Endometrial Evaluation in Elagolix-Treated Women With Uterine Fibroids and Heavy Menstrual Bleeding [25G]

INTRODUCTION: Elagolix, an oral gonadotropin-releasing hormone antagonist, with and without add-back therapy, was evaluated in premenopausal women with heavy menstrual bleeding (HMB; >80mL/month) associated with uterine fibroids (UF). METHODS: This double-blind phase-2b study (NCT01817530) enrolled women 18–51y in 2 cohorts, with 4 arms/cohort: elagolix alone as 300mg twice daily (cohort 1) and 600mg once daily (cohort 2) and, in both cohorts, placebo and elagolix with add-back therapy of estradiol (E2)/norethindrone acetate (NETA) at low dose (0.5mg E2/0.1mg NETA [LDA]) or standard dose (1.0mg E2/0.5mg NETA [SDA]). Endometrial thickness and biopsies were evaluated at baseline and month 6. RESULTS: 567 randomized patients were treated. Mean baseline endometrial thickness evaluated with transvaginal ultrasound was 6.6–7.9mm across both cohorts. At treatment month 6, mean change in endometrial thickness in both placebo groups ranged from 0.4–2.1mm, but decreased in all elagolix groups in both cohorts (–0.5 to –1.5mm), reaching significance vs placebo for elagolix 300mg+LDA (P=.018) and elagolix 600mg alone (P=.039). Mean endometrial thickness at month 6 ranged from 8.2–9.7mm in both placebo groups and 5.7–6.9mm across elagolix groups. Baseline endometrial biopsies in both cohorts were categorized as normal-quiescent/minimally-stimulated (3.1%–13.8%), proliferative (44.2%–57.1%), and normal-secretory/mixed/breakdown/menstrual (32.5%–45.5%). At month 6, there were more normal-quiescent/minimally-stimulated biopsies in all elagolix arms vs placebo: elagolix alone, 33.8%–43.1%; LDA, 21.1%–39.1%; SDA, 36.4%–41.5%; placebo, 2.6%–6.2%. No endometrial biopsies were abnormal. CONCLUSION: After 6 months of treatment, in both cohorts, elagolix with and without add-back therapy was associated with benign endometrial pathology and reduction in endometrial thickness vs placebo in women with HMB associated with UF.