OBJECTIVE: To evaluate elagolix, an oral gonadotropin-releasing hormone receptor 
antagonist, alone or with add-back therapy, in premenopausal women with heavy 
menstrual bleeding (greater than 80 mL per month) associated with uterine 
leiomyomas.
METHODS: This double-blind, randomized, placebo-controlled, parallel-group study 
evaluated efficacy and safety of elagolix in cohorts 1 (300 mg twice daily) and 
2 (600 mg daily) with four arms per cohort: placebo, elagolix alone, elagolix 
with 0.5 mg estradiol/0.1 norethindrone acetate, and elagolix with 1.0 mg 
estradiol/0.5 mg norethindrone acetate. A sample size of 65 per group was 
planned to compare elagolix with add-back to placebo on the primary end point: 
the percentage of women who had less than 80 mL menstrual blood loss and 50% or 
greater reduction in menstrual blood loss from baseline to the last 28 days of 
treatment. Safety assessments included changes in bone mineral density.
RESULTS: From April 8, 2013, to December 8, 2015, 571 women were enrolled, 567 
were randomized and treated (cohort 1=259; cohort 2=308), and 80% and 75% 
completed treatment, respectively. Participants had a mean±SD age of 43±5 years 
(cohort 2, 42±5 years), and 70% were black (cohort 2, 74%). Primary end point 
responder rates in cohort 1 (cohort 2) were 92% (90%) for elagolix alone, 85% 
(73%) for elagolix with 0.5 mg estradiol/0.1 mg norethindrone acetate, 79% (82%) 
for elagolix with 1.0 mg estradiol/0.5 mg norethindrone acetate, and 27% (32%) 
for placebo (all P<.001 vs placebo). Elagolix groups had significant decreases 
compared with placebo in lumbar spine bone mineral density, which was attenuated 
by adding 1.0 mg estradiol/0.5 mg norethindrone acetate.
CONCLUSION: Elagolix with and without add-back significantly reduced menstrual 
blood loss in women with uterine leiomyomas. Add-back therapy reduced 
hypoestrogenic effects on bone mineral density.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01817530; EU Clinical Trial 
Register, 2013-000082-37.