BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and 
disability. Progesterone is a potential neuroprotective drug to treat patients 
with TBI.
OBJECTIVES: To assess the effectiveness and safety of progesterone in people 
with acute TBI.
SEARCH METHODS: We searched: the Cochrane Injuries Group's Specialised Register 
(13 July 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 
7, 2012), MEDLINE (Ovid) (1950 to August week 1, 2012), EMBASE (Ovid) (1980 to 
week 32 2012), LILACS (12 August 2012), Zetoc (13 July 2012), Clinicaltrials.gov 
(12 August 2012), Controlled-trials.com (12 August 2012).
SELECTION CRITERIA: We included published and unpublished randomised controlled 
trials (RCTs) of progesterone versus no progesterone (or placebo) for the 
treatment of people with acute TBI.
DATA COLLECTION AND ANALYSIS: Two review authors independently screened search 
results to identify the full texts of potentially relevant studies for 
inclusion. From the results of the screened searches two review authors 
independently selected trials meeting the inclusion criteria, with no 
disagreement.
MAIN RESULTS: Three studies were included with a total of 315 people. Two 
included studies were of high methodological quality, with low risk of bias in 
allocation concealment, blinding and incomplete outcome data. One study did not 
use blinding and had unclear risk of bias in allocation concealment and 
incomplete outcome data. All three studies reported the effects of progesterone 
on mortality. The pooled risk ratio (RR) for mortality at end of follow-up was 
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 to be 0.77, 95% CI 0.62 to 0.96. Data from two studies showed 
no difference in mean intracranial pressure or the rate of adverse and serious 
adverse events among people in either group. One study presented blood pressure 
and temperature data, and there were no differences between the people in the 
progesterone or control groups. 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.