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Female sex and oral contraceptive use accelerate nicotine metabolism
Author(s) -
Benowitz Neal L.,
LessovSchlaggar Christi.,
Swan Gary E.,
Jacob Peyton
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2006.01.008
Subject(s) - cotinine , nicotine , cyp2a6 , medicine , physiology , obstetrics , metabolism , cytochrome p450 , cyp1a2
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 < .001); they were also higher among women taking oral contraceptives than in those who were not taking oral contraceptives (nicotine clearance, 22.5 ± 6.6 mL · min −1 · kg −1 in women taking oral contraceptives versus 17.6 ± 6.1 mL · min −1 · kg −1 in those who were not; P < .05). Women who were menopausal or postmenopausal were not different from men. Among oral contraceptive users, nicotine metabolism was accelerated among those taking combined and estrogen‐only contraceptives but not progesterone‐only contraceptives. 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 nicotine clearance could affect smoking behaviors, as well as response to nicotine medications, and could be a marker for altered metabolism of nicotine‐derived carcinogens. Clinical Pharmacology & Therapeutics (2006) 79 , 480–488; doi: 10.1016/j.clpt.2006.01.008