二甲双胍联合醋酸甲地孕酮与单用醋酸甲地孕酮作为非典型子宫内膜增生和分化良好的子宫内膜癌患者的生育保留治疗的比较：一项随机对照试验。

Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial.

机构信息

Department of Gynaecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.

Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China.

出版信息

BJOG. 2020 Jun;127(7):848-857. doi: 10.1111/1471-0528.16108. Epub 2020 Feb 16.

DOI:10.1111/1471-0528.16108

PMID:31961463

Abstract

OBJECTIVE

To assess the efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC).

DESIGN

A randomised, single-centre, open-label, controlled trial conducted between October 2013 and December 2017.

SETTING

Shanghai OBGYN Hospital of Fudan University, China.

POPULATION

A total of 150 patients (18-45 years old) with primary AEH or well-differentiated EEC were randomised into an MA group (n = 74) and an MA plus metformin group (n = 76).

METHODS

Patients with AEH or EEC were firstly stratified, then randomised to receive MA (160 mg orally, daily) or MA (160 mg orally, daily) plus metformin (500 mg orally, three times a day).

MAIN OUTCOMES AND MEASURES

The primary efficacy parameter was the cumulate complete response (CR) rate within 16 weeks of treatment (16w-CR rate); the secondary efficacy parameters were 30w-CR rate and adverse events.

RESULTS

The 16w-CR rate was higher in the metformin plus MA group than in the MA-only group (34.3 versus 20.7%, odds ratio [OR] 2.0, 95% confidence interval [CI] 0.89-4.51, P = 0.09) but the difference was more significant in 102 AEH patients (39.6 versus 20.4%, OR 2.56, 95% CI 1.06-6.21, P = 0.04). This effect of metformin was also significant in non-obese (51.4 versus 24.3%, OR 3.28, 95% CI 1.22-8.84, P = 0.02) and insulin-sensitive (54.8 versus 28.6%, OR 3.04, 95% CI 1.03-8.97, P = 0.04) subgroups of AEH women. No significant result was found in secondary endpoints.

CONCLUSION

As a fertility-sparing treatment, metformin plus MA was associated with a higher early CR rate compared with MA alone in AEH patients.

TWEETABLE ABSTRACT

For AEH patients, metformin plus MA might be a better fertility-sparing treatment to achieve a higher early CR rate compared with MA alone.

摘要

目的

评估二甲双胍在醋酸甲地孕酮（MA）为基础的保留生育力治疗不典型子宫内膜增生（AEH）和子宫内膜样腺癌（EEC）患者中的疗效。

设计

一项于 2013 年 10 月至 2017 年 12 月期间在中国复旦大学妇产科医院进行的随机、单中心、开放标签、对照试验。

设置

中国复旦大学妇产科医院。

人群

共纳入 150 名（18-45 岁）原发性 AEH 或高分化 EEC 患者，随机分为 MA 组（n=74）和 MA 加二甲双胍组（n=76）。

方法

AEH 或 EEC 患者首先分层，然后随机接受 MA（160mg 口服，每日一次）或 MA（160mg 口服，每日一次）加二甲双胍（500mg 口服，每日三次）治疗。

主要结局和测量指标

主要疗效参数为治疗 16 周内的累积完全缓解（CR）率（16w-CR 率）；次要疗效参数为 30w-CR 率和不良事件。

结果

二甲双胍加 MA 组的 16w-CR 率高于 MA 单药组（34.3%比 20.7%，比值比[OR]2.0，95%置信区间[CI]0.89-4.51，P=0.09），但在 102 名 AEH 患者中差异更为显著（39.6%比 20.4%，OR 2.56，95%CI 1.06-6.21，P=0.04）。二甲双胍在非肥胖（51.4%比 24.3%，OR 3.28，95%CI 1.22-8.84，P=0.02）和胰岛素敏感（54.8%比 28.6%，OR 3.04，95%CI 1.03-8.97，P=0.04）亚组的 AEH 患者中也有显著效果。次要终点无显著结果。