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

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.