Is progesterone a candidate neuroprotective factor for treatment following ischemic stroke?

Gender differences in stroke outcome have implicated steroid hormones as potential neuroprotective candidates. However, no clinical trials examining hormone replacement therapy on outcome following ischemic stroke have investigated the effect of progesterone-only treatment. In this review the authors examine the experimental evidence for the neuroprotective potential of progesterone and give an insight into potential mechanisms of action following ischemic stroke. To date, 17 experimental studies have investigated the neuroprotective potential of progesterone for ischemic stroke in terms of ability to both reduce cell loss and increase functional outcome. Of these 17 published studies the majority reported a beneficial effect with three studies reporting a nil effect and only one study reporting a negative effect. However, there are important issues that the authors address in this review in terms of the methodological quality of studies in relation to the STAIR recommendations. In terms of the proposed mechanisms of progesterone neuroprotection we show that progesterone is versatile and acts at multiple targets to facilitate neuronal survival and minimize cell damage and loss. A large amount of experimental evidence indicates that progesterone is a neuroprotective candidate for ischemic stroke; however, to progress to clinical trial a number of key experimental studies remain outstanding.