Liu Chongdong, Lu Qi, Qu Hong, Geng Li, Bian Meilu, Huang Minli, Wang Huilan, Zhang Youzhong, Wen Zeqing, Zheng Shurong, Zhang Zhenyu
Department of Obstetrics and Gynaecology, Peking University First Hospital Department of Obstetrics and Gynaecology,Beijing Chaoyang Hospital Department of Obstetrics and Gynaecology, Peking University Third Hospital Department of Obstetrics and Gynaecology, China-Japan Friendship Hospital, Beijing Department of Obstetrics and Gynaecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai Department of Obstetrics and Gynaecology, The Second Hospital of Hebei Medical University, Hebei Department of Obstetrics and Gynaecology, Qilu Hospital of Shandong University, Shandong Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Shandong, China.
Medicine (Baltimore). 2017 Feb;96(7):e6124. doi: 10.1097/MD.0000000000006124.
To evaluate the efficacy and safety of 10 mg and 25 mg mifepristone per day compared with 3.75 mg enantone in treating uterine fibroids.
This is a Multicenter randomized controlled trial. A total of 501 subjects with symptomatic uterine fibroids were enrolled and randomized into the group of 10mg, 25mg mifepristone and 3.75 enantone (with 307, 102 and 92 subjects respectively), with 458 subjects completed the treatment. Three months of daily therapy with oral mifepristone (at a dose of either 10 mg or 25 mg) or once-monthly subcutaneous injections of enantone (at a dose of 3.75 mg) were used. Change in volume of the largest uterine fibroid was the primary efficacy variable, and secondary efficacy variables included changes in anemia and relevant symptom. Safety evaluation included the analyses of adverse events, laboratory values, and relevant endometrial changes.
After three months of treatment, the mean volume of the largest leiomyoma was significantly reduced by mifepristone 10 mg or 25 mg or enantone 3.75 mg (40.27%, 42.59% and 44.49% respectively) (P < 0.0001). Percentage change from baseline in largest leiomyoma volume was not statistically significant among the three groups (P = 0.1057). Most of the patients in all groups experienced amenorrhea after the treatment. There were also significant elevations in red blood cell count, hemoglobin and hematocrit (P < 0.0001), and significant reductions in prevalence of dysmenorrhea, pelvic pressure, non-menstrual abdominal pain (P < 0.0001) in each group, while no significant difference among the three groups.All study medications are well-tolerated, and no serious adverse event was reported. Treatment-related adverse event rate was significantly lower in mifepristone 10 mg group, compared to Enantone 3.75 mg group (13.59% vs. 32.58%, P = 0.0002). In both mifepristone groups, estradiol levels were maintained in the premenopausal range, whereas patients in the enantone group had a significant reduction to postmenopausal levels (P < 0.0001).
10mg is as effective as 25mg mifepristone and 3.75 mg enantone with minimal drug-related side effects, and may provide an alternative for clinical application, especially for patient who are in perimenopause with uterine fibroids.
评估每日服用10毫克和25毫克米非司酮与3.75毫克孕三烯酮治疗子宫肌瘤的疗效和安全性。
这是一项多中心随机对照试验。共纳入501例有症状的子宫肌瘤患者，随机分为10毫克米非司酮组、25毫克米非司酮组和3.75毫克孕三烯酮组（分别为307例、102例和92例），458例患者完成治疗。采用每日口服米非司酮（剂量为10毫克或25毫克）或每月皮下注射一次孕三烯酮（剂量为3.75毫克），疗程三个月。最大子宫肌瘤体积的变化是主要疗效变量，次要疗效变量包括贫血和相关症状的变化。安全性评估包括对不良事件、实验室检查值和相关子宫内膜变化的分析。
治疗三个月后，10毫克米非司酮组、25毫克米非司酮组和3.75毫克孕三烯酮组最大平滑肌瘤的平均体积均显著缩小（分别为40.27%、42.59%和44.49%）（P<0.0001）。三组间最大平滑肌瘤体积较基线的变化百分比差异无统计学意义（P=0.1057）。所有组中的大多数患者治疗后出现闭经。各组红细胞计数、血红蛋白和血细胞比容也显著升高（P<0.0001），痛经、盆腔压迫感、非经期腹痛的发生率显著降低（P<0.0001），但三组间差异无统计学意义。所有研究药物耐受性良好，未报告严重不良事件。10毫克米非司酮组与3.75毫克孕三烯酮组相比，治疗相关不良事件发生率显著较低（13.59%对32.58%，P=0.0002）。在两个米非司酮组中，雌二醇水平维持在绝经前范围内，而孕三烯酮组患者的雌二醇水平显著降至绝经后水平（P<0.0001）。
10毫克米非司酮与25毫克米非司酮及3.75毫克孕三烯酮疗效相当，且药物相关副作用最小，可为临床应用提供一种选择，尤其是对于围绝经期子宫肌瘤患者。
