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

Hoffmann S 1 , Gerhardt S 1 , Mühle C 1 , Reinhard I 1 , Reichert D 1 , Bach P 1 Show all authors , Boroumand-Jazi R 1 , Kuehner C 1 , Aguilera A 1 , Aslan A 1 , Bahr NS 1 , Belanger M 1 , Deeken F 1 , Ebrahimi C 1 , Fischbach PC 1 , Ganz M 1 , Garbusow M 1 , Großkopf CM 1 , Heigert M 1 , Hentschel A 1 , Karl D 1 , Liu S 1 , Mazza M 1 , Pelz P 1 , Pinger M 1 , Reichl M 1 , Riemerschmid C 1 , Rosenthal A 1 , Steffen J 1 , Strehle J 1 , Wedemeyer F 1 , Weiss F 1 , Wenzel J 1 , Wieder G 1 , Wieland A 1 , Zaiser J 1 , Zech HG 1 , Zimmermann S 1 , Kornhuber J 1 , Müller CP 1 , Sommer WH 1 , Spanagel R 1 , Banaschewski T 1 , Deserno L 1 , Ebner-Priemer UW 1 , Flor H 1 , Kirsch P 1 , Rietschel M 1 , Vollstädt-Klein S 1 , Walter H 1 , Meyer-Lindenberg A 1 , Rapp MA 1 , Witt S 1 , Smolka MN 1 , Heinz A 1 , Tost H 1 , Kiefer F 1 , Reichert M 1 , Lenz B 1 , ReCoDe Consortium 1

Affiliations 

  • 1 Department of Addictive Behavior and Addiction Medicine (Hoffmann, Gerhardt, Bach, Boroumand-Jazi, Aslan, Karl, Mazza, Reichl, Zaiser, Zimmermann, Vollstädt-Klein, Kiefer, Lenz), Department of Biostatistics (Hoffmann, Reinhard), Department of Psychiatry and Psychotherapy (Kuehner, Ganz, Ebner-Priemer, Meyer-Lindenberg, Tost, M. Reichert), Department of Clinical Psychology (Pinger, Weiss, Kirsch), Institute of Psychopharmacology (Müller, Sommer, Spanagel), Department of Child and Adolescent Psychiatry and Psychotherapy (Banaschewski), and Department of Genetic Epidemiology in Psychiatry (Rietschel, Witt), Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Mannheim Center for Translational Neurosciences, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany (Vollstädt-Klein, Meyer-Lindenberg, Kiefer, Lenz); Department of Psychiatry and Psychotherapy, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany (Mühle, Kornhuber, Müller); Mental mHealth Lab, Institute of Sports and Sports Science, Karlsruhe Institute of Technology, Karlsruhe, Germany (D. Reichert, Ebner-Priemer, M. Reichert); Department of eHealth and Sports Analytics, Faculty of Sports Science, Ruhr University Bochum, Bochum, Germany (D. Reichert, M. Reichert); Center for Information Services and High Performance Computing (Aguilera, Strehle, Wieder) and Department of Psychiatry and Psychotherapy (Belanger, Fischbach, Großkopf, Hentschel, Steffen, Zech, Deserno, Smolka), Technische Universität Dresden, Dresden, Germany; Department of Psychiatry and Neurosciences, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin (Bahr, Ebrahimi, Garbusow, Heigert, Liu, Pelz, Riemerschmid, Rosenthal, Wedemeyer, Wenzel, Walter, Heinz); Department of Social and Preventive Medicine, University of Potsdam, Potsdam, Germany (Deeken, Rapp); Center for Drug Research, Universiti Sains Malaysia, Penang, Malaysia (Müller); Bethanian Hospital for Psychiatry, Psychosomatics, and Psychotherapy, Greifswald, Germany (Sommer); Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University of Würzburg, Würzburg, Germany (Zech, Deserno); Deutsches Zentrum für psychische Gesundheit (German Center for Mental Health), Partner Site Mannheim-Heidelberg-Ulm (Sommer, Spanagel, Banaschewski, Ebner-Priemer, Flor, Kirsch, Rietschel, Meyer-Lindenberg, Tost, Kiefer), Partner Site Berlin-Potsdam (Rapp, Heinz); Department of Psychology, Clinical Psychology, and Psychotherapy, MSB Medical School Berlin (Garbusow)
Am J Psychiatry, 2024 May 01;181(5):445-456.
PMID: 38196336 DOI: 10.1176/appi.ajp.20230027

Abstract

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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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