Progesterone to treat severe traumatic brain injury
a systematic review and meta-analysis
Keywords:
TRAUMATIC BRAIN INJURIES, PROGESTERONE, META-ANALYSIS
Abstract
Objective: to systematically review evidence on the administration of progesterone after a traumatic brain injury in adults and its relationship with mortality and neurological head prognosis.
Inclusion criteria: randomized clinical trials that include: patients older than 12 years old, having had an injury (Glasgow <8), comparing the administration of Progesterone versus the control group (placebo or no administration).
Methods: we searched the following databases: MEDLINE, the Central Register of Controlled Trials (CENTRAL); PubMed, HINARI, EMBASE; Cochrane Injury Group and reference list of articles.
Results: there was no reduction in mortality in patients in the control group (RR 0.93, 95% CI 0.79-1.10 p = 0.41), there were no differences between progesterone and the control group in favorable or adverse neurological outcomes (RR 1.07, 95% CI: 0.97-1.17 p = 0.20, RR 0.94, 95% CI: 0.81 -1,08 p= 0.27), respectively.
Conclusions: there is no evidence that the administration of progesterone after a traumatic brain injury reduces or improves neurological results, although further good quality studies are required to obtain conclusive results.
References
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(20) Xiao G, Wei J, Wu Z, Wang W, Jiang Q, Cheng J, et al. Clinical study on the therapeutic effects and mechanism of progesterone in the treatment for acute severe head injury. Zhonghua Wai Ke Za Zhi 2007; 45(2):106-8.
(21) Aminmansour B, Nikbakht H, Ghorbani A, Rezvani M, Rahmani P, Torkashvand M, et al. Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury: a randomized clinical trial with placebo group. Adv Biomed Res 2012; 1:58.
(22) Raheja A, Sinha S, Samson N, Bhoi S, Subramanian A, Sharma P, et al. Serum biomarkers as predictors of long-term outcome in severe traumatic brain injury: analysis from a randomized placebo-controlled Phase II clinical trial. J Neurosurg 2016; 125(3):631-41.
(23) Wright D, Ritchie J, Mullins R, Kellermann A, Denson D. Steady-state serum concentrations of progesterone following continuous intravenous infusion in patients with acute moderate to severe traumatic brain injury. J Clin Pharmacol 2005; 45(6):640-8.
(24) Aboukhabar H, Abouelela A, Shaban S. Impact of progesterone administration on outcome in patients with severe traumatic brain injury. Res Opin Anesth Intensive Care 2017; 4(2):84-9.
(25) Wright D, Yeatts S, Silbergleit R, Palesch Y, Hertzberg V, Frankel M, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med 2014; 371(26):2457-66.
(26) Wright D, Kellermann A, Hertzberg V, Clark P, Frankel M, Goldstein F, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 2007; 49(4):391-402, 402.e1-2.
(27) Shakeri M, Boustani M, Pak N, Panahi F, Salehpour F, Lotfinia I, et al. Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma. Clin Neurol Neurosurg 2013; 115(10):2019-22.
(28) Sinha S, Raheja A, Samson N, Goyal K, Bhoi S, Selvi A, et al. A randomized placebo-controlled trial of progesterone with or without hypothermia in patients with acute severe traumatic brain injury. Neurol India 2017; 65(6):1304-11
(29) Skolnick B, Maas AI, Narayan R, Gerritsen R, MacAllister T, Wars J, et al. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med 2014; 371(26):2467-76.
(30) Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care 2008; 12(2):R61.
(31) Gibson C, Gray L, Bath P, Murphy S. Progesterone for the treatment of experimental brain injury; a systematic review. Brain 2008; 131(Pt 2):318-28.
(32) Lancel M, Faulhaber J, Holsboer F, Rupprecht R. Progesterone induces changes in sleep comparable to those of agonistic GABAA receptor modulators. Am J Physiol 1996; 271(4 Pt 1):E763-72.
(33) Deutsch E, Espinoza T, Atif F, Woodall E, Kaylor J, Wright D. Progesterone’s role in neuroprotection, a review of the evidence. Brain Res 2013; 1530:82-105.
(34) Loane D, Faden A. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends Pharmacol Sci 2010; 31(12):596-604.
(35) Pan Z, Zhao Y, Huang W, Xiao Z, Li Z. Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials. Drug Des Devel Ther 2019; 13:265-73.
(2) Alarcon J, Rubiano A, Chirinos M, Valderrama A, Gich I, Bonfill X, et al. Clinical practice guidelines for the care of patients with severe traumatic brain injury: a systematic evaluation of their quality. J Trauma Acute Care Surg 2013; 75(2):311-9.
(3) Langlois J, Rutland-Brown W, Thomas K. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta (GA): Centers for Disease Control and Prevention. National Center for Injury Prevention and Control, 2006.
(4) Alali A, Fowler R, Mainprize T, Scales D, Kiss A, de Mestral C, et al. Intracranial pressure monitoring in severe traumatic brain injury: results from the American College of Surgeons Trauma Quality Improvement Program. J Neurotrauma 2013; 30(20):1737-46.
(5) McGarry L, Thompson D, Millham F, Cowell L, Snyder P, Lenderking W, et al. Outcomes and costs of acute treatment of traumatic brain injury. J Trauma 2002; 53(6):1152-9.
(6) Godoy D, Panhke P, Piñero G, Videtta W, Aguilera S. Cuidados intensivos en trauma craneoencefálico grave. Neuroc Colomb 2016; 23(3):193-234.
(7) Guzman F. Pathophysiology of traumatic brain injury. Colomb Méd 2008; 39(Supl 3): 78-84.
(8) Alderson P, Roberts I. Corticosteroids for acute traumatic brain injury. Cochrane Database Syst Rev 2005; (1):CD000196.
(9) Arango M, Bainbridge D. Magnesium for acute traumatic brain injury. Cochrane Database Syst Rev 2008; (4):CD005400.
(10) Ma J, Huang S, Qin S, You C, Zeng Y. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev 2016; 12(12):CD008409.
(11) Schumacher M, Baulieu E. Neurosteroids: synthesis and functions in the central and peripheral nervous systems. Ciba Found Symp 1995; 191:90-106.
(12) Singh M, Su C. Progesterone-induced neuroprotection: factors that may predict therapeutic efficacy. Brain Res 2013; 1514:98-106.
(13) Toran-Allerand C. Sex steroids and the development of the newborn mouse hypothalamus and preoptic area in vitro. II. Morphological correlates and hormonal specificity. Brain Res 1980; 189(2):413-27.
(14) Simpkins J, Green P, Gridley KE Singh M, de Fiebre N, Rajakumar G. Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer’s disease. Am J Med 1997; 103(3A):19S-25S.
(15) Singh M, Meyer E, Simpkins J. The effect of ovariectomy and estradiol replacement on brain-derived neurotrophic factor messenger ribonucleic acid expression in cortical and hippocampal brain regions of female Sprague-Dawley rats. Endocrinology 1995; 136(5):2320-4.
(16) Asbury E, Fritts M, Horton J, Isaac W. Progesterone facilitates the acquisition of avoidance learning and protects against subcortical neuronal death following prefrontal cortex ablation in the rat. Behav Brain Res 1998; 97(1-2):99-106.
(17) Moher D, Liberati A, Tetzlaff J, Altman D. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Version 2. BMJ 2009; 339:b2535.
(18) Higgins J, Green S, eds. Cochrane Handbook for Systematic Reviews of Interventions: version 5.1.0, updated March 2011. London: The Cochrane Collaboration, 2011.
(19) Mofid B, Soltani Z, Khaksari M, Shahrokhi N, Nakhaee N, Karamouzian S, et al. What are the progesterone-induced changes of the outcome and the serum markers of injury, oxidant activity and inflammation in diffuse axonal injury patients? Int Immunopharmacol 2016; 32:103-10.
(20) Xiao G, Wei J, Wu Z, Wang W, Jiang Q, Cheng J, et al. Clinical study on the therapeutic effects and mechanism of progesterone in the treatment for acute severe head injury. Zhonghua Wai Ke Za Zhi 2007; 45(2):106-8.
(21) Aminmansour B, Nikbakht H, Ghorbani A, Rezvani M, Rahmani P, Torkashvand M, et al. Comparison of the administration of progesterone versus progesterone and vitamin D in improvement of outcomes in patients with traumatic brain injury: a randomized clinical trial with placebo group. Adv Biomed Res 2012; 1:58.
(22) Raheja A, Sinha S, Samson N, Bhoi S, Subramanian A, Sharma P, et al. Serum biomarkers as predictors of long-term outcome in severe traumatic brain injury: analysis from a randomized placebo-controlled Phase II clinical trial. J Neurosurg 2016; 125(3):631-41.
(23) Wright D, Ritchie J, Mullins R, Kellermann A, Denson D. Steady-state serum concentrations of progesterone following continuous intravenous infusion in patients with acute moderate to severe traumatic brain injury. J Clin Pharmacol 2005; 45(6):640-8.
(24) Aboukhabar H, Abouelela A, Shaban S. Impact of progesterone administration on outcome in patients with severe traumatic brain injury. Res Opin Anesth Intensive Care 2017; 4(2):84-9.
(25) Wright D, Yeatts S, Silbergleit R, Palesch Y, Hertzberg V, Frankel M, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med 2014; 371(26):2457-66.
(26) Wright D, Kellermann A, Hertzberg V, Clark P, Frankel M, Goldstein F, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med 2007; 49(4):391-402, 402.e1-2.
(27) Shakeri M, Boustani M, Pak N, Panahi F, Salehpour F, Lotfinia I, et al. Effect of progesterone administration on prognosis of patients with diffuse axonal injury due to severe head trauma. Clin Neurol Neurosurg 2013; 115(10):2019-22.
(28) Sinha S, Raheja A, Samson N, Goyal K, Bhoi S, Selvi A, et al. A randomized placebo-controlled trial of progesterone with or without hypothermia in patients with acute severe traumatic brain injury. Neurol India 2017; 65(6):1304-11
(29) Skolnick B, Maas AI, Narayan R, Gerritsen R, MacAllister T, Wars J, et al. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med 2014; 371(26):2467-76.
(30) Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Crit Care 2008; 12(2):R61.
(31) Gibson C, Gray L, Bath P, Murphy S. Progesterone for the treatment of experimental brain injury; a systematic review. Brain 2008; 131(Pt 2):318-28.
(32) Lancel M, Faulhaber J, Holsboer F, Rupprecht R. Progesterone induces changes in sleep comparable to those of agonistic GABAA receptor modulators. Am J Physiol 1996; 271(4 Pt 1):E763-72.
(33) Deutsch E, Espinoza T, Atif F, Woodall E, Kaylor J, Wright D. Progesterone’s role in neuroprotection, a review of the evidence. Brain Res 2013; 1530:82-105.
(34) Loane D, Faden A. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends Pharmacol Sci 2010; 31(12):596-604.
(35) Pan Z, Zhao Y, Huang W, Xiao Z, Li Z. Effect of progesterone administration on the prognosis of patients with severe traumatic brain injury: a meta-analysis of randomized clinical trials. Drug Des Devel Ther 2019; 13:265-73.
Published
2020-03-31
How to Cite
1.
Flórez Perdomo W, Durán M, Laiseca EF, Serrato SA, Quesada MF. Progesterone to treat severe traumatic brain injury. Rev. Méd. Urug. [Internet]. 2020Mar.31 [cited 2024Nov.25];36(1):74-. Available from: http://www2.rmu.org.uy/ojsrmu311/index.php/rmu/article/view/503
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