BACKGROUND Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. CONCLUSIONS Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).

中文翻译：

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Elagolix 用于患有子宫肌瘤的女性月经过多。

背景子宫肌瘤是与大量月经出血相关的激素反应性肿瘤。Elagolix 是一种口服促性腺激素释放激素拮抗剂，可快速、可逆地抑制卵巢性激素，可减少肌瘤相关出血。方法 我们进行了两项相同、双盲、随机、安慰剂对照、为期 6 个月的 3 期试验（Elaris 子宫肌瘤 1 和 2 [UF-1 和 UF-2]），以评估 elagolix 的疗效和安全性在患有肌瘤相关出血的女性中，每天两次服用 300 毫克，并使用激素“反加”疗法（以替代降低的内源性激素水平；在这种情况下，雌二醇，1 毫克，醋酸炔诺酮，0.5 毫克，每天一次）。包括单独使用 elagolix 的组，以评估加回疗法对 elagolix 的低雌激素作用的影响。主要终点是治疗的最后一个月的月经失血量少于 80 ml，并且从基线到最后一个月的月经失血量至少减少 50%；使用多重插补法对缺失数据进行插补。结果 UF-1 中的 412 名女性和 UF-2 中的 378 名女性接受了随机分组，接受了 Elagolix 或安慰剂，并被纳入分析。UF-1 组 206 名女性中有 68.5% 和 UF-2 组 189 名女性中有 76.5% 达到了主要终点标准，这些女性接受了 Elagolix 加反加疗法，而 102 名女性中有 8.7% 和 UF-2 女性中有 10%分别有 94 名女性接受了安慰剂（两项试验的 P<0.001）。在单独接受 Elagolix 治疗的女性中，UF-1 组 104 名女性中有 84.1% 达到主要终点，UF-2 组 95 名女性中有 77% 达到主要终点。热潮红（在两项试验中）和子宫出血（在 UF-1 中）与安慰剂相比，elagolix 加反加疗法的发生率明显更高。elagolix 的低雌激素作用，尤其是降低骨矿物质密度，可通过反加疗法减弱。结论 Elagolix 与反向添加疗法可有效减少患有子宫肌瘤的女性的大量月经出血。（由艾伯维资助；Elaris UF-1 和 Elaris UF-2 ClinicalTrials.gov 编号，NCT02654054 和 NCT02691494。）。