Efficacy and safety of elagolix with add-back therapy in women with uterine fibroids and coexisting adenomyosis


VOLUME 2, ISSUE 3, P338-346, SEPTEMBER 01, 2021


Ozgul Muneyyirci-Delale, M.D., David F. Archer, M.D., Charlotte D. Owens, M.D., Kurt T. Barnhart, M.D., M.S.C.E., Linda D. Bradley, M.D., Eve Feinberg, M.D., Veronica Gillispie, M.D., Sandra Hurtado, M.D., Jin Hee Kim, M.D., Alice Wang, M.A., Hui Wang, Ph.D., Elizabeth A. Stewart, M.D.



To determine if coexisting adenomyosis limits the efficacy of elagolix, an oral gonadotropin-releasing hormone antagonist, with hormonal add-back therapy in reducing heavy menstrual bleeding in women with uterine fibroids.


Pooled analysis of two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids [UF]-1 and UF-2).


A total of 153 gynecological clinical care settings in the United States and Canada.


Premenopausal women (18–51 years) with >80 mL of menstrual blood loss (MBL)/cycle and uterine fibroids with and without coexisting adenomyosis diagnosed by ultrasound and/or magnetic resonance imaging at baseline.


Participants were randomized 1:1:2 to placebo, elagolix 300 mg twice daily alone, or elagolix 300 mg twice daily with estradiol 1 mg/norethindrone acetate 0.5 mg once daily.

Main Outcome Measure(s)

The primary endpoint was the proportion of women who had <80 mL of MBL during the final month and ≥50% reduction in MBL from baseline to the final month. Adverse events were monitored.


Of 786 women treated across the two trials, 16% (126 women) had coexisting adenomyosis. Among this subset, a significantly greater proportion of women who received elagolix with add-back therapy (77.1% [95% confidence interval, 66.2, 88.0]) met both primary endpoint criteria compared with women who received placebo (12.2% [95% confidence interval, 1.0, 23.4]). Adverse events most frequently reported in the elagolix with add-back adenomyosis subset were hot flushes (18.3%), nausea (11.7%), and night sweats (8.3%).


Elagolix with add-back therapy significantly reduced heavy menstrual bleeding in women with uterine fibroids and coexisting adenomyosis, suggesting that elagolix efficacy was not adversely affected by the presence of adenomyosis (Elaris UF-1 and UF-2 Clinical-Trials.gov numbers, NCT02654054 and NCT02691494).