Hormonal milieu influences whole-brain structural dynamics across the menstrual cycle using dense sampling in multiple individuals

Carina Heller^#^{1

2

3

4

5

6}, Daniel Güllmar^#⁷, Lejla Colic^{8

9

10}, Laura Pritschet¹¹, Martin Gell^{12

13

14}, Nooshin Javaheripour⁸, Feliberto de la Cruz¹⁵, Philine Rojczyk^{16

17}, Carina J Koeppel^{9

18}, Bart Larsen^{12

19

20}, Habib Ganjgahi^{21

22}, Frederik J Lange²³, Ann-Christine Buck²⁴, Tim L Jesgarzewsky²⁴, Robert Dahnke²⁵, Michael Kiehntopf²⁶, Emily G Jacobs^{27

28}, Zora Kikinis¹⁷, Martin Walter^{8

9

10}, Ilona Croy^{9

10

24

29}, Christian Gaser^{8

9

10

25}

Affiliations

¹ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany. carina.heller@uni-jena.de.
² Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA. carina.heller@uni-jena.de.
³ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. carina.heller@uni-jena.de.
⁴ Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA. carina.heller@uni-jena.de.
⁵ German Center for Mental Health (DZPG), Jena-Magdeburg-Halle, Germany. carina.heller@uni-jena.de.
⁶ Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany. carina.heller@uni-jena.de.
⁷ Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany.
⁸ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
⁹ German Center for Mental Health (DZPG), Jena-Magdeburg-Halle, Germany.
¹⁰ Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany.
¹¹ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
¹² Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
¹³ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
¹⁴ Institute of Neuroscience and Medicine (INM-7: Brain & Behaviour), Research Centre Jülich, Jülich, Germany.
¹⁵ Lab for Autonomic Neuroscience, Imaging and Cognition (LANIC), Department of Psychosomatic Medicine and Psychotherapy, Jena University Hospital, Jena, Germany.
¹⁶ cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
¹⁷ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁸ Department of Psychiatry and Neurosciences, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁹ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
²⁰ Institute of Child Development, Univeristy of Minnesota, Minneapolis, MN, USA.
²¹ Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
²² Department of Statistics, University of Oxford, Oxford, UK.
²³ Oxford University Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
²⁴ Department of Clinical Psychology, Friedrich Schiller University Jena, Jena, Germany.
²⁵ Department of Neurology, Jena University Hospital, Jena, Germany.
²⁶ Institute of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany.
²⁷ Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
²⁸ Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, USA.
²⁹ Department of Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

^# Contributed equally.

PMID: 41006668
DOI: 10.1038/s41593-025-02066-2

Hormonal milieu influences whole-brain structural dynamics across the menstrual cycle using dense sampling in multiple individuals

Carina Heller et al. Nat Neurosci. 2025.

. 2025 Sep 26.

doi: 10.1038/s41593-025-02066-2. Online ahead of print.

Authors

Affiliations

¹ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany. carina.heller@uni-jena.de.
² Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA. carina.heller@uni-jena.de.
³ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. carina.heller@uni-jena.de.
⁴ Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA. carina.heller@uni-jena.de.
⁵ German Center for Mental Health (DZPG), Jena-Magdeburg-Halle, Germany. carina.heller@uni-jena.de.
⁶ Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany. carina.heller@uni-jena.de.
⁷ Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena, Germany.
⁸ Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.
⁹ German Center for Mental Health (DZPG), Jena-Magdeburg-Halle, Germany.
¹⁰ Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Jena-Magdeburg-Halle, Germany.
¹¹ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
¹² Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA.
¹³ Department of Psychiatry and Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA.
¹⁴ Institute of Neuroscience and Medicine (INM-7: Brain & Behaviour), Research Centre Jülich, Jülich, Germany.
¹⁵ Lab for Autonomic Neuroscience, Imaging and Cognition (LANIC), Department of Psychosomatic Medicine and Psychotherapy, Jena University Hospital, Jena, Germany.
¹⁶ cBRAIN, Department of Child and Adolescent Psychiatry, Psychosomatics, and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany.
¹⁷ Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
¹⁸ Department of Psychiatry and Neurosciences, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁹ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
²⁰ Institute of Child Development, Univeristy of Minnesota, Minneapolis, MN, USA.
²¹ Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, Oxford, UK.
²² Department of Statistics, University of Oxford, Oxford, UK.
²³ Oxford University Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
²⁴ Department of Clinical Psychology, Friedrich Schiller University Jena, Jena, Germany.
²⁵ Department of Neurology, Jena University Hospital, Jena, Germany.
²⁶ Institute of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany.
²⁷ Department of Psychological and Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
²⁸ Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA, USA.
²⁹ Department of Psychotherapy and Psychosomatic Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

^# Contributed equally.

PMID: 41006668
DOI: 10.1038/s41593-025-02066-2

Abstract

Gonadal hormone receptors are widely distributed across the brain, yet their influence on brain structure remains understudied. Here, using precision imaging, we examined four females, including one with endometriosis and one using oral contraceptives (OC), across a monthly period. Whole-brain analyses revealed spatiotemporal patterns of brain volume changes, with substantial variations across the monthly period. In typical cycles, spatiotemporal patterns were associated with serum progesterone levels, while in cycles with endometriosis and during OC intake, patterns were associated with serum estradiol levels. The volume changes were widely distributed rather than region-specific, suggesting a widespread but coordinated influence of hormonal fluctuations. These findings underscore the importance of considering diverse hormonal milieus beyond typical menstrual cycles in understanding structural brain dynamics and suggest that hormonal rhythms may drive widespread structural brain changes.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

1. Fehring, R. J., Schneider, M. & Raviele, K. Variability in the phases of the menstrual cycle. J. Obstet. Gynecol. Neonatal Nurs. 35, 376–384 (2006). - PubMed - DOI
1. Roos, J. et al. Monitoring the menstrual cycle: comparison of urinary and serum reproductive hormones referenced to true ovulation. Eur. J. Contracept. Reprod. Health Care 20, 438–450 (2015). - PubMed - DOI
1. Abraham, G. E., Odell, W. D., Swerdloff, R. S. & Hopper, K. Simultaneous radioimmunoassay of plasma FSH, LH, progesterone, 17-hydroxyprogesterone, and estradiol-17β during the menstrual cycle. J. Clin. Endocrinol. Metab. 34, 312–318 (1972). - PubMed - DOI
1. Österlund, M. K., Gustafsson, J. Å., Keller, E. & Hurd, Y. L. Estrogen receptor β (ERβ) messenger ribonucleic acid (mRNA) expression within the human forebrain: distinct distribution pattern to ERα mRNA. J. Clin. Endocrinol. Metab. 85, 3840–3846 (2000). - PubMed
1. Brinton, R. D. et al. Progesterone receptors: form and function in brain. Front. Neuroendocrinol. 29, 313 (2008). - PubMed - PMC - DOI

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Hormonal milieu influences whole-brain structural dynamics across the menstrual cycle using dense sampling in multiple individuals

Affiliations

Hormonal milieu influences whole-brain structural dynamics across the menstrual cycle using dense sampling in multiple individuals

Authors

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources