Hormone replacement therapy confers many benefits, including a decreased risk of osteoporosis and cardiovascular disease, but it is also associated with risks, such as an increased incidence of breast and endometrial cancers. Extrapolation of data from available studies to the general population of women may be problematic, since women who receive hormone replacement therapy are often healthier initially than the general population of women of the same age and those who continue to take hormones are generally disease-free. Thus, decreased rates of mortality among women who receive hormone replacement therapy may be misattributed to the use of hormones. Grodstein and colleagues investigated the association between mortality and hormone use among participants in the Nurses' Health Study.

Women in this longitudinal study were between 30 and 55 years of age when they entered the study in 1976. Biennial questionnaires have been used to follow study subjects. A total of 3,637 postmenopausal women in this study died between 1976 and 1994, and data on these participants were used in the authors' analysis. Of the 3,637 women who died, 461 (12.8 percent) died of coronary heart disease, 167 (4.6 percent) died of stroke and 1,985 (54.6 percent) died of cancer. Of women who died of cancer, 425 died of breast cancer and 58 of endometrial cancer.

Among the women who died, 15.8 percent reported current hormone use on the last questionnaire they completed before they died, 27.8 reported past use, and 56.4 percent had never used hormones. Each woman who died was matched with 10 control subjects who were alive at the time of the case subject's death. The authors determined the status of hormone use on the basis of information on the last questionnaire completed before death or before the diagnosis of the disease that led to death. This approach reduced the bias that would be caused by discontinuation of hormone use between the diagnosis of a potentially fatal disease and death.

The data revealed that current hormone users had a lower risk of death (relative risk of 0.63) than women who had never received hormone replacement therapy. Survival benefit decreased with long-term hormone use of 10 or more years (relative risk of death: 0.80), primarily because of a 43 percent increase in mortality resulting from breast cancer.

Women with cardiovascular risk factors derived the most benefit from hormone replacement therapy. Women with at least one major cardiovascular risk factor had the largest reduction in mortality. Among this group, there was a 49 percent decrease in deaths from all causes for current hormone users, compared with those who had never used hormones. Substantially less benefit was found in women with a low risk of cardiovascular disease. The cardiovascular benefits disappeared within five years after discontinuing hormone replacement therapy.

The authors conclude that their population had a similar number of deaths caused by heart disease and breast cancer. They note that in the general population, heart disease is more prevalent. While the data indicate that survival benefits from hormone replacement therapy appear to outweigh the risks, the risks and benefits vary and depend on the presence of risk factors and the duration of hormone replacement therapy.