title: Anthropometric measures and serum estrogen metabolism in postmenopausal women: the Women's Health Initiative Observational Study.
abstract: Several anthropometric measures have been associated with hormone-related cancers. However, it is unknown whether estrogen metabolism plays an important role in these relationships. We examined whether measured current body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported BMI at age 18 years were associated with serum estrogens/estrogen metabolites using baseline, cross-sectional data from 1835 postmenopausal women enrolled in the Women's Health Initiative Observational Study.
  
  
  
  Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry. Geometric means (GMs) of estrogens/estrogen metabolites (in picomoles per liter) were estimated using inverse probability weighted linear regression, adjusting for potential confounders and stratified on menopausal hormone therapy (MHT) use.
  
  
  
  Among never or former MHT users, current BMI (≥30 vs. <25 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM 432 vs. 239 pmol/L for estrone, 74 vs. 46 pmol/L for estradiol; p-trend < 0.001 for both) and all of the 2-, 4-, and 16-pathway estrogen metabolites evaluated (all p-trend ≤ 0.02). After additional adjustment for estradiol, unconjugated methylated 2-catechols were inversely associated (e.g., 2-methoxyestrone multivariable GM 9.3 vs. 12.0 pmol/L; p-trend < 0.001). Among current MHT users, current BMI was not associated with parent estrogens but was inversely associated with methylated catechols (e.g., 2-methoxyestrone multivariable GM 216 vs. 280 pmol/L; p-trend = 0.008). Similar patterns of association were found with WHR; however, the associations were not independent of BMI. Height and BMI at age 18 years were not associated with postmenopausal estrogens/estrogen metabolite levels.
  
  
  
  Our data suggest that postmenopausal BMI is associated with increased circulating levels of parent estrogens and reduced methylation of catechol estrogen metabolites, the estrogen metabolism patterns that have previously been associated with higher breast cancer risk.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA. hannah.oh@nih.gov.
authors.forename: Hannah
authors.identifier: 0000-0002-8368-3032
authors.initials: H
authors.lastname: Oh
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Sally B
authors.initials: SB
authors.lastname: Coburn
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Matthews
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Roni T
authors.initials: RT
authors.lastname: Falk
authors.affiliation: Center for Health Research, Kaiser Permanente NW, Portland, OR, USA.
authors.forename: Erin S
authors.initials: ES
authors.lastname: LeBlanc
authors.affiliation: Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
authors.forename: Jean
authors.initials: J
authors.lastname: Wactawski-Wende
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Sampson
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wentzensen
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.affiliation: Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Chu
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Nursing, University of Washington, Seattle, WA, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Zaslavsky
authors.affiliation: Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E332, Bethesda, MD, 20892, USA.
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001837:Body Weights and Measures / Q000706:statistics & numerical data*; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D003430:Cross-Sectional Studies; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D055432:Metabolomics; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000378:metabolism; D017698:Postmenopause / Q000097:blood*; D062486:Public Health Surveillance; D012307:Risk Factors; D053719:Tandem Mass Spectrometry; D016387:Women's Health / Q000706:statistics & numerical data*
chemical_list: D004967:Estrogens
keywords: BMI; Estrogen; Estrogen metabolites; Height; Postmenopausal; Sex hormones; WHR