Effect of hormone replacement
therapy on cardiac risk for diabetic women may depend on premenopausal
cardiovascular health
Data from a large observational study of hormone replacement therapy
in women with diabetes suggest that the effect of therapy may depend
on whether an individual woman had a previous myocardial infarction,
according to an article in the December 3rd rapid access issue of
Circulation.
One notable finding was in diabetic women
who had not had a myocardial infarction within a year of enrollment:
For this group, replacement therapy was associated with a 16 percent
lower risk of future myocardial infarction compared with no replacement
therapy.
“Our results are inconsistent with the results
from the Women’s Health Initiative, a randomized trial in women
without heart disease, which reported a 30 percent increased risk
of heart disease in women taking hormone replacement therapy compared
with women on placebo,” said lead author Assiamira Ferrara, M.D.,
Ph.D.
“Dr. Ferrara’s research adds to the pool of literature regarding
the cardiovascular effects of hormone replacement therapy in postmenopausal
women, but observational studies such as this, as opposed to prospective
clinical trials like the Women’s Health Initiative, are not definitive
and often raise more questions than they answer,” said American
Heart Association President Robert Bonow, M.D. “And this study does
raise an important question about hormone replacement therapy in
diabetic women - a question that can only be answered by a randomized
clinical trial.”
As was noted widely in the professional and
lay press, the Women’s Health Initiative trial was stopped in July
2002 when the study demonstrated no benefit, and possibly an increased
risk, for myocardial infarction and stroke in women taking combined
replacement therapy with estrogen and progestin.
In the current study, an American team followed
24,420 women (average age 65 years) with no history of myocardial
infarction within the past year and 580 women (average age 69 years)
with a recent infarction.
Among women without a recent myocardial infarction,
2,526 were using estrogen alone and 2,088 were using estrogen plus
progestin as replacement therapy. After an average of three years
of follow-up, there were 256 fatal myocardial infarctions and 854
nonfatal infarctions. Current use of estrogen plus progestin was
associated with a 22 percent lower rate of myocardial infarction
compared with the rate among women who did not take hormone replacement
therapy. The infarction rate among women on estrogen alone was 11
percent lower, but this difference was not statistically significant.
Risk estimates did not change significantly after researchers adjusted
for heart disease risk factors, ethnicity, education, and body mass
index.
“Another key finding was that women taking
low or medium doses of estrogen had a lower risk of heart attack,
but women taking high doses did not,” Ferrara noted.
Women on low doses had a 51 percent lower
risk and women on medium doses had a 19 percent lower risk of myocardial
infarction than women who did not take estrogen. High dose estrogen
was associated with a 7 percent increased risk of myocardial infarction.
In addition to differences based on dosage of estrogen, researchers
found that duration of replacement therapy was significant among
women without previous myocardial infarction. Risk of infarction
for women using replacement therapy for less than one year was about
the same as the risk for women who did not use replacement therapy.
For women on replacement therapy for longer than one year, risk
of myocardial infarction was 19 percent lower than among women who
did not use it.
In the group of 580 women with a recent myocardial
infarction, 15 percent were using hormone replacement therapy at
baseline. After an average follow-up of 2.5 years, women on replacement
therapy had a 78 percent higher risk of recurrent myocardial infarction
than women who did not use hormones. In addition, women who used
replacement therapy for less than one year had nearly a four-fold
increased risk for recurrent infarction than women who did not use
replacement therapy. There was no association between hormone replacement
therapy and risk of recurrent infarction in women who took hormones
for one year or longer.
In an editorial that will appear in the printed
issue of Circulation, David M. Herrington, M.D., notes that this
study illustrates yet another “awkward reality” of clinical research
on hormone replacement therapy.
“Observational studies like this one are likely
to provide an overly optimistic view of the effect of hormone replacement
therapy because they are not well suited to detect early adverse
effects,” he writes. “That is a likely explanation for the difference
between the Ferrara study and Women’s Health Initiative results.”
In the absence of data from randomized
clinical trials involving women with diabetes, the American Heart
Association advises that women should not start or continue combined
hormone replacement therapy to prevent coronary heart disease.
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