Increasing progesterone levels are associated with smoking abstinence among free-cycling women smokers who receive brief pharmacotherapy

Abstract

Introduction: Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature.

Methods: Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly.

Results: Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females.

Conclusions: This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medication-based treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed.

Trial registration: ClinicalTrials.gov NCT00664755.

© The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Schematic of the timing of hormone and smoking abstinence assessments. Panel A is a diagrammatic overview of the 5-week period during which participants received pharmacotherapy, either varenicline tablets and placebo patches or placebo tablets and nicotine patches. The figure shows that 1-week of medication titration precedes the quit date and the ensuing 4 weeks of treatment. Asterisks and number signs indicate when plasma samples (for hormone level determination) and smoking abstinence assessments were performed, respectively. Panel B indicates how the static and change in hormone levels were determined. Briefly, for any given week Y, smoking abstinence was assessed retrospectively at visit C. Static hormone level for week Y was obtained at the beginning of the week, during visit B. Change in hormone level for week Y was the difference between the level obtained at visits A and B (visit B-visit A). Thus, a positive (or negative) change value represented an increase (or decrease) in either estradiol or progesterone during the week (X) preceding week Y.

Figure 2.

Participant estradiol (open circles) and progesterone (solid squares) levels during the course of study procedures; participant data is anchored to self-report onset of menses (center of x-axis denoted as day 0). The solid and dashed lines are LOESS regression curves that characterize the change in progesterone and estradiol levels, respectively, across participant menstrual cycles.