Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.

OBJECTIVE: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. METHODS: In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. RESULTS: Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: -61, 95% CI=-105.492, -16.095; -78, 95% CI=-119.322, -37.039; and -71, 95% CI=-114.568, -27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. CONCLUSIONS: These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.

Temporal discounting and smoking cessation: choice consistency predicts nicotine abstinence in treatment-seeking smokers.

INTRODUCTION: Smokers discount delayed rewards steeper than non-smokers or ex-smokers, possibly due to neuropharmacological effects of tobacco on brain circuitry, or lower abstinence rates in smokers with steep discounting. To delineate both theories from each other, we tested if temporal discounting, choice inconsistency, and related brain activity in treatment-seeking smokers (1) are higher compared to non-smokers, (2) decrease after smoking cessation, and (3) predict relapse. METHODS: At T1, 44 dependent smokers, 29 non-smokers, and 30 occasional smokers underwent fMRI while performing an intertemporal choice task. Smokers were measured before and 21 days after cessation if abstinent from nicotine. In total, 27 smokers, 28 non-smokers, and 29 occasional smokers were scanned again at T2. Discounting rate k and inconsistency var(k) were estimated with Bayesian analysis. RESULTS: First, k and var(k) in smokers in treatment were not higher than in non-smokers or occasional smokers. Second, neither k nor var(k) changed after smoking cessation. Third, k did not predict relapse, but high var(k) was associated with relapse during treatment and over 6 months. Brain activity in valuation and decision networks did not significantly differ between groups and conditions. CONCLUSION: Our data from treatment-seeking smokers do not support the pharmacological hypothesis of pronounced reversible changes in discounting behavior and brain activity, possibly due to limited power. Behavioral data rather suggest that differences between current and ex-smokers might be due to selection. The association of choice consistency and treatment outcome possibly links consistent intertemporal decisions to remaining abstinent.