The second half of the data from the Women's Health Initiative Memory Study
(WHIMS) has now been analyzed, and the answer is clear: For women to avoid
increasing their risk of developing dementia as they get older, they should
just say "no" to hormone replacement therapy.
A great deal of the data from the Women's Health Initiative of the National
Institutes of Health has served to debunk a few well-worn tenets of women's
health in the last two years, one of which is that hormone replacement wards
off dementia, including Alzheimer's disease. Last year researchers reported
that combination hormone therapy—estrogen plus progestins—doubled
the risk of dementia in older women and did not benefit global cognition,
including memory, concentration, language abilities, or abstract
Now two new reports in the June 23/30 issue of the Journal of the
American Medical Association detail the results of the same study, only
for women who took estrogen without any progestins.
"The use of estrogen by women 65 years and older to prevent dementia
or cognitive decline is not recommended," said Sally Shumaker, Ph.D.,
NIH's principal investigator for WHIMS and an associate dean for research and
professor of public health sciences at Wake Forest University Baptist Medical
Center in Winston-Salem, N.C. "We found a similar, but slightly weaker,
trend toward increased risk of dementia among the women taking estrogen
She added, "Women should follow the Food and Drug Administration's
recommendation that those who want to use menopausal hormone therapy to
control their menopausal symptoms should use it at the lowest effective dose
for the shortest time necessary."
Shumaker defined the risk this way: "In a population of 10,000 older
women, all taking estrogen alone, there would be an additional 12 cases of
dementia per year. For 10,000 women taking the combined hormone therapy, there
would be an additional 23 cases of dementia per year. Clearly, hormone therapy
does not prevent dementia—as was thought when we began this important
The Women's Health Initiative trial using combined hormone therapy with
both estrogen and progestin was halted by NIH in July 2002, when researchers
discovered an increased risk of breast cancer, heart disease, stroke, and
blood clots in the subjects. They also determined that combined hormone
therapy decreased the risk of hip fracture and colorectal cancer but that the
possible benefits were overwhelmingly outweighed by the increased risk of
morbidity and mortality.
In February the remaining estrogenonly arms of the study were halted as
well, when analysis revealed an increased risk of stroke and no reduction in
risk of heart disease. At that time, Shumaker and her colleagues at the 39
study sites said they did not believe that continuing the study until its
planned conclusion next year would add any new information. In April the
researchers reported that they had found an increased risk of blood clots in
women using estrogen alone, but no significant effect on breast or colorectal
cancers. Subjects did not have a reduced risk of fractures.
In the second JAMA report, Shumaker's colleague Mark Espeland,
Ph.D., also a professor of public health sciences at Wake Forest University
Baptist Medical Center, reported that beginning estrogen-only therapy after
the age of 65 can have profound negative effects. Not only is there no
cognitive protection effects, but also there may be a small negative effect on
overall cognition. In addition, this negative cognitive effect may be greater
for women who have cognitive difficulties to begin with.
"Conjugated Equine Estrogens and Incidence of Probable
Dementia and Mild Cognitive Impairment in Postmenopausal Women," is
posted online at<http://jama.ama-assn.org/cgi/content/abstract/291/24/2947>;"
Conjugated Equine Estrogens and Global Cognitive Function in
Postmenopausal Women," is posted at<http://jama.ama-assn.org/cgi/content/abstract/291/24/2959>.▪