我国示范乡镇卫生院基本药物循证评价与遴选之十七:子宫肌瘤

Evidence-Based Evaluation and Selection of Essential Medicine for Township Health Centre in China: 17.Uterine Neoplasms

目的基于疾病负担循证评价与遴选我国乡镇卫生院治疗子宫肌瘤基本药物。方法应用本系列研究之二制定的基本药物循证评价与遴选标准、方法、流程,循证评价并推荐相关药物。结果①共纳入6个指南,含循证指南3个。②指南涉及子宫肌瘤治疗药物3类9种及手术后辅助用药3类5种。③根据WHO EML(2011)、NEML(2009)、CNF(2010)和指南推荐药物的证据数量和质量,强推荐甲羟孕酮、缩宫素、麦角新碱;弱推荐丙酸睾酮、甲睾酮、三苯氧胺、米非司酮、氨甲环酸、益母草等;不推荐丹那唑和芳香化酶抑制剂。④米非司酮、甲睾酮、三苯氧胺、缩宫素、益母草国内均查见相关文献并评价证据,米非司酮其配伍甲睾酮、三苯氧胺用于子宫肌瘤保守治疗,缩宫素和益母草用于子宫肌瘤术后减少出血。每日费用米非司酮片(25 mg/d)13.0～27.5元,甲睾酮(5 mg/d)0.074元,三苯氧胺(20 mg/d)0.6～1.4元,益母草注射液(25 mg/mL)15元/次,缩宫素注射剂(10U)1.5元/次。⑤国内研究表明,米非司酮配伍甲睾酮、三苯氧胺保守治疗子宫肌瘤安全可行,缩宫素和益母草能有效预防子宫肌瘤术后出血,联合应用有促子宫收缩作用,安全有效。结论①治疗围绝经期子宫肌瘤推荐使用三种用药方案:(A)米非司酮片25 mg,qd;(B)米非司酮25 mg+甲睾酮5 mg,qd;(C)米非司酮25 mg+三苯氧胺10 mg,bid。三种方案均从月经周期第1天起,连服3个月。②术后辅助用药,益母草注射液(20 mg/mL)1～2mL/次、缩宫素注射液(10 U/mL)10 U/次,用于减少术后阴道流血。③基层医疗机构医务人员应严格掌握用药适应证,严密随访,动态监测肌瘤变化和月经改变,结合患者实际情况作出调整。

Objective To evaluate and select essential medicine for uterine neoplasms using evidence-based methods based on the burden of disease.Methods By means of the approaches,criteria,and workflow set up in the second article of this series,we referred to the recommendations of evidence-based or authority guidelines from inside and outside China,collected relevant evidence from domestic clinical studies,and recommended essential medicine based on evidence-based evaluation.Data were analyzed by Review Manager（RevMan） 5.1 and GRADE profiler 3.6 to evaluate quality of evidence.Results （1） Six guidelines were included,three of which were evidence-based.（2） Retrieved guidelines related to nine medicines（of three classes） for uterine neoplasms and five adjuvant drugs（of three classes） used after relevant surgery.（3） According to WHOEML（2011）,NEML（2009）,CNF（2010）,other guideline and the quantity and quality of evidence,we offered a strong recommendation for medroxyprogesterone acetate,oxytocin,ergometrine and a weak recommendation for testosterone propionate,methyltestosterone,tamoxifen,mifepristone,tranexamic acid,leonurus heterophyllus used in the treatment of uterine neoplasms.We offered a recommendation against danazol and aromatase inhibitors.（4） We found relevant domestic literature on mifepristone,methyltestosterone,tamoxifen,oxytocin and leonurus heterophyllus.Mifepriston combined with methyltestosterone or tamoxifen was recommended to use as a conservative therapy for uterine neoplasms.Oxytocin,and leonurus heterophyllus were used to reduce bleeding after the surgery of uterine neoplasms.As to daily expense,mifepriston（25 mg/d） cost 13.0 to 27.5 yuan,methyltestosterone（5 mg/d） 0.074 yuan,tamoxifen（20 mg/d） 0.6 to 1.4 yuan,leonurus heterophyllus（injection,1 mL） 15 yuan and oxytocin（injection,20 U） 1.5 yuan.（5） Results of domestic studies indicated that mifepristone,mifepristone plus methyltestosterone,and mifepristone plus tamoxifen were proved to be safe and applicable for the treatment of uterine neoplasms.Oxytocin and leonurus heterophyllus are effective in preventing postoperative bleeding and the combination of two effectively and safely promoted uterine contraction.Conclusion （1） We offer a recommendation for three medication plans used in the treatment uterine neoplasms during perimenopause,including： a） Mifepristone（25 mg/ tablet,once daily）;b） Mifepristone（25 mg/ tablet,once daily） plus methyltestosterone（5 mg/tablet,once daily）;c） Mifepristone（25 mg/ tablet,once daily） plus tamoxifen（10 mg/tablet,twice daily）.The three plans mentioned above should be used from first day of menstrual cycle,continuously for three months.（2） Adjuvant drugs such as oxytocin（injection,1 to 2 mL） and leonurus heterophyllus（injection,10 U） can be applied to reduce vaginal bleeding flow after the surgery of uterine neoplasms.（3） Personnel in elementary healthcare institution should stick to drug indication,carefully make follow-up,and dynamically monitor the change of uterine neoplasms and menstruation so as to adjust medication plan according to patients’ situation.