THE RISK OF MYOCARDIAL-INFARCTION ASSOCIATED WITH THE COMBINED USE OFESTROGENS AND PROGESTINS IN POSTMENOPAUSAL WOMEN

Background: While observational studies have suggested that unopposed estrogens reduce the incidence of coronary disease in postmenopausal w omen, there are few data on the effect of combined therapy with estrog ens and progestins-a regimen adopted in recent years to minimize the r isk of endometrial hyperplasia and cancer. In clinical trials, the add ition of progestins has an adverse effect on serum lipid levels, and t hese lipid effects have raised the question of whether combined estrog en-progestin therapy increases the risk of coronary disease compared w ith the use of estrogen alone. Methods: We conducted a population-base d, case-control study among enrollees of Group Health Cooperative of P uget Sound. Cases were postmenopausal women who sustained an incident fatal or nonfatal myocardial infarction in 1986 through 1990. Controls were a stratified random sample of female Group Health Cooperative en rollees frequency matched to the cases by age and calendar year. We re viewed the medical records of the 502 cases and 1193 controls and cond ucted brief telephone interviews with consenting survivors. The health maintenance organization's computerized pharmacy database was used to ascertain the use of postmenopausal hormones. For the primary analysi s of current use, we classified women into one of three groups: (1) no nusers of hormones; (2) users of estrogens alone; or (3) users of comb ined therapy including both estrogens and progestins. Each group of ho rmone users was compared with nonusers. Results: After adjustment for potential confounding factors, the risk ratio of myocardial infarction associated with current use of estrogens alone was 0.69 (95% confiden ce interval, 0.47 to 1.02); and the risk ratio of myocardial infarctio n associated with current use of combined therapy was 0.68 (95% confid ence interval, 0.38 to 1.22). Duration of combined-therapy use was rel atively short, averaging less than 2 years in cases and controls. Conc lusions: In this case-control study, the reduced risk of myocardial in farction associated with the use of estrogens alone was consistent wit h previous observational studies. Although the 95% confidence interval only excluded a risk above 1.22, the current use of combined therapy was not associated with an adverse effect on the incidence of myocardi al infarction in postmenopausal women.