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Restoring remembering: Hormones and memory
When Barbara Sherwin discovered the relationship between estrogen loss and a slight but consistent decline in memory in menopausal women, she was "petrified" to submit it for publication. The year was 1988.
PHOTO: Claudio Calligaris
"I wondered what the social ramifications of it might be. I didn't want to see any radical interpretations of what I found," she later told New York magazine.
Sherwin, a psychologist who is cross-appointed in the Departments of Psychology and Obstetrics and Gynecology, worried that simple-minded media outlets looking for a sensational story would leap to say that menopausal and postmenopausal women couldn't be relied upon because, as their estrogen levels declined with menopause, so did their verbal, or short-term, memory.
Still, her fear didn't prevent her from publishing her results, results that earned Sherwin widespread attention. Twenty-five years after she began her research, Sherwin is still a force to be reckoned with. She has recently been recognized by both McGill and the Canadian Institutes of Health Research, earning a James McGill Professorship from the University and a five-year distinguished scientist award from the CIHR.
When Sherwin began studying the role of hormones in the cognitive function of menopausal women while working on her master's and doctoral theses at Concordia University, there was little known about menopause and cognitive function. It was happenstance that she chose a field that has grown to be a hot topic.
"One day at Concordia, I found a book on psychoendocrinology and I was determined then to know what hormones did to behaviour."
Today, of course, there is far greater professional and lay interest in hormones and health due, in part, to the fact that baby boomer women are either entering or into menopause. These women want to know whether or not to take some form of HRT, hormone replacement therapy, consisting of estrogen or a combination of estrogen and the other female sex hormone, progesterone.
Initially, estrogen was prescribed to ease such menopausal symptoms as hot flashes. But since the 1980s, HRT has been widely prescribed, not only to ease symptoms, but to reduce the risk of such conditions as osteoporosis, the process of bone loss common in elderly Caucasian women, heart disease and, more recently, Alzheimer's disease -- the latter afflicting twice as many women as men!
That the relationship between changing estrogen levels and the incidence and onset of Alzheimer's disease -- and loss of cognitive functioning in general -- is now under long-term study is thanks, in part, to Sherwin's pioneering and ongoing work.
In the 1988 publication of her results, for instance, she established that estrogen maintains verbal memory and enhances the capacity to learn new things in postmenopausal women. Subsequently, she showed that HRT has the same effect on women in their 30s and 40s who have had their ovaries, where 90 per cent of estrogen is produced, surgically removed.
"Women who were given a placebo after their surgery complained of not being able to remember things, of having to make lists, which they never needed to do in the past. They also had lower scores on tests of verbal memory," she notes, explaining that one test of verbal memory is to have the women read a standard paragraph of prose, after which they are asked to recall the content. This is a measure of immediate memory. One hour later, after doing various other activities, the women are asked again to recall the paragraph.
The link between menopause, verbal memory loss and possibly Alzheimer's disease has caught the public's attention.
Now, when Sherwin crosses the border into the United States -- where she sits on numerous advisory boards related to menopause, Alzheimer's disease, and aging and women's health -- she's often questioned at the border.
The immigration officers aren't interested in the contents of Sherwin's baggage; when they find out who she is, they want to know about the effect of hormones on the brain. "They'll ask: 'What kinds of hormones could help my grandmother who has Alzheimer's disease?'" recounts Sherwin.
That's not a question that Sherwin can answer with absolute certainty right now because the studies done on the relationship between estrogen and Alzheimer's disease have involved relatively small samples of women and have not been long-term.
Also, until the launching in 1995 of a massive American study, the Women's Health Initiative of the National Institute of Health -- a study involving 27,000 women in their 60s and 70s, to last until 2005 -- little was known about normal aging in women.
"We could never define women's health," exclaims Sherwin, who, having established one of Canada's first menopause clinics (in 1982 at the Jewish General Hospital and now run from the Royal Victoria Hospital under Sherwin's co-direction), was invited by the NIH to help put together research guidelines establishing a definition of women's health.
"Until then, all the studies were done on men."
Another complicating factor is that the 25 per cent to 30 per cent of urban Canadian and American women who take estrogen tend to be middle class, well educated and in good health. These characteristics bias the results. In other words, these women might not have got Alzheimer's disease in any case, estrogen notwithstanding, explains Sherwin.
The number of years of education, as it turns out, is a good defence against the disease. "I always tell my students to stay in school as a preventive against cognitive aging," she says with a smile. "The onset of Alzheimer's disease will be delayed because you have a neuronal reserve."
By the year 2005, Sherwin and the numerous researchers involved with the WHI's Memory Study (where Sherwin sits on the external advisory board) will know for certain if estrogen does delay the disease. Since 1995, 10,000 women age 69 or older have been taking either a placebo or the estrogen randomly assigned to them and they will do so for a total of nine years.
Until the results are in from the WHI studies on estrogen's relationship, not only to memory, but to osteoporosis, heart disease and breast cancer, no one knows for sure just what the long-term benefits and risks, in the case of breast cancer, are. Still, Sherwin believes that HRT is beneficial to certain women but that it's an individual choice, one determined by lifestyle and family medical history.
An advocate of keeping the lives of aging women enjoyable and productive for as long as possible, she has little patience for those who dismiss HRT because it is "unnatural."
"What's not natural is to live to 80," she counters. "Women now live an average of 83 years and have from one-third to one-half of their lives to live after menopause. At the turn of the century, on the other hand, the average lifespan for women was 54 years and diseases of aging like osteoporosis and heart disease weren't an issue."
At the same time, Sherwin warns that estrogen is no panacea to the process of aging. Estrogen doesn't spring from the Fountain of Youth. "Enhancing quality of life is not the same as getting rid of the phenomenon of aging."
Interestingly enough, just as increased longevity has created a bevy of possibilities and problems for women, so it does for men, though in a less dramatic way.
In a study published last year in the Journal of the North American Menopause Society, Sherwin and her team found that in a study of 23 men, 23 women on HRT and 10 women who were not -- all of whom were in their early 70s -- the men had higher estrogen levels than the women not on HRT and outperformed them on verbal memory tests. The same group of men shared equal memory scores with the women taking the supplement.
This research led to an invitation by the New York foundation, The Institute for the Study of Aging, to apply for a grant. Sherwin did and now has $250,000 to use to study the possibility of using estrogen to prevent or put off the onset of Alzheimer's in 40 elderly men who have mild cognitive impairment, such as memory loss.
"Fifteen per cent of such diagnoses will convert to Alzheimer's disease within a year," says Sherwin, who will conduct this first-ever study on men, cognitive function and estrogen at the Jewish General Hospital with medicine professor Howard Chertkow.
Just as men have estrogen, so do women have testosterone and Sherwin is equally curious to see if this "male" hormone may also have a role to play in different kinds of memory. "My graduate students and I are looking at the two hormones to see if they might have selective effects on different aspects of memory, such as visual, or spatial, memory in the case of testosterone versus verbal memory in the case of estrogen." This time, the research will involve not only psychological testing but imaging of the brain using scanners.
When all the current and outstanding results are combined, it may just be that biology, after all, may be destiny but with the proviso that biology need not be a fixed entity.