Female sex and oral contraceptive use accelerate nicotine metabolism
Abstract
Background Several studies have reported that female smokers have a higher risk of lung cancer than male smokers. This could be related to sex differences in nicotine metabolism and related smoking behavior. This study tested the hypothesis that women metabolize nicotine more rapidly than men and that, among women, oral contraceptive users metabolize nicotine more rapidly than nonusers of oral contraceptives. Methods Two hundred seventy-eight healthy volunteers who were twins and 16 who were siblings of twins, recruited from the Northern California Twin Registry, received an infusion of deuterium-labeled nicotine and cotinine with frequent blood sampling. The plasma clearances of nicotine and cotinine, the clearance of nicotine to cotinine (an index of cytochrome P450 [CYP] 2A6 activity), and the ratio of trans-3'-hydroxycotinine to cotinine (another indicator of CYP2A6 activity) were measured. Results The clearances of nicotine and cotinine, the clearance of nicotine to cotinine, and the trans-3'-hydroxycotinine/cotinine ratio were significantly higher in women than in men (nicotine clearance, 15.6 +/- 4.3 mL.min(-1).kg(-1) in men versus 18.8 +/- 6.6 mL.min(-1).kg(-1) in women; P Conclusions Sex hormones influence nicotine metabolism. Nicotine and cotinine metabolism is faster in women than in men and is faster in women taking oral contraceptives compared with those who are not. Accelerated nicotine metabolism appears to be a result of estrogen. Sex-related differences in ni…
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These limitations may restrict the generalizability to all tobacco/nicotine product users, particularly since differences in male and female nicotine PK have been reported by Benowitz et al. (2006).
“Nonetheless, these limitations may restrict the generalizability to all tobacco/nicotine product users, particularly since differences in male and female nicotine PK have been reported by Benowitz et al. (2006).”
From Nicotine pharmacokinetics and subjective responses after using nicotine pouches with different nicotine levels compared to combustible cigarettes and moist smokeless tobacco in adult tobacco users (2022) · cites this paper as Benowitz et al. (2006)
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“Due to the presence of higher level of estrogen, females metabolize nicotine faster and experience lower rewarding effects of nicotine than males [16].”
BackgroundCosgrove, K. P., Mitsis, E. M., Bois, F., Frohlich, E., Tamagnan, G. D., Krantzler, E., Perry, E., Maciejewski, P. K., Epperson, C. N., Allen, S., et al. (2007) · Journal of Nuclear Medicine · doi:10.2967/jnumed.107.042317 · Cited by 31 · see citing works
Ng, T. H. J., Sarikahya, M. H., Hudson, R., Szkudlarek, H. J., Pérez-Valenzuela, E., Uzuneser, T. C., Proud, E., Gummerson, D., Youssef, M., Machado, M., et al. (2024) · Neuropsychopharmacology · doi:10.1038/s41386-024-01853-y · Cited by 23 · see citing works
- Authors
- BENOWITZ, N., LESSOVSCHLAGGAR, C., SWAN, G., & JACOBIII, P.
- Venue
- Clinical Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2006-05
- Volume
- 79
- Issue
- 5
- Pages
- 480-488
- ISSN
- 0009-9236
- Cited by
- 407
- References
- 0
- Language
- en
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