The Effects of Menstrual Cycle Hormones on Responses to Varenicline and Naltrexone Among Female Heavy Drinking Smokers

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. Short Summary: When the ratio of progesterone (P4) to estradiol (E2) is high, as we would expect in the luteal phase of the menstrual cycle, women may experience an added benefit of naltrexone compared with when P4/E2 ratios are low, as we would expect in the follicular phase.