ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Impact of exogenous estradiol on task-based and resting-state neural signature during and after fear extinction in healthy women.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Hormonal contraceptives and the brain: A systematic review on 60 years of neuroimaging, EEG, and biochemical studies in humans and animals.Frontiers in neuroendocrinology · 2023Pooled it
- Hormonal mechanisms of women's risk in the face of traumatic stress.Proceedings of the National Academy of Sciences of the United States of America · 2025Trial
- Effects of exogenous oxytocin and estradiol on resting-state functional connectivity in women and men.Scientific reports · 2023Trial
- Lasting effects of oral contraceptives on fear responses to a safe context.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- A systematic review of spontaneous recovery in human fear conditioning.Frontiers in behavioral neuroscience · 2026Review
- Early menopause is associated with reduced global brain activity.bioRxiv : the preprint server for biology · 2025Article
- Dimensional Affective Sensitivity to Hormones across the Menstrual Cycle (DASH-MC): A transdiagnostic framework for ovarian steroid influences on psychopathology.Molecular psychiatry · 2025Review
- The Impacts of Sex Differences and Sex Hormones on Fear Extinction.Current topics in behavioral neurosciences · 2023Article
- Morphologic alterations of the fear circuitry: the role of sex hormones and oral contraceptives.Frontiers in endocrinology · 2023Article
- Revisiting sex differences in the acquisition and extinction of threat conditioning in humans.Learning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- Estrogen, Cognitive Performance, and Functional Imaging Studies: What Are We Missing About Neuroprotection?Frontiers in cellular neuroscience · 2022Review
- Using Translational Models of Fear Conditioning to Uncover Sex-Linked Factors Related to PTSD Risk.Journal of psychiatry and brain science · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Fluctuations of endogenous estrogen modulates fear extinction, but the influence of exogenous estradiol is less studied. Moreover, little focus has been placed on the impact of estradiol on broad network connectivity beyond the fear extinction circuit. Here, we examined the effect of acute exogenous estradiol administration on fear extinction-induced brain activation, whole-brain functional connectivity (FC) during the fear extinction task and post-extinction resting-state. Ninety healthy women (57 using oral contraceptives [OC], 33 naturally cycling [NC]) were fear conditioned on day 1. They ingested an estradiol or placebo pill prior to extinction learning on day 2 (double-blind design). Extinction memory was assessed on day 3. Task-based functional MRI data were ascertained on days 2 and 3 and resting-state data were collected post-extinction on day 2 and pre-recall on day 3. Estradiol administration significantly modulated the neural signature associated with fear extinction learning and memory, consistent with prior studies. Importantly, estradiol administration induced significant changes in FC within multiple networks, including the default mode and somatomotor networks during extinction learning, post-extinction, and during extinction memory recall. Exploratory analyses revealed that estradiol impacted ventromedial prefrontal cortex (vmPFC) activation and FC differently in the NC and OC women. The data implicate a more diffused and significant effect of acute estradiol administration on multiple networks. Such an effect might be beneficial to modulating attention and conscious processes in addition to engaging neural processes associated with emotional learning and memory consolidation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.