The Journal of Nutrition Nutrition and Disease Green Tea Catechin Extract Supplementation Does Not Infuence Circulating Sex Hormones and Insulin-Like Growth Factor Axis Proteins in a Randomized Controlled Trial of Postmenopausal Women at High Risk of Breast Cancer Hamed Samavat, 1,2,3 Anna H Wu, 4 Giske Ursin, 4,5,6 Carolyn J Torkelson, 7 Renwei Wang, 2 Mimi C Yu, 8 Douglas Yee, 9,10,11 Mindy S Kurzer, 3 and Jian-Min Yuan 1,2 1 Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, 2 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; 3 Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN; 4 Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA; 5 Cancer Registry of Norway, Oslo, Norway; 6 Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; 7 Department of Family Medicine and Community Health, University of Minnesota Medical School, Minneapolis, MN; 8 Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA (retired); 9 Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 10 Department of Medicine, University of Minnesota, Minneapolis, MN, and 11 Department of Pharmacology, University of Minnesota, Minneapolis, MN ABSTRACT Background: Consumption of green tea has been associated with reduced risk of breast cancer. Hormonal modulation has been suggested as one of the potential underlying mechanisms; however, it has yet to be fully elucidated in large, long-term human clinical trials. Objective: We investigated the effects of decaffeinated green tea extract (GTE) on circulating sex hormones and insulin- like growth factor (IGF) proteins. Methods: We conducted a placebo-controlled double-blind randomized clinical trial recruiting from 8 clinical centers in Minnesota. Participants were 538 healthy postmenopausal women randomly assigned to the GTE group (463 completed the study; mean age = 60.0 y) and 537 to the placebo group (474 completed; mean age = 59.7 y). Women in the GTE group orally took 4 decaffeinated capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3- gallate daily for 1 y, whereas women in the placebo group took similar capsules containing no tea catechins. Blood sex hormones (estrone, estradiol, androstenedione, testosterone, and sex hormone-binding globulin) and IGF proteins (IGF-1 and IGF binding protein-3) were quantifed at baseline and months 6 (for IGF proteins only) and 12, and were assessed as secondary outcomes of the study using a mixed-effect repeated-measures ANOVA model. Results: Women in the GTE group had signifcantly higher blood total estradiol (16%; P = 0.02) and bioavailable estradiol (21%; P = 0.03) than in the placebo group at month 12. There was a statistically signifcant interaction between GTE supplementation and duration of treatment on estradiol and bioavailable estradiol (both Ps for interaction = 0.001). The catechol-O-methyltransferase genotype did not infuence blood sex hormones before or after GTE supplementation. The circulating concentrations of IGF proteins were comparable between GTE and placebo groups at all 3 time points. Conclusion: These results suggest that a 12-mo GTE supplementation signifcantly increases circulating estradiol concentrations in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00917735. J Nutr 2019;149:619–627. Keywords: green tea extract, catechins, sex hormones, insulin-like growth factors, postmenopausal women, breast cancer Introduction Breast cancer mortality dropped by 39% in the United States between 1989 and 2015, yet no signifcant reduction in breast cancer incidence has occurred. Substantial evidence suggests that sex hormones may play a carcinogenic role in the development of breast cancer (1), particularly among Copyright C  American Society for Nutrition 2019. All rights reserved. Manuscript received September 4, 2018. Initial review completed November 15, 2018. Revision accepted December 14, 2018. First published online March 30, 2019; doi: https://doi.org/10.1093/jn/nxy316. 619 Downloaded from https://academic.oup.com/jn/article-abstract/149/4/619/5423559 by guest on 04 July 2020