ESTROGEN AND ALZHEIMER'S
Scientists are surprised to find no substantial difference in disease symptoms when estrogen treatment is given to women with established dementia. When it first became clear that the use of estrogen by postmenopausal women might actually reduce their risk of developing Alzheimer's, researchers, patients and their loved ones jumped on the idea that the hormone might also be useful in treating the disease.
Unfortunately, that seems not to be the case. According to a recent article published by Keck School researchers in the journal Neurology, estrogen is not an effective treatment for women with Alzheimer's disease, which is currently destroying the memory and cognitive ability of some 4 million Americans, hitting women twice as often as men. Right now, there are no definitive therapies to ward off or reverse the dementia.
Which is why there was so much excitement about estrogen, says Victor H. Henderson, M.D., the Kenneth and Bette Volk Professor of Neurology at the Keck School of Medicine, and the lead author on the Neurology study. And initial results backed up that excitement: Some small studies suggested that, among women who already have Alzheimer's disease, the use of estrogen may lead to a better performance on several cognitive tests, and even may lead to an improvement in the disease's symptoms.
To evaluate further the possibility that estrogen may ameliorate Alzheimer's, the researchers (who hailed from institutions across the country in addition to USC) undertook a short-term, randomized, double-blind, placebo-controlled trial of estrogen for women with mild-to-moderate dementia due to the disease. Their hypothesis was that estrogen would reduce the severity of disease symptoms and improve the women's ability to function in their daily lives.
There is a strong biological basis for that assumption, Henderson notes. Neurons in the brain often display estrogen receptors, and the hormone has been found to protect the brain from damage, to promote the growth of brain cells and to increase their ability to recover after injury. In addition, in the laboratory, estrogen appears to reduce the production of ß-amyloid-a protein that is thought to be a major player in the development of Alzheimer's.
The researchers enrolled 42 women from five university-affiliated clinics into the study; 21 began taking 1.25 milligrams of estrogen per day and 21 were given an identical-looking placebo. Of those, 40 women stayed in the study for four weeks and 36 women (18 taking estrogen, 18 taking placebo) for the full 16 weeks.
When they looked at a number of different measures of both mood and cognitive ability, the scientists were surprised to find no significant differences between the group taking the estrogen and the group being given a placebo.
"In our study, we conclude that estrogen therapy is unlikely to make a substantial difference in disease symptoms when treatment is initiated in women who already have established dementia," says Henderson.
This finding flies in the face of the previous, positive-response studies of estrogen for Alzheimer's, notes Henderson. But most of those previous studies were limited in some way: Some of them did not have a randomized, controlled design; others were extremely small; and still others were of very short duration.
Henderson's findings were further validated when a second study with similar results was published in the Journal of the American Medical Association.
Of course, Henderson admits, his study really only addresses what the effects of relatively short-term estrogen therapy may be; it does not rule out the possibility that long-term therapy might have more of an impact. It also does not comment on whether there might be subgroups of women in whom estrogen is more useful than in others, whether beginning it earlier in the disease course may have a more significant effect, or whether it can reduce a woman's risk of developing Alzheimer's disease.
"Based on data by my USC collaborators-particularly Dr. Annlia Paganini-Hill, a coauthor on this study-and that of others, I continue to believe that estrogen therapy may help reduce a woman's risk of developing Alzheimer's disease, but firm proof for this contention is lacking," says Henderson. "And based primarily on others' data, I believe that estrogen therapy may affect memory and other aspects of cognition in healthy older women. But I do not yet know whether the effect is large enough to be clinically important."
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