Estrogens and the Brain

Evan R. Simpson, Ph.D., F.A.A.

The use of estrogen as hormonal therapy for postmenopausal women continues to be a controversial issue. This is particularly true in terms of the role of estrogens in the brain. Many in vitro studies as well as those using animal models, including non-human primates, suggest important roles for estrogens in the brain. Additionally, favorable outcomes of exogenous estrogen administration have been reported in many observational studies, however the same is not true of some major randomized clinical trials, including that conducted under the auspices of the Women's Health Initiative. It seems highly relevant therefore to devote an issue of Seminars in Reproductive Medicine to this topic in order that these issues may be addressed once again, and this time in the light of the most recent observations. To do this, we have solicited articles from individuals who are internationally recognized as leaders in their respective fields of expertise.

To capture the spectrum of experimental approaches to the study of the role of estrogens in brain function, we have included articles from individuals with expertise in in vitro studies, animal models including transgenic models, pharmacologic challenge studies both in animal models and in humans, and neuroimaging as well as epidemiologic studies in humans.

We hope that by including the entire spectrum of experimental approaches that bear on this topic in the one issue, the reader will be best informed regarding reports of the positive and negative effects of both endogenous and exogenous estrogens on brain function. In turn, we anticipate that this may provide new impetus for experimental approaches, both basic and clinical, which will lead to a better understanding of the full spectrum of estrogen action on brain function. This will in turn help to resolve the issues that at present confound our judgments and will eventually lead to improved translational and clinical outcomes.