低剂量米非司酮用于子宫肌瘤的术前治疗:多中心随机双盲、安慰剂、平行对照研究

Preoperative treatment of uterine fibroids with low-dose mifepristone:a multicenter,randomized,double-blind,placebo-controlled,parallel-group study

目的评估口服米非司酮(10 mg/d)与安慰剂在手术前治疗子宫肌瘤的临床疗效和安全性。方法本研究为多中心随机双盲、安慰剂、平行对照试验。共入组132例有症状的子宫肌瘤患者,按随机数字表法随机分为试验组和对照组,每组各66例。试验组患者口服米非司酮1片/d(剂量为10 mg/片),对照组患者口服安慰剂1片/d,两组均治疗3个月。主要疗效指标为最大肌瘤体积变化率,次要疗效指标包括闭经率、主观症状和贫血状况改善情况,安全性评价包括不良事件、辅助检查指标的变化。结果治疗结束时,试验组最大肌瘤体积变化率为-25.97%(95%CI为-34.79%~-15.95%),而对照组为-1.51%(95%CI为-13.03%~11.54%);试验组治疗前后最大肌瘤体积变化率显著高于对照组,且试验组与对照组最大肌瘤体积变化率之差为-24.84%(95%CI为-36.56%~-10.94%),在95%CI区间内,远高于本研究设定的10%优效界值的目标。在治疗结束时,试验组患者的完全闭经率[84%(52/62)]、痛经消除率[98%(61/62)]、月经失血消失率[87%(54/62)]均显著高于对照组(P<0.05)。治疗结束时,试验组血红蛋白[(131±13)g/L]、红细胞计数[(4.5±0.4)×10^(12)/L]和血细胞比容(0.39±0.03)均较治疗前显著升高(P均<0.05);治疗结束时,两组患者上述3个指标分别比较均有显著差异(P<0.01)。试验组治疗结束时血清雌二醇水平显著低于对照组(P<0.01),两组之间FSH和皮质醇水平在治疗前、后分别比较均无显著差异(P>0.05)。两组之间任何不良事件的整体发生率分别比较均无显著差异(P>0.05);腹痛是试验组最常见的不良事件[9%(6/65)],但与对照组[3%(2/64)]相比,发生率并未显著增加(P>0.05)。结论与安慰剂相比,口服米非司酮10 mg/d缩小子宫肌瘤体积、改善贫血状况的临床疗效明显优于安慰剂,且无明显不良反应,可作为子宫肌瘤患者术前的药物治疗。

Objective To evaluate the clinical efficacy and safety of oral mifepristone(10 mg/day)versus placebo in the preoperative treatment of uterine fibroids.Methods This study was a multi-center,randomized,double-blind,placebo,parallel controlled trial.A total of 132 patients with uterine fibroids were randomly divided into study group and control group,with 66 cases in each group.The patients in the study group orally took 1 tablet/day of mifepristone(dose of 10 mg/tablet),the patients in the control group orally took 1 tablet/day of placebo,and both groups were treated for 3 months.The primary efficacy evaluation indicators were the change rate of maximum fibroid volume;the secondary efficacy evaluation indicators included amenorrhea rate,improvement of subjective symptoms and anemia;the safety evaluation indicators included the analysis of adverse events and changes in laboratory biochemical indicators.Results At the end of treatment,the maximum leiomyoma volume was reduced by 25.97%(95%CI:-34.79%--15.95%)in the study group and reduced by 1.51%(95%CI:-13.03%-11.54%)in the control group.The change rate of the maximum leiomyoma volume before and after treatment in the study group was significantly greater than that in the control group,and the difference in the change rate of the maximum leiomyoma volume between the two groups was-24.84%(95%CI:-36.56%--10.94%),which was much higher than the 10% superiority threshold goal set by this study within the 95%CI interval.At the end of treatment,the complete amenorrhea rate[84%(52/62)],dysmenorrhea elimination rate[98%(61/62)],and menstrual blood loss disappearance rate[87%(54/62)]in the study group were significantly higher than those in the control group(all P<0.05).At the end of treatment,the mean hemoglobin[(131±13)g/L],red blood cell count[(4.5±0.4)×1012/L]and hematocrit(0.39±0.03)in the study group were significantly increased compared with the baseline,and the differences had statistical significance(all P<0.05);after treatment,the differences in the above three indicators between the two groups had statistical significance(all P<0.01).The serum estradiol level in the study group was significantly lower than that in the control group at the end of treatment,and the difference was statistically significant(P<0.01).There were no significant differences in follicle-stimulating hormone and cortisol levels before and after treatment between the two groups(P>0.05).The overall incidences of any adverse event were not significantly different between the two groups(all P>0.05).Abdominal pain was the most common adverse event in the study group[9%(6/65)],but the incidence was not significantly increased compared with the control group[3%(2/64);P>0.05].Conclusion Compared with placebo,oral mifepristone 10 mg/day is significantly superior to placebo in reducing the size of uterine fibroids and improving anemia,without significant adverse reactions,and could be used as a drug treatment for patients with of uterine fibroids before surgery.