• Bruce R Carr, Elizabeth A Stewart, David F Archer, Ayman Al-Hendy, Linda Bradley, Nelson B Watts, Michael P Diamond, Jingjing Gao, Charlotte D Owens, Kristof Chwalisz, W Rachel Duan, Ahmed M Soliman, Matthew B Dufek, and James A Simon.
• University of Texas Southwestern Medical Center, Dallas, Texas; the Mayo Clinic, Rochester, Minnesota; Eastern Virginia Medical School, Norfolk, Virginia; the University of Illinois at Chicago, Chicago, Illinois; Cleveland Clinic, Cleveland, Ohio; Mercy Health Osteoporosis and Bone Health Services, Cincinnati, Ohio; Augusta University, Augusta, Georgia; AbbVie Inc., North Chicago, Illinois; and George Washington University, Washington, DC.
• Obstet Gynecol. 2018 Nov 1; 132 (5): 1252-1264.

ObjectiveTo 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.MethodsThis 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.ResultsFrom 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.ConclusionElagolix 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 RegistrationClinicalTrials.gov, NCT01817530; EU Clinical Trial Register, 2013-000082-37.

41 keywords...

hide…