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Long-Term Hormone Therapy No Help for Alzheimer's

In a study of rats, it made memory worse

TUESDAY, Oct. 29, 2002 (HealthDayNews) -- Long-term hormone therapy, taken in the traditional continuous manner, doesn't improve symptoms of Alzheimer's disease in women and may make memory loss worse, a new rat study suggests.

The findings reflect those of a human study, published in 2000 in the Journal of the American Medical Association, in which researchers found that women with mild to moderate Alzheimer's who were put on hormone replacement therapy initially had better mental functioning than women with the disease who weren't on the therapy. However, then the hormone-supplemented group's mental skills dropped below that of the women not on the therapy.

Hormone therapy "is seen as a neuroprotective agent," says Gary L. Wenk, a researcher at the University of Arizona.

His team found otherwise, at least when the therapy was given continuously.

For the study, published in the October issue of Behavioral Neuroscience, the researchers induced ovarian failure in female rats and produced low levels of chronic inflammation in their brains, similar to Alzheimer's disease conditions in older women. Then they tested the rats' ability to perform a water maze task.

Removal of the ovaries alone was not enough to decrease performance, the scientists found. But if they introduced either sustained estrogen replacement therapy or chronic brain inflammation, the animals performed more poorly on the memory task.

"We thought the estrogen [administered continuously to the rats without ovaries, similar to continuous hormone replacement therapy in human females] would be beneficial," Wenk says.

The problem, he adds, may be the continuous nature of the hormone therapy. The fact that younger rats with ovaries didn't suffer mental decline may have something to do with the ovaries being intact and the way they function normally, he says.

"Ovaries release more than estrogen," Wenk says. "It may be the cycling estrogen or something to do with the interaction with progesterone."

If there's a way to mimic more closely the hormone levels of animals with functioning ovaries that might be promising, he says.

"Long-term chronic daily therapy may be what we just need to throw out," he says.

The study "pretty much is backing up the human study," says Jon Nilsen, a research assistant professor of pharmacology and toxicology at the University of Southern California School of Pharmacy.

Echoing Wenk's suggestion, Nilsen says the new findings also lend support to the idea that fluctuating hormone levels in animals or humans with ovaries or the balance of estrogen and progesterone in younger women may be the key to finding a therapy regimen that works for older women.

Next, Wenk says, he wants to conduct research introducing variable hormone replacement therapy into animals that would mimic the levels of an animal with functioning ovaries to see if that approach might improve memory and help Alzheimer's symptoms.

Meanwhile, the take-home point for women hoping to minimize or avoid Alzheimer's disease, he says, is that hormone replacement therapy as typically given "is not beneficial for prevention, the evidence isn't there, and certainly not for treatment."

What To Do

For more information on Alzheimer's disease and its treatment, visit the Alzheimer's Association.

SOURCES: Gary L. Wenk, Ph.D., Arizona Research Laboratories, University of Arizona, Tucson; Jon Nilsen, Ph.D., research assistant professor, pharmacology and toxicology, University of Southern California School of Pharmacy, Los Angeles; October 2002 Behavioral Neuroscience
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