Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

Hormone therapy and cerebrovascular events: a population-based nested case-control study

Arana, Alejandro MD, MPH, FISPE1; Varas, Cristina MD, PhD1; González-Pérez, Antonio BPharm, MSc2; Gutiérrez, Lia BN, MPH1; Bjerrum, Lars MD, PhD3; García Rodríguez, Luis A. MD, MSc2

doi: 10.1097/01.gme.0000233494.28335.71

Objective: The relationship between postmenopausal hormone therapy (HT) and cerebrovascular disease has been examined in several epidemiological studies and clinical trials with conflicting results. The authors aimed to evaluate the association between the use of HT and the incidence of first cerebrovascular event.

Design: The study cohort comprised 158,031 women 50 to 69 years old registered in the U.K. General Practice Research Database between 1991 and 1997. The authors conducted a nested case-control analysis using all 920 confirmed cases of cerebrovascular events identified during the follow-up (536 of transient ischemic attack [TIA]; 259 of ischemic stroke; 125 of hemorrhagic stroke) and 10,000 controls.

Results: The odds ratios of TIA, ischemic stroke, and hemorrhagic stroke among women currently using HT were 1.48 (95% CI, 1.17-1.87), 1.12 (95% CI, 0.78-1.59) and 1.21 (95% CI, 0.76-1.93), respectively, compared to never users. The overall risk estimate for having a cerebrovascular event was 1.34 (95% CI, 1.11-1.61). The risk of TIA was greater (1.96) among women using high doses of estrogen (95% CI, 1.34-2.87).

Conclusion: Overall, a small increased risk of stroke associated with HT use of comparable magnitude to the one observed in recent clinical trials was found. The increased risk was more apparent for TIA than for stroke and was greater at higher doses.

In this study, women presented with a 34% increase in the risk of cerebrovascular events associated with current use of hormone therapy. Among subtypes of cerebrovascular accidents, the risk of a transient ischemic accident was the most affected by hormone therapy use, whereas the risk of ischemic and hemorrhagic stroke was only modestly increased, not reaching statistical significance.

From the 1Novartis, Clinical Safety and Epidemiology; 2Centro Español de Investigación Farmacoepidemiólogica (CEIFE), Madrid, Spain; and 3Research Unit of General Practice, University of Southern Denmark, Odense, Denmark.

Received December 27, 2005; revised and accepted January 31, 2006.

This study was funded by a research grant from Novartis. A.A., C.V., and L.G. were employees of Pfizer.

Address correspondence to: Luis A. García Rodríguez, MD, MSc, Centro Español de Investigación Farmacoepidemiólogica (CEIFE), Almirante 28, 2°, 28004 Madrid, Spain. E-mail:

©2006The North American Menopause Society