Elagolix Suppresses Ovulation in a Dose-Dependent Manner: Results From a 3-Month, Randomized Study in Ovulatory Women

J Clin Endocrinol Metab. 2020 Mar 1;105(3):dgz086. doi: 10.1210/clinem/dgz086.


Context: Elagolix is an oral gonadotropin-releasing hormone (GnRH) antagonist recently approved for the treatment of endometriosis-associated pain and being developed for heavy menstrual bleeding associated with uterine fibroids.

Objective: The objective was to evaluate the effects of elagolix on ovulation and ovarian sex hormones.

Design and setting: This was a randomized, open-label, multicenter study.

Participants: Participants were healthy ovulatory women aged 18 to 40 years.

Interventions: Elagolix was administered orally for 3 continuous 28-day dosing intervals at 100 to 200 mg once daily (QD), 100 to 300 mg twice daily (BID), and 300 mg BID plus estradiol/norethindrone acetate (E2/NETA) 1/0.5 mg QD.

Main outcome measures: The main outcomes measures were ovulation rates measured by transvaginal ultrasound, progesterone concentrations, and hormone suppression.

Results: Elagolix suppressed ovulation in a dose-dependent manner. The percentage of women who ovulated was highest at 100 mg QD (78%), intermediate at 150 and 200 mg QD and 100 mg BID (47%-57%), and lowest at 200 and 300 mg BID (32% and 27%, respectively). Addition of E2/NETA to elagolix 300 mg BID further suppressed the ovulation rate to 10%. Elagolix also suppressed luteinizing hormone and follicle stimulating hormone in a dose-dependent manner, leading to dose-dependent suppression of estradiol and progesterone. Elagolix had no effect on serum biomarker of ovarian reserve, and reduced endometrial thickness compared to the screening cycle.

Conclusion: Women being treated with elagolix may ovulate and should use effective methods of contraception. The rate of ovulation was lowest with elagolix 300 mg BID plus E2/NETA 1/0.5 mg QD.

Trial registration: ClinicalTrials.gov NCT01403038.

Keywords: GnRH antagonist; elagolix; endometrial thickness; ovarian reserve; ovulation; sex hormones.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Dose-Response Relationship, Drug
  • Endometrium / drug effects*
  • Female
  • Follow-Up Studies
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Hormone Antagonists / administration & dosage
  • Hormone Antagonists / pharmacology
  • Humans
  • Hydrocarbons, Fluorinated / administration & dosage*
  • Hydrocarbons, Fluorinated / pharmacology
  • Menorrhagia / drug therapy*
  • Ovulation / drug effects*
  • Prognosis
  • Pyrimidines / administration & dosage*
  • Pyrimidines / pharmacology
  • Time Factors
  • Young Adult


  • Hormone Antagonists
  • Hydrocarbons, Fluorinated
  • Pyrimidines
  • Gonadotropin-Releasing Hormone
  • elagolix

Associated data

  • ClinicalTrials.gov/NCT01403038