Risks of hormone replacement not surprising: report

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 available.

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.