Women's Health Initiative (WHI): Risks and benefits of hormone replacement therapy (HRT) and estrogen replacement therapy (ERT)
Hormone replacement therapy (HRT) was part of a large
set of clinical trials called the
Women's Health Initiative (WHI). The HRT portion of
the study was ended 3 years early because of a small but unacceptable increase
in the rate of
breast cancer among the women taking a combination of
0.625 mg of estrogen plus
2.5 mg of progestin daily. As WHI data has
been analyzed, risks of blood clots, heart disease, ovarian cancer, and
dementia have also been identified. Experts do not yet
know whether lower-dose, shorter-term HRT reduces or eliminates these
risks.
HRT use slightly raises the risk of several serious health
problems. This means that in a small number of women, using HRT causes a
serious health problem:
- HRT-related breast cancers first become apparent
after 4 years of HRT use. The number of HRT-related breast cancers increased
with each additional year of HRT use. Women taking HRT generally had larger,
more advanced tumors than women who developed breast cancer while taking
placebo treatment.1
- HRT slightly increases
stroke risk in all healthy postmenopausal women,
regardless of risk factors.1, 2
The increase in strokes first becomes apparent during the second year of HRT
use.3
- In women who are 10 or more years
past menopause, HRT slightly raises the risk of heart disease. Early signs of
heart disease can first become apparent during the first year of hormone
use.4, 5, 6
- HRT slightly raises the risk of blood clots in
the lungs (pulmonary embolism) and legs (deep vein thrombosis) in all healthy postmenopausal women regardless of risk
factors.3
- HRT raises the risk for
Alzheimer’s disease and other
dementias in women ages 65 and older. The increased
risk first becomes apparent in women taking HRT for more than 4 years. The WHI
researchers have concluded that HRT does not provide protection from dementia
or
cognitive impairment, as was previously
believed.7
- HRT slightly raises ovarian cancer risk. This means that for a
small number of women, taking HRT causes ovarian cancer.8
- Among HRT users, the number of abnormal
mammograms increases by approximately 4% each year,
first apparent after 1 year of HRT use. (Daily estrogen plus progestin
increased breast density compared with estrogen alone or
placebo.) Although the abnormal mammograms required
additional medical evaluation, they were not linked to the increase in breast
cancer. Studies are ongoing to determine the significance of this
finding.9
Estrogen replacement therapy (ERT) use
causes stroke and ovarian cancer in a small number of women. For this reason,
the Women's Health Initiative ERT trial was stopped sooner than originally
planned. Other ERT results show that women using ERT had no change in heart
disease risk and had fewer hip fractures (a sign of estrogen's bone-protecting
effect).10
Estrogen, progestin, and breast, ovarian, and endometrial cancer risks
Taking estrogen with progestin (HRT) or estrogen without
progestin (ERT) raises the risk of breast cancer and ovarian cancer. Taking
estrogen raises the risk of endometrial (uterine) cancer.11, 8 These increased cancer risks are
relatively low for the general population of postmenopausal women. But your
personal risk that hormone therapy may stimulate cancerous cell growth may be
significantly lower or higher, depending on your risk factors. For more
information about cancer risk factors, see the topics Breast Cancer, Ovarian
Cancer, and Endometrial Cancer.
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