Estrogen enhances hippocampal gray-matter volume in young and older postmenopausal women: a prospective dose-response study

Neurobiol Aging. 2017 Aug;56:1-6. doi: 10.1016/j.neurobiolaging.2017.03.033. Epub 2017 Apr 8.


Estrogen administration following menopause has been shown to support hippocampally mediated cognitive processes. A number of previous studies have examined the effect of estrogen on hippocampal structure to determine the mechanism underlying estrogen effects on hippocampal function. However, these studies have been largely observational and provided inconsistent results. We examined the effect of short-term estradiol administration on hippocampal gray-matter volume in a prospective study with multiple doses of estradiol (placebo, 1 mg, and 2 mg). Following 3 months of estradiol administration, bilateral posterior hippocampal voxel-based gray-matter volume was increased in women who received 2-mg estradiol. There were no significant differences in total hippocampal volume and no significant effects on gray-matter volume in women who received placebo or 1-mg estradiol. These findings accord with previous animal studies and provide evidence of estrogen effects on hippocampal morphology that may represent a neurobiological mechanism for estrogen effects on cognition in postmenopausal women.

Keywords: Estrogen; Gray-matter volume; Hippocampus; MRI; Volume.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cognition / drug effects
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage*
  • Estradiol / pharmacology*
  • Female
  • Gray Matter / diagnostic imaging
  • Gray Matter / drug effects*
  • Gray Matter / pathology
  • Hippocampus / diagnostic imaging
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Humans
  • Magnetic Resonance Imaging
  • Middle Aged
  • Neuroimaging
  • Organ Size / drug effects*
  • Postmenopause* / psychology


  • Estradiol