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Long-Term
Hormone Therapy May Reduce Alzheimer's Risk for Women
By GINA KOLATA
NY Times, November 6, 2002
Women who take hormone therapy after menopause and continue with it for
10 years or more may have a reduced risk of Alzheimer's disease,
researchers report.
But scientists, including the study's lead investigator, caution that
the study's findings are suggestive, not definitive, in part because of
the study's design and because relatively few women who took part
developed the disease. For now, medical experts say, there is not enough
evidence to tell women, even those at high risk of Alzheimer's, to take
estrogen to lower their risk.
The Alzheimer's study, by Dr. John C. Breitner of the Veterans Affairs
Puget Sound Health System and his colleagues, involved 1,357 elderly men
and 1,889 elderly women living in Cache County, Utah. The researchers
questioned the study participants and gave them memory tests for
Alzheimer's. Three years later, they tested them again. During that time,
35 men and 88 women developed Alzheimer's. Using statistical modeling, the
investigators concluded that estrogen might cut a woman's risk in half,
but only if she took it for 10 years or more.
Dr. Breitner emphasized, however, that his study "does not rise to
the level of evidence that would warrant physicians prescribing hormone
therapy for this indication or for women to start using it for this
indication."
Dr. Bill Thies, the vice president for medical and scientific affairs
at the Alzheimer's Association, agreed. "Any effect of estrogen on
cognitive functioning is not well enough established to make that the
determining factor," Dr. Thies said.
The new paper, published today in The Journal of the American Medical
Association, comes on the heels of a major reassessment of postmenopausal
hormone therapy. In the 1990's, many doctors told women to start taking
hormones at menopause and to continue for the rest of their lives to
protect their health. But in July, a large federal study reported that
hormone therapy involving estrogen and progestin had slight risks — of
heart attacks, stroke, blood clots and breast cancer — that were not
balanced by its slight benefits, a small reduction in bone fractures and
in colon cancer. In response, leading medical groups said healthy women
should not use hormone therapy except to relieve disabling symptoms of
menopause, like severe hot flashes.
Researchers said that if estrogen reduced the risk of Alzheimer's
disease, that might swing the balance, making it advisable for some women
to take it.
Alzheimer's studies, however, have had conflicting results. Animal and
laboratory studies indicated that estrogen might protect the brain. But
clinical studies have failed so far to make the case. Dr. Breitner said
his findings might explain the previous studies by positing that there is
a critical period, years before Alzheimer's symptoms emerge, when a woman
must take estrogen if she is to reduce her risk.
"What's new here is that the benefits, if there are any, are
delayed a long time after treatment," Dr. Breitner said in a
telephone interview this week.
He explained, however, that his study observed whether women who chose
to take estrogen were less likely to develop Alzheimer's disease. One
problem is that women who take hormones after menopause are different from
those who do not take the drugs. Hormone users tend to be more educated,
for example, and healthier. Some of the very features that make them
likely to take hormone therapy are also features that, independently, are
associated with a lower risk of Alzheimer's disease. Scientists use
statistical adjustments to try to correct for the differences between
hormone users and nonusers, but they can never be sure they have
succeeded.
"The danger is that it is not the use of hormones that is driving
this relationship, but it is being the kind of woman who uses hormone
therapy," Dr. Breitner said. "There is no way you can get around
that except by doing a randomized controlled trial," in which women
are randomly assigned to take, or not take, the drugs. Such studies of
estrogen and Alzheimer's risk are now under way.
In fact, it was observational studies that helped convince medical
experts — incorrectly, as it turned out — that estrogen protected
women from heart attacks and strokes.
Such studies can have other drawbacks as well, and some occurred in Dr.
Breitner's study. For example, its conclusions were based on just 88 women
who developed Alzheimer's in the study period. The researchers subdivided
those women into hormone users and nonusers and, among the users, into
those taking hormones currently and those who took them previously. They
also took into account the duration of the drug therapy. The number of
women who fell into any of these groups was small, making the study's
conclusions less certain.
In addition, about 20 percent of the women declined to participate. It
is possible, said Dr. James Robins, a professor of biostatistics at the
Harvard School of Public Health, that they might have included a
disproportionate number of women in the early stages of Alzheimer's. Their
exclusion may have altered the study's results if they were also more
likely — or less likely — than the others to be taking hormones.
Even determining who took estrogen, and when, can be fraught with
difficulty. Dr. Norman Relkin, a neurologist at Cornell Medical School,
noted, for example, that the researchers ascertained hormone use by asking
the study subjects.
"Even a small number of women making a misrecollection could bias
the results," Dr. Relkin said.
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