Meireles Cinthia G, Pereira Sidney A, Valadares Luciana P, Rêgo Daniela F, Simeoni Luiz A, Guerra Eliete N S, Lofrano-Porto Adriana
Molecular Pharmacology Laboratory, Health Sciences Faculty, University of Brasilia, Brasilia, Brazil.
Molecular Pharmacology Laboratory, Health Sciences Faculty, University of Brasilia, Brasilia, Brazil; Gonadal and Adrenal Diseases Clinics, University Hospital of Brasilia, University of Brasilia, Brasilia, Brazil.
Gynecol Oncol. 2017 Oct;147(1):167-180. doi: 10.1016/j.ygyno.2017.07.120. Epub 2017 Jul 29.
Endometrial cancer is one of the most common gynecological cancers, which is frequently preceded by atypical endometrial hyperplasia, a premalignant lesion. Metformin, an antidiabetic drug, has emerged as a new adjunctive strategy for different cancer types, including endometrial cancer. This systematic review and meta-analysis aimed to evaluate the effects of metformin in atypical endometrial hyperplasia and endometrial cancer patients.
The search was conducted on January 2017 and the articles were collected in Cochrane, LILACS, PubMed, Scopus and Web of Science. A grey literature search was undertaken using Google SCHOLAR, ProQuest and Open Grey. Nineteen studies were included, which contained information about the following outcomes: reversal of atypical endometrial hyperplasia, cellular proliferation biomarkers expression and overall survival in metformin-users compared to non-users.
Metformin was associated with reversion of atypical endometrial hyperplasia to a normal endometrial, and with decreased cell proliferation biomarkers staining, from 51.94% (CI=36.23% to 67.46%) to 34.47% (CI=18.55% to 52.43%). However, there is a high heterogeneity among studies. Metformin-users endometrial cancer patients had a higher overall survival compared to non-metformin users and non-diabetic patients (HR=0.82; CI: 0.70-0.95; p=0.09, I=40%).
Regardless the high heterogeneity of the analyzed studies, the present review suggests that adjunct metformin treatment may assist in the reversal of atypical endometrial hyperplasia to normal endometrial histology, in the reduction of cell proliferation biomarkers implicated in tumor progression, and in the improvement of overall survival in endometrial cancer. Further work on prospective controlled trials designed to address the effects of adjunct metformin on clinical outcomes is necessary for definite conclusions.
子宫内膜癌是最常见的妇科癌症之一，通常由癌前病变非典型子宫内膜增生发展而来。二甲双胍作为一种抗糖尿病药物，已成为包括子宫内膜癌在内的不同癌症类型的新辅助治疗策略。本系统评价和荟萃分析旨在评估二甲双胍对非典型子宫内膜增生和子宫内膜癌患者的影响。
检索于2017年1月进行，在Cochrane、LILACS、PubMed、Scopus和Web of Science数据库中收集文章。使用谷歌学术、ProQuest和Open Grey进行灰色文献检索。纳入了19项研究，这些研究包含以下结果的信息：与未使用二甲双胍的患者相比，使用二甲双胍患者的非典型子宫内膜增生逆转情况、细胞增殖生物标志物表达以及总生存率。
二甲双胍与非典型子宫内膜增生逆转至正常子宫内膜有关，并且细胞增殖生物标志物染色减少，从51.94%（CI = 36.23%至67.46%）降至34.47%（CI = 18.55%至52.43%）。然而，各研究之间存在高度异质性。与未使用二甲双胍的患者和非糖尿病患者相比，使用二甲双胍的子宫内膜癌患者总生存率更高（HR = 0.82；CI：0.70 - 0.95；p = 0.09，I² = 40%）。
尽管所分析的研究存在高度异质性，但本综述表明，辅助使用二甲双胍治疗可能有助于将非典型子宫内膜增生逆转至正常子宫内膜组织学，降低与肿瘤进展相关的细胞增殖生物标志物水平，并提高子宫内膜癌患者的总生存率。为得出明确结论，有必要进一步开展前瞻性对照试验，以研究辅助使用二甲双胍对临床结局的影响。
