A prospective, observational study of postmenopausal hormone therapy and primary prevention of cardiovascular disease

Background: Most primary prevention studies have found that long-term users of postmenopausal hormone therapy are at lower risk for coronary events, b ut numerous questions remain. An adverse influence of hormone therapy on ca rdiovascular risk has been suggested during the initial year of use; howeve r, few data are available on short-term hormone therapy. In addition, the c ardiovascular effects of daily doses of oral conjugated estrogen lower than 0.625 mg are unknown, and few studies have examined estrogen plus progesti n in this regard. Objective: To investigate duration, dose, and type of postmenopausal hormon e therapy and primary prevention of cardiovascular disease. Design: Prospective, observational cohort study. Setting: Nurses' Health Study, with follow-up from 1976 to 1996. Patients: 70 533 postmenopausal women, in whom 1258 major coronary events ( nonfatal myocardial infarction or fatal coronary disease) and 767 strokes w ere identified. Measurements: Details of postmenopausal hormone use were ascertained by usi ng biennial questionnaires. Cardiovascular disease was established by using a questionnaire and was confirmed by medical record review. Logistic regre ssion models were used to calculate relative risks and 95% Cls, adjusted fo r confounders. Results: When all cardiovascular risk factors were considered, the risk for major coronary events was lower among current users of hormone therapy, in cluding short-term users, compared with never-users (relative risk, 0.61 [9 5% CI, 0.52 to 0.71]). Among women taking oral conjugated estrogen, the ris k for coronary events was similarly reduced in those currently taking 0.625 mg daily (relative risk, 0.54 [CI, 0.44 to 0.67]) and those taking 0.3 mg daily (relative risk, 0.58 [CI, 0.37 to 0.92]) compared with never-users. H owever, the risk for stroke was statistically significantly increased among women taking 0.625 mg or more of oral conjugated estrogen daily (relative risk, 1.35 [CI, 1.08 to 1.68] for 0.625 mg/d and 1.63 [CI, 1.18 to 2.26] fo r greater than or equal to1.25 mg/d) and those taking estrogen plus progest in (relative risk, 1.45 [CI, 1.10 to 1.92]). Overall, little relation was o bserved between combination hormone therapy and risk for cardiovascular dis ease (major coronary heart disease plus stroke) (relative risk, 0.91 [CI, 0 .75 to 1.11]). Conclusions: Postmenopausal hormone use appears to decrease risk for major coronary events in women without previous heart disease. Furthermore, 0.3 m g of oral conjugated estrogen daily is associated with a reduction similar to that seen with the standard dose of 0.625 mg. However, estrogen at daily doses of 0.625 mg or greater and in combination with progestin may increas e risk for stroke.