BACKGROUND: Uterine fibroids are one of the most common neoplasms found among 
women globally, with a prevalence of approximately 11 million women in the 
United States alone. The morbidity of this common disease is significant because 
it is the leading cause of hysterectomy and causes significant functional 
impairment for women of reproductive age. Factors including age, body mass 
index, race, ethnicity, menstrual blood loss, fibroid location, and uterine and 
fibroid volume influence the incidence of fibroids and severity of symptoms. 
Elagolix is an oral gonadotropin-releasing hormone receptor antagonist that 
competitively inhibits pituitary gonadotropin-releasing hormone receptor 
activity and suppresses the release of gonadotropins from the pituitary gland, 
resulting in dose-dependent suppression of ovarian sex hormones, follicular 
growth, and ovulation. In Elaris Uterine Fibroids 1 and Uterine Fibroids 2, 2 
replicate multicenter, double-blind, randomized, placebo-controlled, phase 3 
studies, treatment of premenopausal women with elagolix with hormonal add-back 
therapy demonstrated reduction in heavy menstrual bleeding associated with 
uterine fibroids.
OBJECTIVE: This analysis aimed to evaluate the safety and efficacy of elagolix 
(300 mg twice a day) with add-back therapy (1 mg estradiol/0.5 mg norethindrone 
acetate once a day) in reducing heavy menstrual bleeding associated with uterine 
fibroids in various subgroups of women over 6 months of treatment.
STUDY DESIGN: Data were pooled from Elaris Uterine Fibroid-1 and Uterine 
Fibroid-2 studies, which evaluated premenopausal women (18-51 years) with heavy 
menstrual bleeding (>80 mL menstrual blood loss per cycle, alkaline hematin 
methodology) and ultrasound-confirmed uterine fibroid diagnosis. Subgroups 
analyzed included age, body mass index, race, ethnicity, baseline menstrual 
blood loss, fibroid location, and uterine and primary fibroid volume (largest 
fibroid identified by ultrasound). The primary endpoint was the proportion of 
women with <80 mL menstrual blood loss during the final month and ≥50% menstrual 
blood loss reduction from baseline to final month. Secondary and other efficacy 
endpoints included mean change in menstrual blood loss from baseline to final 
month, amenorrhea, symptom severity, and health-related quality of life. Adverse 
events and other safety endpoints were monitored.
RESULTS: The overall pooled Elaris Uterine Fibroid-1 and Uterine Fibroid-2 
population was typical of women with fibroids, with a mean age of 42.4 (standard 
deviation, 5.4) years and a mean body mass index of 33.6 (standard deviation, 
7.3) kg/m2 and 67.6% of participants being black or African American women. A 
wide range of baseline uterine and fibroid volumes and menstrual blood loss were 
also represented in the overall pooled study population. In all subgroups, the 
proportion of responders to the primary endpoint, mean change in menstrual blood 
loss, amenorrhea, reduction in symptom severity, and improvement in 
health-related quality of life were clinically meaningfully greater for women 
who received elagolix with add-back therapy than those who received placebo and 
consistent with the overall pooled study population for the primary endpoint 
(72.2% vs 9.3%), mean change in menstrual blood loss (-172.5 mL vs -0.8 mL), 
amenorrhea (50.4% vs 4.5%), symptom severity (-37.1 vs -9.2), and health-related 
quality of life score (39.9 vs 8.9). Adverse events by subgroup were consistent 
with the overall pooled study population.
CONCLUSION: Elagolix with hormonal add-back therapy was effective in reducing 
heavy menstrual bleeding associated with uterine fibroids independent of age, 
body mass index, race, ethnicity, baseline menstrual blood loss, fibroid 
location, and uterine and primary fibroid volume.