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 [¹⁸F]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.