The influence of gonadal hormones on conditioned fear extinction in healthy humans
Open accessAbstract
Recent rodent studies suggest that gonadal hormones influence extinction of conditioned fear. Here we investigated sex differences in, and the influence of estradiol and progesterone on, fear extinction in healthy humans. Men and women underwent a two-day paradigm in which fear conditioning and extinction learning took place on day 1 and extinction recall was tested on day 2. Visual cues were used as the conditioned stimuli and a mild electric shock was used as the unconditioned stimulus. Skin conductance was recorded throughout the experiment and used to measure conditioned responses (CRs). Blood samples were obtained from all women to measure estradiol and progesterone levels. We found that higher estradiol during extinction learning enhanced subsequent extinction recall but had no effects on fear acquisition or extinction learning itself. Sex differences were only observed during acquisition, with men exhibiting significantly higher CRs. After dividing women into low- and high-estradiol groups, men showed comparable extinction recall to high-estradiol women, and both of these groups showed higher extinction recall than low-estradiol women. Therefore, sex differences in extinction memory emerged only after taking into account women's estradiol levels. Lower estradiol may impair extinction consolidation in women. These findings could have practical applications in the treatment of anxiety disorders through cognitive and behavioral therapies.
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Extinction memory varies across the menstrual cycle in females.
“it varies across the menstrual cycle in females [225, 226]”
From Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory (2015) · cites this paper as [226]
Extinction memory is sexually dimorphic (better in males).
“extinction memory is sexually dimorphic (better in males)”
From Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory (2015) · cites this paper as [226]
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- Authors
- Milad, M. R., Zeidan, M. A., Contero, A., Pitman, R. K., Klibanski, A., Rauch, S. L., & Goldstein, J. M.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Brigham and Women's Hospital (US)
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 168
- Issue
- 3
- Pages
- 652-658
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC2881679
- OpenAlex
- W1980515611
- Cited by
- 320
- References
- 49
- Citations by year
- 2026: 12 · 2025: 20 · 2024: 17 · 2023: 10 · 2022: 21 · 2021: 29 · 2020: 17 · 2019: 26 · 2018: 22 · 2017: 17 · 2016: 23 · 2015: 29 · 2014: 32 · 2013: 21 · 2012: 14
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5p50mh082679-05)
- National Institute of Mental Health (P50-MH082679, K01MH080346)
- National Center for Research Resources (UL1RR025758)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- gonadal hormones, estradiol, progesterone, sex differences, fear conditioning, extinction memory consolidation, skin conductance, anxiety disorders
- MeSH terms
- Adolescent, Adult, Conditioning, Classical, Estradiol, Extinction, Psychological, Fear, Female, Humans, Male, Progesterone, Sex Factors, Young Adult
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