Background: This study was conducted to determine sex/gender differences in smoke exposure and to quantify the role of potential predictors including puffing behaviors, nicotine dependence, and non-nicotinic factors. Methods: The Pennsylvania Adult Smoking Study (PASS) of 332 adult cigarette smokers utilized portable handheld topography devices to capture the smokers' profiles in a naturalistic environment. Sex/gender differences in salivary biomarkers were modeled using ANCOVA to account for measures of dependence (Fagerstrom Test for Nicotine Dependence, nicotine metabolite ratio [3-hydroxycotinine/cotinine]), and nondependence covariates including anthropomorphic factors and stress. The Blinder-Oaxaca method was used to decompose the sex/gender differences in nicotine uptake due to covariates. Results: Men had significantly higher cotinine levels (313.5 ng/mL vs. 255.8 ng/mL, p < 0.01), cotinine +3-hydroxycotinine levels, (0.0787 mol/L vs. 0.0675 mol/L, p = 0.01), puff volumes (52.95 mL vs. 44.77 mL, p < 0.01), and a lower nicotine metabolite ratio (0.396 vs. 0.475, p = 0.01) than women. The mean Fagerström Test for Nicotine Dependence score did not differ between men and women (p = 0.24). Women had a higher mean Hooked on Tobacco Checklist score than men (7.64 vs. 6.87, p < 0.01). In multivariate analysis, nicotine metabolite levels were not significantly different by sex. Decomposition results show that ten predictors can explain 83% of the sex/gender differences in cotinine uptake. Height was the greatest contributor to these differences, followed by average puff volume. Conclusion and Impact: The higher levels of nicotine metabolites in men, compared to women, can be explained by height, weight, puff volume, and nicotine metabolism.
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