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DO ESTROGENS PROTECT AGAINST CORONARY HEART DISEASE?

(November 2001)

Estrogen hormone treatment after the menopause relieves hot flashes and other menopausal symptoms and helps prevent osteoporosis (bone thinning). For a long time, it was thought estrogen administration also markedly reduced the risk of coronary heart disease. This was based primarily on analyses of estrogen use by women who had already developed coronary heart disease and controls who did not develop the disease. The conclusion about the effectiveness of estrogens has also been based on analyses of groups of women, some of whom took estrogens, comparing the frequency of coronary heart disease during follow up among those who did and those who did not take estrogens. But, no study had been carried out in which a group of women were chosen randomly to receive either estrogen or a placebo in blinded fashion (so the women did not know whether they received estrogen or an inactive placebo) and then the entire group would be followed for the development of coronary heart disease.

The lack of that type of definitive study left open the possibility that, despite the encouraging results from the other types of studies, estrogens actually do not reduce the likelihood of coronary heart disease.

In 1998, the first real challenge came from a study that showed that, in women who already had coronary heart disease, estrogen administration had no beneficial effects in reducing the risk of further coronary heart disease events or episodes. That came as a shocker - but, it has been supported by a report in The New England Journal of Medicine August 14, 2000 of 309 women with coronary heart disease who were given estrogens or an inactive placebo and followed for an average of three years. There was no evidence that estrogens lessened progression of the disease and, importantly, it did not matter whether the women had mild, moderate, or severe damage to their coronary blood vessels - estrogens did not reduce progression, no matter what the stage of the disease at the onset of treatment. If estrogens failed to halt the progression of mild coronary heart disease, it suggests that estrogens may not prevent the development of heart disease in healthy people.

In the same issue of The New England Journal of Medicine is an article from the renowned Nurse’s Health Study that involved 86,000 women ages 34 to 59 years. The authors found that, between 1980 and 1994, the occurrence of new cases of coronary heart disease among the nurses fell by a remarkable 31 percent. The investigators then analyzed the factors that related to the decline. About two-thirds of the reduction in occurrence could be explained by three variables. The two most important factors were a reduction in smoking and a better diet, but taking estrogens post-menopausally also appeared to have a moderate, though much smaller, beneficial effect in reducing the risk of coronary heart disease.

The very modest benefit apparently found for estrogens makes it clear that we still do not know whether estrogens can lower the risk of subsequent coronary heart disease in women who have no evidence of coronary heart disease; and we will not know for sure until ongoing studies are completed in which women with no evidence of coronary heart disease are randomly assigned to either estrogen or placebo, and then are followed for years in regard to development of coronary heart disease.

Where do we stand in regard to estrogen treatment post-menopausally?

• Estrogen treatment is unequivocally helpful in preventing osteoporosis (bone thinning) and fractures.

• Estrogens are very effective in relieving menopausal symptoms.

• Estrogens with progesterone do not increase the risk of uterine cancer, but there is a small increase in risk of breast cancer. However, these breast cancers should be detected by mammography and most studies show no increased death rate from estrogen-induced breast cancers, suggesting the estrogen-induced cancers are of a less severe, less dangerous type.

• Estrogens do not appear to be effective in preventing the progression of either mild or more severe coronary heart disease.

• Estrogens given post-menopausally may or may not help prevent coronary heart disease. Until definitive studies are completed, the possible prevention of coronary heart disease should not be part of the decision-making process for women considering the use of post-menopausal estrogens.