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Contact:
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April 16, 2003
Could
Heart Risks of Estrogen Replacement Be "Patched" Up?
First
head-to-head comparison shows estrogen pills increase heart disease risk factor,
but transdermal estrogen patches do not.
(BETHESDA,
MD)—The choice of pill or patch may be a key to evaluating potential heart
disease risks facing postmenopausal women who use estrogen replacement therapy,
according to a new study in the April 16, 2003 issue
of the Journal of the American College of Cardiology. In
a three-part study in which women alternated between estrogen pills, estrogen
patches and placebos, only the estrogen pills raised the level of C-reactive protein,
which is associated with higher risks of heart disease. "I'm
not going to say that women who need to take hormone replacement therapy now need
to change to the patch, but I think it is intriguing that there was so much difference
in terms of how our bodies handle the hormones. The route of administration may
play a very important role," said Wanpen Vongpatanasin, MD, FACC at the University
of Texas Southwestern Medical Center in Dallas, Texas. Researchers
in Texas and at the University of California at Davis Medical Center in Sacramento,
California enrolled 21 postmenopausal women in the study. The women were given
pills and patches that contained either estrogen or placebo. In random order,
each woman rotated through three possible combinations: estrogen pills and placebo
patches, placebo pills and estrogen patches, or placebo in both the pills and
patches. Each combination was used for eight weeks. The women did not know which
combination they were on at any given time. By using this type of crossover study
design, the response of each woman to one combination was compared to her own
responses to the other combinations. "We
drew blood samples and found that indeed the C-reactive protein increased when
they took the oral estrogen, but not when they were on the patch. Also, the inflammatory
cytokines, which are produced elsewhere in the body and not in the liver, were
not changed at any time. So it appeared that the liver was over-stimulated by
the oral administration of estrogen and produced the C-reactive protein, which
may be harmful," Dr. Vongpatanasin said. Whereas oral medications are processed
through the liver before circulating through the body, transdermal medications
enter the bloodstream directly. On
average, eight weeks of oral estrogen doubled C-reactive protein levels, which
is associated with increased heart disease risk. In addition, oral estrogen suppressed
blood levels of insulin-like growth factor (IGF-1). IGF-1 may offer some anti-inflammatory
benefits. There was no difference between estrogen patches and placebo in blood
test results. Dr.
Vongpatanasin said it is important to note that this study did not look at long-term
effects or actual heart disease events. "We cannot conclude that transdermal
estrogen will be safer because the right studies have not been done. However,
we cannot lump oral estrogen and transdermal estrogen together. More clinical
studies need to be done to see if transdermal estrogen might be better for some
women," she said. Cynthia
A. Stuenkel, MD, at the University of California at San Diego, who was not part
of the research team noted, "This is the first randomized controlled trial
to compare head to head oral conjugated equine estrogen with transdermal estrogen.
The rise in C-reactive protein with oral therapy could be hypothesized to contribute
to early cardiovascular events reported in" other recent trials of hormone
replacement therapy. Dr. Stuenkel said the suppression of insulin-like growth
factor (IGF-1) may be even more important than the increase in C-reactive protein. "For
women making a choice about short term hormone therapy for symptom relief, transdermal
therapy might be seen as the lesser of the two "evils". I would be cautious
in taking that stance, because in this trial, C-reactive protein is simply a surrogate
marker and not a clinical outcome." Elsa-Grace
V. Giardina, MD, at Columbia University in New York, New York, who has published
other research pointing to differences between oral and transdermal patches also
said this new study needs to be followed by more thorough research before women
can conclude that estrogen patches may be safer than pills. "So
I'm not sure that we can make that leap of faith. That is to say, I'm not sure
that cardiologists should go around recommending the transdermal formulation of
estrogen. However, it is a very interesting observation and probably would need
to be tested in a large clinical study, where they compare the transdermal formulation
to the oral formulation to see if this finding holds true for large numbers of
women." The
American College of Cardiology, a 28,000-member nonprofit professional medical
society and teaching institution, is dedicated to fostering optimal cardiovascular
care and disease prevention through professional education, promotion of research,
leadership in the development of standards and guidelines, and the formulation
of health care policy.
The
American College of Cardiology (ACC) provides these new reports of clinical studies
published in the Journal
of the American College of Cardiology as a service to physicians, the media,
the public, and other interested parties. However, statements or opinions expressed
in these reports reflect the view of the author(s) and do not represent official
policy of the ACC unless stated so.
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