Elagolix Alone and With Add-Back Decreases Heavy Menstrual Bleeding in Women With Uterine Fibroids [21H]

INTRODUCTION: Elagolix, an oral gonadotropin-releasing hormone antagonist, with and without add-back therapy, was evaluated in premenopausal women with heavy menstrual bleeding (HMB; greater than 80 mL/month menstrual blood loss [MBL]) associated with uterine fibroids (UF). METHODS: This double-blind, randomized, placebo-controlled, parallel group study evaluated the efficacy and safety of 6 months of treatment in 2 cohorts, with four arms/cohort: elagolix alone as 300 mg twice daily in cohort 1 (C1) and 600 mg once daily in cohort 2, and in both cohorts, placebo, elagolix with add-back therapy of estradiol (E2)/norethindrone acetate (NETA), low dose 0.5 mg E2/0.1 mg NETA (LDA), or standard dose 1.0 mg E2/0.5 mg NETA (SDA). The primary endpoint was the percentage of women with less than 80 mL MBL assessed by the alkaline-hematin-method and at least 50% reduction in MBL from baseline to the last 28 days of treatment. Adverse events (AE), changes in bone mineral density (BMD) and quality of life (QoL) were assessed. RESULTS: In C1, 259 women were randomized and treated; 80% completed treatment. C1 responses for the primary endpoint were 92% in elagolix alone, 85% elagolix+LDA, 79% elagolix+SDA, and 27% placebo (all p < .001 vs. placebo). Add-back therapy attenuated hot flushes and lumbar spine BMD decreases in a dose-dependent manner; there were no statistically significant differences in BMD between elagolix+SDA and placebo at month 6. All elagolix treatments were associated with improved QoL. Results were similar in C2. CONCLUSION: Elagolix with or without add-back significantly reduced MBL in UF-associated HMB. Hot flushes and BMD decreases were reduced by add-back in a dose-dependent manner.