Brain Advance Access first published online on August 21, 2007
This version published online on August 23, 2007
Brain, doi:10.1093/brain/awm183
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Review Article |
Progesterone for the treatment of experimental brain injury; a systematic review
1School of Psychology, University of Leicester, Lancaster Road, Leicester, LE1 9HN, UK, 2Division of Stroke Medicine, University of Nottingham, City Hospital Campus, Nottingham, UK and 3Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA, USA
Correspondence to:
Dr Claire L. Gibson, School of Psychology, Henry Wellcome Building, Lancaster Road, Leicester, LE1 9HN, UK E-mail: cg95{at}le.ac.uk
Steroid sex hormones are potential neuroprotective candidates following CNS injury. All clinical trials to date have examined the effects of oestrogen alone or oestrogen-progestin combination therapy. Experimental studies have suggested that progesterone, in its own right, is a potential neuroprotective agent following acute cerebral injury. We performed a systematic review of controlled animal studies that administered progesterone before, or after, acute cerebral injury and measured lesion volume. Relevant studies were found from searching PubMed, Embase and Web of Science. From 119 identified publications, data from 18 studies using 480 experimental subjects met specific criteria and were analysed using the Cochrane Review Manager software. Following cerebral ischaemia, a significant benefit of progesterone was observed regardless of the assigned study quality score (P = 0.0002) whereas, following traumatic brain injury (TBI) a significant benefit of progesterone was only observed in studies that obtained the highest quality score of 5 (P = 0.02). Progesterone reduced lesion volume in a dose-dependent manner following either cerebral ischaemia (P < 0.001) or TBI (P = 0.03) with the most effective progesterone dose varying according to experimental injury model used. Progesterone treatment was only effective at reducing lesion volume when administered immediately following (i.e. 0–2 h) cerebral ischaemia (P = 0.0008). No studies using models of cerebral ischaemia or TBI assessed efficacy when progesterone was administered at later than 6 h following the onset of cerebral injury. Limited data were available for different groups of animals according to age/hormonal status and the full dose–response relationship was not available in all experimental groups. Although this systematic review provides some supporting evidence for a neuroprotective role of progesterone following either cerebral ischaemia or TBI importantly it highlights areas which need further pre-clinical investigation.
Key Words: progesterone; stroke; traumatic brain injury; systematic review; neuroprotection
Abbreviations: SMD, standardized mean difference; TBI, traumatic brain injury
Received March 15, 2007. Revised June 25, 2007. Accepted July 10, 2007.
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  G. M. Sare, L. J. Gray, and P. M.W. Bath Association between hormone replacement therapy and subsequent arterial and venous vascular events: a meta-analysis Eur. Heart J., July 3, 2008; (2008) ehn299v1. [Abstract] [Full Text] [PDF]
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