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Older
women taking combination hormone therapy had twice the rate of dementia, including
Alzheimer's disease (AD), compared with women who did not take the medication,
according to new findings from a memory substudy of the Women's Health Initiative
(WHI). The research, part of the Women's Health Initiative Memory Study (WHIMS)
and reported in the May
28, 2003, Journal of the American Medical Association (JAMA), found the
heightened risk of developing dementia in a study of women 65 and older taking
Prempro™,
a particular form of estrogen plus progestin hormone therapy.
The study also found that the combination therapy did not
protect against the development of Mild Cognitive Impairment,
or MCI, a form of cognitive decline less severe than dementia.
"Because of possible harm in some areas and lack of
a demonstrated benefit in others, we have concluded that
combination hormone
therapy should not be prescribed at this time for older,
postmenopausal women to maintain or improve cognitive function," says
Judith A. Salerno, M.D., M.S., Deputy Director of the National
Institute on Aging (NIA) at the National Institutes of
Health (NIH), U.S. Department of Health and Human Services.
The findings were reported by WHIMS Principal Investigator
Sally A. Shumaker, Ph.D., Wake Forest University School of
Medicine, Winston-Salem, NC, and colleagues at the 39 sites
involved in the study.
The memory substudy WHIMS was funded by Wyeth Pharmaceuticals,
which manufactures Prempro™, which it provided for
use in the WHI trials. The larger WHI trials are supported
by the National Heart, Lung, and Blood Institute (NHLBI)
of the NIH. The NIA has been involved in reviewing
the current findings as the NIH's lead institute on
age-related memory change and dementia.
Importantly, the women in the combined estrogen plus
progestin (E+P) arm of the WHI and substudies such
as WHIMS are no longer taking the combination therapy
as part of the research trials. In July 2002, all combination
therapy components of the WHI were halted when it was
found that increased risk of breast cancer, heart disease,
stroke, and blood clots among participating women on
combined estrogen plus progestin therapy outweighed
benefits for hip fractures and colorectal cancer.
As they did in the July 2002 report on increased risk
of breast cancer, heart disease, and
stroke, researchers stress with today's announcement
that the data should
be viewed in perspective. While the increased
risk of dementia is significant when calculated over
a large
population of women, the risk to any
individual older woman is actually relatively small.
(For a detailed
discussion of relative versus absolute
risk, see the NIA Fact Sheet Understanding
Risk: What Do All Those
Headlines Mean? online at www.nia.nih.gov.)
The current findings address combined estrogen plus
progestin therapy, specifically Prempro
™, among women 65 years of age and older. For younger
women, the cognitive
risks and benefits of this combination
therapy are unknown. Short-term hormone therapy in
younger women
for some symptoms of menopause has been
approved by the U.S. Food and Drug Administration and
the new findings
do not directly address decisions about
such treatment. Researchers and officials at the NIH
suggest that women
of any age consult with a physician about
their individual risks and benefits.
The
memory study findings on women 65 and older showed that
over a 5-year period:
The risk for dementia among women taking estrogen
and progestin was twice that of women taking
placebo pills. This represents an increase per year
from 22
women per 10,000 at risk of dementia in
the placebo group to 45 women per 10,000 in the combination
therapy
group, an additional 23 cases per 10,000
per year among women taking combination therapy.
Sixty-one
cases of
dementia were diagnosed among the 4,500
women participating in the study; 66 percent of those
cases
occurred among
women on combination therapy while 34 percent
occurred in women taking placebo.
Most
of the dementia found among women participating in
the study was
classified as probable
Alzheimer's disease, with vascular dementia ranking
second. There
were 20 cases of Alzheimer's disease
among the 40 dementia cases in women in the combination
therapy group (50
percent of the cases); in women on placebo,
12 of the 21 cases (57 percent) of dementia were
deemed Alzheimer's
disease.
There
was no significant difference in the risk of being
diagnosed with MCI
alone when the placebo and
combination therapy groups were compared.
About 4,500 women participated in the WHIMS substudy
of women 65 and older. Once the women met the criteria
for participation, including screening tests to make
sure they did not have dementia at the study's start,
they were randomly assigned to take estrogen plus progestin
therapy (one pill per day of conjugated equine estrogen
(CEE), 0.625 mg, plus medroxyprogesterone acetate (MPA),
2.5 mg - brand name Prempro™) or a look-alike placebo.
Cognitive status was evaluated annually, and women
who showed signs of decline were examined in greater
depth to further characterize their cognitive status.
The researchers looked at several other factors that
might influence cognitive status, including socioeconomic
status, educational attainment, prior estrogen or
progestin use history, and use of cholesterol lowering
medications
or aspirin or other non-steroidal anti-inflammatory
drugs. These factors were not significantly different
between the therapy group and the placebo group and
did not account for the differences in rates of cognitive
decline,
the researchers said.
A second report in the same issue of JAMA showed
general cognitive status to be adversely affected
by the combination
therapy in older women. WHIMS investigator Stephen
Rapp, Ph.D., Wake Forest University School of Medicine,
and colleagues at the other sites examined the participants'
performance on an often-used test, the Modified Mini-Mental
State Exam (3MS). All participants' average performance
on the cognitive tests actually improved over time,
which researchers suggest may be due to a "practice
effect" as a result of taking the same tests
every year. However, the rate of increase in the
performance
of women on the 3MS was somewhat lower for women
in the combination therapy group when compared with
women
receiving the placebo.
About 3,000 women are continuing to participate in a second arm of the WHIMS
research, a study of the effects on cognition of estrogen-only therapy in women
who have had a hysterectomy. A Data Safety Monitoring Board will continue to
monitor the risks and benefits for that part of the study.
The NIH is considering implications of the dementia findings for other clinical
studies involving E + P.
More details on the studies' findings and their implications for women can
be found in a question-and-answer format prepared by the NIA for consumers.
Go to the NIA website www.nia.nih.gov or
call the NIA's Alzheimer's Disease Education
and Referral (ADEAR)
Center at 1-800-438-4380.
General information on hormone therapy and the Women's Health Initiative
specifically can be found on the NIH Web site, Menopausal
Hormone Therapy.
The NIA leads the Federal research effort on aging in general and on aging and memory, including Alzheimer's
disease. For more information on these topics, the public and media are invited to visit the NIA's websites.
Information on memory and Alzheimer's disease may be viewed at www.alzheimers.org, the ADEAR Center website.
The general public also may call the ADEAR Center
toll free at 1-800-438-4380 for information and publications.
General information on health and aging may be viewed
at www.nia.nih.gov, and publications may be ordered
by calling the NIA Information Center toll free at
1-800-222-2225.
The media may contact the NIA Office of Communications
and Public Liaison at 301-496-1752.
Radio editors, please note: An audio report will be
available after May 27, 4 p.m. ET, from the NIH Radio
News Service, by calling 1-800-MED-DIAL, or 1-800-633-3425.
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