The study revealed that HRT was associated with sparing of grey matter in prefrontal, temporal and parietal cortical regions, and that longer duration of therapy was associated with greater sparing. A sparing effect of HRT was also observed in the anterior hippocampus. The results of the study suggest that estrogen has a protective sparing role in cortical regions during aging that may provide cognitive benefit, as well as protection from neurodegenerative disorders. Finally, estrogen has also been shown to enhance dendritic spine density in the prefrontal cortex of young and aged monkeys and in young rats [279–281], which may explain the prefrontal cognitive enhancing effects of estrogen. As a whole, these findings provide support for the prefrontal cortex being considered, along with the hippocampus, as a potential key target for estrogen actions on cognition. The mechanisms that underlie estrogen regulation of synaptic plasticity will be discussed in the following section.