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

2007; Elsevier BV; Volume: 53; Issue: 1 Linguagem: Inglês

10.1016/j.yhbeh.2007.08.014

1095-6867

Jacqueline Compton, Michael J. Travis, Ray Norbury, Kjell Erlandsson, Thérèse van Amelsvoort, Eileen Daly, Wendy A. Waddington, Páll Matthíasson, Jos Eersels, Malcolm Whitehead, Robert Kerwin, Peter J. Ell, Declan Murphy,

Cancer Risks and Factors

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 123I-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.