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Cancer Prev Res (Phila). 2018 May 1. pii: canprevres.0398.2017. doi: 10.1158/1940-6207.CAPR-17-0398. [Epub ahead of print]

Prospective randomized biomarker study of metformin and lifestyle intervention for prevention in obese women at increased risk for endometrial cancer.

Author information

1
Gynecologic Oncology & Reproductive Medicine, University of Texas MD Anderson Cancer Center MSYates@mdanderson.org.
2
Behavioral Science, University of Texas MD Anderson Cancer Center.
3
Gynecologic Oncology, M. D. Anderson Cancer Center.
4
Gynecologic Oncology & Reproductive Medicine, University of Texas MD Anderson Cancer Center.
5
Department of Gynecologic Oncology and Reproductive Medicine, M. D. Anderson Cancer Center.
6
University of Texas MD Anderson Cancer Center.
7
Biostatistics, University of Texas MD Anderson Cancer Center.
8
Pathology, University of Texas MD Anderson Cancer Center.
9
Behavioral Sciences, UT M. D. Anderson Cancer Center.

Abstract

Obesity increases risk of endometrial cancer through dysregulation of estrogen and insulin signaling. The primary aim of this study was to evaluate the impact of metformin or lifestyle intervention on endometrial proliferation in postmenopausal obese women. Secondary aims included evaluating obesity-related biomarkers and adverse events experienced. Obese, postmenopausal women with pre-diabetes were randomized into four groups for a 16-week intervention using a 2 (metformin 1700 mg/day vs placebo) x 2 (lifestyle intervention vs no lifestyle intervention) factorial design. Pre- and post-intervention endometrial proliferation, anthropometrics, body composition, and serum biomarkers (sex hormones, sex hormone binding globulin, IGF-1, adiponectin, omentin, insulin, glucose, and others) were assessed. Data were analyzed with linear regression models and false-discovery rate correction. Of 576 women approached for the study, 52 attended initial screening, 29 were eligible and randomized, and 26 completed the study. Lifestyle intervention resulted in significant loss of weight (-4.23 kg, p=0.006) and total fat mass (-3.23 kg, p<0.001). Participants receiving metformin lost 3.43 kg of weight (p=0.023), but this was not statistically significant after multiple comparisons adjustment controlling false-discovery rate to 10%. Endometrial proliferation was low at baseline (mean 7.1%) and remained unchanged by 16 weeks, but included substantial variability. Metformin and lifestyle intervention produced minor changes to serum biomarkers. Lifestyle intervention produced the most significant changes in weight and body composition. While it is known that obese postmenopausal women are at increased risk for endometrial cancer, improved biomarkers are needed to stratify risk and test prevention strategies, particularly at the endometrial tissue level.

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