51 Similarly, ERT in postmenopausal women appears to be associated with a higher risk of venous thrombosis during the first year of use.52 However, whether ERT imposes a risk for ischemic stroke in postmenopausal women is unclear. We now understand that the dose of clearly estrogen administered and the route of estrogen delivery are key components in determining clotting potential. At higher Inhibitors,research,lifescience,medical doses, oral estrogen, which enters the body via the enterohepatic
system, can stimulate the production of thrombogenic factors53,54 predominantly through its actions on the liver. Alternatively, lower doses of estrogen, delivered orally or transdermally, may not significantly
affect hemostasis.53,55-57 Importantly, transdermal delivery of estrogen bypasses enterohepatic circulation and may thus prevent estrogen-mediated stimulation of thrombogenic factors in the liver. Inhibitors,research,lifescience,medical Collectively, these findings highlight the importance of low, physiological doses in estrogen replacement of postmenopausal women. ERT and stroke: overview of clinical studies Studies have only begun to explore the actions of hormone replacement on stroke in the clinical setting. Data from several human studies clearly indicate that Inhibitors,research,lifescience,medical estrogen exerts protection against stroke58-61; however, many studies report cither protective selleck chemical trends or no significant, Inhibitors,research,lifescience,medical effect, of estrogen58,59,62-72 and few
report deleterious effects of estrogen.62,66,73,74 Preliminary results from the latest clinical study, the Women’s Estrogen for Stroke Trial (WEST), indicate that estrogen docs not protect against the rate of either nonfatal stroke or death in postmenopausal women with a history of stroke.75 In parallel with studies that fail to detect estrogen-mediated protection of the heart in women with cardiovascular disease,16 or of the brain in women with AD,43 the results of WEST suggest that estrogen does not effectively protect against, or Inhibitors,research,lifescience,medical reverse a disease process that has already been initiated. To date, clinical studies have mainly probed whether ERT significantly affects the incidence and mortality of stroke. The outcomes of many of these studies are varied and often appear to be contradictory. Thus, we cannot yet draw clear conclusions Dacomitinib from the existing data due to several confounding issues. The lack of uniformity among the data in clinical reports may result, from several inconsistencies.44 First, stroke is a mixed group of diseases with varying etiologies. If ERT decreases or increases the risk of specific stroke subtypes, effects of estrogen may be distorted and/or masked when strokes arc grouped together and classified differently among the studies.
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