ArticleProceedings of the National Academy of Sciences of the United States of America2024
Hormonal basis of sex differences in anesthetic sensitivity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- The epidemiology and phenomenology of non-antipsychotic-induced dystonia: a hybrid systematic-narrative review.European psychiatry : the journal of the Association of European Psychiatrists · 2025Pooled it
- Determinants of procedural sedation requirements during endovascular treatment for acute anterior circulation ischaemic stroke: a post-hoc analysis of the INDIVIDUATE trial.European stroke journal · 2026Trial
- Liposomal bupivacaine for popliteal sciatic and saphenous nerve blocks in patients undergoing foot and ankle surgery: a single-center, double-blind, randomized controlled trial.Frontiers in medicine · 2026Trial
- Anesthesia unconsciousness recruits dynamic parabrachial activity within a distributed brain-wide ensemble.bioRxiv : the preprint server for biology · 2026Article
- Brief, Repeated Isoflurane Anaesthesia Elicits Sex-Dependent Behavioural, Cerebrovascular and Microglial Alterations in Mice.The European journal of neuroscience · 2026Article
- Revisiting MAC as a static measure of anaesthesia: evidence for dynamic responses under isoflurane in male mice.British journal of anaesthesia · 2026Article
- Corticosterone-linked microglial activity underpins sexually dimorphic neuroplasticity after ketamine anesthesia.Science advances · 2026Article
- From identity to function: unveiling the cellular complexity of hypothalamic feeding circuits.Reviews in endocrine & metabolic disorders · 2026Review
- Subcortical recruitment dissociates isoflurane emergence from distinct wakeful states in mice.bioRxiv : the preprint server for biology · 2026Article
- Evaluation of the efficacy and safety of a modified anesthetic protocol using dexmedetomidine, midazolam, and butorphanol in mice.The Journal of veterinary medical science · 2026Article
- Retinal OCT Parameters and Physiological Dynamics as an Effect of Anesthesia in C57BL/6J Mice.Investigative ophthalmology & visual science · 2026Article
- Role of Dorsomedial Periaqueductal Gray Glutamatergic Neurons in Promoting Arousal under Multiple General Anesthetics in Mice.Anesthesiology · 2026Article
- Article
- Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil.Scientific reports · 2026Observational
- Effects of Repeated Early-life Anesthesia Exposure on Visual System Development in Mice.Anesthesiology · 2026Article
- Impact of Body Weight on Sedation-Related Outcomes in Complex Electrophysiological Interventions.Healthcare (Basel, Switzerland) · 2026Article
- Testosterone effect on anesthesia depth in micropenis hypospadias surgery: A prospective cohort study.Pakistan journal of medical sciences · 2026Article
- Sex differences in propofol-induced loss of consciousness: a clinical study on effect-site concentration and electroencephalographic features.American journal of translational research · 2026Article
- Convergent Control of NREM Sleep and Anesthesia by Prefrontal Layer 5 Extratelencephalic Neurons.Research square · 2025Article
- Evaluation of a modified triple-combination anesthesia using dexmedetomidine in mice.Animal models and experimental medicine · 2025Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
General anesthesia-a pharmacologically induced reversible state of unconsciousness-enables millions of life-saving procedures. Anesthetics induce unconsciousness in part by impinging upon sexually dimorphic and hormonally sensitive hypothalamic circuits regulating sleep and wakefulness. Thus, we hypothesized that anesthetic sensitivity should be sex-dependent and modulated by sex hormones. Using distinct behavioral measures, we show that at identical brain anesthetic concentrations, female mice are more resistant to volatile anesthetics than males. Anesthetic sensitivity is bidirectionally modulated by testosterone. Castration increases anesthetic resistance. Conversely, testosterone administration acutely increases anesthetic sensitivity. Conversion of testosterone to estradiol by aromatase is partially responsible for this effect. In contrast, oophorectomy has no effect. To identify the neuronal circuits underlying sex differences, we performed whole brain c-Fos activity mapping under anesthesia in male and female mice. Consistent with a key role of the hypothalamus, we found fewer active neurons in the ventral hypothalamic sleep-promoting regions in females than in males. In humans, we demonstrate that females regain consciousness and recover cognition faster than males after identical anesthetic exposures. Remarkably, while behavioral and neurocognitive measures in mice and humans point to increased anesthetic resistance in females, cortical activity fails to show sex differences under anesthesia in either species. Cumulatively, we demonstrate that sex differences in anesthetic sensitivity are evolutionarily conserved and not reflected in conventional electroencephalographic-based measures of anesthetic depth. This covert resistance to anesthesia may explain the higher incidence of unintended awareness under general anesthesia in females.
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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.