Maturitas. 2016 Jun 4. pii: S0378-5122(16)30122-0. doi: 10.1016/j.maturitas.2016.05.014.

Author
Vargas KG¹, Milic J¹, Zaciragic A¹, Wen KX¹, Jaspers L¹, Nano J¹, Dhana K¹, Bramer WM², Kraja B³, van Beeck E⁴, Ikram MA⁵, Muka T⁶, Franco OH¹.

Author information

• ¹Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
• ²Medical Library, Erasmus MC, Rotterdam, The Netherlands.
• ³Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Biomedical Sciences, Faculty of Medicine, University of Medicine, Tirana, Albania; University Clinic of Gastrohepatology, University Hospital Center Mother Teresa, Tirana, Albania.
• ⁴Department of Public Health, Erasmus University Medical Center, The Netherlands.
• ⁵Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands; Department of Neurology, Erasmus University Medical Center, The Netherlands; Department of Radiology, Erasmus University Medical Center, The Netherlands.
• ⁶Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. Electronic address: t.muka@erasmusmc.nl.

Abstract

Females have unique and additional risk factors for neurological disorders. Among classical estrogen receptors, estrogen receptor beta (ERβ) has been suggested as a therapeutic target. However, little is known about the role of ERβ in the female brain. Six electronic databases were searched for articles evaluating the role of ERβ in the female brain and the influence of age and menopause on ERβ function. After screening 3186 titles and abstracts, 49 articles were included in the review, all of which were animal studies. Of these, 19 focused on cellular signaling, 7 on neuroendocrine pathways, 8 on neurological disorders, 4 on neuroprotection and 19 on psychological and psychiatric outcomes (6 studies evaluated two or more outcomes). Our findings showed that ERβ phosphorylated and activated intracellular second messenger proteins and regulated protein expression of genes involved in neurological functions. It also promoted neurogenesis, modulated the neuroendocrine regulation of stress response, conferred neuroprotection against ischemia and inflammation, and reduced anxiety- and depression-like behaviors. Targeting ERβ may constitute a novel treatment for menopausal symptoms, including anxiety, depression, and neurological diseases. However, to establish potential therapeutic and preventive strategies targeting ERβ, future studies should be conducted in humans to further our understanding of the importance of ERβ in women's mental and cognitive health.

Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

KEYWORDS:

Brain; Estrogen receptor beta; Menopause; Neurological disorders; Psychiatry; Systematic review