Background Use of postmenopausal hormone replacement therapy (HRT) used to be promoted to reduce the risk of ischemic cardiovascular diseases, a concept which has been challenged by results of the large Women's Health Initiative trial in users of estrogen and progestin. It is postulated that the type of progestin used in HRT affects the cardiovascular risk.

Methods We used the UK-based General Practice Research Database to conduct a follow-up study with a nested case-control analysis. We assessed and compared the risk of developing myocardial infarction, thrombotic stroke or venous thromboembolism in estradiol/dydrogesterone users, users of other HRT, or non-users of HRT.

Results The incidence rates of myocardial infarction, thrombotic stroke and venous thromboembolism in estradiol/dydrogesterone users were 0.40 (95% confidence interval (CI) 0.18-0.76), 0.27 (95% CI 0.10-0.58) and 0.31 (95% CI 0.13-0.64) per 1000 person-years, respectively. As compared to non-users of HRT, the adjusted relative risk estimates (odds ratios) in the nested case-control analysis for estradiol/dydrogesterone users or users of other HRT were 1.06 (95% CI 0.48-2.36) and 1.12 (95% CI 0.84-1.51) for myocardial infarction, 0.50 (95% CI 0.21-1.22) and 1.18 (95% CI 0.94-1.48) for thrombotic stroke, and 0.84 (95% CI 0.37-1.92) and 1.42 (95% CI 1.10-1.82) for venous thromboembolism, respectively.

Conclusion The study provides evidence that estradiol/dydrogesterone use of several months to a few years is not associated with a higher risk of cardiovascular events than use of other HRT.