Aims Women often experience poorer smoking cessation outcomes in comparison to men. Menstrual cycle phase and sex hormones may influence smoking behavior and alter response to opioid antagonist medications. Less is known about the effects of sex hormones in response to pharmacotherapy for female heavy drinking smokers. Methods This study is a secondary analysis of premenopausal female heavy drinking smokers who completed a 12-week randomized clinical trial comparing varenicline plus placebo versus varenicline plus naltrexone for smoking cessation and drinking reduction. Participants (n = 26; total observations = 66) provided saliva samples for assays of progesterone (P4) and estradiol (E2) post-randomization at Weeks 4, 8 and 12. We examined the effects of P4/E2 ratio and medication on smoking and drinking outcomes. Results For drinking outcomes, there was a significant interaction for percent days abstinent (b = 0.017, P = 0.05), suggesting that greater P4/E2 ratio is associated with greater percent days abstinent for women assigned to the varenicline plus naltrexone condition. There were no interaction effects for the remaining drinking outcomes (P’s ≥ 0.12). Results found no significant interaction effect of P4/E2 ratio and medication on smoking abstinence (P = 0.19). Conclusion Our results imply that when women show a greater P4/E2 ratio, typically observed during the luteal phase of the menstrual cycle, they experience an added benefit of naltrexone, versus placebo, for drinking outcomes as shown by greater percent days abstinent. Additional studies in larger samples are warranted as sex hormones offer important information above and beyond comparing women versus men.

中文翻译：

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月经周期激素对女性大量饮酒吸烟者对伐尼克兰和纳曲酮反应的影响

目标 与男性相比，女性的戒烟效果通常较差。月经周期阶段和性激素可能会影响吸烟行为并改变对阿片拮抗剂药物的反应。关于性激素对女性大量饮酒吸烟者的药物治疗反应的影响知之甚少。方法 本研究是对完成一项为期 12 周的随机临床试验的绝经前女性大量饮酒吸烟者的二次分析，该试验比较了伐尼克兰加安慰剂与伐尼克兰加纳曲酮在戒烟和减少饮酒方面的效果。参与者（n = 26；总观察值 = 66）在第 4、8 和 12 周随机化后提供唾液样本，用于测定孕酮 (P4) 和雌二醇 (E2)。我们检查了 P4/E2 比率和药物对吸烟的影响和饮酒结果。结果 对于饮酒结果，戒断天数百分比有显着的交互作用（b = 0.017，P = 0.05），这表明较大的 P4/E2 比率与分配到伐尼克兰加纳曲酮条件的女性的戒断天数较高有关。其余饮酒结果没有交互作用（P ≥ 0.12）。结果发现P4/E2比值和药物对戒烟没有显着的交互作用（P = 0.19）。结论 我们的结果表明，当女性表现出更高的 P4/E2 比率（通常在月经周期的黄体期观察到）时，与安慰剂相比，纳曲酮对饮酒结果的额外益处，如更大的禁欲天数所示。有必要对更大样本进行进一步的研究，因为性激素提供的重要信息超出了女性与男性的比较。