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The authors evaluated the risk of venous thromboembolism associated with hormone replacement therapy in a cohort of 265,431 women aged 45-79 years who did not have major risk factors for venous thromboembolism. Through review of hospital charts, 171 cases were confirmed (pulmonary embolism = 77; deep venous thrombosis = 94). Ten thousand controls were randomly sampled. The risk of venous thromboembolism among nonusers of hormone replacement therapy was 1.3 per 10,000 women per year. Current users of hormone replacement therapy had 2.3 times higher risk of venous thromboembolism (95 percent confidence interval 1.0-5.3) compared with nonusers. The increased risk was restricted to the first year of treatment.

Background-Epidemiological studies suggest a decreased risk of coronary heart disease (CHD) in healthy women taking hormonal replacement therapy (HRT). Whether this effect is shared by oral and transdermal preparations is unknown. Methods and Results-We conducted a population-based case-control study nested in a cohort of women 50 to 74 years of age without cardiovascular disease history in the United Kingdom. Among 164 769 women from the General Practice Research Database (January 1, 1991, to December 31, 1995), we identified 1242 first acute myocardial infarctions (AMI) and confirmed 1013 after medical record review. We randomly selected 5000 age-frequency-matched control subjects. AMI incidence was 1.6 per 1000 person-years; 13% and 17% of cases and control subjects used HRT within 6 months before the index date. Risk factor and comorbidity-adjusted OR of AMI for current-recent HRT users compared with nonusers was 0.72 (95% CI 0.59 to 0.89). The OR was similar within 30 days before the index date. The beneficial effect was present after 1 year of use (OR 0. 68; 95% CI 0.53 to 0.86), with no increase in risk within the first year. ORs for unopposed and opposed therapy were 0.52 (95% CI 0.35 to 0.78) and 0.79 (95% CI 0.59 to 1.08); 79% and 21% used oral and transdermal therapy. The protective effect was present at medium-high doses of estrogens with ORs for oral and transdermal therapy of 0.63 (95% CI 0.46 to 0.86) and 0.62 (95% CI 0.37 to 1.06) and ceased after 2 to 3 years since stopping HRT. Conclusions-Results are consistent with those previously reported in women without CHD who were taking oral HRT and, although based on few users, suggest that transdermal therapy might have similar cardioprotective effects.