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.
