Background: 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. Methods: Fifteen urinary estrogens and estrogen metabolites (jointly called EM) were measured by liquid chromatography-tandem mass spectrometry in luteal phase urines collected during 1996-99 from 603 premenopausal women in Nurses' Health Study II (35 current, 140 former, 428 never smokers). We calculated geometric means and percent differences of individual EM (pmol/mg creatinine), metabolic pathway groups, and pathway ratios, by smoking status and cigarettes per day (CPD). Results: Total EM and parent estrogens were nonsignificantly lower in current compared to never smokers, with estradiol significant (pmultivariate=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 vs. 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). Conclusions: 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. Impact: Our study suggests how smoking might influence estrogen-related cancers and conditions.
- Received August 1, 2012.
- Revision received October 5, 2012.
- Accepted October 14, 2012.
- Copyright © 2012, American Association for Cancer Research.