Progesterone Resource
Center
Estrogen-Alone
Hormone Therapy Could Increase Risk of Dementia
in Older Women
article syndicated from NIH
Older women using estrogen-alone hormone therapy could
be at a slightly greater risk of developing dementia,
including Alzheimer's disease (AD), than women who
do not use any menopausal hormone therapy, according
to a new report by scientists with the Women's Health
Initiative Memory Study (WHIMS). The scientists also
found that estrogen alone did not prevent cognitive
decline in these older women. These findings from WHIMS
appear in the June 23/30, 2004, Journal of the American
Medical Association*.
"These studies further support last year's recommendations
that menopausal hormone therapy should not be used
to prevent cognitive decline or dementia in older postmenopausal
women," stated Judith A. Salerno, MD, MS, Deputy
Director of the National Institute on Aging (NIA). "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."
The
latest findings were reported by WHIMS Principal Investigator
Sally
A. Shumaker, PhD, Wake Forest University
School of Medicine, and her colleagues at the 39 study
sites. This research was funded by Wyeth Pharmaceuticals,
which manufactures Premarin™, the conjugated equine
estrogens used in this trial, and Wake Forest University
Baptist Medical Center. WHIMS is a substudy of the
Women's Health Initiative (WHI) Hormone Trial, which
is funded by the National Institutes of Health (NIH)
at the Department of Health and Human Services (DHHS).
The National Institute on Aging (NIA), a component
of NIH, has been involved in reviewing the current
findings as the lead NIH institute on age-related cognitive
change and dementia.
The WHI Hormone Trial using estrogen plus progestin
was stopped early in July 2002 when researchers found
an increased risk of breast cancer, along with greater
risks of heart disease, stroke, and blood clots, and
determined that these risks outweighed the benefits
of reduced risks of hip fracture and colorectal cancer.
In May 2003, WHIMS investigators reported the results
of the estrogen plus progestin part of their memory
substudy**. They found that
estrogen plus progestin increased the risk of probable
dementia in women 65 and older and did not preserve
cognitive function. This part of WHIMS was also stopped
in July 2002.
At the end of February 2004, the remaining parts of
the WHI Hormone Trial and WHIMS, the estrogen-alone
components, were halted because results were showing
an increased risk of stroke and no reduction in the
risk of heart disease in the women using estrogen alone.
Scientists further believed that continuing the study
until its planned conclusion next year would probably
not add new information. In April 2004, the WHI investigators
reported that they found an increased risk of blood
clots, but no significant effect on breast or colorectal
cancer and also a reduced risk of fractures in those
women using estrogen alone.
Now,
the WHIMS scientists have evaluated the cognition and
dementia data from
the estrogen-alone part of the
trial. Some 2,947 women age 65 to 79 at the beginning
of the trial received estrogen alone (a daily dose
of 0.625 mg of Premarin™) or a placebo. (The women
received estrogen alone because they had all had hysterectomies
at some time before beginning the study. A progestin
is used with estrogen in menopausal hormone therapy
in any woman with a uterus to prevent thickening and,
sometimes, cancer of the lining of the uterus, the
endometrium. Because the uterus is removed in a hysterectomy,
there is no need for progestin when women who have
had hysterectomies use menopausal hormone therapy.)
Participants were determined to be dementia free before
they were enrolled in WHIMS. At the beginning and then
annually for the more than 5-year average duration
of the trial, WHIMS participants were evaluated to
determine if they might have developed dementia or
mild cognitive impairment (MCI). All women received
the Modified Mini Mental State Exam (3MSE), and those
suspected of having dementia also received an extensive
clinical evaluation by a specialist physician.
At
the end of the study, the risk of dementia in the estrogen-alone
group
was 49% higher than the risk
in women using the placebo. That is, among 10,000 women
using conjugated equine estrogens, 37 could be expected
to develop dementia, compared to 25 in 10,000 women
using the placebo — 12 extra cases of dementia
in every 10,000 women using estrogen alone each year.
This increased risk was not statistically significant.
Last
year WHIMS scientists reported a 105% increase
in the risk of dementia in older women using estrogen
plus progestin compared to those using a placebo. That
means, on average, each year in 10,000 women over age
65 using estrogen plus progestin there might be 45
cases of dementia compared to 22 cases in 10,000 older
women on placebo.
Almost
half of the dementia cases in the estrogen-alone study — 46% in older women using estrogen
alone and 47% of those in older women using the
placebo — were Alzheimer's disease (AD). Similarly,
in the estrogen plus progestin study, 50% of the
cases in older women using estrogen plus progestin
and 57% of those in older women using placebo
were classified as AD.
A second article on general cognitive function *** from
Mark A. Espeland, PhD, and other WHIMS investigators
appears in the same issue of JAMA. It reports
that beginning estrogen-alone hormone therapy after
age 65 can have a small negative effect on overall
cognitive abilities and that this negative effect may
be greater in women with existing cognitive problems.
The differences in scores on cognitive testing for
the estrogen-alone and placebo groups were statistically
significant, but the differences were so small that
they are not considered clinically relevant by the
investigators.
As with the earlier WHI and WHIMS result reports,
these increases in risk must be viewed in perspective.
Significant increases in risk are important for public
health officials who are concerned with large groups
in the population, where a small increase could have
health implications for millions of people. For an
individual woman, however, the increased risk is still
quite small. (A detailed discussion of risk is presented
in the NIA Fact Sheet, Understanding Risk: What
Do Those Headlines Really Mean?, available
online at http://www.niapublications.org/engagepages/risk.asp.)
Further,
these findings relate to women age 65 and older taking
this particular
estrogen-alone hormone
therapy. The cognitive risks and benefits for younger
women using Premarin™ or other estrogen formulations
are unknown. Any younger woman who is considering menopausal
hormone therapy because of her menopausal symptoms
should talk to her doctor about how the various Women's
Health Initiative study findings relate to her own
medical history and treatment.
General
information on menopause, menopausal hormone therapy,
and the Women's Health Initiative can be found
on the NIH home page or
by going directly to www.nih.gov/PHTindex.htm.
*
Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, Fillit H, Stefanick
ML, Hendrix S, Lewis CE, Masaki K, Coker LH, Conjugated Equine Estrogens
and Incidence of Probable Dementia and Mild Cognitive Impairment in Postmenopausal
Women: Women's Health Initiative Memory Study. JAMA. 2004; 291: 2947-2958.
**
Shumaker SA, Legault C, Rapp SR. Estrogen plus progestin and the incidence
of dementia and mild cognitive impairment in postmenopausal women. The Women's
Health Initiative Memory Study: a randomized controlled trial. JAMA.
2003; 289:2651-2662.
Rapp S, Espeland MA, Shumaker SA, et al. Effect
of estrogen plus progestin on global cognitive function
in postmenopausal women: Women's Health Initiative
Memory Study; A Randomized Controlled Trial. JAMA.
2003; 289: 2663-2672.
***
Espeland MA, Rapp SR, Shumaker SA, Brunner R, Manson JE, Sherwin BB, Hsia J,
Margolis KL, Hogen PE, Wallace R, Dailey M, Freeman R, Hays J for the Women's
Health Initiative Memory Study. Conjugated Equine Estrogens and Global Cognitive
Function in Postmenopausal Women: Women's Health Initiative Memory Study. JAMA.
2004; 291: 2959-2968
article
syndicated from National
Institutes of Health:
http://www.nih.gov/news/pr/jun2004/nia-22.htm
EMBARGOED
FOR RELEASE - Tuesday, June 22, 2004 - 4:00 p.m.
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