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Are we asking the right questions about hormones? | page 1, 2
Neuropsychologists act as though memory is an entity that can be quantified via testing. Down deep we all know differently. Memory isn't a white-blood-cell count or an X-ray. Anyone who has given any thought to the false memory/recovered memory controversy understands the slippery nature of the very process of remembering. Anyone who has taken speed or much caffeine or stayed up all night cramming for an exam or had major test anxiety understands how memory itself is affected by a wide variety of biological, psychological and environmental factors. Compare the following: Psychologists at Montreal's McGill University have recently concluded that estrogen maintains verbal memory in women, may prevent or forestall the deterioration in memory that occurs with normal aging and may decrease the incidence of Alzheimer's disease and/or retard its onset.
Conversely, doctors from the Yale University department of internal medicine and a group of Finnish doctors feel that there is inadequate evidence to say that HRT improves cognitive function in post-menopausal women or women with Alzheimer's disease.
Ask Dr. Bob Dr. Robert Burton, who is a neurologist and novelist, answers health questions every Monday in Salon Health & Body. Please e-mail your queries to him at AskDrBob@ Is one study is better than the other? What should we conclude? A study from Holland may shed some light on the problem. Sixty-two healthy post-menopausal women were given either HRT or a placebo and were told the purpose of the study. Those given HRT reported better sleep patterns as well as improved psychological and memory function than before taking the HRT, yet didn't do better on memory testing than did the controls (the women who didn't get the estrogen). Then the researchers repeated the study, but without telling the women the purpose of the experiment. This time no positive effects of HRT could be detected. There are many possible interpretations, but one jumps out at me. Estrogen therapy can't be given blindly -- there are too many physiological changes that are easily detectable by the subjects, such as relief from hot flashes and/or vaginal dryness. So, in the first part of the study, the subjects knew what they were taking and what the researchers were looking for. They felt better (though not measurably better than the controls). When they knew what they were taking, but not what the researchers were looking for, however, they didn't feel better. Is the difference between the various studies I've cited due to a placebo effect, merely a reflection of how the researchers asked the questions, what kind of perfume the head nurse was wearing or whether free coffee and doughnuts were passed out along with the questionnaires? Were the subjects subliminally prodded toward the proper responses? Besides the notoriously difficult-to-analyze placebo effect, I wonder how those in the control group felt about not getting estrogen, about having more hot flashes than those in the other group? Was the control group resentful, glad not to be taking estrogen, pleased to be part of a study, indifferent or a combination of the above? What if one member of the control group read an Internet article about some new negative effects of estrogen and passed the word to the others in the group? If expectation influences results, what role does control-group psychology play? Is there such a thing as a control-group effect? And how would you know? Certainly not by comparing control groups -- which would result in an infinite regression. Surely there must be some shred of objectivity we can bring to the question. A Yale pediatrician, Sally E. Shaywitz, has used functional magnetic resonance imaging to compare brain patterns of post-menopausal women taking estrogen supplements and those on a placebo. While on estrogen, the women showed brain patterns similar to those seen in functional MRI scans of young people. The areas of the brain that lighted up more extensively than predicted correspond to regions of the brain known to be rich in estrogen receptors. Aha, you might think -- at last a definitive objective measure of increased brain activity when administering estrogen. So far, so good. But Shaywitz made the mistake of testing the patients to see if they also performed better. Unfortunately, they didn't. Objective evidence of brain activation wasn't accompanied by any detectable change in memory function. Her conclusion: More subjects needed to be studied. Nevertheless, on April 7, 1999, the Associated Press headline about the study read: "Estrogen may improve memory in post-menopausal women" (a true but potentially misleading statement). This problem of subjectivity extends to much of medicine, whether one is analyzing treatments for chronic pain, depression, social phobias, chronic fatigue or even the effects of zinc lozenges on the common cold. Symptom relief makes a lousy scientific endpoint. We are stuck. We need a new way of asking medical questions and we need a new way of reporting results. For starters, I'd suggest that each medical article clarify whether the effects being studied were objectively measured (bone density) or were based upon a subjective endpoint (changes in memory, reduction in back pain, feelings of well-being). The article should address the very knotty problem of whether the question being asked can be answered. As consumers, we need to be comfortable with these distinctions, to know when an article represents a true scientific determination and when it simply represents subjective opinion. Only then can medical news avoid the horrible to-and-fro swings in opinion that do nothing but enhance our already considerable health anxieties. I think of the judges at an Olympic diving competition. Each holds up two score cards -- one for technical difficulty and one for artistic merit. Maybe each new medical study should be similarly judged. The connection between estrogen and bone density is a simple question. That between estrogen and memory is profoundly more difficult. We should have different expectations, depending upon what is possible. And we should know what parameters scientists are using. An old story illustrates this: A scientist is seen crawling around under a streetlight. A bystander walks up to him and asks what he's doing. The scientist says that he's looking for his keys. The bystander asks him where he lost them, and the scientist points into the darkness beyond the pool of light from the street lamp. "So, why don't you look out there?" the bystander asks. "Because I can see here," the scientist says, continuing to search in the pool of light. It is scientists' obligation to tell us why they are looking where they are. It is up to us to know whether the keys can be found where the scientists are looking. Meanwhile, here is an interesting, well-balanced Web site dealing with HRT.
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