Abstract 2519: Is accelerometer-measured physical activity associated with urinary estrogens and estrogen metabolites among postmenopausal women?.
Authors: Dallal Cher M. , Brinton Louise A. , Matthews Charles E. , Pfeiffer Ruth , Hartman Terryl , Lissowska Jolanta , Falk Roni , Garcia-Closas Montserrat , Xu Xia , Veenstra Timothy D. , Gierach Gretchen L. 
Published: August 2014

Abstract
Studies suggest that higher levels of physical activity may reduce the risk of breast cancer among postmenopausal women, potentially by lowering endogenous estrogen levels. However, few studies have assessed the influence of physical activity on estrogen metabolism; these studies mainly used self-reported measures and focused on only two metabolites, 2-hydroxyestrone and 16α-hydroxyestrone. Estrogen metabolism occurs via hydroxylation at the C-2,-4, or -16 positions, resulting in at least 13 metabolites with potentially different genotoxic and mitogenic effects. In the NCI Polish Breast Cancer Study, we previously reported significant reductions in breast cancer risk with objective measures of activity. Here we present the first study to date to assess the role of accelerometer-measured physical activity on a comprehensive profile of 15 urinary estrogens and estrogen metabolites (EM) among postmenopausal women (N=540) ages 40 to 74 years, not currently on menopausal hormone therapy. Participants were controls from a population-based case-control study conducted in Warsaw, Poland from 2000 to 2003. Women wore an accelerometer on their waist during waking hours for 7 days and provided a 12-hour urine sample. Overall activity was defined by counts per day and was averaged for monitored days with at least 10 hours of wear time. Urinary EM were measured using liquid chromatography-tandem mass spectrometry; EM were standardized by creatinine, assessed by enzyme linked immunoassay. EM were log transformed and analyzed individually, in metabolic pathways (C-2, -4, or -16), and as ratios relative to the parent estrogens (estradiol and estrone). Geometric means of EM by tertiles of activity, adjusted for age and body mass index, were computed based on linear models. Statistical heterogeneity in mean EM levels across activity tertiles was assessed using a Wald test (p-het). High overall activity was associated with lower mean levels of estrone (p-het=0.02) and estradiol (p-het=0.009). With regard to individual metabolites, high activity was inversely associated with 2-methoxyestrone (p-het=0.02), 2-methoxyestradiol (p-het=0.04), estriol (p-het=0.03), and 17-Epiestriol (p-het=0.03). No other significant associations were observed for the individual EM. Examination of specific hydroxylation pathways relative to the parent estrogens revealed that women in the highest tertile of activity had increased hydroxylation at the C-2, -4, and -16 sites (p-het ≤ 0.03). Analyses by intensity of activity and sedentary behavior are ongoing. Our findings with accelerometer-measured physical activity are consistent with prior studies reporting a reduction in estrogen levels with increased activity. Furthermore, our results suggest that increased physical activity may lower endogenous estrogens by increasing hydroxylation, and subsequent metabolism, of estrogens.
Citation Format: Cher M. Dallal, Louise A. Brinton, Charles E. Matthews, Ruth Pfeiffer, Terryl Hartman, Jolanta Lissowska, Roni Falk, Montserrat Garcia-Closas, Xia Xu, Timothy D. Veenstra, Gretchen L. Gierach. Is accelerometer-measured physical activity associated with urinary estrogens and estrogen metabolites among postmenopausal women?. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2519. doi:10.1158/1538-7445.AM2013-2519