摘要
目的分析醋酸甲地孕酮(MA)联合二甲双胍治疗子宫内膜不典型增生(EAH)及子宫内膜样癌(EEC)的远期结局。方法本研究为随机对照试验。2013年10月至2017年10月,共入组150例就诊于复旦大学附属妇产科医院的初诊EAH和EEC患者,根据病理类型分层,按1∶1的比例采用随机数字表法分配进入MA联合二甲双胍治疗组和MA单药治疗组。比较两组患者的基线数据,应用Kaplan-Meier生存曲线计算累积完全缓解率和累积无复发生存率,采用Log-rank检验进行组间比较,采用Cox比例风险回归模型分析无复发生存的相关因素。计量资料以M(Q_(1),Q_(3))表示。结果150例患者中,MA联合二甲双胍治疗组和MA单药治疗组分别为76和74例,年龄分别为32.5(28.0,36.0)和32.0(28.0,36.0)岁。截至本研究随访结束时,共有96.7%(145例)患者达到完全缓解,随访时间为57.7(26.7,70.5)个月。MA联合二甲双胍治疗组和MA单药治疗组的完全缓解时间分别为6.3(3.5,8.3)和6.8(4.0,9.3)个月(P=0.193),2年累积完全缓解率分别为98.6%和98.5%(P=0.879),无复发生存时间分别为28.1(12.5,57.3)和33.3(14.1,62.5)个月(P=0.213);累积无复发生存率分别为61.9%和65.8%(P=0.560)。在体质指数<28 kg/m 2的EAH患者群体中,MA联合二甲双胍治疗组和MA单药治疗组无复发生存时间分别为25.7(7.6,60.3)和47.3(17.5,64.8)个月(P=0.033);累积无复发生存率分别为57.5%和80.6%(P=0.029)。是否进行辅助生育治疗(HR=2.358,95%CI:1.069~5.204,P=0.034)是子宫内膜病变完全缓解后无复发生存的相关因素。结论长期随访结果表明,相比于MA单药治疗,MA联合二甲双胍治疗EAH及EEC的完全缓解时间及无复发生存时间无差异。
Objective To assess the long-term efficacy of metformin in megestrol acetate(MA)-based fertility-sparing treatment for patients with endometrial atypical hyperplasia(EAH)and endometrioid endometrial cancer(EEC).Methods The randomized controlled trail study was conducted from October 2013 to October 2017 in the Obstetrics and Gynecology Hospital of Fudan University,Shanghai,China.Patients with EAH or EEC were firstly stratified according to pathology,and randomized to receive MA(160 mg orally,daily)plus metformin(500 mg orally,three times a day)or MA(160 mg orally,daily).Baseline data between two groups of patients were compared.Estimates of time to complete remission(CR)and recurrence-free survival(RFS)were calculated using the Kaplan-Meier method.Cox proportional-hazards regression model was used to estimate hazard ratios(HR)of related factors for recurrence-free survival.Quantitative data were represented by M(Q_(1),Q_(3)).Results A total of 150 patients were included,and 76 patients were allocated to receive MA plus metformin with the age of 32.5(28.0,36.0),while 74 patients received MA alone with the age of 32.0(28.0,36.0).By the end of follow-up period,96.7%(n=145)of patients achieved complete remission,with a median follow-up time of 57.7(26.7,70.5)months.The median CR time for the MA plus metformin group and the MA alone group were 6.3(3.5,8.3)months and 6.8(4.0,9.3)months,respectively(P=0.193),with 2-year cumulative CR rate of 98.6%and 98.5%,respectively(P=0.879).The median time of RFS was 28.1(12.5,57.3)months for the MA plus metformin group and 33.3(14.1,62.5)months for the MA alone group(P=0.213),with a cumulative RFS rate of 61.9%and 65.8%,respectively(P=0.560).In the subgroup of non-obese(body mass index<28 kg/m 2)patients with EAH,the median RFS times were 25.7(7.6,60.3)months and 47.3(17.5,64.8)months for the MA plus metformin group and the MA alone group,respectively(P=0.033),with a cumulative RFS rate of 57.5%and 80.6%,respectively(P=0.029).According to Cox proportional hazards regression analysis,undergoing assisted reproductive treatment(HR=2.358,95%CI:1.069-5.204,P=0.034)was identified as an independent risk factor for recurrence-free survival after complete remission of endometrial lesions.Conclusion The long-term follow-up outcome indicates that there is no significant difference in CR time and RFS time between MA plus metformin therapy and MA alone therapy for patients with EAH or EEC.
作者
董悠婷
管隽
杨冰义
古丽娜孜·伊尔甫拉提
薛誉
陈晓军
Dong Youting;Guan Jun;Yang Bingyi;Gulinazi Yierfulati;Xue Yu;Chen Xiaojun(Department of Gynecology,Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200092,China)
出处
《中华医学杂志》
CAS
CSCD
北大核心
2024年第10期729-735,共7页
National Medical Journal of China
基金
申康临床科技创新项目(SHDC22021219)
关键词
癌
子宫内膜样
子宫内膜不典型增生
保育治疗
醋酸甲地孕酮
二甲双胍
Carcinoma,endometrial
Endometrial atypical hyperplasia
Fertility-sparing treatment
Megestrol acetate
Metformin
作者简介
通信作者:薛誉,Email:xueyu_shuang@163.com
