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

Background: Preclinical studies demonstrate that 17 beta -estradiol (E-2) 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 [F-18]altanserin in five postmenopausal women. Subjects were imaged at baseline, following 8 to 14 weeks of transdermal E-2, 0.1 mg/d, and following 2 to 6 weeks of E-2 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 E-2 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 E-2 + P administration. Biol Psychiatry 2000;48:854-860 (C) 2000 Society of Biological Psychiatry.