Women receiving bupropion SR were more likely to be abstinent at the end of a 6-week treatment trial if quit date occurred during the luteal phase of the menstrual cycle. This is consistent with Allen et al. (2008)
who studied outcome related to cycle phase at quit date in the absence of pharmacotherapy, and differs from findings utilizing nicotine replacement (Carpenter et al., 2008
; Franklin et al., 2008
). Also consistent with Allen et al (2008)
, relapse was more likely to occur in the same phase (follicular versus luteal) as the one in which a quit date occurred, which may be due to the rapidity of relapse for many.
Our results and those of Allen and colleagues are supported by evidence that gonadal hormones likely influence the reinforcing effect of drugs such as nicotine (Lynch, 2006
; Lynch et al., 2009
), and other recent data suggesting that brain dopaminergic functioning in reward areas is enhanced during the mid-follicular phase when estrogen is relatively unopposed by progesterone (Dreher et al., 2007
). Given that estrogen may sensitize women to the reinforcing properties of nicotine, lapse behavior during follicular phase may be more likely to progress to relapse (Allen et al., 2008
Bupropion attenuates the reinforcing properties of nicotine (Cousins et al., 2001
), and may contribute to quit success through reductions in negative affect and withdrawal symptoms (Hurt et al., 1997
; Lerman et al., 2002
; Shiffman et al., 2000
). The latter are generally greater during luteal phase (Allen et al., 2009
; Carpenter et al., 2006
) and the positive effect of bupropion on these symptoms may account, at least in part, for better outcome when quitting in luteal phase. However, it is currently unknown whether bupropion differentially affects outcomes by menstrual cycle phase and our study could not address this question without a placebo or behavioral treatment only group.
Results of the current study differ from two investigations utilizing nicotine replacement showing better outcomes when quit date occurs during follicular phase (Carpenter et al., 2008
; Franklin et al., 2008
). The reason for this difference is currently unclear. While it is known that estrogen increases the metabolism of intravenous nicotine in healthy volunteers (Benowitz et al., 2006
) and that faster metabolism of nicotine replacement has been associated with poor treatment outcomes (Lerman et al., 2006
; Schnoll et al., 2009
), it is unknown whether nicotine replacement alters estrogen-related increases in nicotine reinforcement during follicular phase. Studies assessing how various forms of nicotine affect metabolism and reinforcement across menstrual cycle phases would serve to clarify these outcomes.
Limitations in the current report are that women were not randomized to quit date by menstrual cycle phase, and phase was determined by retrospective daily menstrual cycle calendar, not by measurement of ovarian hormones. However, participants provided data for 3 menstrual cycles prior to enrollment and reported regular menstrual cycles during the trial, and self-reported cycle phase has demonstrated excellent convergence with biochemical confirmation of cycle phase (Allen et al., 2000
). The study did not have a placebo control group, which would have allowed a more direct causal link between quit status and menstrual phase. Moreover, this could have enabled us to determine if bupropion SR provided additional assistance with moderating variables like negative affect, particularly in luteal phase. As strengths, this is the only study examining menstrual cycle phase in women taking bupropion, a pharmacotherapy that has been shown to be an effective smoking cessation treatment for women.