Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials

Abstract

ObjectiveTo evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI).MethodsPubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI.ResultsA total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57–1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78–1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96–4.66).ConclusionsDespite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.

Neuroprotection by Estrogen and Progesterone in Traumatic Brain Injury and Spinal Cord Injury

“…Despite the growing data of evidence in the literature of effectiveness of estrogen and progesterone in animal models of TBI, the human clinical data has not demonstrated a clinical benefit. To this end, two recent meta-analyses failed to demonstrate a reduction in mortality or clinical benefit after progesterone treatment in acute TBI compared to placebo [ 53 , 54 ]. There are several possible reasons for the negative findings.…”

The currency, completeness and quality of systematic reviews of acute management of moderate to severe traumatic brain injury: A comprehensive evidence map

“…As such, the following 11 interventions are underpinned by current, complete and high quality systematic review(s) that include one or more RCT: red blood cell transfusion [ 39 ], hypothermia [ 49 ], management guided by intracranial pressure [ 64 ], various pharmacological agents (progesterone [ 73 ], antifibrinolytic agents [ 76 , 77 ], aminosteroids [ 81 ], beta-blockers [ 82 ], tromethamine [ 84 ]), and prehospital intubation [ 89 ].…”

The neuroprotective steroid progesterone promotes mitochondrial uncoupling, reduces cytosolic calcium and augments stress resistance in yeast cells

“…Interestingly, preclinical data strongly suggest that (high doses of) progesterone may positively affect recovery from traumatic brain injury (TBI) in model organisms 34567, if administered before or shortly after TBI. Two clinical studies could confirm a neuroprotective effect of progesterone when administered shortly after TBI 89, while some more recent clinical data seem to disprove this hypothesis 101112. Therefore, it remains an open question if progesterone affects the recovery and survival after TBI in humans and to which extent it promotes cellular restauration.…”