The role of sex hormones in targeting stress-induced tobacco craving, stress-reactivity, and smoking with guanfacine among women who smoke

Women who smoke are particularly vulnerable to tobacco craving, smoking behaviors, and relapse in the context of stress when compared to men who smoke. One factor in this sex difference may be sex hormones, including estradiol and progesterone; however, smoking cessation medication trials often do not explore the impact of sex hormones on drug effects. This secondary analysis of a double-blind, placebo-controlled study explored the impact of levels of actual estradiol and progesterone on guanfacine, a noradrenergic α2a agonist, which attenuates stress-induced smoking behaviors in women. Women who smoke (n = 43) completed a stress induction laboratory paradigm followed by an ad-libitum smoking period. Assessment of tobacco craving, and stress-reactivity (via cortisol response) occurred pre- and post-stress induction. Results indicated that guanfacine attenuated stress-induced tobacco craving (F = 10.94, p = 0.02) and cortisol response (F = 14.23, p < 0.001); however, high levels of estradiol overrode guanfacine's effect on craving (F = 4.00, p = 0.05), cortisol response (F = 14.23, p < 0.001), and smoking during the ad-libitum period (F = 12.23, p = 0.001). Additionally, progesterone proved to be protective against tobacco craving and enhanced guanfacine's medication effect on craving (F = 5.57, p = 0.02). The present study found that sex hormones had a significant impact on medication effects in a smoking cessation trial and thus underscore the importance of examining the role of sex hormones in future medication trials.