FDA Statement on the Results of the
Women's Health
Initiative (8/13/2002)
Women’s Health Initiative (WHI) Results Signal Need for
Reassessment of Risks and Benefits of Conjugated Equine Estrogens/medroxyprogesterone
Acetate (Prempro) in Postmenopausal Women
On July 9, 2002, the National Heart, Lung, and Blood Institute
(NHLBI) announced that it was stopping the combination conjugated equine
estrogen/medroxyprogesterone acetate (Prempro) study being performed as a part
of the Women’s Health Initiative (WHI). This study was conducted to assess
whether long term use of Prempro would reduce the risk of coronary heart
disease (CHD) in postmenopausal women. It was stopped early (after an average
of 5.2 years on study) because the overall health risks of Prempro,
particularly for invasive breast cancer and CHD, exceeded the benefits of the
drug, which included a lower rate of fractures and a reduction in the risk of
colorectal cancer.
No estrogen or estrogen/progestin combination product has been
approved by the FDA for prevention of CHD or other cardiovascular disease. In
recent years, based on epidemiologic data that suggested a possible
cardiovascular benefit, estrogens or combination products have been prescribed
for postmenopausal women specifically for preventing CHD. The WHI study was
initiated to evaluate the long-term benefits and risks of therapy with
estrogen or combination products in postmenopausal women. The WHI now
establishes that Prempro should not be prescribed to postmenopausal women for
cardiovascular protection. Another WHI study is assessing whether long term
use of an estrogen preparation (Premarin), in postmenopausal women who do not
have a uterus, will decrease the risk of CHD in that population. This study is
still ongoing. Until this study is completed, long-term use of estrogen
products to prevent cardiovascular disease should be considered
investigational.
Prempro is currently FDA-approved for: 1) treatment of
moderate-to-severe vasomotor symptoms associated with the menopause 2)
treatment of vulvar and vaginal atrophy, and 3) prevention of postmenopausal
osteoporosis. Estrogen products are not FDA-approved for prevention of
cognitive deficits. Although the recently stopped WHI study did not target
symptomatic women or those at risk for osteoporotic complications, the study
does provide data on the long-term risks of Prempro in postmenopausal women.
The increased risks of breast cancer and thromboembolic disease associated
with estrogen and combination estrogen/progestin had previously been known or
suspected. The increased risk of cardiovascular disease, including heart
attack and stroke, in healthy women, is new information. Women taking Prempro
or other combination estrogen/progestin therapy should consult with their
healthcare provider about the relevance of this new information to their
treatment. The decision whether to continue therapy must be individualized,
taking into account the known benefits and risks of therapy, as well as
alternative treatments. As is true for all medications, the lowest effective
dose should be sought.
Because of differences in estrogenic potency and product
composition, the extent that the new findings about risks are generalizable to
other combination estrogen/progrestin products is not known. The long-term
risks of lower doses of Prempro were not evaluated in the WHI trial.
The Department of Health and Human Services will host public
sessions on this issue in the fall. More information on this will follow.
Consideration will be given to the extent to which the WHI results might be
extrapolated to other combination estrogen/progestin products and doses, an
assessment of known benefits for approved indications in the light of these
new data, and the WHI's implications for future clinical trials of hormonal
therapy.
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FDA/Center for Drug Evaluation and Research
Last Updated: January 8, 2003
Originator: OTCOM/DLIS
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