Effect of Smoking on Stress-Induced Allopregnanolone Response in Women by Menstrual Phase

Cigarette smoking persists as the leading cause of preventable morbidity and mortality. Thus, finding ways to maximize quitting behavior is critical. Women have a more difficult time achieving smoking abstinence than men. The risk for smoking relapse appears to vary by menstrual phase such that the follicular phase is associated with greater risk compared to the luteal phase. Women are also more likely to smoke in response to stressful stimuli than men. Allopregnanolone (ALLO) is a stress-reducing neuroactive steroid that is primarily metabolized from the sex hormone progesterone and, therefore, varies by menstrual phase in women. Recent preclinical literature has indicated that ALLO may protect against drug abuse behaviors. Unfortunately, ALLO remains largely unexplored in clinical samples containing women.

In this study we aim to characterize the effect of smoking on stress-induced ALLO response in women by menstrual phase. To achieve this goal, we will recruit a sample of premenopausal women who smoke (n=30) and do not smoke (n=30) to participate in a controlled cross-over study. All participants will complete two four-hour lab sessions timed to occur in the Follicular (F; low ALLO) and Luteal (L; high ALLO) menstrual phases. Each lab session will contain an acute stressor along with a timed series of assessments including blood samples (for ALLO measurement) and self-report of mood and perceived stress.