Estrogen May Ward Off Memory Loss
After creeping corpulence, perhaps the most common complaint of aging is what the experts politely call “benign” memory loss, and the rest of us, less politely, sometimes call CRS, for Can’t Remember (you know what).
For men with sluggish memories, the best advice science can offer to slow this process is this: Exercise (to increase blood flow to the brain); stay mentally active (to enhance connections between brain cells); and take nonsteroidal anti-inflammatory drugs such as ibuprofen (perhaps one a day), 800 international units of vitamin E and maybe a little ginkgo (though the data on ginkgo is less compelling). For women past a certain age, however, there’s an additional option: estrogen, which is increasingly being touted as a way to ward off not only normal age-related memory loss but Alzheimer’s disease as well.
The bio-logic behind this is respectable. Estrogen facilitates connections between nerve cells in the brain and enhances cerebral blood flow. It boosts brain chemicals such as serotonin, acetylcholine and dopamine and acts as an antioxidant, which means it might prevent some of the damage that occurs in Alzheimer’s disease. Even before the memory connection was made, of course, many women were already convinced of estrogen’s virtues: Hormone therapy is a huge industry that’s likely to grow to as much as a $5-billion market by 2005, based on estrogen’s proven ability to reduce menopausal symptoms such as hot flashes and to help prevent osteoporosis.
But does it really work on the brain? The answer, unfortunately, depends on whom you ask, how you measure memory and, perhaps most important, whether the researcher conducts actual experiments or simply surveys older women (including those with memory problems) about their memories and estrogen use.
For the moment, the best guess is that estrogen seems to protect against some kinds of normal memory loss, may help prevent Alzheimer’s disease as well, but probably does no good at all, at least without other drugs, once Alzheimer’s is already established.
One of the key research problems is that “there is no one, unitary thing called memory,” says Patricia Tun, associate director of the memory and cognition lab at Brandeis University in Waltham, Mass. And that, says Dr. Elizabeth Barrett-Connor, a professor of family and preventive medicine at UC San Diego, means “nobody knows exactly what to test for.”
Although some kinds of memory decline with age, some--such as vocabulary--actually get better with the years, notes Tun. Estrogen is probably not going to turn out to be a panacea for memory, she says, because men and women show similar patterns of memory change as they age, yet only women experience sharp declines in estrogen at menopause.
Nonetheless, there is a growing body of evidence that estrogen does play some role in protecting memory and enhancing learning as well, says Susan Resnick, a neuropsychologist at the National Institute on Aging. “From our studies, we know that women who use estrogen perform better on memory tests than women who don’t.”
Recent studies by Resnick and others using brain-imaging technology--not just clinical tests of memory--are encouraging; they show that estrogen seems to affect blood flow to areas of the brain, such as the hippocampus, known to be involved with memory.
Intensive research on estrogen and memory began more than a decade ago, when researchers in western Ontario showed that, in premenopausal women, performance on tests of certain cognitive skills--such as being able to pronounce tongue-twisters fluently--fluctuated with the menstrual cycle, with better scores on some tests occurring when levels of natural estrogen were highest.
In post-menopausal women too, Barbara Sherwin, a psychologist at McGill University in Montreal, has shown that “scores on tests of memory are better for estrogen users than nonusers.”
In several randomized studies, Sherwin tested women who were scheduled for surgery to remove their ovaries (which make estrogen) and uteri. The women were then assigned either to receive estrogen supplements or not. Those who took estrogen were able to maintain their pre-surgery scores on tests of memory; those who did not showed declines.
Sherwin says estrogen seems better at protecting verbal memory than visual memory. But last April, a randomized study published in Psychopharmacology suggested estrogen may enhance visual memory too. Women ages 55 to 75 who had never taken hormone therapy were assigned either to wear an estrogen skin patch or not for three weeks--and those who did showed benefits in visual memory.
Besides such randomized studies, there have been a number of observational studies that don’t assign women to take estrogen or not but simply follow them over time, test their memories and correlate that with estrogen use. These studies are more difficult to interpret.
In one such study, Barrett-Connor of San Diego found no effect of estrogen on cognition, despite the fact that her team used 12 types of memory tests. The study of about 3,000 women was published in 1993 in the Journal of the American Medical Assn.
More recently, an observational study of more than 21,000 women ages 70 to 78--the Nurses’ Health Study--also found no significant differences on several cognitive tests between estrogen users and nonusers, though the estrogen users did have an advantage in verbal fluency. The study was published last July in the journal of the American Geriatric Society.
But an observational study of more than 700 women in New York City published in 1998 in Neurology found that women who had ever taken estrogen performed better on verbal memory tests than those who hadn’t. The Baltimore Longitudinal Study on Aging found a similar effect for visual memory in results published in 1997.
Finally, a study of more than 8,000 women who were not taking estrogen also suggested a link between natural estrogen levels and cognitive function. Published last year, the study by Dr. Kristine Yaffe, an assistant professor of psychiatry, neurology and epidemiology at UC San Francisco, showed that women with more severe osteoporosis had poorer cognitive function than those with less severe cases of the bone-thinning disease. Low natural levels of estrogen are known to trigger osteoporosis and may explain the poorer cognitive function as well.
And what of estrogen’s ability to prevent and treat Alzheimer’s disease, as opposed to protecting against normal age-related memory loss?
An analysis of data pooled from 10 observational studies published in 1998 in the Journal of the American Medical Assn. showed a 29% lower risk of Alzheimer’s disease among estrogen users. Other studies--including one done in New York City in 1996--suggest as much as a 50% reduced risk of Alzheimer’s in women who have ever taken estrogen supplements.
For treatment, the results are less rosy. One study published last February followed women taking one of two doses of estrogen for one year. All had been diagnosed with mild to moderate Alzheimer’s. Even at the higher dose, estrogen did not slow progression of the disease. Two other studies last year also showed that estrogen does not slow progression of Alzheimer’s, suggesting that once brain damage occurs, estrogen cannot fix it.
“We were all surprised and disappointed about these findings because some of the prior research had suggested estrogen would help,” says Dr. Marilyn Albert, director of the gerontology research unit at Massachusetts General Hospital.
The new studies now underway should provide increasingly solid evidence of the pros and cons of estrogen as a memory booster. “Before long,” she says, “we will know whether or not estrogen is effective and what doses people should take if it is.”
Recent studies by Resnick and others using brain scans, for instance, not just clinical tests of memory, are encouraging; they show that estrogen seems to affect blood flow to areas of the brain such as the hippocampus known to be involved with memory.
Still, crucial questions will probably remain. If estrogen does truly protect memory, is this benefit offset if women take another hormone called progestin, which is used to protect the uterus against cancer-inducing effects of estrogen? Perhaps more important, would the memory-boosting effects of estrogen justify the increased risk of breast cancer known to be associated with hormone therapy?
For now, it’s still a guessing game. But many women are betting that estrogen may help.
*
Judy Foreman writes a syndicated column on health issues. She is a fellow in medical ethics at Harvard Medical School. She can be reached at foreman@bellatlantic.net. Her column will run occasionally in Health.
