Differences in Combustible Cigarette Smoking-Related Biomarkers by Hormonal Contraceptive Use: An Exploratory Study

Introduction: Hormonal contraceptives (HCs), which contain synthetic forms of estrogen (ie, ethinyl estradiol) and/or progesterone (ie, progestin), are commonly used by women who smoke combustible cigarettes. Prior research has demonstrated that HCs containing ethinyl estradiol influence nicotine metabolism, though less is known about the role of progestins. We sought to examine the association between HC use and smoking-related biomarkers. Methods: This exploratory secondary-data analysis included females, ages of 18-45, who currently smoked classified into three groups based on current HC use: (1) combination HCs (C-HC; contains ethinyl estradiol and progestin), (2) progestin-only HCs (P-HC; contains progestin only with no ethinyl estradiol), and (3) no use of hormonal contraceptives (no-HC; no current use of ethinyl estradiol nor progestins). Group differences in expired carbon monoxide, urinary total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) (NNAL), nicotine metabolite ratio (NMR), total nicotine equivalent (TNE), and the ratio of TNE to cigarettes/day were assessed. Results: The C-HC (n = 22), P-HC (n = 67), and no-HC (n = 59) groups did not vary by age or race. Smoking-related biomarkers did not vary between the P-HC and no-HC groups. In adjusted analyses, the C-HC group had a lower TNE level (median = 41.22, interquartile range [IQR]: 32.10, 60.93) versus the P-HC group (median = 59.70, IQR = 44.89, 83.19; adjusted p-value = .006) and the no-HC group (median = 65.90, IQR = 57.55, 85.92; adjusted p-value = .010). Conclusion: Smoking-related biomarkers were comparable between those who used progestin-only hormonal contraceptives to those who did not use any hormonal contraceptive. In contrast, TNE varied in those who used hormonal contraceptives with ethinyl estradiol. Additional research is needed to replicate these observations.