April 4, 2000 Reported by The Washington Post
and The Los Angeles Times
"Estrogen Use Tied to Slight Rise in Heart Risk"
Largest Study Ever on HRT
25,000 women taking part in a federal study of hormone replacement
therapy have been informed by researchers that, far from
protecting the heart as many researchers had assumed, the therapy
may have put the women at a slightly higher risk of heart attacks
study, known as the Hormone Replacement Therapy trial of the
Women's Health Initiative, is the first large-scale controlled
clinical trial asking whether the therapy prevents heart disease
in healthy post-menopausal women.
in letters sent out on Friday, participants were told that those
who had been randomly assigned to take estrogen were having
slightly more heart attacks, strokes and blood clots in the lungs
than those who had been assigned to take dummy pills for
comparison. While the effect was not sufficiently pronounced to
stop the study, the researchers themselves were taken aback.
estimated 10 million American women take Premarin, an estrogen
that was approved only to alleviate the symptoms of menopause,
like hot flashes, and for the prevention and management of
drug's maker, Wyeth-Ayerst Laboratories, a subsidiary of the
American Home Products Corporation, says the estrogen is the
best-selling prescription drug in America.
and individual women say that one reason for estrogen's popularity
is that there is a widespread belief that it will prevent heart
disease. But that hypothesis came from indirect evidence.
Claude Lenfant, director of the National Heart, Lung and Blood
Institute, said in a statement on Monday that the new information
is "preliminary." It does not address the larger issue
of long-term benefits and risks of hormone replacement therapy, he
said, "and, therefore, it should not influence current
studies have shown that women who take estrogen after menopause
have fewer heart attacks than women who do not.
since women who take the hormone tend to be better educated, less
likely to smoke and more likely to eat balanced diets and
exercise, it was hard for researchers to tell whether the therapy
or other factors in their lives contributed to their lower risk.
The only way to know for sure was to do a large study like the
Jacques E. Rossouw, who is acting director of the hormone
replacement trial, said in an interview yesterday that even though
it was too soon to say whether the increased risk of heart attacks
and strokes would hold up as the study continued, he felt morally
obliged to inform the women about the finding.
wasn't anticipated when they enrolled," Dr. Rossouw said.
"We told them all about the risks and benefits but we didn't
tell them there might be an increased risk of heart disease."
added that he fervently hoped that the women would stay in the
study and that other women would not panic because the number of
women who had had heart attacks and strokes was minuscule.
my women friends ask me, 'How does this affect me?', my advice is
it doesn't change a thing," Dr. Rossouw said. "I would
say there never was proof that hormones help heart disease and
there still isn't. The only qualifier is, if you're expecting an
early benefit from heart disease it looks less likely."
emphasize that only a small number of women in the study actually
had heart attacks, strokes or blood clots in the lungs or the
legs. The exact numbers were in the hands of an independent
committee that oversees the study, and its members would not
reveal them even to the study investigators.
But overall, only
about 1 percent of all the women, who were 50 to 79, had these
problems in the first two years of the study. The effect seems to
be diminishing as the study continues, the researchers say. Yet
apparently, these grave medical problems were disproportionately
concentrated in the women taking hormones that were supposed to
is the most widely prescribed drug in America," said Cindy
Pearson, the executive director of the National Women's Health
Network, an advocacy group in Washington. "A lot of the women
are taking it because they've been told by their doctors that it
will prevent a heart attack. Those are the women who should be
sitting up and taking notice and going to their doctors and
saying, 'Why am I taking this? What's the point of this?' "
Pearson said that in her opinion no woman should be taking
estrogen to prevent heart disease outside of a clinical trial
asking if it has that effect.
heart disease researchers said that they already were wary about
estrogen because it can elicit blood clots, which can cause heart
attacks and strokes. Birth control pills, which contain estrogen,
may cause clots, and a recent study found that women who already
had heart attacks might not be protected from new ones if they
study, directed by Dr. Stephen Hulley of the University of
California at San Francisco, found that in the first year, women
taking estrogen actually had more heart attacks and other
manifestations of heart disease than those taking a placebo. The
effect diminished in subsequent years, and by the fifth year the
women taking estrogen did better than those taking the placebo.
But the study failed to show that overall, women who had had heart
attacks were helped by estrogen.
study, decades ago, in which men took estrogen in the hope of
preventing heart attacks, had to be discontinued because the
hormone was causing heart attacks instead.
who hoped estrogen might benefit healthy women pointed to the
studies showing that women who happened to take estrogen had fewer
heart attacks than those who happened not to take it. They also
noted that estrogen increased the amount of beneficial cholesterol
in the blood, the HDL fraction, while decreasing the fraction of
the harmful LDL cholesterol. But, Dr. Hulley noted, his study of
women who had had heart attacks indicated that those changes could
investigators said, the Women's Health Initiative remains
scientists' best hope of learning whether estrogen replacement
therapy is helpful or harmful to healthy women.
one else is going to do a study this big on hormone replacement
therapy," said Dr. Marcia Stefanick, a Stanford University
professor who is chairwoman of the study's steering committee.
"If we don't answer the questions on hormones, they're never
going to be answered."
the letters they received, participants in the Women's Health
Initiative were urged to stay in the study. The study, they were
told, "is more important than ever." So far, said Dr.
Rossouw, the women are reacting calmly.
the meantime, said Dr. Michael Criqui, an investigator in the
study who is a professor of family and preventive medicine at the
University of California at San Diego, "one cannot recommend
to a woman to take estrogen to prevent heart disease at this
time." So far, he said, "there's no evidence that it