炔雌醇环丙孕酮与雌孕激素序贯疗法治疗青春期功血的疗效与安全性Meta分析

Meta-analysis:Efficacy and Safety of Sequential Therapy with Ethinyl Estradiol and Cyproterone,Estrogen and Progesterone to Treat Adolescent Uterine Bleeding

目的系统评价炔雌醇环丙孕酮与雌孕激素序贯疗法治疗青春期功血的安全性和有效性。方法计算机检索PubMed、The Cochrane Library、EMbase、CNKI、VIP、万方,纳入有关炔雌醇环丙孕酮与雌孕激素序贯疗法治疗青春期功血的的随机对照试验,检索时间截止至2020年3月。根据Cochrane系统评价的方法,使用Review Manager 5.3软件对整体有效性和安全性进行Meta分析,使用STATA 14.0软件egger's test对发表偏倚进行定量分析。结果共纳入15项RCTs,包括1523例青春期功血患者,其中试验组(炔雌醇环丙孕酮) 809例,对照组(雌孕激素序贯疗法) 714例。Meta分析显示:与传统雌孕激素联合法相比,炔雌醇环丙孕酮可明显提高青春期功血治疗的总有效率(OR=4.89,95%CI:3.07~7.79,P<0.01)和痊愈率(OR=2.28,95%CI:1.79~2.90,P <0.01),缩短控制出血时间(WMD=-1.26,95%CI-1.43^-1.10,P<0.01)和完全止血时间(WMD=-16.11,95%CI:-18.98^-13.89,P<0.01),减少不良反应发生率(RR=0.31,95%CI:0.23~0.41,P<0.01)和突破性出血发生率(RR=0.09,95%CI:0.03~0.25,P<0.01),两组间比较,差异均有统计学意义(P<0.01)。结论炔雌醇环丙孕酮在治疗青春期功血的总有效率、痊愈率、控制出血时间、完全止血时间方面具有优势,且不良反应和突破性出血发生率较低。但由于纳入文献综合质量不高,存在偏倚风险,仍需要临床开展高质量的RCT评价炔雌醇环丙孕酮治疗青春期功血的有效性和安全性。

Objective To systematically evaluate safety and effectiveness of sequential therapy with ethinyl estradiol and cyproterone,estrogen and progesterone to treat adolescent uterine bleeding.Methods PubMed,The Cochrane Library,EMbase,CNKI,VIP,Wanfang were searched.Randomized controlled trials of sequential therapy of ethinyl estradiol and cyproterone and estrogen and progesterone to treat adolescent dysfunctional uterine bleeding were included.Search time was up to March 2020.According to Cochrane systematic review method,Review Manager 5.3 software was used to conduct a meta-analysis of overall effectiveness and safety,and STATA 14.0 software egger’s test was used to quantitatively analyze publication bias.Results 15 RCTs were included that had 1523 adolescent patients with dysfunctional uterine bleeding,including 809 cases in test group(sequential therapy with ethinyl estradiol and cyproterone)and 714 cases in control group(sequential therapy with estrogen and progesterone).Meta-analysis showed that compared with traditional combination of estrogen and progesterone,ethinyl estradiol and cyproterone could significantly improve total effective rate of adolescent uterine bleeding(OR=4.89,95%CI 3.07~7.79,P<0.01)and recovery rate(OR=2.28,95%CI 1.79~2.90,P<0.01),shorten control bleeding time(WMD=-1.26,95%CI-1.43^-1.10,P<0.01)and complete hemostasis time(WMD=-16.11,95%CI-18.98^-13.89,P<0.01),reduce incidence of adverse reactions(RR=0.31,95%CI 0.23~0.41,P<0.01)and incidence of breakthrough bleeding(RR=0.09,95%CI:0.03~0.25,P<0.01)with statistically significant difference between two groups(P<0.01).Conclusion Ethinyl estradiol and cyproterone have advantages in total effective rate,recovery rate,control bleeding time and complete hemostasis time to treat pubertal uterine bleeding.Incidence of adverse reactions and breakthrough bleeding would be relatively low.However,due to low comprehensive quality of included literature and bias risk,high-quality RCTs are still needed to evaluate effectiveness and safety of ethinyl estradiol and cyproterone to treat adolescent uterine bleeding.