Study says pivotal hormone therapy trial was flawed

By Deena Beasley

LOS ANGELES (Reuters) – A 2002 study showing that hormone
replacement therapy raises the risk of heart disease and breast
cancer — scaring many women away from the drugs — was
fundamentally flawed, according to new research.

“Women are now being told not to take hormones for heart
disease prevention, and that may be totally wrong,” said Dr.
Edward Klaiber, a Worcester, Massachusetts endocrinologist and
lead author of the study to be published on Friday in the
journal Fertility and Sterility.

Hormone replacement therapy was once routinely prescribed
to women as they reached menopause in the belief that it would
relieve unpleasant symptoms like hot flashes while protecting
against heart disease and osteoporosis.

In July 2002, women taking estrogen and progestin were told
to visit their doctors and perhaps stop after the Women’s
Health Initiative (WHI) said a trial of Wyeth’s Prempro showed
that the drug raised the risk of heart attack, stroke and some
forms of cancer.

But Prempro combines estrogen and progestin in a daily pill
– a regimen that had never been associated with heart
protection, Klaiber said.

At the time of the WHI trial’s design, hormone replacement
therapy usually involved cyclical progesterone, meaning that it
was taken just 10 or 12 days a month, he said.

But the daily combined drug was deemed more convenient
because patients didn’t have to remember which days to take a
second pill and because it eliminated a monthly menstrual
period, the researcher said.

“The results might have been different if they had used a
different form of estrogen that resembled a normal cycle,”
Klaiber said.

The WHI study’s other major flaw was that participants were
older — the mean age was 62.7 — and thus at greater risk of
cardiovascular problems.

“The incidence of heart disease is 12 times higher for
women in their 80s than it is in the 50s,” Klaiber said.

As a result, the WHI study began hormone therapy for the
first time in women who already had heart disease, and “we know
that’s not a good idea,” he added.

Klaiber believes that earlier studies showing that cyclical
hormones are protective against heart disease are probably
valid.

“One of the reasons we started giving estrogen to
menopausal women was because of the gender differential — men
have a lot more heart attacks and have them earlier,” he said.

He is hopeful that a multi-center trial launched last year
by the Phoenix-based Kronos Longevity Research Institute will
eventually show that hormone replacement therapy is not risky
in women who are just beginning to go through menopause.

The Kronos study will treat women age 40 to 55 with hormone
pills, hormones delivered through a skin patch, or placebo, but
results won’t be available until 2010.

“The studies conducted through the WHI make an important
contribution to our knowledge, but they do not provide a
complete answer,” Dr. Joseph Sanfilippo, president of the
American Society for Reproductive Medicine, said in a
statement.

Regardless of its flaws, the WHI study was very useful
because it showed that “Prempro was a mistake,” Klaiber said.