Reuters Health
August 15, 2005


QUOTABLE: "Among the recommendations Krieger and her colleagues make
is that the 'precautionary principle' be applied to any drug being
studied for preventive medicine. 'That is,' Krieger said, 'You don't
prescribe healthy people potentially dangerous drugs.'"

By Amy Norton

NEW YORK (Reuters Health) -- The risks of hormone replacement therapy
(HRT) have made headlines only in recent years, but there had long
been warning signs that supplemental estrogen might be more hazardous
than healthful, a new report contends.

In 2002, a large US clinical trial called the Women's Health
Initiative (WHI) was stopped when early findings showed that HRT after
menopause slightly raised a woman's risk of breast cancer, heart
attack, stroke and blood clots.

Given the long-standing belief that HRT helped protect older women
from cardiovascular disease, the findings were widely received with
disappointment and surprise.

But no one should have been caught off guard, a group of researchers
and women's health advocates argues in a perspective piece published
in the Journal of Epidemiology and Community Health.

Not only had the potential cancer risks of estrogen replacement been
known for decades, the presumed heart benefits were being questioned
as early as the mid-1970s, according to the authors, led by Professor
Nancy Krieger of the Harvard School of Public Health in Boston.

"There were good grounds to have concerns before" the recent findings,
Krieger told Reuters Health.

The potential for estrogen replacement to promote cancer has been
recognized since the 1930s, when synthetic estrogens first became

Still, long-term HRT was for years prescribed as a way to battle the
diseases of aging, including osteoporosis and cardiovascular disease.
For many women, it was thought, the slightly increased risk of breast
cancer might be offset by a lower risk of heart disease and stroke --
far bigger killers than breast cancer.

But there was always uncertainty about the cardiovascular benefits of
HRT, Krieger and her colleagues note.

Krieger pointed to one study, started in the late 1960s, that found
that giving men estrogen raised their risk of cardiovascular disease
rather than lowering it, as expected.

And when it came to women, the research evidence was often conflicting
and indirect -- for example, coming from observational studies in
which women on hormone replacement were found to have lower rates of
heart disease.

The problem with such evidence, as many researchers have noted, is
that other differences between HRT users and non-users may have
explained the lower heart risk; women on HRT, for example, tended to
more affluent and in better overall health.

But such cautions, as well as negative study findings, Krieger and her
colleagues contend, "were dwarfed by the proliferation of studies
favorable to HRT."

In their view, an aggressive pharmaceutical industry, the regulatory
framework and a general perception of menopause as a "disease" were
all central to the issue.

Once a drug is approved for a specific use, doctors are free to
prescribe that medication for other conditions as well. This fact,
coupled with industry influence, the report authors contend, were key
to the growth of HRT.

There was reason to believe HRT could have offered heart benefits,
Krieger acknowledged, noting, for instance, that it was "biologically
plausible" and had support from animal research.

But, she argued, given the known cancer risks of estrogen, the
evidence for HRT should not have been enough.

Among the recommendations Krieger and her colleagues make is that the
"precautionary principle" be applied to any drug being studied for
preventive medicine. That is, Krieger said, "You don't prescribe
healthy people potentially dangerous drugs."

SOURCE: Journal of Epidemiology and Community Health, September 2005.

Copyright Reuters 2005.