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Published Online: 10 January 2024

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

Sabine Hoffmann, M.A., Sarah Gerhardt, M.Sc., Christiane Mühle, Ph.D., Iris Reinhard, Ph.D., Dominic Reichert, M.Sc., Patrick Bach, M.D., Ph.D., Rafat Boroumand-Jazi, M.Sc., Show All , Christine Kuehner, Ph.D., Alvaro Aguilera, Dipl.Inf., Acelya Aslan, M.A., Nadja S. Bahr, M.Sc., Matthew Belanger, M.Sc., Friederike Deeken, Ph.D., Claudia Ebrahimi, Dr.rer.nat., Pascale C. Fischbach, M.Sc., Marvin Ganz, M.Sc., Maria Garbusow, Dr.rer.nat., Charlotte M. Großkopf, M.D., Marie Heigert, M.Sc., Angela Hentschel, M.Sc., Damian Karl, M.Sc., Shuyan Liu, Ph.D., Massimiliano Mazza, M.D., Patricia Pelz, Dr.rer.medic., Mathieu Pinger, M.Sc., Matthias Reichl, M.D., Carlotta Riemerschmid, M.Sc., Annika Rosenthal, M.Sc., Johannes Steffen, M.Sc., Jens Strehle, Dipl.Math., Friederike Wedemeyer, M.D., Franziska Weiss, Ph.D., Julia Wenzel, Dipl.Psych., Gesine Wieder, Dr.rer.nat., Alfred Wieland, M.Sc., Judith Zaiser, M.Sc., Hilmar G. Zech, M.Sc., Sina Zimmermann, M.Sc., Johannes Kornhuber, M.D., Christian P. Müller, Ph.D., Wolfgang H. Sommer, M.D., Ph.D., Rainer Spanagel, Ph.D., Tobias Banaschewski, M.D., Ph.D., Lorenz Deserno, M.D., Ulrich W. Ebner-Priemer, Ph.D., Herta Flor, Ph.D., Peter Kirsch, Ph.D., Marcella Rietschel, M.D., Sabine Vollstädt-Klein, Ph.D., Henrik Walter, M.D., Ph.D., Andreas Meyer-Lindenberg, M.D., Ph.D., Michael A. Rapp, M.D., Ph.D., Stephanie Witt, Ph.D., Michael N. Smolka, M.D., Andreas Heinz, M.D., Ph.D., Heike Tost, M.D., Ph.D., Falk Kiefer, M.D., Markus Reichert, Ph.D., and Bernd Lenz, M.D. bernd.lenz@zi-mannheim.de ReCoDe ConsortiumAuthors Info & Affiliations
Publication: American Journal of Psychiatry

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.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 445 - 456
PubMed: 38196336

History

Received: 10 January 2023
Revision received: 9 June 2023
Accepted: 5 July 2023
Published online: 10 January 2024
Published in print: May 01, 2024

Keywords

  1. Alcohol Use Disorder
  2. Substance-Related and Addictive Disorders
  3. Addiction Psychiatry
  4. Progesterone:Estradiol
  5. Ecological Momentary Assessment

Authors

Details

Notes

Send correspondence to Dr. Lenz (bernd.lenz@zi-mannheim.de).

Author Contributions

Dr. M. Reichert and Dr. Lenz contributed equally to this work.

Funding Information

The project was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), project number 402170461 (https://gepris.dfg.de/gepris/projekt/402170461, TRR 265, Heinz et al. 2020). Dr. Mühle is a member of the research training group 2162 “Neurodevelopment and Vulnerability of the Central Nervous System” of the DFG (GRK2162/270949263).Dr. Banaschewski has served as an adviser or consultant for Eye Level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda; he has received conference support or speaking fees from Janssen, Medice, and Takeda; and he receives royalties from CIP Medien, Hogrefe, Kohlhammer, and Oxford University Press. Dr. Ebner-Priemer has served as a consultant for Boehringer Ingelheim, including UE-P reports consultancy, and he has received a speaker honorarium from Angelini Pharma. Dr. Meyer-Lindenberg has served as a consultant for Daimler und Benz Stiftung, EPFL Brain Mind Institute, Fondation FondaMental, Hector Stiftung II, Invisio, Janssen-Cilag GmbH, Lundbeck A/S, Lundbeckfonden, Lundbeck International Neuroscience Foundation, MedinCell, Neurotorium, The LOOP Zürich, University Medical Center Utrecht, University of Washington, Verein für Mentales Wohlbefinden, and von Behring-Röntgen-Stiftung; he has received speaking fees from Ärztekammer Nordrhein, Caritas, Clarivate, Dt. Gesellschaft für Neurowissenschaftliche Begutachtung, Gentner Verlag, Landesärztekammer Baden-Württemberg, LWL Bochum, Northwell Health, Ruhr University Bochum, Pennsylvania State University, the Society of Biological Psychiatry, University Prague, and Vitos Klinik Rheingau, and he has received editorial and/or author fees from the American Association for the Advancement of Science, the European College of Neuropsychopharmacology, Servier International, and Thieme Verlag. The other authors report no financial relationships with commercial interests.

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