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.