Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.
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Hoffmann Sabine, Gerhardt Sarah, Mühle Christiane, Reinhard Iris, Reichert Dominic, Bach Patrick, Boroumand-Jazi Rafat, Kuehner Christine, Aguilera Alvaro, Aslan Acelya, Bahr Nadja S, Belanger Matthew, Deeken Friederike, Ebrahimi Claudia, Fischbach Pascale C, Ganz Marvin, Garbusow Maria, Großkopf Charlotte M, Heigert Marie, Hentschel Angela, Karl Damian, Liu Shuyan, Mazza Massimiliano, Pelz Patricia, Pinger Mathieu, Reichl Matthias, Riemerschmid Carlotta, Rosenthal Annika, Steffen Johannes, Strehle Jens, Wedemeyer Friederike, Weiss Franziska, Wenzel Julia, Wieder Gesine, Wieland Alfred, Zaiser Judith, Zech Hilmar G, Zimmermann Sina, Kornhuber Johannes, Müller Christian P, Sommer Wolfgang H, Spanagel Rainer, Banaschewski Tobias, Deserno Lorenz, Ebner-Priemer Ulrich W, Flor Herta, Kirsch Peter, Rietschel Marcella, Vollstädt-Klein Sabine, Walter Henrik, Meyer-Lindenberg Andreas, Rapp Michael A, Witt Stephanie, Smolka Michael N, Heinz Andreas, Tost Heike, Kiefer Falk, Reichert Markus, Lenz Bernd, ReCoDe Consortium
Аннотация
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.