NEW YORK (Reuters Health) - The effect of hormone replacement therapy (HRT) on levels of HDL, or "good," cholesterol may depend at least in part on a woman's genes, results of a new study suggest.

In the study of 309 postmenopausal women with coronary artery disease who were taking hormones or a placebo, levels of HDL cholesterol were more than doubled in women with a common gene variation.

The effects of this variation on the cardiovascular risk of women taking HRT is still uncertain, but the findings raise the possibility of using genetic screening to decide whether a woman will benefit from HRT, according to the study's lead author.

High levels of HDL are known to protect against heart disease, but "we don't know for sure" whether the dramatic increases in good cholesterol in the study will translate into dramatic decreases in heart attacks, explained Dr. David M. Herrington of Wake Forest University School of Medicine in Winston-Salem, North Carolina.

More research is needed, Herrington said in an interview, to see whether the high levels of HDL linked to the gene variation can protect women against heart disease. The researcher added that it will be important to see whether the variation affects other favorable effects of estrogen including increased bone density and relief of menopausal symptoms such as hot flashes.

The influence of the variation on negative effects of estrogen, such as an increased risk of breast cancer and certain blood clots, also needs "to be looked at carefully," Herrington said.

Estrogen raises HDL levels in women, which is often considered one of the reasons that the risk of heart disease is low in women before menopause. For years, HRT was widely thought to reduce the risk of heart disease in postmenopausal women, but recent studies have failed to document its protective effects.

The effects of estrogen--both natural and HRT--on HDL levels have been shown to vary widely, and genetic factors are thought to be involved.

Herrington and his colleagues report in the March 28th issue of The New England Journal of Medicine that when women with a certain type of variation in the estrogen receptor alpha gene were taking HRT, their HDL levels were more than twice as high as in women who did not have such a variation. About 18% of women in the study had one of several closely related variations in this gene.

The idea that a person's genes can influence the effects of medications is not new, Herrington said. Genes have been shown to affect several commonly used drugs, including cholesterol-lowering medications called statins, diuretics used to treat high blood pressure and some asthma medications, he pointed out.

Within the next decade or so, according to Herrington, doctors should be able to conduct simple genetic tests in their offices that will help them select the most appropriate type and dose of medication. Though this type of genetic testing is not available now, Herrington said, "This is right around the corner."

The benefits of screening for gene variations that are involved in HRT's effects on HDL levels are still uncertain, however, since the variation has not been shown to reduce the risk of heart disease, Dr. Ronald M. Krauss of the University of California at Berkeley cautions in a related editorial.

But Krauss states that "it is conceivable" that one day it will be possible to tailor HRT to the needs of individual women. He points out, however, that the increasing availability of other drugs that prevent and treat cardiovascular disease, such as statins, "may obviate the need to deal with the complexities of HRT for many women."

SOURCE: The New England Journal of Medicine 2002;346:967-974, 1017-1018.

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