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WHI
Study Finds No Heart Disease Benefit, Increased
Stroke Risk With Estrogen Alone
article syndicated from NIH
A large, multi-center heart disease prevention study,
part of the Women's Health Initiative (WHI), found
that estrogen-alone hormone therapy had no effect on
coronary heart disease risk but increased the risk
of stroke for postmenopausal women. The study also
found that estrogen-alone therapy significantly increased
the risk of deep vein thrombosis, had no significant
effect on the risk of breast or colorectal cancer,
and reduced the risk of hip and other fractures.
The WHI is sponsored by the National Heart, Lung,
and Blood Institute (NHLBI), part of the National Institutes
of Health (NIH).
The estrogen-alone study was stopped at the end of
February 2004 because the hormone increased the risk
of stroke and did not reduce the risk of coronary heart
disease, a key question of the trial. The study was
to have ended in March 2005. Initial findings appear
in the April 14 issue of The Journal of the American
Medical Association.
A separate report on the WHI Memory Study of estrogen
alone's effects on dementia and cognitive function
will be published soon.
"These findings confirm that estrogen-alone therapy
should not be used to prevent chronic disease," said
NHLBI Acting Director Dr. Barbara Alving. "We
believe the findings support current FDA recommendations
that hormone therapy only be used to treat menopausal
symptoms and that it be used at the smallest effective
dose for the shortest possible time."
"The results make clear that hormone therapy
does not protect women against coronary heart disease
and increases their risk for stroke," said Dr.
Jacques Rossouw, WHI Project Officer at NHLBI. "This
may be especially true for older women, such as those
aged 60 and older in this study."
As of July 2003, about 10 million American women were
taking some form of hormone therapy. It is estimated
that about 6.7 million of those take estrogen alone
and 3.3 million take estrogen plus progestin. The drugs
tested in the WHI are those most commonly used in the
United States.
The estrogen-alone study involved 40 clinical centers
and 10,739 generally healthy postmenopausal women ages
50-79 who did not have a uterus. Their average age
at enrollment was nearly 64 and about 70 when the study
stopped. They enrolled in the study between 1993 and
1998.
About 75 percent of the women were white, 15 percent
black, and 6 percent Hispanic. Most of the women were
overweight and about 8 percent had diabetes. About
35 percent of the women had used hormone therapy in
the past and about 13 percent were current users at
the time they enrolled in the study.
The
women were randomized to two groups-one received 0.625
mg/day of conjugated
equine estrogens (Premarin™)
and the other a placebo. Premarin™ and the placebo
were supplied by Wyeth-Ayerst Research.
The women were followed for an average of 6.8 years.
They visited their clinic at least once a year, and
had annual mammograms and clinical breast exams.
The study was carefully monitored by an independent
Data and Safety Monitoring Board (DSMB). The NIH made
the decision at the beginning of February 2004 to stop
the study drugs. The JAMA article includes data collected
through February 2004.
For every 10,000 women each year, on average, estrogen-alone
use compared to placebo resulted in:
| Increased
risk for — |
| |
Stroke (fatal and non-fatal) |
12 cases more (44 cases in those
on estrogen alone and 32 in those on placebo) |
| |
Venous thrombosis
(blood clot, usually
in one of the
deep veins of the legs) |
6 cases more
(21 cases in those on estrogen alone and
15 in those on placebo) (An
increased risk of pulmonary embolism — blood
clots in the lungs — was not statistically
significant — there were 13 cases in those
on estrogen alone and 10 in those on placebo.) |
| No
difference in risk or uncertain effect for — |
| |
Coronary heart disease |
No significant
difference in risk (neither increased nor
decreased) — 5 fewer
cases (49 cases in those on estrogen alone
and 54 in those on placebo). During the first
two years
of use, risk was slightly increased for estrogen
alone, but it appeared to diminish over time. |
| |
Colorectal cancer or total cancer |
No significant
difference in risk (neither increased nor
decreased) — 1 more
case for colorectal cancer and 7 fewer cases
for total cancer (for colorectal cancer,
17 cases in
those on estrogen alone and 16 in those on
placebo; for total cancer, 103 cases in those
on estrogen
alone and 110 in those placebo) |
| |
All deaths or those for a specific
cause |
No significant
difference in risk (neither increased nor
decreased) — 3 more
deaths (for all deaths, 81 in those on estrogen
alone and 78 in those on placebo) |
| |
Breast cancer |
Uncertain effect — 7
fewer cases (26 cases in those on estrogen
alone and
33 in those on placebo). This finding was not
statistically significant. |
| Increased
benefit for — |
| |
Bone fractures |
6 fewer hip fractures (11 cases
in those on estrogen alone and 17 cases in those
on placebo) |
The results above were not affected by race or ethnicity,
or body mass index (BMI).
Another WHI hormone study, the estrogen-plus-progestin
trial, was also stopped early. It was halted in July
2002 after 5.6 years of followup because of an increased
risk of breast cancer and because the increased risks
of breast cancer, coronary heart disease, stroke, and
blood clots outweighed the benefits of a reduced risk
of hip fracture and colorectal cancer.
The
combined hormone therapy study involved 16, 608 participants,
who
were randomly assigned to receive
either a daily intake of 0.625 mg of conjugated equine
estrogens plus 2.5 mg of medroxyprogesterone (Prempro™),
or a placebo. Combination therapy is used when women
have a uterus to prevent the development of endometrial
cancer.
Key findings of estrogen plus progestin compared to
the placebo for every 10,000 women each year were:
more strokes (8 more cases); an increased risk of breast
cancer (8 more breast cancers); an increase in heart
attacks (7 more heart attacks); a higher risk of blood
clots (8 more women with blood clots in the lungs and
18 more with blood clots in the legs or lungs); a reduction
in hip fractures (5 fewer hip fractures); and a drop
in the risk of colorectal cancer (6 fewer colorectal
cancers).
Rossouw
cautioned that the findings for the two hormone therapy
studies
should not be compared directly. "At
baseline, the women in the estrogen-alone study had
a higher risk of cardiovascular disease than those
in the estrogen-plus-progestin trial. Those in the
estrogen-alone study were more likely to have such
heart disease risk factors as high blood pressure,
high blood cholesterol, diabetes, and obesity."
Women in both hormone trials are now in a followup
phase, due to last until 2007, during which their health
will be closely monitored.
WHI
was launched in 1991 and consists of a set of clinical
trials to
test the preventive effects of postmenopausal
hormone therapy, diet modification, and calcium and
vitamin D supplements on heart disease, fractures,
breast and colorectal cancer, as well as an observational
study, which is looking for predictors and biological
markers for disease. The diet modification trial involves
nearly 49,000 women, the calcium/vitamin D trial about
36,000 women, and the observational study about 94,000
women — all three studies are continuing.
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.
To arrange an interview about the WHI, call the NHLBI
Communications Office at (301) 496-4236.
article
syndicated from National
Institutes of Health:
http://www.nih.gov/news/pr/apr2004/nhlbi-13.htm
EMBARGOED FOR RELEASE - Tuesday, April 13, 2004 -
4:00 p.m. ET
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