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.

Consistency of the "central vein sign" in chronic multiple sclerosis lesions.

BACKGROUND: In recent years, there has been an increasing interest in the central vein sign (CVS) as a new imaging marker and previous cross-sectional studies demonstrated that the CVS has the potential to discriminate multiple sclerosis (MS) lesions from non-MS lesions. The aim of this study was to investigate the consistency of the CVS in a longitudinal magnetic resonance imaging (MRI) data set. METHODS: 3T MRI datasets from seventy-one people with MS acquired at baseline and after 12 months-follow-up were analyzed. Chronic lesions were identified on fluid-attenuated inversion recovery (FLAIR) images. Co-registered susceptibility-weighted/FLAIR images were analyzed for the presence of a CVS at baseline and follow-up. RESULTS: A total of 183 chronic lesions were included in the final analysis. At baseline MRI, a CVS was detectable in 141/183 (77%) lesions. Overall, the CVS was consistent in 114/141 (81%) lesions (Cohen's kappa = 0.46, standard error = 0.07). CONCLUSION: The CVS is a rather stable feature in chronic MS lesions and therefore represents a robust imaging marker that could increase the specificity of MRI in MS.