Estrogen pendulum in schizophrenia and Alzheimer’s disease: Review of therapeutic benefits and outstanding questions

•Schizophrenia and Alzheimer’s disease are linked to estrogen signaling in the brain•Estrogen replacement emerges as an adjunct intervention for these diseases.•For the lack of RCTs, estrogen replacement therapy remains experimental. Although produced largely in the periphery, gonadal steroids play...

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Bibliographic Details
Published in:Neuroscience letters 2021-08, Vol.759, p.136038-136038, Article 136038
Main Authors: Androvičová, Renáta, Pfaus, James G., Ovsepian, Saak V.
Format: Article
Language:English
Subjects:
Adjuvant therapy
Alzheimer Disease - drug therapy
Alzheimer Disease - metabolism
Animal models
Animals
Cognitive deficit
Estrogen Replacement Therapy - methods
Estrogens - metabolism
Estrogens - pharmacology
Humans
Menopause
Neuroprotection
Plasticity
Schizophrenia - drug therapy
Schizophrenia - metabolism
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Summary:•Schizophrenia and Alzheimer’s disease are linked to estrogen signaling in the brain•Estrogen replacement emerges as an adjunct intervention for these diseases.•For the lack of RCTs, estrogen replacement therapy remains experimental. Although produced largely in the periphery, gonadal steroids play a key role in regulating the development and functions of the central nervous system and have been implicated in several chronic neuropsychiatric disorders, with schizophrenia and Alzheimer’s disease (AD) most prominent. Despite major differences in pathobiology and clinical manifestations, in both conditions, estrogen transpires primarily with protective effects, buffering the onset and progression of diseases at various levels. As a result, estrogen replacement therapy (ERT) emerges as one of the most widely discussed adjuvant interventions. In this review, we revisit evidence supporting the protective role of estrogen in schizophrenia and AD and consider putative cellular and molecular mechanisms. We explore the underlying functional processes relevant to the manifestation of these devastating conditions, with a focus on synaptic transmission and plasticity mechanisms. We discuss specific effects of estrogen deficit on neurotransmitter systems such as cholinergic, dopaminergic, serotoninergic, and glutamatergic. While the evidence from both, preclinical and clinical reports, in general, are supportive of the protective effects of estrogen from cognitive decline to synaptic pathology, numerous questions remain, calling for further research.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2021.136038