Hormone replacement therapy and stroke: risk, protection or no effect?

Despite declining death rates due to stroke over the last several decades, stroke remains the third leading killer (after heart disease and cancer) of women in most developed countries. Because stroke not only kills but also leaves many survivors mentally and physically impaired, control of the disease must be through primary prevention. Several observations lead to the speculation that estrogen may reduce stroke risk. This paper reviews the epidemiologic studies that have evaluated the association of hormone replacement therapy (HRT) and stroke. In the past 25 years, 29 studies have produced no conclusive evidence of a beneficial effect. The lack of consistency in stroke endpoints, definition of HRT user, estrogen preparation, and influence of combined regimen might account in part for the unclear relationship. Nonetheless, the preponderance of evidence suggests that HRT does not increase stroke risk. Some data indicate that estrogen users have a moderately reduced risk of fatal stroke, but details about the optimal dose, duration and type of estrogen are insufficient. The apparent difference in the findings of studies of fatal and non-fatal stroke suggests that estrogen may prevent the most lethal form of stroke or may improve survival. Additional data from ongoing randomized clinical trials in the coming years may help resolve the question of the effect of HRT on stroke morbidity and mortality.