Abstract

BackgroundSex differences in tobacco-related morbidity and mortality exist, with women experiencing more severe health consequences and greater difficulty with smoking cessation than men. One factor that likely contributes to these sex differences is menstrual cycle phase and associated neural and cognitive changes associated with ovarian hormone fluctuations across the menstrual cycle. Previously, we showed that naturally cycling, cigarette-dependent women in the follicular phase of their menstrual cycle showed greater reward-related neural activity and greater craving during smoking cue exposure. To better understand our results and the observed sex differences in smoking behavior and relapse, we explored potential menstrual cycle phase differences in resting-state functional connectivity (rsFC) in naturally cycling, cigarette-dependent women. Understanding how menstrual cycle phase affects neural processes, cognition, and behavior is a critical step in developing more efficacious treatments and in selecting the best treatment option based on a patient’s needs.MethodsResting-state functional connectivity analyses were used to examine connectivity strength differences between naturally cycling, premenopausal, cigarette-dependent women who were in the follicular phase (FPs; n = 22) and those in the luteal phase (LPs, n = 16) of their menstrual cycle. We also explored associations between connectivity strength and attentional bias to smoking cues.ResultsCompared with LPs, FPs showed decreased rsFC between the dorsal anterior cingulate cortex (dACC) and the subgenual anterior cingulate cortex, medial orbitofrontal cortex (mOFC), and ventral striatum. Among FPs, rsFC strength between the dACC and the bilateral dorsolateral prefrontal cortex (DLPFC), the bilateral dorsal striatum, and the left temporal gyrus was inversely correlated with attentional bias to smoking cues.ConclusionsThis is the first study to explore menstrual cycle phase differences in rsFC among cigarette-dependent women, and results suggest that FPs show differences in rsFC underlying cognitive control, which could place them at greater risk for continued smoking and relapse. These findings provide new insights toward individualized treatment strategies.Electronic supplementary materialThe online version of this article (doi:10.1186/s13293-016-0078-6) contains supplementary material, which is available to authorized users.

Highlights

  • Sex differences in tobacco-related morbidity and mortality exist, with women experiencing more severe health consequences and greater difficulty with smoking cessation than men

  • Resting-state functional connectivity analyses Analyses examining menstrual cycle phase differences in resting-state connectivity in cigarette-dependent women revealed no significant differences in resting-state functional connectivity (rsFC) of the medial orbitofrontal cortex (mOFC) between follicular phase (FPs) and luteal phase (LPs)

  • For the dorsal anterior cingulate cortex (dACC), FPs showed decreased rsFC between the dACC and a large cluster spanning the left subgenual anterior cingulate cortex, mOFC, and ventral striatum compared with LPs (Fig. 1)

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Summary

Introduction

Sex differences in tobacco-related morbidity and mortality exist, with women experiencing more severe health consequences and greater difficulty with smoking cessation than men. Preclinical and clinical research suggests that ovarian hormones (i.e., estradiol and progesterone), which fluctuate over the course of the menstrual cycle [9], influence smoking behavior, and relapse vulnerability. Female smokers who were administered exogenous progesterone exhibited decreased positive subjective effects of cigarette smoking [16] and reduced urges to smoke [16, 17] These studies suggest that estradiol enhances reward and vulnerability to continued smoking and relapse in women; whereas, progesterone may protect against smoking-related behaviors and relapse [15, 18, 19], and as such, the fluctuation in ovarian hormones that occurs across the menstrual cycle may contribute to sex differences in smoking behavior and relapse

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