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Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):58-68. doi: 10.1158/1055-9965.EPI-12-0909. Epub 2012 Oct 25.

Urinary concentrations of estrogens and estrogen metabolites and smoking in caucasian women.

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National Cancer Institute, 6120 Executive Blvd, Room 7110, Bethesda, MD 20892, USA.



Smoking has been hypothesized to decrease biosynthesis of parent estrogens (estradiol and estrone) and increase their metabolism by 2-hydroxylation. However, comprehensive studies of smoking and estrogen metabolism by 2-, 4-, or 16-hydroxylation are sparse.


Fifteen urinary estrogens and estrogen metabolites (jointly called EM) were measured by liquid chromatography/tandem mass spectrometry (LC/MS-MS) in luteal phase urine samples collected during 1996 to 1999 from 603 premenopausal women in the Nurses' Health Study II (NHSII; 35 current, 140 former, and 428 never smokers). We calculated geometric means and percentage differences of individual EM (pmol/mg creatinine), metabolic pathway groups, and pathway ratios, by smoking status and cigarettes per day (CPD).


Total EM and parent estrogens were nonsignificantly lower in current compared with never smokers, with estradiol significant (P(multivariate) = 0.02). We observed nonsignificantly lower 16-pathway EM (P = 0.08) and higher 4-pathway EM (P = 0.25) and similar 2-pathway EM in current versus never smokers. EM measures among former smokers were similar to never smokers. Increasing CPD was significantly associated with lower 16-pathway EM (P-trend = 0.04) and higher 4-pathway EM (P-trend = 0.05). Increasing CPD was significantly positively associated with the ratios of 2- and 4-pathway to parent estrogens (P-trend = 0.01 and 0.002), 2- and 4-pathway to 16-pathway (P-trend = 0.02 and 0.003), and catechols to methylated catechols (P-trend = 0.02).


As hypothesized, we observed lower urinary levels of total EM and parent estrogens in active smokers. Our results also suggest smoking is associated with altered estrogen metabolism, specifically increased 2- and 4-hydroxylation, decreased 16-hydroxylation, and decreased catechol methylation.


Our study suggests how smoking might influence estrogen-related cancers and conditions.

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