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Last updated January 1, 2014

Estrogen modifies brain cortical serotonin receptors

Improvements seen in working memory and verbal fluency in postmenopausal women taking estrogen therapy.

Medaus Pharmacy

Research suggests that estrogen has a significant effect on serotonin receptors in the brain, which may partly explain the observed beneficial effects of the hormone on cognition and mood.

"Prefrontal serotonin 2A receptors, shown to increase in rodents following estrogen administration, are one component relating to cognition/mood and actions of antipsychotics/antidepressants," explain Dr. Akira Kugaya (VA Connecticut Healthcare System, West Haven, USA) and colleagues.

They carried out positron emission tomography (PET) of serotonin receptor binding with [18F]deuteroaltanserin in 10 postmenopausal women before and after an average of 10 weeks' treatment with estrogen replacement therapy (ERT).

The results showed that serotonin receptor binding in the right prefrontal cortex was significantly increased after ERT. Of particular interest, these changes occurred in areas linked to working memory. Supporting these findings, the participants also showed improvements in verbal fluency and trail-making tests after taking ERT.

In summary, "estrogen increases serotonin receptor binding in human prefrontal regions," the researchers conclude.


American Journal of Psychiatry 2003; 160: 1522-4.

Increase in prefrontal cortex serotonin 2A receptors following estrogen treatment in postmenopausal women.

Kugaya A, Epperson CN, Zoghbi S, van Dyck CH, Hou Y, Fujita M, Staley JK, Garg PK, Seibyl JP, Innis RB. Department of Psychiatry, Yale University, New Haven, Conn 06516, USA.

OBJECTIVE: This study investigated the effect of estrogen on brain serotonin 2A (5-HT(2A)) receptors in postmenopausal women and whether there was any correlation of receptor changes with cognition and mood.

METHOD: Ten postmenopausal subjects underwent positron emission tomography measurements of 5-HT(2A) receptor binding with [(18)F]deuteroaltanserin before and after estrogen replacement therapy.

RESULTS: 5-HT(2A) receptor binding was significantly increased after estrogen replacement therapy in the right prefrontal cortex (right precentral gyrus [Brodmann's area 9], inferior frontal gyrus [Brodmann's area 47], medial frontal gyrus [Brodmann's area 6, 10] and the anterior cingulate cortex [Brodmann's area 32]). In the inferior frontal gyrus [Brodmann's area 44]), receptor up-regulation was correlated with change in plasma estradiol. Verbal fluency and Trail Making Test performance, but not mood, were significantly improved by estrogen without correlation with receptor changes.

CONCLUSIONS: Estrogen increases 5-HT(2A) receptor binding in human prefrontal regions.




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