Estradiol's effects on learning and neuronal morphology vary with route of administration.

Estrogen's effects on performance and neuronal morphology are variable, and the reasons for this variability are not yet understood. In this study, the authors compared the effects of 2 delivery routes of 17 beta-estradiol on spatial learning and dendritic spine densities in young ovariectomized rats; estradiol was administered by implanted capsules or by daily oral gavage. Estradiol treatment via capsules improved performance in the radial-arm water maze and increased spine densities on dendrites of CA1 pyramidal neurons in the hippocampal formation. In contrast, daily oral administration of estradiol did not affect either measure. These data demonstrate that estradiol delivery is a critical variable in animal studies and that clinical studies comparing the effects of different estradiol treatment routes on cognition are warranted.