June 27, 1994

The Risk of Myocardial Infarction Associated With the Combined Use of Estrogens and Progestins in Postmenopausal Women

Author Affiliations

From the Cardiovascular Health Research Unit, Departments of Medicine (Drs Psaty, Atkins, Koepsell, and Siscovick), Epidemiology (Drs Psaty, Heckbert, Lemaitre, Koepsell, and Siscovick), Biostatistics (Dr Wahl), and Health Services (Drs Psaty, Koepsell, and Wagner), University of Washington, Seattle; and the Center for Health Studies, Group Health Cooperative of Puget Sound, Seattle (Dr Wagner).

Arch Intern Med. 1994;154(12):1333-1339. doi:10.1001/archinte.1994.00420120047005

Background:  While observational studies have suggested that unopposed estrogens reduce the incidence of coronary disease in postmenopausal women, there are few data on the effect of combined therapy with estrogens and progestins—a regimen adopted in recent years to minimize the risk of endometrial hyperplasia and cancer. In clinical trials, the addition of progestins has an adverse effect on serum lipid levels, and these lipid effects have raised the question of whether combined estrogen-progestin therapy increases the risk of coronary disease compared with the use of estrogen alone.

Methods:  We conducted a population-based, case-control study among enrollees of Group Health Cooperative of Puget 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 enrollees frequency matched to the cases by age and calendar year. We reviewed the medical records of the 502 cases and 1193 controls and conducted 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 analysis of current use, we classified women into one of three groups: (1) nonusers of hormones; (2) users of estrogens alone; or (3) users of combined therapy including both estrogens and progestins. Each group of hormone 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% confidence interval, 0.47 to 1.02); and the risk ratio of myocardial infarction associated with current use of combined therapy was 0.68 (95% confidence interval, 0.38 to 1.22). Duration of combined-therapy use was relatively short, averaging less than 2 years in cases and controls.

Conclusions:  In this case-control study, the reduced risk of myocardial infarction associated with the use of estrogens alone was consistent with 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 myocardial infarction in postmenopausal women.(Arch Intern Med. 1994;154:1333-1339)