ReviewCurrent neuropharmacology2020
The Critical Period for Neuroprotection by Estrogen Replacement Therapy and the Potential Underlying Mechanisms.
Review in Current neuropharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses 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
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- A Pilot Systematic Review and Meta-analysis of Neuroprotective Studies in Female Rodent Models of Ischemic Stroke.Translational stroke research · 2024Pooled it
- Use of Hormone Therapy in Postmenopausal Women with Alzheimer's Disease: A Systematic Review.Drugs & aging · 2021Pooled it
- Dementia risk across distinct metabolic profiles in the UK Biobank.GeroScience · 2026Article
- The Neurology of Menopause.Current neurology and neuroscience reports · 2026Review
- Six promising drug repurposing candidates for Alzheimer's disease and their sex-specific mechanisms and efficacy.Neural regeneration research · 2026Article
- Impact of Orchiectomy on Oxidative Stress-Induced Neurodegeneration in the Male Rat Retina: A Proteomic Analysis.Antioxidants (Basel, Switzerland) · 2026Article
- Women's reproductive factors predict local brain aging profiles mapped using deep neural networks.GeroScience · 2026Article
- Protective Effects of Estradiol on Disease Progression in a Murine Model of Fuchs Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2025Article
- Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.Molecular neurobiology · 2025Review
- Combination Therapy of Estrogen and Progesterone Attenuates Behavioral Impairments and Autophagy via circLrp1b/miR-27a-3p/Dram2 Pathway After Traumatic Brain Injury.Molecular neurobiology · 2025Article
- Icaritin alleviates motor impairment and osteoporosis in Parkinson's disease mice via the ER-PI3K/Akt pathway.Scientific reports · 2025Article
- Exploring the role of sex hormones and gender diversity in multiple sclerosis.Nature reviews. Neurology · 2025Article
- Sex Differences in Astrocyte Activity.Cells · 2024Review
- Hormonal Therapies in Multiple Sclerosis: a Review of Clinical Data.Current neurology and neuroscience reports · 2024Review
- Supraphysiologic doses of 17β-estradiol aggravate depression-like behaviors in ovariectomized mice possibly via regulating microglial responses and brain glycerophospholipid metabolism.Journal of neuroinflammation · 2023Article
- Transcriptomic Profile Identifies Hippocampal Sgk1 as the Key Mediator of Ovarian Estrogenic Regulation on Spatial Learning and Memory and Aβ Accumulation.Neurochemical research · 2022Article
- Estradiol treatment in young postmenopausal women with self-reported cognitive complaints: Effects on cholinergic-mediated cognitive performance.Human psychopharmacology · 2022Article
- N-myc Downstream-Regulated Gene 2 (Ndrg2): A Critical Mediator of Estrogen-Induced Neuroprotection Against Cerebral Ischemic Injury.Molecular neurobiology · 2022Article
- Estrogen rapid effects: a window of opportunity for the aging brain?Neural regeneration research · 2022Review
- Neurovascular Dysfunction in Diverse Communities With Health Disparities-Contributions to Dementia and Alzheimer's Disease.Frontiers in neuroscience · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
17β-Estradiol (estradiol or E2) is a steroid hormone that has been broadly applied as a neuroprotective therapy for a variety of neurodegenerative and cerebrovascular disorders such as ischemic stroke, Alzheimer's disease, and Parkinson's disease. Several laboratory and clinical studies have reported that Estrogen Replacement Therapy (ERT) had no effect against these diseases in elderly postmenopausal women, and at worst, increased their risk of onset and mortality. This review focuses on the growing body of data from in vitro and animal models characterizing the potential underlying mechanisms and signaling pathways that govern successful neuroprotection by ERT, including the roles of E2 receptors in mediating neuroprotection, E2 genomic regulation of apoptosis- related pathways, membrane-bound receptor-mediated non-genomic signaling pathways, and the antioxidant mechanisms of E2. Also discussed is the current evidence for a critical period of effective treatment with estrogen following natural or surgical menopause and the outcomes of E2 administration within an advantageous time period. The known mechanisms governing the duration of the critical period include depletion of E2 receptors, the switch to a ketogenic metabolic profile by neuronal mitochondria, and a decrease in acetylcholine that accompanies E2 deficiency. Also the major clinical trials and observational studies concerning postmenopausal Hormone Therapy (HT) are summarized to compare their outcomes with respect to neurological disease and discuss their relevance to the critical period hypothesis. Finally, potential controversies and future directions for this field are discussed throughout the review.
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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.