Peltier MacKenzie R, McKee Sherry A
Department of Psychiatry, Yale School of Medicine, 2 Church Street South, Suite 109, Yale School of Medicine, New Haven, CT 06519, USA.
Psychology Service, VA Connecticut Healthcare System West Haven, CT 06516, USA.
Addict Neurosci. 2023 Sep;7. doi: 10.1016/j.addicn.2023.100084. Epub 2023 Apr 3.
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 ( = 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 ( = 10.94, = 0.02) and cortisol response ( = 14.23, < 0.001); however, high levels of estradiol overrode guanfacine's effect on craving ( = 4.00, = 0.05), cortisol response ( = 14.23, < 0.001), and smoking during the ad-libitum period ( = 12.23, = 0.001). Additionally, progesterone proved to be protective against tobacco craving and enhanced guanfacine's medication effect on craving ( = 5.57, = 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.
与吸烟男性相比，吸烟女性在压力环境下特别容易产生烟草渴望、出现吸烟行为并复吸。这种性别差异的一个因素可能是性激素，包括雌二醇和孕酮；然而，戒烟药物试验通常不会探讨性激素对药物效果的影响。这项对一项双盲、安慰剂对照研究的二次分析，探讨了实际雌二醇和孕酮水平对胍法辛（一种去甲肾上腺素能α2a激动剂）的影响，该药物可减轻女性压力诱导的吸烟行为。43名吸烟女性完成了压力诱导实验室范式，随后是自由吸烟期。在压力诱导前后对烟草渴望和应激反应性（通过皮质醇反应）进行了评估。结果表明，胍法辛减轻了压力诱导的烟草渴望（F = 10.94，p = 0.02）和皮质醇反应（F = 14.23，p < 0.001）；然而，高水平的雌二醇抵消了胍法辛对渴望（F = 4.00，p = 0.05）、皮质醇反应（F = 14.23，p < 0.001）以及自由吸烟期吸烟量（F = 12.23，p = 0.001）的影响。此外，孕酮被证明对烟草渴望有保护作用，并增强了胍法辛对渴望的药物效果（F = 5.57，p = 0.02）。本研究发现，性激素在戒烟试验中对药物效果有显著影响，因此强调了在未来药物试验中研究性激素作用的重要性。
