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Reviewing Estradiol for Alzheimer's 10 Years Later

Lydia DonCarlos, PhD and colleagues explore new therapies that provide the benefits of estrogen without the cancer risks.

An influential article in the journal Progress in Neurobiology provided one of the first comprehensive reviews of how estrogen potentially can protect against Alzheimer's disease and other neurological disorders.

The article by senior author Lydia DonCarlos, PhD and colleagues detailed how estrogen "decreases the risk and delays the onset and progression of Alzheimer's disease and schizophrenia, and may also enhance recovery from traumatic neurological injury such as stroke."

The article recently reached the milestone of having been cited 500 times in scholarly articles, books, theses, abstracts, etc., according to a count by Google Scholar.

Another citation index, Thomson Reuters' Web of Science, has counted 471 citations for the article. By comparison, the median number of citations for other papers on neuroscience and behavior published the same year is 34.5.

DonCarlos' article, "Neuroprotection by Estradiol," was published in January, 2001. Since publication, further data from the Women's Health Initiative and other studies have refined scientists' understanding of the benefits and risks of estrogen exposure, DonCarlos said. DonCarlos, a neuroendocrinologist at Loyola University Health System, has written subsequent review articles about estrogen and the brain.

Estrogen can protect against dementia and other neurological disorders by decreasing inflammatory responses and by enhancing cells' ability to survive damage. "It's a natural way for the brain to protect itself, since the brain normally makes neuroprotective estrodial in response to injury," DonCarlos said.

But there also are risks. The Women's Health Initiative found that taking estrogen plus progestin increased women's risks of heart disease, blood clots, stroke and breast cancer.

DonCarlos and other researchers are studying agents called selective estrogen receptor modulators (SERMs) that potentially could provide the benefits of estrogen without the risks. One such agent is tamoxifen, which reduces the risk of breast cancer by blocking estrogen receptors in the breast. In the bones, tamoxifen has the opposite effect by acting like estrogen. This has the beneficial effect of reducing the risk of osteoporosis, DonCarlos said.

"We are looking for other SERMs that potentially could help protect the brain, without increasing the risk of breast cancer or other negative effects," DonCarlos said.

Most studies suggest that estrogen has beneficial effects on cognitive function, DonCarlos added. "But we still have a lot of research to do before recommending the use of estrogens in the clinic for this purpose."

Source: Loyola University Health System