Sex-based and hormonal contraception effects on the metabolism of nicotine among adolescent tobacco-dependent smokers.

Variations in nicotine metabolism influence smoking patterns. Differences between sexes or related to sex hormones may affect nicotine metabolism. Because smoking initiation starts during adolescence, observations gathered from adolescent smokers might broaden our understanding of such sex-based differences. We tested the hypothesis that nicotine metabolism--as indexed primarily by the ratio of trans-3'-hydroxycotinine (3HC) to cotinine--is more rapid among adolescent girl smokers compared with boys and that regular use of hormonal contraceptives influences nicotine and cotinine metabolism. We also hypothesized that more rapid nicotine metabolism is associated with higher nicotine dependence as indexed by smoking frequency and morning urgency. Plasma samples of nicotine, cotinine, and 3HC concentrations were obtained from 120 adolescents (36 boys). Plasma nicotine and cotinine concentrations were similar in boys and girls. Median plasma 3HC concentrations were 44.45 ng/ml for girls versus 35.74 ng/ml for boys (p = .025), and median plasma 3HC-cotinine ratios were significantly higher in girls than in boys (0.317 vs. 0.253, p = .025). After stratifying girls into two groups based on use versus nonuse of hormonal contraception, plasma 3HC-cotinine ratios in girls using hormonal contraception (0.47) were substantially higher (p<.0001) than in boys (0.25) and were significantly higher than in girls not using hormonal contraception (0.28). Controlling for cigarettes smoked per day, ethnicity, and age did not modify these results. Although plasma nicotine, cotinine, or 3HC concentrations were significantly lower in less dependent adolescent smokers, nicotine and cotinine metabolite ratios were similar. This study showed that hormonal contraception in adolescent girls may accelerate cotinine metabolism, an effect likely related to induction of cytochrome P450 2A6 and independent of ethnicity and cigarette consumption. Prospective controlled studies are needed to further evaluate the role of hormonal contraception in patterns of adolescent smoking and nicotine metabolism.