To the Editor: We commend Akira Kugaya, M.D., Ph.D., and colleagues (1) on their brief report on serotonin 2A (5-HT2A) receptors in postmenopausal women. Characterization of the effects of gonadal steroids on neuroreceptor pharmacology and cognitive function holds great importance to clinical care and cognitive neuroscience research. Consistent with the article by Dr. Kugaya et al., we previously reported that 5-HT2A receptor binding potential significantly increased in postmenopausal women during administration of transdermal estradiol, 0.1 mg/day for 8 to 14 weeks, followed by combined transdermal estradiol and progesterone, 100 mg b.i.d. (2 to 6 weeks), with positron emission tomography and the selective 5-HT2A receptor radioligand [18F]altanserin. Dr. Kugaya et al. correctly cited this publication as reporting a "subthreshold" effect of estradiol alone on increasing 5-HT2A receptor binding potential in specific brain regions of interest. However, we alert readers to our more recent publication (2), in which our original image data were analyzed voxel by voxel using statistical parametric mapping, a technique similar to that applied by Dr. Kugaya et al. Consistent with the work of Dr. Kugaya et al., this approach showed that administration of estradiol alone increased 5-HT2A receptor binding potential in multiple brain regions that had not been examined in our initial region-of-interest analysis (3), which included the right superior frontal gyrus, the right ventrolateral prefrontal cortex, the left inferior parietal cortex, and the left temporal polar cortex. Furthermore, in a post hoc analysis that employed a lower significance threshold for identifying voxels with increased 5-HT2A receptor binding potential after estradiol treatment (the same threshold used by Dr. Kugaya et al.), we observed widespread increases in estradiol-related cortical 5-HT2A receptor binding potential.