Long-term estrogen therapy and 5-HT 2A receptor binding in postmenopausal women; a single photon emission tomography (SPET) study

Abstract

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-HT 2A receptor in human brain. We investigated the effect of long-term ET on cortical 5-HT 2A receptor availability in postmenopausal women. In a cross-sectional study, we compared cortical 5-HT 2A 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-HT 2A receptor ligand 123I-5-I-R91150. Also, we used the Revised Wechsler Memory Scale to relate memory function to 5-HT 2A receptor availability. Never-users had significantly higher 5-HT 2A 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-HT 2A 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-HT 2A 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-HT 2A 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-HT 2A receptor in hippocampus is associated with poorer memory function.