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

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.

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