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Long-term estrogen therapy and 5-HT2A receptor binding in postmenopausal women; a single photon emission tomography (SPET) study

Research output: Contribution to journalArticle

J Compton, M J Travis, R Norbury, K Erlandsson, T Van Amelsvoort, E Daly, W Waddington, P Matthiasson, J L H Eersels, M Whitehead, R W Kerwin, P J Ell, D G M Murphy

Original languageEnglish
Pages (from-to)61 - 68
Number of pages8
JournalHormones and Behavior
Issue number1
Publication statusPublished - Jan 2008

King's Authors


Variation in estrogen level is reported by some to affect brain maturation and memory. The neurobiological basis for this may include modulation of the serotonergic system. No neuroimaging studies have directly examined the effect of extended estrogen therapy (ET), on the 5-HT2A receptor in human brain. We investigated the effect of long-term ET on cortical 5-HT2A receptor availability in postmenopausal women. In a cross-sectional study, we compared cortical 5-HT2A receptor availability in 17 postmenopausal ERT-naive women and 17 long-term oophorectomised estrogen-users, age- and IQ-matched using single photon emission tomography and the selective 5-HT2A receptor ligand I-123-5-I-R91150. Also, we used the Revised Wechsler Memory Scale to relate memory function to 5-HT2A receptor availability. Never-users had significantly higher 5-HT2A receptor availability than estrogen-users in hippocampus (1.17 vs. 1.11, respectively, p=0.02), although this did not remain significant after correction for multiple comparisons. Hippocampal 5-HT2A receptor availability correlated negatively with verbal and general memory and delayed recall (r=-0.45, p=0.01; r=-0.40, p=0.02; r=-0.36, p=0.04). Right superior temporal 5-HT2A receptor availability correlated negatively with verbal memory (r=-0.36, p=0.04). In estrogen-users, receptor availability correlated negatively with verbal and general memory (r=-0.70, p=0.002; r=-0.69, p=0.002); and in never-users, receptor availability negatively correlated with attention and concentration (r=-0.54, p = 0.02). Long-term ET may be associated with lower 5-HT2A receptor availability in hippocampus. This may reflect increased activity within the serotonergic pathway leading to down-regulation of post-synaptic receptor. Also, increased availability of the 5-HT2A receptor in hippocampus is associated with poorer memory function. (c) 2007 Elsevier Inc. All rights reserved

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