Progesterone selectively increases amygdala reactivity in women
Open accessAbstract
The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of gamma-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.
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Progesterone and its neurosteroid metabolites, which rise and begin to fluctuate during puberty, upregulate social behaviors, increase social threat monitoring, and regulate the HPA axis.
“Progesterone and its neurosteroid metabolites, which rise and begin to fluctuate during puberty, upregulate social behaviors [40], increase social threat monitoring [41,42], and regulate the HPA axis [43].”
From HPA axis response and psychosocial stress as interactive predictors of suicidal ideation and behavior in adolescent females: a multilevel diathesis-stress framework (2018) · cites this paper as [42]
The Results report that progesterone increased amygdala responses during a task using angry and fearful faces, which is relevant to social threat processing. But the Behavioral task section says the contrast measures a general response to salient stimuli, not an emotion-specific effect; the study did not measure social threat monitoring itself. The citation is attached to that clause, not to the separate claims about puberty, social behavior, or the HPA axis. (LLM, conf=0.83)
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References 77 · Cited by 273
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- [12]12. Smith SS, Gong QH, Hsu FC, Markowitz RS, ffrench-Mullen JM, Li X. GABA(A) receptor alpha4 subunit suppression prevents with- drawal properties of an endogenous steroid. Nature 1998; 392: 926-930.
- Authors
- van Wingen, G. A., van Broekhoven, F., Verkes, R. J., Petersson, K. M., Bäckström, T., Buitelaar, J. K., & Fernández, G.
- Affiliations
- Radboud University Nijmegen (NL)
- University Hospital of Umeå (SE)
- Venue
- Molecular Psychiatry
- Published
- 2007-06-19
- Volume
- 13
- Issue
- 3
- Pages
- 325-333
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2112445335
- Semantic Scholar
- 4e14e1b1516ae0bbd706a39778623452f03929e9
- Cited by
- 273
- References
- 77
- Citations by year
- 2026: 7 · 2025: 19 · 2024: 18 · 2023: 11 · 2022: 14 · 2021: 16 · 2020: 13 · 2019: 14 · 2018: 21 · 2017: 15 · 2016: 16 · 2015: 16 · 2014: 17 · 2013: 23 · 2012: 14
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Max Planck Digital Library (submittedVersion, other-oa)
- Pure Amsterdam UMC (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- Radboud Universiteit
- Vetenskapsrådet
- Radboud Universitair Medisch Centrum
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- progesterone, allopregnanolone, pregnanolone, neurosteroids, amygdala reactivity, anxiety, mood, functional connectivity, women, follicular phase, GABAergic inhibition
- MeSH terms
- Adult, Amygdala, Brain Mapping, Double-Blind Method, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Menstrual Cycle, Oxygen, Photic Stimulation, Progestins, Progesterone, Psychomotor Performance, Radioimmunoassay, Randomized Controlled Trials as Topic, Cross-Over Studies
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