Background
Traumatic brain injury is a leading cause of death and disability. Progesterone is a potential neuroprotective drug to treat patients with traumatic brain injury.

Objectives
To assess the effectiveness and safety of progesterone in people with acute traumatic brain injury (TBI).

Search strategy
We searched: the Cochrane Injuries Group's Specialised Register (to April 2010), Cochrane Central Register of Controlled Trials 2010, Issue 1 (The Cochrane Library), MEDLINE (Ovid) (1950 to April week 1 2010), EMBASE (Ovid) (1980 to week 14 2010), LILACS (to 17 April 2010 ), Zetoc (to 21 April 2010), Clinicaltrials.gov (17 April 2010 ), Controlled-trials.com (17 April 2010).

Selection criteria
We included published and unpublished randomised controlled trials (RCTs) of progesterone versus no progesterone (or placebo) for the treatment of acute TBI.

Data collection and analysis
Two authors independently screened search results to identify the full texts of potentially relevant studies for inclusion. From the results of the screened searches two authors independently selected trials meeting the inclusion criteria, with no disagreement.

Main results
Three studies were included with 315 patients. All three studies reported the effects of progesterone on mortality. The pooled relative risk (RR) for mortality at end of follow-up is 0.61, 95% confidence interval (CI) 0.40 to 0.93. Three studies measured disability and found the RR of death or severe disability in patients treated with progesterone was 0.77, 95% confidence interval (CI) 0.62 to 0.96. Two studies presented data on intracranial pressure and adverse events. One study presented blood pressure and temperature data. There was no substantial evidence for the presence of heterogeneity.

Authors' conclusions
Current clinical evidence from three small RCTs indicates progesterone may improve the neurologic outcome of patients suffering TBI. This evidence is still insufficient and further multicentre randomised controlled trials are required.