Cinthia G Meireles1, Sidney A Pereira1, Luciana P Valadares2, Daniela F Rêgo3, Luiz A Simeoni1, Eliete N S Guerra3, Adriana Lofrano-Porto4. 1. Molecular Pharmacology Laboratory, Health Sciences Faculty, University of Brasilia, Brasilia, Brazil. 2. 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. 3. Laboratory of Oral Histopathology, Health Sciences Faculty, University of Brasilia, Brasilia, Brazil. 4. 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. Electronic address: adlofrano@uol.com.br.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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, I2=40%). CONCLUSION: 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.
BACKGROUND: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 cancerpatients. METHODS: 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. RESULTS: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 cancerpatients had a higher overall survival compared to non-metformin users and non-diabeticpatients (HR=0.82; CI: 0.70-0.95; p=0.09, I2=40%). CONCLUSION: 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.
Authors: Marcia A Ciccone; Stephanie A Whitman; Charlotte L Conturie; Niquelle Brown; Christina E Dancz; Begum Özel; Koji Matsuo Journal: Arch Gynecol Obstet Date: 2019-01-31 Impact factor: 2.344
Authors: Veronika Piskovatska; Nadiya Stefanyshyn; Kenneth B Storey; Alexander M Vaiserman; Oleh Lushchak Journal: Biogerontology Date: 2018-09-25 Impact factor: 4.277