Al-Hendy A, Lukes AS, Poindexter AN, et al. - In women with uterine fibroids and heavy bleeding, treatment with the combination of relugolix (an oral gonadotropin-releasing hormone-receptor antagonist), estradiol, and norethindrone acetate, administered once daily, may have efficacy while avoiding hypoestrogenic effects. Two replicate international, double-blind, 24-week, phase 3 trials were conducted involving women with fibroid-associated heavy menstrual bleeding. Researchers randomized a total of 388 women in trial L1 and 382 in trial L2. Participants were assigned to receive once-daily placebo, relugolix combination therapy (40 mg of relugolix, 1 mg of estradiol, and 0.5 mg of norethindrone acetate), or delayed relugolix combination therapy (40 mg of relugolix monotherapy, followed by relugolix combination therapy, each for 12 weeks). Outcomes revealed a significant reduction in menstrual bleeding in women with uterine fibroids in correlation with receiving once-daily relugolix combination therapy, as compared with placebo, along with preserved bone mineral density.