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For some time, anecdotal evidence has suggested that estrogen-replacement therapy can improve cognitive processes in postmenopausal women. New findings just released indicate that this commonly prescribed hormone may indeed activate genes that maintain the nerve cells associated with memory.
What's more, the manner in which estrogen reacts with memory cells could also point the way to a potential therapy for sufferers of Alzheimer's disease, according to research presented at the annual meeting of the Society of Neuroscience, held in New Orleans the week of Nov. 6.
Although estrogen is often used in various medical treatments, scientists still have little understanding of how the female hormone works in the brain. To work toward solving that mystery, researchers at Johns Hopkins Medical School, led by Dr. Vassilis Koliatsos, focused on estrogen's effect on the genes that control specific neurons in the basal forebrain, where memories are formed and retained.
"NEW APPROACH." The scientists compared gene activity in rats whose ovaries had been removed to simulate menopause with gene activity in two other groups: normal rats and rats given additional estrogen. They found that nerve-cell genes in rats with typical estrogen levels were turned "on," as were genes that allowed these neurons to communicate with each other. The highest level of gene activity was in rodents with added estrogen. The rats without estrogen had low or nonexistent activity in the key genes.
To date, studies have found that estrogen on its own has no effect on slowing the progression of the disease in Alzheimer's patients. But Koliatsos says the hormone may have a role in enhancing the now-limited performance of the few drugs on the market that do slow memory loss in Alzheimer's patients. "We're laying the scientific foundation for a new approach," says Koliatsos.
Bolstering that approach is a small study from Seattle's University of Washington School of Medicine that found estrogen treatment improved memory and enhanced the ability of older postmenopausal women to carry out daily living activities. The researchers, led by Dr. Sanjay Asthana, divided 18 women age 56 to 84 into three groups: one group was given oral estrogen alone for three months, a second was treated with estrogen and progesterone (a male hormone), and the third group received a placebo.
SPATIAL MEMORY BOOST. The researchers found that those women who received either estrogen or estrogen and progesterone together demonstrated significant memory improvement and were quicker in performing daily living tasks that require cognitive skills, such as doing laundry. No improvement, however, was seen in the women on the placebo.
In a separate study, Asthana's team looked at the impact of estrogen therapy on men, building on their earlier discovery that testosterone replacement had helped improve spatial and verbal memory in older men. Testosterone is converted into a form of estrogen, called estradiol, in men. The six-week study examined 32 men, also divided into three groups, with an average age of 64. One group received weekly injections of testosterone, a second received testosterone plus a drug that blocks its conversion to estradiol, and the third group received placebos.
Asthana reported marked improvements in spatial memory in the group that received testosterone plus the estrogen blocker. But group with both high testosterone and estrogen levels saw significant improvements in verbal memory as well. Given that the loss of both spatial and verbal memory are hallmarks of the early stages of Alzheimer's, the researchers suggested that estrogen therapy may improve cognition and possibly help prevent the development of the disease in both men and women.
By Catherine Arnst in New Orleans Edited by Alex Salkever
Copyright 2000, by The McGraw-Hill Companies Inc. All rights reserved.
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