Effects of long-term hormone therapy on cholinergic synaptic concentrations in healthy postmenopausal women

Experimental evidence suggests that gonadal steroids regulate brain neuroch emical systems associated with cognitive function, such as the cholinergic system. This study examines the effect of long-term postmenopausal hormone therapy on the brain concentrations of cholinergic synaptic terminals in wo men using single photon emission computed tomography and the radiotracer [I -123]iodobenzovesamicol ([I-123]IBVM). [I-123]IBVM labels the vesicular ace tylcholine transporter (VAChT) located in the presynaptic terminals of thes e neurons. Sixteen healthy women treated with hormone therapy since the men opause and 12 women not treated with hormones were studied. There were no s ignificant differences in regional IBVM binding indexes between the 2 group s. The length of hormone replacement therapy correlated positively with VAC hT binding indexes in multiple cortical areas (P < 0.05): frontal cortex (S pearman rank correlation: <rho> = 0.79), parietal cortex (rho = 0.62), temp oral cortex (rho = 0.80), anterior cingulate (rho = 0.71), and posterior ci ngulate (rho = 0.63), but not in the basal ganglia (rho = 0.35; P = 0.2). A n earlier onset of menopause in hormone-treated women was associated with h igher VAChT indexes in the anterior cingulate (rho = -0.56; P = 0.02) and p osterior cingulate (rho = -0.63; P = 0.01). The opposite was found in the p osterior cingulate of women not treated with hormones (rho = 0.58; P = 0.04 ). Women treated with estrogen alone also showed higher VAChT indexes than women treated with estrogen and progestin in the posterior cingulate cortex (by Mann-Whitney U test: z = 2.42; P = 0.015). Although an overall effect of postmenopausal hormone therapy was not found, associations between an in dex of cortical cholinergic terminal concentrations and the length of hormo nal replacement suggest that hormone therapy may influence the survival or plasticity of these cells in postmenopausal women. The data also suggest po ssible differential effects of estrogen and estrogen with progestin treatme nts in brain areas critical for cognitive processing.