Estrogen Metabolism in Premenopausal Women Is Related to Early Life Body Fatness

Abstract

Background: Estrogen metabolism in premenopausal women may be related to early life body fatness.Methods: Premenopausal women participating in the Nurses' Health Study II recalled their body fatness at ages 5, 10, and 20 years using a validated 9-level pictogram. Fifteen estrogens and estrogen metabolites (EM) were measured using LC/MS-MS in luteal phase urines from 603 women ages 32-54 years. Geometric means of individual EM, metabolic pathway groups, and pathway ratios were examined by body fatness categories using linear mixed models.Results: Body fatness at each age was inversely associated with adult concentrations of all EM combined, parent estrogens (estrone, estradiol), and the 2-hydroxylation pathway. Women in the top (vs. bottom) category of body fatness at age 10 had 21% lower levels of all EM (P_trend = 0.003), 24% lower parent estrogens (P_trend = 0.002), and 36% lower 2-pathway (P_trend = 0.0003). Body fatness at age 10 was inversely associated with 2-catechols (35% lower, P_trend = 0.0004) and 2-methylated catechols (30% lower, P_trend = 0.002). After adjusting for premenopausal body mass index (BMI), these associations remained inverse but were attenuated; only parent estrogens remained statistically significant (21% lower, P_trend = 0.01). Body fatness at ages 5 and 20 were similarly, but more weakly, associated with estrogen pathways.Conclusions: Estimates of body fatness during early life were inversely associated with premenopausal levels of all EM combined, parent estrogens, and 2-pathway estrogen metabolites. These relationships were not fully explained by adult BMI.Impact: These findings inform investigations of diseases linked to early life body fatness and estrogen metabolism. Cancer Epidemiol Biomarkers Prev; 27(5); 585-93. ©2018 AACR.