TY - JOUR
T1 - Prospective randomized biomarker study of metformin and lifestyle intervention for prevention in obese women at increased risk for endometrial cancer
AU - Yates, Melinda S.
AU - Coletta, Adriana M.
AU - Zhang, Qian
AU - Schmandt, Rosemarie E.
AU - Medepalli, Meena
AU - Nebgen, Denise
AU - Soletsky, Beth
AU - Milbourne, Andrea
AU - Levy, Erma
AU - Fellman, Bryan
AU - Urbauer, Diana
AU - Yuan, Ying
AU - Broaddus, Russell R.
AU - Basen-Engquist, Karen
AU - Lu, Karen
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/8
Y1 - 2018/8
N2 - 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 prediabetes were randomized into four groups for a 16-week intervention using a 2 (metformin 1700 mg/day vs. placebo) 2 (lifestyle intervention vs. no lifestyle intervention) factorial design. Pre- and postintervention endometrial proliferation, anthropometrics, body composition, and serum biomarkers (sex hormones, sex hormone binding globulin, IGF-I, 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 ¼ 0.006) and total fat mass (3.23 kg, P < 0.001). Participants receiving metformin lost 3.43 kg of weight (P ¼ 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.
AB - 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 prediabetes were randomized into four groups for a 16-week intervention using a 2 (metformin 1700 mg/day vs. placebo) 2 (lifestyle intervention vs. no lifestyle intervention) factorial design. Pre- and postintervention endometrial proliferation, anthropometrics, body composition, and serum biomarkers (sex hormones, sex hormone binding globulin, IGF-I, 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 ¼ 0.006) and total fat mass (3.23 kg, P < 0.001). Participants receiving metformin lost 3.43 kg of weight (P ¼ 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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U2 - 10.1158/1940-6207.CAPR-17-0398
DO - 10.1158/1940-6207.CAPR-17-0398
M3 - Article
C2 - 29716897
AN - SCOPUS:85050968671
SN - 1940-6207
VL - 11
SP - 477
EP - 490
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 8
ER -