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Cancer Epidemiol Biomarkers Prev. 2018 May;27(5):585-593. doi: 10.1158/1055-9965.EPI-17-0595. Epub 2018 Mar 6.

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

Author information

1
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York. lh2746@cumc.columbia.edu.
2
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
3
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
4
Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, Massachusetts.
5
Sanofi, Bridgewater, New Jersey.
6
Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland.
7
Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York.
#
Contributed equally

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 (Ptrend = 0.003), 24% lower parent estrogens (Ptrend = 0.002), and 36% lower 2-pathway (Ptrend = 0.0003). Body fatness at age 10 was inversely associated with 2-catechols (35% lower, Ptrend = 0.0004) and 2-methylated catechols (30% lower, Ptrend = 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, Ptrend = 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.

PMID:
29511040
PMCID:
PMC5932230
DOI:
10.1158/1055-9965.EPI-17-0595
[Indexed for MEDLINE]
Free PMC Article

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