NIH Asks Participants in Women’s
Health Initiative Estrogen-Alone Study to Stop Study
Pills, Begin Follow-up Phase
Statement from Barbara Alving, M.D., Director
of the Women’s Health Initiative
and Acting Director of the National Heart, Lung, and
Blood Institute
The National Institutes of Health (NIH) has instructed
participants in the estrogen-alone study of the Women’s
Health Initiative (WHI), a large multi-center trial,
to stop taking their study pills and to begin the
follow-up phase of the study.
Letters have been sent to all participants in the estrogen-alone
study, 11,000 healthy postmenopausal women who have
had a hysterectomy, informing them of a recent NIH
review of the study data. After careful consideration
of the data, NIH has concluded that with an average
of nearly 7 years of follow-up completed, estrogen
alone does not appear to affect (either increase or
decrease) heart disease, a key question of the study.
At the same time, estrogen alone appears to increase
the risk of stroke and decrease the risk of hip fracture.
It has not increased the risk of breast cancer during
the time period of the study.
The increased risk of stroke in the estrogen-alone
study is similar to what was found in the WHI study
of estrogen plus progestin when that trial was stopped
in July 2002. In that study, women taking estrogen
plus progestin had 8 more strokes per year for every
10,000 women than those taking the placebo. The NIH
believes that an increased risk of stroke is not acceptable
in healthy women in a research study. This is especially
true if estrogen alone does not affect (either increase
or decrease) heart disease, as appears to be the case
in the current study.
The NIH has determined that the results would not likely
change if the estrogen trial continued to its planned
completion in 2005. Furthermore, enough data have
been obtained to assess the overall risks and benefits
of the use of estrogen in this trial. WHI researchers
have begun a detailed analysis of the data from the
estrogen-alone study and expect to report full results
in the next two months. The report, to be published
in a peer-reviewed journal, will include additional
data collected through the end of February 2004.
A separate report will contain information on probable
dementia and/or mild cognitive impairment in the women
age 65 and older who participated in the estrogen-alone
WHI-Memory Study (WHIMS), an ancillary study of the
WHI Hormone Trials. Preliminary data suggest that
for the WHIMS participants who were on estrogen alone
when compared to the women who were taking the placebo,
there was a trend toward increased risk of probable
dementia and/or mild cognitive impairment.
The WHI estrogen study was designed to assess the effect
of long-term use of hormone therapy in healthy postmenopausal
women on the prevention of heart disease and hip fractures,
and any associated change in risk for breast cancer.
It was not designed to evaluate the short-term risks
and benefits of hormones for the treatment of moderate
to severe menopausal symptoms.
The estrogen-alone study involved women ages 50 to
79 years. Study participants were randomly assigned
to a daily dose of estrogen-- 0.625 mg/day of conjugated
equine estrogen (Premarin™)--or a placebo.
The NIH decision to stop the estrogen-alone trial was
made on February 2, 2004. In November and December
2003, the WHI Data and Safety Monitoring Board (DSMB),
an independent advisory committee which regularly
reviews study data and oversees the safety of study
participants, reviewed the latest data from the estrogen-alone
study. The DSMB was split as to whether the study
pills should be stopped or whether the pills should
be continued, provided that a letter would be sent
to the participants clearly informing them of the
stroke risks and other findings. After careful review,
the NIH decided that women in the estrogen-alone study
should stop taking their study pills.
The NIH advises women to continue to follow the FDA
guidance regarding hormone therapy. Currently the
FDA advises postmenopausal women who use or are considering
using estrogen or estrogen with progestin to discuss
the benefits and risks with their physicians. These
products are approved therapies for relief from moderate
to severe hot flashes and symptoms of vulvar and vaginal
atrophy. Although hormone therapy is effective for
the prevention of postmenopausal osteoporosis, therapy
should only be considered for women at significant
risk of osteoporosis who cannot take non-estrogen
medications. The FDA recommends that estrogens and
progestins should be used at the lowest doses for
the shortest duration needed to achieve treatment
goals.
The WHI involves over 161,000 women who are either
participating in a set of clinical trials to test
preventive measures for heart disease, fractures,
breast and colorectal cancer, or in a large observational
study. In addition to the trials of estrogen alone
and estrogen plus progestin, other WHI trials are
studying a low-fat eating pattern and calcium/Vitamin
D supplementation. These trials are continuing.
Participants in all of the WHI studies will be informed
about the detailed results of the estrogen-alone study
at the time of their publication in the next two months.
The estrogen-plus-progestin trial was stopped after
5.6 years of follow-up because of an increased risk
of breast cancer and because the risk of breast cancer,
coronary heart disease, stroke, and blood clots outweighed
the benefits on hip fracture and colorectal cancer.
Participants in the combined hormone therapy study
were assigned to either estrogen plus progestin (0.625
mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone
acetate) or to a placebo. Since these women had a
uterus, they were given progestin in combination with
estrogen, a practice known to prevent endometrial
cancer. Women who were enrolled in the active phase
of the estrogen-plus-progestin study are currently
in a follow-up phase and, like participants in the
estrogen-alone study, will be monitored to assess
long-term effects of hormone use.
WHI is sponsored by the National Heart, Lung, and Blood
Institute (NHLBI) in collaboration with the National
Cancer Institute, the National Institute of Arthritis
and Musculoskeletal and Skin Diseases, the National
Institute on Aging, and the Office of Research on
Women’s Health. Note: Wyeth Ayerst Research
provided the active hormone for the estrogen-alone
study and funded the WHIMS study.
NHLBI is part of the National Institutes of Health
(NIH), the Federal Government’s primary agency
for biomedical and behavioral research. NIH is a component
of the U.S. Department of Health and Human Services.
Additional information on menopausal hormone therapy,
including the WHI estrogen-plus-progestin study, can
be found on the NIH Website:
www.nih.gov, on the NHLBI
Website: www.nhlbi.nih.gov, and on the FDA
Website: www.fda.gov.
Additional information:
- Women’s
Health Initiative (www.nhlbi.nih.gov/whi)
- Questions
and Answers About the Estrogen-Alone Study (www.nhlbi.nih.gov/whi/e-a_faq.htm)
- Women's
Health Initiative Memory Study (WHIMS) (www.wfubmc.edu/whims/)
- FDA
Statement on Postmenopausal Hormone Therapy
(www.fda.gov/cder/drug/infopage/estrogens_progestins/default.htm)
- Postmenopausal
Hormone Therapy (NHLBI) (www.nhlbi.nih.gov/health/women/index.htm)
- Menopausal
Hormone Therapy Information (NIH) (www.nih.gov/PHTindex.htm)
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