02691494