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Gene Enhances Effects of Estrogen on Good Cholesterol Reports Researcher from Wake Forest University Baptist Medical Center

WINSTON-SALEM, N.C. – A genetic variant seems to determine how well women’s good cholesterol responds to estrogen therapy, reports David Herrington, M.D., from Wake Forest University Baptist Medical Center in this week’s New England Journal of Medicine. The finding could help doctors identify women most likely to gain a heart benefit from hormone therapy.

“If our findings hold true, a simple gene test could help doctors and women make better decisions about the use of hormone replacement therapy for prevention of heart disease,” said Herrington, a professor of cardiology.

In an analysis of 309 women with heart disease who took hormone replacement therapy or placebo, Herrington found that women with a common mutation in the estrogen receptor alpha gene had dramatic increases in high-density lipoprotein (HDL), or the “good” cholesterol.

“The increase in HDL was more than twice as much as in women without the gene variant,” said Herrington. These findings are important since increases in HDL cholesterol are believed to be helpful to prevent heart disease, especially in women.

Herrington found that 18 percent of women had a genetic predisposition to high levels of HDL cholesterol when taking estrogen. The HDL increase was dramatic – it was two or three times what is normally achieved with cholesterol drugs used to raise HDL.

“More research is needed to see if the higher HDL levels translate into fewer heart attacks,” said Herrington. “We also need to know if women with the gene variant are more sensitive to estrogen’s other effects. But, this finding is exciting because it shows the potential for doctors to use genetic testing to improve decisions about drug therapy.”

There are similar reports that different gene variants influence the effects of other commonly used medications, such as cholesterol lowering drugs and drugs to treat high blood pressure and asthma.

“Previous studies of cholesterol drugs show that raising HDL to this extent might reduce heart disease events by 25 to 40 percent,” said Herrington. “Studies with estrogen haven’t shown the same connection between HDL raising and heart disease benefit, but it’s possible this was because we were focusing on all women, rather than the sub-group with this gene variant.”

Herrington’s research is the latest development in the story of hormone replacement and heart disease. For years, doctors prescribed hormone replacement therapy to prevent heart disease in postmenopausal women. These treatment decisions were based on observational studies showing that women who took estrogen had fewer heart attacks.

But recently, assumptions about the heart disease benefits of hormone therapy have been questioned. Several major studies have shown that in women with heart disease, taking hormone replacement does not slow heart disease progression.

“Our research suggests that genetics may identify some women who respond more favorably to hormone replacement therapy than others,” said Herrington.

He said additional research is needed to learn if this gene variant also makes women more sensitive to other beneficial effects of estrogen – including maintaining bone mineral density and reducing hot flashes – as well as to negative effects of estrogen, such as formation of blood clots in the legs.

“It makes sense that if one area – cholesterol – is affected, others might be too.”

Herrington said it is too soon for doctors to begin testing for this gene variant and they should continue to follow the American Heart Association’s guidelines concerning the use of estrogen and other therapies for preventing heart disease in women.

“However, if findings such as this are confirmed in other studies, it’s likely that testing for gene variants will soon become a regular part of the practice of medicine,” said Herrington. ###

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