Abstract
BackgroundPrevious studies have suggested that metformin may be useful for preventing and treating endometrial cancer (EC), while the results have been inconsistent. This systematic review and meta-analysis aimed to investigate the association between metformin use and risk and prognosis of patients with EC.MethodsPubMed, Embase, and the Cochrane Library databases were searched for observational studies evaluating the effect of metformin on EC prevention or treatment. The odds ratio (OR) was used for analyzing risks, and the hazard ratio (HR) was used for analyzing survival outcomes. A random-effects model was used for data analysis.ResultsSeven studies reported data on EC risk. The pooled results suggested that metformin was not significantly associated with a lower risk of EC [OR = 1.05, 95% confidence interval (CI) 0.82–1.35, P = 0.70]. For patients with diabetes, metformin showed no advantage in reducing the EC risk compared with other interventions (OR = 0.99, 95% CI 0.78–1.26, P = 0.95). Further, seven studies were included for survival analysis. The pooled data showed that metformin could significantly improve the overall survival of patients with EC (HR = 0.61, 95% CI 0.48–0.77, P < 0.05) and reduce the risk of EC recurrence (OR = 0.50, 95% CI 0.28–0.92, P < 0.05) Finally, we noted metformin was associated with significantly improving the overall survival of EC patients among diabetes (HR = 0.47; 95%CI 0.33–0.67, P < 0.05).ConclusionsThis meta-analysis did not prove that metformin was beneficial for preventing EC. However, metformin could prolong the overall survival of patients with EC and reduce their risk of cancer relapse.
Highlights
Previous studies have suggested that metformin may be useful for preventing and treating endometrial cancer (EC), while the results have been inconsistent
Inclusion criteria Articles were included in the study if they met the following criteria: (1) used metformin for preventing or treating EC; (2) evaluated the incidence of EC or survival outcomes; the survival endpoints were overall survival (OS), recurrence-free survival (RFS)/disease-free survival, or the recurrence rate; (3) directly reported the effect estimates of odds ratio (OR), hazard ratio (HR), or relative risk (RR); (4) indirectly reported data allowing for the calculation of these effect estimates; and (5) the study with observational design
Study characteristics and quality evaluation The characteristics of the seven studies on EC risk are shown in Table 1, including two case–control studies [34, 39], four retrospective studies [36,37,38, 40], and one prospective study [35]
Summary
Previous studies have suggested that metformin may be useful for preventing and treating endometrial cancer (EC), while the results have been inconsistent. Endometrial cancer (EC), a tumor originating from the endometrium, is a major cause of morbidity and mortality in women. Hyperplastic endometrium may be a result of exposure to unopposed estrogen, leading to the progression of cancer. It is the most common malignancy of the female genital tract in the United States, with approximately 54,870 new cases and 10,170 related deaths in 2015 [1]. EC was associated with higher cancer mortality and poor prognosis in developing countries [1,2,3].
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