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Eur J Cancer. 2015 Dec;51(18):2747-58. doi: 10.1016/j.ejca.2015.08.031. Epub 2015 Nov 18.

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis.

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School of Medicine, Universidad Peruana de Ciencias Aplicadas (UPC), Lima 9, Peru; Health Outcomes and Clinical Epidemiology Section, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, 44195 USA. Electronic address:
Department of Medicine, Case Western Reserve University, Cleveland, OH, 44106 USA. Electronic address:
Faculty of Human Medicine, Postgraduate Section, Universidad de San Martin de Porres, Lima 12, Peru. Electronic address:
Department of Medicine, Case Western Reserve University, Cleveland, OH, 44106 USA. Electronic address:
Medicine Institute Center for Value Based Care Research, Cleveland Clinic, Cleveland, OH, 44195 USA. Electronic address:
Department of Obstetrics and Gynecology, University of Zaragoza Faculty of Medicine and Lozano Blesa University Hospital, Domingo Miral s/n, Zaragoza 50009, Spain. Electronic address:



It has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC.


We searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by Newcastle-Ottawa scale. Random-effects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC.


Twenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n = 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04-52.85, p = 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n = 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08-0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n = 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20-2.06, p = 0.02). There was moderate-to-high heterogeneity among the included studies.


Currently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMA-IR values.


Endometrial cancer; Insulin resistance; Meta-analysis

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