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Study: Key hormone therapy trial was flawed

A 2002 study showing that hormone replacement therapy raises the risk of heart disease and breast cancer was fundamentally flawed, according to new research.
/ Source: 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 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.

Older women tested
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.