The study examined the effect of body mass on the link between estrogen replacement therapy (ERT) and mortality. Overall, the risk of death from all causes was about 20% lower for women taking estrogen than for those who did not take it. Results showed that estrogen use did not raise the overall risk of dying from all cancers combined.

The researchers examined estrogen use among 290,827 postmenopausal women who were free of cancer and heart disease when first enrolled in the ACS Cancer Prevention Study II in 1982 and were followed for 12 years. The study revealed thin women reporting estrogen replacement therapy (ERT) use at the beginning of the study were about half as likely to die of heart disease in the next 12 years, compared with those who never used ERT. Women using estrogen who were not quite as thin but still at a healthy weight lowered their heart disease risk by about one-quarter. Obese women got no heart disease protection at all from ERT.

Although the Cancer Prevention Study II focuses mainly on the relationships between deaths from cancer and suspected cancer risk factors, information collected from study participants also can help researchers learn more about risks for other diseases

"There?s no question estrogen helps protect the heart against disease," says Carmen Rodriguez, MD, a Senior Epidemiologist with the ACS and lead author of the study. "But after menopause, the main source of estrogen in women?s bodies is the adipose tissue ? fat cells. In obese women, the large amount of adipose tissue produces enough estrogen so that the amount added by ERT doesn?t offer enough additional protection to show up statistically."

That is unfortunate because obese women are the ones most at risk for coronary heart disease, for reasons unrelated to estrogen, she adds. "The way to lower the risk for coronary heart disease for obese women may not be estrogen replacement therapy. There might be another way to lower risk for obese women," Rodriguez says.

Thin women may get more protection against heart disease because ERT gives them a large amount of estrogen in comparison to that being produced by their small amounts of fat tissue, Rodriguez says. However, she notes that a thin woman?s risk of developing breast cancer may go up with use of ERT. That is because estrogen can increase the rate of breast cell replication, thus increasing the risk of a random genetic error that could lead to cancer.

ERT has minimal impact on breast cancer risk among obese women because their fat cells already produce levels of estrogen high enough to stimulate breast cell replication.

Still, no increased risk of death from breast cancer was found in the thin or obese women on ERT in this study. "In the time studied [1982-1994], ERT was usually only prescribed to women asking for relief from menopausal symptoms. Women using it were more likely to be under a doctor?s care, so more likely to have early detection of any breast cancer that did develop, reducing their chances of dying from it," Rodriguez says.

Today, hormone replacement therapy (HRT), which combines estrogen and the hormone progestin, is very commonly prescribed to treat menopausal symptoms and to protect against heart disease and thinning of the bones. Until recently, it was believed HRT provided that protection regardless of a woman?s weight.

Rodriguez says more research will be needed to confirm the findings of the ACS study, but the apparent lack of protection against heart disease in obese women is another reason for doctors and patients to consider body size in deciding whether using estrogen makes sense for the individual.

"Weight in proportion to height should be considered, along with other factors, by those weighing the risks and benefits of hormone replacement therapy," she says.