Hormone replacement therapy and the risk of venous thromboembolism: a population‐based study

Summary. Background: Hormone replacement therapy (HRT) using oral estrogen alone or combined with a progestogen is associated with an increased risk of venous thromboembolism (VTE) in postmenopausal women. This risk may differ for tibolone and transdermal HRT. Methods: Among the United Kingdom’s General Practice Research Database, we identified the cohort of all women aged 50–79 between 1 January 1987 and 1 March 2008. Using a nested case–control approach, all incident cases of VTE occurring during the study period were identified and matched with up to 10 controls selected from the cohort members. Rate ratios (RR) of VTE with current use of tibolone, transdermal and oral HRT were estimated using conditional logistic regression. Results: The cohort of 955 582 postmenopausal women included 23 505 cases of VTE matched with 231 562 controls. The risk of VTE was not increased with current use of transdermal estrogen alone (RR 1.01; 95% CI, 0.89–1.16) or combined with a progestogen (RR 0.96; 95% CI, 0.77–1.20), or with current use of tibolone (RR 0.92; 95% CI: 0.77–1.10), relative to non‐use. On the other hand, the risk was increased with current use of oral estrogen (RR 1.49; 95% CI, 1.37–1.63) and oral estrogen–progestogen (RR 1.54; 95% CI, 1.44–1.65), and increased with estrogen dosage. The risks with oral formulations were particularly elevated during the first year of use but disappeared 4 months after discontinuation. Conclusion: Transdermal HRT and tibolone were not associated with an increased risk of VTE in postmenopausal women.