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