Editors' ChoicePostmenopausal Estrogen Therapy

A Little Estrogen Goes a Long Way

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Science Translational Medicine  31 Mar 2010:
Vol. 2, Issue 25, pp. 25ec51
DOI: 10.1126/scitranslmed.3001099

Several randomized clinical trials report the benefits of postmenopausal estrogen therapy on cognitive function because estrogens are known to affect several aspects of brain structure, function, and chemistry. However, although the role of estrogen on enhancing mental processing has been correlated with an increase in estrogen brain receptors, the adverse health effects of estrogen, including cardiac and cancer risks, limit its current widespread use. Because data suggest that even short-term estrogen treatment during the early postmenopausal period may have an enduring positive impact on cognition, Rodgers et al. sought to identify a role for postmenopausal estrogen therapy that would minimize the harmful sequelae.

Moderately aged animals with surgically removed ovaries were exposed to one of three treatment conditions: no treatment, brief estrogen exposure, or continuous estrogen exposure over a course of 40 days. In their short-term study, the three groups were trained on a working memory task for 2 months and then were evaluated. The long-term study exposed the three groups to behavioral testing on a maze every other month beginning after estrogen exposure, for 8 months.

The results demonstrated that the rats treated with short-term estrogen therapy had improved spatial working memory as well as reduction in cognitive impairment caused by periods of chemically induced amnesia. Moreover, these benefits lasted up to 7 months after treatment. When levels of estrogen receptors in the brain were examined, the rats treated with short-term estrogen had higher levels than those of the untreated rats and levels similar to those of rats treated continuously with estrogen.

These results are promising in that they provide support for a brief course of estrogen therapy in the early postmenopausal period that may have long-lasting benefits on cognitive function. This short treatment course may avoid the adverse effects imposed by long-term estrogen therapy in postmenopausal women.

S. P. Rodgers et al., Transient estradiol exposure during middle age in ovariectomized rats exerts lasting effects on cognitive function and the hippocampus. Endocrinology 1 March 2010 (10.1210/en.2009-1245). [Abstract]

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