1. ¹Institute of Cell Signalling, Queen's Medical Centre, University of Nottingham, Nottingham, UK
2. ²Institute of Neuroscience, Queen's Medical Centre, University of Nottingham, Nottingham, UK

Correspondence: Dr C Gibson, School of Psychology, University of Leicester, Henry Wellcome Building, Lancaster Road, Leicester LE1 9HN, UK. E-mail: cg95@le.ac.uk

Received 11 July 2005; Revised 17 November 2005; Accepted 25 November 2005; Published online 25 January 2006.

Abstract

Estrogens are believed to provide females with endogenous protection against cerebrovascular events although clinical trials studying long-term hormone replacement have yielded disappointing results. In contrast, estrogens might be neuroprotective after experimental ischemia. We performed a systematic review of controlled experimental studies that administered estrogens before, or after, cerebral ischemia and measured lesion volume. Relevant studies were found from searching PubMed, Embase and Web of Science. From 161 identified publications, 27 studies using 1304 experimental subjects were analyzed using the Cochrane Review Manager software. Estrogens reduced lesion volume in a dose-dependent manner, after either transient (P<0.001) or permanent (P<0.001) ischemia and whether administered before or up to 4 h after ischemia onset; no studies assessed efficacy for later time periods. The effect size for estrogens decreased with increasing quality scores for studies of transient ischemia. Estrogens reduced lesion volume when administered to ovariectomized females and young adult males, but had no effect in intact females. Limited data were present for aged animals and the full dose–response relationship was not available in all experimental groups. On the basis of these data, estrogens are a candidate treatment for ischemic stroke, although further preclinical studies are also warranted.