Effects of estradiol and progesterone administration on human serotonin 2A receptor binding: a PET study

Background: Preclinical studies demonstrate that 17β-estradiol (E2) increases serotonin-2A receptor (5-HT2AR) density in rat frontal cortex. Methods: We investigated the impact of hormone replacement therapy on 5-HT2AR binding potential (BP) using positron emission tomography and [18F]altanserin in five postmenopausal women. Subjects were imaged at baseline, following 8 to 14 weeks of transdermal E2, 0.1 mg/d, and following 2 to 6 weeks of E2 plus micronized progesterone (P) 100 mg per os twice daily. Regional BPs in the anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex were calculated by Logan analysis. Results: There was a main effect of time (p = .017) for 5-HT2AR BP, which increased 21.2% ± 2.6% following combined E2 and P administration relative to baseline. This effect was evident in all cerebral cortex regions examined. Conclusions: 5-HT2AR BP increased in widespread areas of the cerebral cortex following combined E2 + P administration.