Cardiovascular and cancer morbidity and mortality and sudden cardiac death in postmenopausal women on oestrogen replacement therapy (ERT)

BACKGROUND: Advantages and disadvantages of postmenopausal oestrogen replacement therapy (ERT) are still not clear. We aimed to analyse the relation between postmenopausal oestrogen replacement therapy (ERT), cardiovascular disease, and cancer.

METHODS: We examined 7944 women born between 1923 and 1930, who participated in a mammography screening for breast cancer, and who were followed up from 1987 to 1995. The follow-up consisted of 53,305 person-years. 988 women were current users and 757 were former users of ERT. Information about hormone use and health events was obtained through biennial questionnaires and recording and linking information from the hospital discharge registers of the region, the national cancer register, the social insurance reimbursement register, and the national death register. We used proportional-hazards models to calculate risk ratios and 95% CIs, adjusted for eight confounding variables.

FINDINGS: Current ERT was associated with decreased cardiovascular mortality and a decrease in sudden cardiac death. Adjusted risk ratio (RR) for cardiovascular mortality in current users was 0.21 (95% CI 0.08-0.59) and in former users 0.75 (0.41-1.37). Absolute risk per 1000 person-years for deaths from acute myocardial infarction (AMI) was 1.1 in never users, 1.2 in former users, and 0.45 in current users (p=0.197). Corresponding absolute risk for other coronary-artery-disease (CAD) deaths was 1.0, 0.81, and 0 (p=0.009), and for deaths from stroke 1.2, 1.0, and 0.15 (p=0.012). Absolute risk for sudden cardiac death was 1.6 in never users, 1.0 in former users, and 0 in current users (p<0.001). Cardiovascular morbidity was not decreased by ERT: the RR for current use was 1.07 (0.86-1.32) and for former use 1.11 (0.89-1.39). Incidence of cardiovascular disease per 1000 person-years was 24.9 in never users, 23.4 in former users, and 20.9 in current users (p=0.153). Breast-cancer morbidity did not increase with current ERT--the RR was 0.57 (0.27-1.20). Incidence of breast cancer was 1.8, 1.6, and 1.0 in never, former, and current users (p=0.242). Endometrial cancer increased with current ERT--the RR was 5.06 (2.47-10.41). Incidence of endometrial cancer was 0.52 in never users, 0.51 in former users, and 2.1 in current users (p<0.001).

INTERPRETATION: Current ERT reduced primarily sudden cardiac death and predicted reduced cardiovascular mortality, but did not reduce morbidity. ERT did not increase the risk of breast cancer, but was associated with increased risk of endometrial cancer.