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

Nicotine Tob Res. 2015 Apr;17(4):398-406. doi: 10.1093/ntr/ntu262.


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: NCT00664755.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Benzazepines / administration & dosage*
  • Estradiol / blood
  • Estradiol / metabolism*
  • Female
  • Humans
  • Menstrual Cycle*
  • Middle Aged
  • Nicotine / administration & dosage*
  • Nicotinic Agonists / administration & dosage*
  • Progesterone / blood
  • Progesterone / metabolism*
  • Quinoxalines / administration & dosage*
  • Smoking Cessation / methods*
  • Transdermal Patch
  • Treatment Outcome
  • Varenicline
  • Women's Health


  • Benzazepines
  • Nicotinic Agonists
  • Quinoxalines
  • Progesterone
  • Estradiol
  • Nicotine
  • Varenicline

Associated data