Timing of HRT Key to Heart Benefit

Estrogen May Protect From Heart Disease, Stroke If Taken at Onset of Menopause

From the WebMD Archives

March 3, 2003 -- It turns out timing may be everything when it comes to hormone replacement therapy (HRT) and heart disease. A new review of the major research shows that taking estrogen around the time of menopause may protect against heart disease, but starting it later in life increases the risk.

The findings should reassure women who are worried that taking HRT for menopausal symptoms will increase their risk of heart disease. But the evidence is not strong enough to suggest that women take estrogen solely to protect their hearts.

"Recent clinical studies in older women have not refuted earlier studies suggesting a heart benefit for younger women," says researcher Richard H. Karas, MD. "The vast majority of women who are starting hormone replacement in this country are doing it around the time of menopause, and they have been unnecessarily scared to death about HRT."

Karas tells WebMD that news accounts of the widely reported Women's Health Initiative (WHI) gave the public the false impression that hormone replacement therapy increases the risk of heart disease and stroke in all women who take it. Findings from the study, released in July of 2001, led the American Heart Association (AHA) to advise doctors to stop prescribing the treatment for the prevention of heart disease.

Although the WHI findings showed an association between long-term hormone therapy and heart disease, stroke, and pulmonary embolism, most of the women in the study were well past the age of menopause. In their review, published in the winter issue of the journal Menopausal Medicine, Karas and colleague Thomas Clarkson, DVM, reviewed WHI and other major studies assessing heart disease risk in women taking hormone therapy.

"The literature demonstrates that HRT has beneficial effects in inhibiting the early stages of heart vessel disease but can have deleterious effects if initiated at older ages when some women have already developed disease," Clarkson says in a news release.

Clarkson's own studies in monkeys showed that animals treated with HRT at the onset of estrogen deficiency had a 70% inhibition in the arterial plaque buildup that leads to heart disease. No such benefit was seen when estrogen replacement was delayed following surgical menopause for a period equaling six years in women.

"This suggests that the WHI data and the observational studies showing HRT to be protective against heart disease may both be right," Karas says, adding that the older women in the WHI were far more likely to have early signs of heart disease than the younger women in the observational studies.

Karas says large clinical studies similar to WHI are needed in younger women to determine whether HRT is protective in this group, but cardiologist and AHA spokeswoman Rita Redberg, MD, says it is highly unlikely that these studies will ever be done.

"It took 40 years to get the WHI done, and it cost several hundred million dollars," Redberg tells WebMD. "You would need an even larger study with a longer follow-up in younger women, and I can't imagine who would fund that."

Redberg says women who take HRT for just a few years during menopause have little to worry about, but they should take it to relieve symptoms and not to prevent heart disease.

"There isn't anything more effective for women with the vasomotor symptoms of menopause," she says. "But we now have very large clinical trials that don't show a benefit to the heart."

Show Sources

SOURCES: Menopausal Medicine, winter issue. Richard H. Karas, MD, PhD, director, preventive cardiology center, Tufts-New England Medical Center. Thomas B. Clarkson, DVM, professor of comparative medicine, Wake Forest University Baptist Medical Center, Winston-Salem, N.C. Rita Redberg, MD, professor of medicine, director of cardiovascular women's health, University of California at San Francisco; spokesperson, American Heart Association.
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