Associations between postmenopausal hormone therapy and strokes in a National cohort study

The Women Health Initiative randomized clinical studies on effects of two postmenopausal hormone therapies (HT) were stopped prematurely mainly due to stroke risk. The purpose of the present study was to assess the risk with HT of all strokes, ischemic and hemorrhagic, with focus on effects of regimen and route of administration. Methods: Principal: In a national Danish historical cohort from 1995 to2010women freeof previous cardiovascular diseaseor cancer aged 51–70were included by linkage of fiveNational Registries. Information on HT exposure was captured from the National Prescription Registry and strokes from the National Patient Registry or the Cause of Death Registry. Registries also provided information on potential confounders. Poisson regressionmodels provided multiple adjusted rate ratios (RR) with time-varying covariates. Results: Of 1,063,131 included women 19,500 suffered strokes, 78% ischemic, 12% hemorrhagic and 10% subarachnoid hemorrhage. During the study period 36% used HT. Compared to never user’s currentuseof anyHTconferredaRRof strokesof 1.16 (95%CI: 1.12–1.22), and the regimens oral continuous and cyclic combined estrogen progestin therapy and oral estrogen alone conferred a RR of 1.29 (1.21–1.37), 1.11 (1.04–1.20) and 1.18 (1.10–1.26), respectively. The elevated risk of strokes associated with HT was based on increased risk of ischemic strokes, not hemorrhagic. Dermal applications of neither unopposed estrogen nor combined progestin estrogen were associated with risk of strokes. Vaginal applicationwasassociatedwith significantlydecreased risk of strokes of 0.64 (0.59–0.70), both ischemic and hemorrhagic. Conclusion: In a large study in a national setting we found increased risk estimates associatedwith oral continuous combined regimens and estrogen alone HT comparable to findings from the randomized Women’s Health Initiative. Furthermore we found no risk associated dermal application and reduced risk associatedwith vaginal application.