Objective: Gonadal steroids are important modulators of neuronal function and associated behavioral states. Sex steroid excursions have been implicated in premenstrual dysphoric disorder, postpartum depression, perimenopausal and menopausal mood changes, Alzheimer's Disease (AD), and overall cognitive function. A critical neuronal system mediating mood and cognition is serotonin. Methods to directly assess the effects of sex steroids upon central serotonergic function in humans are expanding with the development of specific serotonin radioligands. Through PET imaging with the 5-HT 2a radioligand [18F]altanserin, we aim to demonstrate that estrogen will upregulate central serotonin function, while progesterone will further modify the effects of estrogen. We also aim to explore the relationships between central 5-HT 2a receptor density, platelet 5-HT 2a and 5-Ht 2a density, and tests of neuropsychological function to determine the sample size needed for future studies to test hypotheses about the interrelationship of these variables. Design: Seven physically and mentally healthy menopausal women will receive 10 weeks of estrogen followed by 2 weeks of combined estrogen progestersone replacement. At three time intervals (baseline, following 10 weeks of unopposed estrogen treatment, and following 2 weeks of combined hormone treatment), subjects will undergo studies of neuropsychological functioning, blood sampling for platelet, serotonin activity, and PET studies with the 5-HT 2a ligand[18F]altanserin.
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