The online version of this article (doi:10.1186/s13058-017-0810-0) contains supplementary material, which is available to authorized users.
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.
Additional file 1: Table S1. Geometric means (pmol/L) and 95% CIs of serum estrogens/estrogen metabolites by current BMI (<25, 25–29.9, 30–34.9, ≥40 kg/m2) in postmenopausal women not using menopausal hormone therapy in the Women’s Health Initiative Observational Study. (PDF 93 kb)13058_2017_810_MOESM1_ESM.pdf
Additional file 2: Figure S1. Percentages of parent estrogens (estradiol and estrone) and child estrogen metabolites (2-, 4-, and 16-hydroxylation pathway metabolites) out of summed estrogens/estrogen metabolites by current BMI among current menopausal hormone therapy users. (PPTX 63 kb)13058_2017_810_MOESM2_ESM.pptx
Additional file 3: Figure S2. Percentages of each pathway estrogens/estrogen metabolites (2-catechols, methylated 2-catechols, 4-catechols, methylated 4-catechols, 16-pathway metabolites) out of summed child estrogen metabolites by current BMI among current menopausal hormone therapy users. (PPTX 70 kb)13058_2017_810_MOESM3_ESM.pptx
Additional file 4: Table S2. Geometric means (pmol/L) and 95% CIs of serum estrogens/estrogen metabolites by waist-to-hip ratio in postmenopausal women currently using menopausal hormone therapy in the Women’s Health Initiative Observational Study. (PDF 95 kb)13058_2017_810_MOESM4_ESM.pdf
Additional file 5: Table S3. Geometric means (pmol/L) and 95% CIs of serum estrogens/estrogen metabolites by BMI at age 18 years in postmenopausal women in the Women’s Health Initiative Observational Study. (PDF 94 kb)13058_2017_810_MOESM5_ESM.pdf
Additional file 6: Table S4. Geometric means (pmol/L) and 95% CIs of serum estrogens/estrogen metabolites by current BMI in postmenopausal women not using menopausal hormone therapy among control subjects only in the Women’s Health Initiative Observational Study. (PDF 103 kb)13058_2017_810_MOESM6_ESM.pdf
Additional file 7: Women’s Health Initiative clinical centers. (DOCX 13 kb)13058_2017_810_MOESM7_ESM.docx
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- Anthropometric measures and serum estrogen metabolism in postmenopausal women: the Women’s Health Initiative Observational Study
Sally B. Coburn
Charles E. Matthews
Roni T. Falk
Erin S. LeBlanc
Ruth M. Pfeiffer
Louise A. Brinton
Garnet L. Anderson
JoAnn E. Manson
- BioMed Central
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