WHI Study of Younger Postmenopausal Women Links
Estrogen Therapy to Less Plaque in Arteries
Experts Caution that Heart Disease Effects
Remain Unclear
New results from a substudy of the Women's Health Initiative (WHI)
Estrogen-Alone Trial show that younger postmenopausal women who
take estrogen-alone hormone therapy have significantly less buildup
of calcium plaque in their arteries compared to their peers who
did not take hormone therapy. Coronary artery calcium is considered
a marker for future risk of coronary artery disease.
Results of the WHI Coronary Artery Calcium Study are published
in the June 21, 2007, issue of the New England Journal of Medicine.
The WHI is sponsored by the National Heart, Lung, and Blood Institute
(NHLBI) of the National Institutes of Health.
"These new results offer some reassurance to younger women who
have had a hysterectomy and who would like to use hormone therapy
on a short-term basis to ease menopausal symptoms," noted Elizabeth
G. Nabel, M.D., NHLBI director. "We must emphasize, however, that
these findings do not alter the current recommendations that when
hormone therapy is used for menopausal symptoms, it should only
be taken at the smallest dose and for the shortest time possible,
and hormone therapy should never be used to prevent heart disease."
The new findings are from an ancillary study of 1064 women who
were 50-59 years of age at the start of the WHI hormone therapy
clinical trial. Participants were randomly assigned to either 0.625
milligrams per day of conjugated equine estrogens (Premarin™)
or placebo (inactive pill). Participants took assigned medication
for an average of nearly seven and one-half years. After slightly
more than one year after treatment ended, researchers used computed
tomography (CT scan) to measure the level of calcium plaque in
the women's coronary arteries. Those who had taken estrogen were
30 to 40 percent less likely to have measurable levels of coronary
artery calcium compared to those on placebo.
"Although our findings lend support to the theory that estrogen
may slow early stages of plaque build-up in the coronary arteries,
estrogen has complex effects and other known risks," said JoAnn
Manson, M.D., chief of Preventive Medicine at Harvard's Brigham
and Women's Hospital and lead author of the paper. “The results
are consistent with our earlier findings that younger women treated
with estrogen had a trend toward fewer heart attacks but, for an
individual woman, it remains uncertain whether the benefits of
estrogen would outweigh the risks. For this reason, estrogen should
not be used for the express purpose of preventing cardiovascular
disease, but it may be appropriate for the short-term treatment
of moderate-to-severe hot flashes or night sweats among recently
menopausal women."
In February 2006, WHI researchers reported that among the women
in the estrogen-alone trial who were 50-59 years of age at study
entry, women in the estrogen group had a non-significant trend
towards lower rates of heart attacks compared to the placebo group,
and significantly fewer women in the estrogen group required procedures
to re-open clogged arteries. There was no suggestion of cardiovascular
benefit in women who were 60 years or older.
“Heart attacks are uncommon among younger women, and the more
relevant question is about long-term benefit as women grow older," noted
Jacques Rossouw, M.D., chief of the NHLBI Women’s Health Initiative
Branch. "Conducting a clinical trial that would start any form
of hormone therapy on postmenopausal women at a younger age and
follow them for decades — when they would be more likely
to have heart attacks — is not feasible.
"We cannot assume that any possible short-term, cardiovascular
benefit from hormone therapy to postmenopausal women in their fifties
would extend into older ages if they were to continue using hormones," Rossouw
cautioned. "We already know that starting hormone therapy in older
women increases their risk of heart disease. And long-term hormone
therapy has other risks such as strokes and blood clots, and, with
the use of combination therapy, breast cancer."
The WHI is a major, 15-year research program designed to address
the most frequent causes of death, disability, and poor quality
of life in postmenopausal women: cardiovascular disease, cancer,
and osteoporosis. The principal findings from the WHI hormone therapy
trials, which studied 27,347 postmenopausal women on estrogen-alone
or estrogen plus progestin, found that the overall risks of hormone
therapy outweigh the benefits. Both of these trials were stopped
early because of increased health risks and failure to prevent
heart disease, a key question of the studies. Even though the risks
for coronary heart disease were less pronounced in the estrogen
alone trial than in the estrogen-plus — progestin trial,
both therapies increased the risk of stroke and of blood clots.
Overall, the estrogen-alone study involved 40 clinical centers
and 10,739 generally healthy postmenopausal women ages 50-79 who
did not have a uterus. The clinical trial was stopped in February
2004 after approximately 7 years of follow up because of increased
risk of stroke and no reduction in risk of coronary heart disease.
The study also found an increased risk of blood clots.
The estrogen-plus-progestin study (conducted in postmenopausal
women with a uterus) was stopped in 2002 due to an increase in
breast cancer. Like estrogen-alone, combination hormone therapy
was also found to increase the risk of stroke and blood clots regardless
of the women's age or time since menopause. Combination therapy
was also found to increase the risk of heart disease in the first
few years.
All women who wish to lower their risk of heart disease should
make healthy lifestyle choices, such as following a diet low in
sodium, saturated fat, transfat and cholesterol; maintaining a
healthy weight; engaging in regular physical activity; and not
smoking. In addition, they should work with their healthcare provider
to identify and manage other known risk factors such as high blood
pressure, high blood cholesterol, and diabetes.
NHLBI collaborates on the WHI with the National Cancer Institute,
the National Institute of Arthritis and Musculoskeletal and Skin
Diseases, and the National Institute on Aging, and the Office of
Research on Women’s Health, all parts of the NIH. Wyeth-Ayerst
Research provided the medication and placebo for both hormone studies.
To interview Dr. Rossouw about the WHI, call the NHLBI Communications
Office at (301) 496-4236. To speak with Dr. Manson, please contact
Brigham and Women's Hospital at (617) 534-1604.
For more information:
Part of the National Institutes of Health, the National Heart,
Lung, and Blood Institute (NHLBI) plans, conducts, and supports
research related to the causes, prevention, diagnosis, and treatment
of heart, blood vessel, lung, and blood diseases; and sleep disorders.
The Institute also administers national health education campaigns
on women and heart disease, healthy weight for children, and other
topics. NHLBI press releases and other materials are available
online at: www.nhlbi.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.
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