Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone

Highlights Progesterone has sex-dependent effects on smoking measures in individuals with Tobacco Use Disorder. Higher conversion of progesterone to allopregnanolone (as indicated by the allopregnanolone:progesterone ratio) was associated with lower nicotine withdrawal in female but not male smokers during a brief abstinence. Higher conversion of progesterone to allopregnanolone was associated with lower ratings of confusion and marginally lower ratings of fatigue in female but not male smokers. Irrespective of sex, higher conversion of progesterone to allopregnanolone was associated with stronger “good effects” and weaker “bad effects” of nicotine during active smoking.