Widespread increases of cortical serotonin type 2A receptor availability after hormone therapy in euthymic postmenopausal women

Objective: To use statistical parametric mapping to determine the extent of previously reported serotonin type 2A (5HT_2A) receptor binding potential (BP) increases in postmenopausal women following hormone therapy. Design: Repeated measures positron emission tomography (PET) study. Setting: Academic research environment. Patient(s): Five healthy, postmenopausal women. Intervention(s): Serial PET images of [¹⁸F]altanserin uptake were acquired to measure 5HT_2A receptor BP at menopausal baseline, following estradiol (E₂), and following combined E₂ + micronized progesterone (P₄). Main Outcome Measure(s): 5HT _2A receptor BP. Result(s): Combined E₂ + P₄ treatment was associated with significant increases in the 5HT_2A receptor BP increases in widespread areas of cerebral cortex. Treatment with E₂ alone was also associated with widespread cortical BP increases, although these changes reached statistical significance in fewer regions. The rate of [¹⁸F]altanserin metabolism was significantly decreased in the E₂ + P₄ condition relative to menopausal baseline, but this difference did not appear to correlate with changes in 5HT _2A receptor BP. Conclusion(s): Estradiol priming followed by combined E₂ + P₄ is associated with widespread increases in 5HT_2A receptor BP in the cerebral cortex, consistent with the E₂-associated increases in 5HT_2A receptor density previously observed in experimental animals.