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

Abstract

Introduction: Hormonal contraceptives (HCs), which contain synthetic forms of estrogen (i.e., ethinyl estradiol) and/or progesterone (i.e., 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=0.006) and the no-HC group (median=65.90, IQR=57.55, 85.92; adjusted p-value=0.010).

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.

Implications: This exploratory study is the first to examine combustible cigarette smoking-related biomarkers by use of hormonal contraceptives with and without ethinyl estradiol as compared to no hormonal contraceptive use. In brief, biomarkers in those using hormonal contraceptives without ethinyl estradiol (i.e., progestin-only) were comparable to biomarkers in those not using any hormonal contraceptives. In contrast, those using hormonal contraceptives with ethinyl estradiol had significantly lower total nicotine equivalent even after adjusting for race. These observations indicate that progestin-only hormonal contraceptives use may not alter smoking-related biomarkers whereas hormonal contraceptives with ethinyl estradiol may influence these biomarkers.