The impact of female sex on traumatic brain injury (TBI) outcomes remains controversial. The combined impact of age and sex on TBI outcomes must be clarified. We hypothesized that females have better outcomes than males in the premenopausal age group.
Data from the 2007–2016 National Trauma Data Bank of the Committee on Trauma-American College of Surgeons were used. Of a total of 686,549 patients with moderate to severe TBI (AIS ≥ 3), 251,491 were female. Comparison analyses of clinical characteristics and outcomes between females and males were conducted at different age groups: < 45 years, 45–55, and > 55 years. Logistic regressions were performed to assess the impact of age and female sex on mortality and complications.
Mortality rate between females and males aged < 45 and 45–55 years was similar, but significantly reduced in the > 55 years group. After multivariate logistic regression analysis controlling for multiple confounding factors, we found that females aged > 55 years had markedly decreased risk of mortality (AOR: 0.857, 95% CI 0.835–0.879, p < 0.001) and complications.
Female patients in the postmenopausal stage have better outcomes following TBI than males, but pre- and perimenopausal females do not, suggesting that female sexual hormones may not provide a significant protective effect on clinical outcomes following isolated moderate to severe TBI.
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Dewan MC, Rattani A, Gupta S, Baticulon RE, Hung YC, Punchak M, Agrawal A, Adeleye AO, Shrime MG, Rubiano AM, et al. Estimating the global incidence of traumatic brain injury. J Neurosurg. 2018;1:1–18.
Meltser I, Tahera Y, Simpson E, Hultcrantz M, Chariditi K, Gustafsson JA, Canlon B. Estrogen receptor beta protects against acoustic trauma in mice. J Clin Invest. 2008;118:1563–70.
Neese SL, Clough RW, Banz WJ, Smith DC. Z-Bisdehydrodoisynolic acid (Z-BDDA): an estrogenic seco-steroid that enhances behavioral recovery following moderate fluid percussion brain injury in male rats. Brain Res. 2010;1362:93–101.
Roof RL, Hall ED. Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. J Neurotrauma. 2000;17:367–88.
Roof RL, Hall ED. Estrogen-related gender difference in survival rate and cortical blood flow after impact-acceleration head injury in rats. J Neurotrauma. 2000;17:1155–69.
Wright DW, Kellermann AL, Hertzberg VS, Clark PL, Frankel M, Goldstein FC, Salomone JP, Dent LL, Harris OA, Ander DS, et al. ProTECT: a randomized clinical trial of progesterone for acute traumatic brain injury. Ann Emerg Med. 2007;49(391–402):402.e1–2.
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. https://doi.org/10.1186/cc6887.
Lin C, He H, Li Z, Liu Y, Chao H, Ji J, Liu N. Efficacy of progesterone for moderate to severe traumatic brain injury: a meta-analysis of randomized clinical trials. Sci Rep. 2015;5:13442. https://doi.org/10.1038/srep13442.
Ma J, Huang S, Qin S, You C, Zeng Y. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev. 2016;12:CD008409. https://doi.org/10.1002/14651858.CD008409.pub4.
Groswasser Z, Cohen M, Keren O. Female TBI patients recover better than males. Brain Inj. 1998;12:805–8.
Coimbra R, Hoyt DB, Potenza BM, Fortlage D, Hollingsworth-Fridlund P. Does sexual dimorphism influence outcome of traumatic brain injury patients? The answer is no! J Trauma. 2003;54:689–700.
Ponsford JL, Myles PS, Cooper DJ, Mcdermott FT, Murray LJ, Laidlaw J, Cooper G, Tremayne AB, Bernard SA. Gender differences in outcome in patients with hypotension and severe traumatic brain injury. Injury. 2008;39:67–766.
Leitgeb J, Mauritz W, Brazinova A, Janciak I, Majdan M, Wilbacher I, Rusnak M. Effects of gender on outcomes after traumatic brain injury. J Trauma. 2011;71(6):1620–6.
Yeung JH, Mikocka-Walus AA, Cameron PA, Poon WS, Ho HF, Chang A, Graham CA, Rainer TH. Protection from traumatic brain injury in hormonally active women vs men of a similar age: a retrospective international study. Arch Surg. 2011;146:436–42.
Davis DP, Douglas DJ, Smith W, Sise MJ, Vilke GM, Holbrook TL, Kennedy F, Eastman AB, Velky T, Hoyt DB. Traumatic brain injury outcomes in pre- and post- menopausal females versus age-matched males. J Neurotrauma. 2006;23:140–8.
Berry C, Ley EJ, Tillou A, Cryer G, Margulies DR, Salim A. The effect of gender on patients with moderate to severe head injuries. J Trauma. 2009;67:950–3.
Ley EJ, Short SS, Liou DZ, Singer MB, Mirocha J, Melo N, Bukur M, Salim A. Gender impacts mortality after traumatic brain injury in teenagers. J Trauma Acute Care Surg. 2013;75:682–6.
Albrecht JS, McCunn M, Stein DM, Simoni-Wastila L, Smith GS. Sex differences in mortality following isolated traumatic brain injury among older adults. J Trauma Acute Care Surg. 2016;81:486–92.
Ottochian M, Salim A, Berry C, Chan LS, Wilson MT, Margulies DR. Severe traumatic brain injury: is there a gender difference in mortality? Am J Surg. 2009;197:155–8.
Munivenkatappa A, Agrawal A, Shukla DP, Kumaraswamy D, Devi BI. Traumatic brain injury: does gender influence outcomes? Int J Crit Illn Inj Sci. 2016;6:70–3.
Skolnick BE, Maas AI, Narayan RK, van der Hoop RG, MacAllister T, Ward JD, Nelson NR, Stocchetti N, SYNAPSE Trial INvestigators. A clinical trial of progesterone for severe traumatic brain injury. N Engl J Med. 2014;371:2467–76.
Wright DW, Yeatts SD, Silbergleit R, Palesch YY, Hertzberg VS, Frankel M, Goldstein FC, Caveney AF, Howlett-Smith H, Bengelink EM, et al. Very early administration of progesterone for acute traumatic brain injury. N Engl J Med. 2014;371:2457–66.
Savitsky B, Givon A, Rozenfeld M, Radomislensky I, Peleg K. Traumatic brain injury: it is all about definition. Brain Inj. 2016;30:1194–200.
Gold EB. The timing of the age at which natural menopause occurs. Obstet Gynecol Clin North Am. 2011;38(3):425–40.
Trevoux R, De Brux J, Castanier M, Nahoul K, Soule JP, Scholler R. Endometrium and plasma hormone profile in the peri-menopause and post-menopause. Maturitas. 1986;8:309–26.
Goldstein FC, Caveney AF, Hertzberg VS, Silbergleit R, Yeatts SD, Palesch YY, Levin HS, Wright DW. Very early administration of progesterone does not improve neuropsychological outcomes in subjects with moderate to severe traumatic brain injury. J Neurotrauma. 2017;34:115–20.
Gupte R, Brooks W, Vukas R, Pierce J, Harris J. Sex differences in traumatic brain injury: what we know and what we should know. J Neurotrauma. 2019;36:3063–91.
Leitgeb J, Mauritz W, Brazinova A, Majdan M, Wilbacher I. Impact of concomitant injuries on outcomes after traumatic brain injury. Arch Orthop Trauma Surg. 2013;133:659–68.
Saadat S, Akbari H, Khorramirouz R, Mofid R, Rahimi-Movaghar V. Determinants of mortality in patients with traumatic brain injury. Ulus Travma Acil Cerrahi Derg. 2012;18:219–24.
Hsiao KY, Hsiao CT, Weng HH, Chen KH, Lin LJ, Huang YM. Factors predicting mortality in victims of blunt trauma brain injury in emergency department settings. Emerg Med J. 2008;25(10):670–3.
Krishnamoorthy V, Vavilala MS, Mills B, Rahbar AR. Demographic and clinical risk factors associated with hospital mortality after isolated severe traumatic brain injury: a cohort study. J Intensive Care. 2015;3:46. https://doi.org/10.1186/s40560-015-0113-4.
McIntyre A, Mehta S, Aubut J, Dijkers M, Teasell RW. Mortality among older adults after a traumatic brain injury: a meta-analysis. Brain Inj. 2013;27:31–40.
Hukkelhoven CWPM, Steyerberg EW, Rampen AJJ, Rampen AJ, Farace E, Habbema JD, Marshall LF, Murray GD, Maas AI. Patient age and outcome following severe traumatic brain injury: an analysis of 5600 patients. J Neurosurg. 2003;99:666–73.
Ho CH, Liang FW, Wang JJ, Chio CC, Kuo JR. Impact of grouping complications on mortality in traumatic brain injury: a nationwide population-based study. PLoS ONE. 2018;13(1):e0190683. https://doi.org/10.1371/journal.pone.0190683.
Cardozo Junior LC, Silva RR. Sepsis in intensive care unit patients with traumatic brain injury: factors associated with higher mortality. Rev Bras Ter Intensiva. 2014;26:148–54.
Prin M, Li G. Complications and in-hospital mortality in trauma patients treated in intensive care units in the United States, 2013. Inj Epidemiol. 2016;3:18. https://doi.org/10.1186/s40621-016-0084-5.
Wagner AK, McCullough EH, Niyonkuru C, Ozawa H, Loucks TL, Dobos JA, Brett CA, Santarsieri M, Dixon CE, Berga SL, et al. Acute serum hormone levels: characterization and prognosis after severe traumatic brain injury. J Neurotrauma. 2011;28:871–88.
Bell TM, Bayt DR, Zarzaur BL. “Smoker’s Paradox” in patients treated for severe injuries: lower risk of mortality after trauma observed in current smokers. Nicotine Tob Res. 2015;17:1499–504.
Lee IN, Lin MH, Chung CY, Lee MH, Weng HH, Yang JT. Chronic cigarette smoke exposure enhances brain-derived neurotrophic factor expression in rats with traumatic brain injury. Metab Brain Dis. 2012;27:197–204.
Brown CV, Rhee P, Neville AL, Sangthong B, Salim A, Demetriades D. Obesity and traumatic brain injury. J Trauma. 2006;61:572–6.
Czorlich P, Dreimann M, Emami P, Westphal M, Lefering R, Hoffman M. Body mass index >35 as independent predictor of mortality in severe traumatic brain injury. World Neurosurg. 2017;107:515–21.
Steinkellner AR, Denison SE, Eldridge SL, Lenzi LL, Chen W, Bowlin SJ. A decade of postmenopausal hormone therapy prescribing in the United States: long-term effects of the Women's Health Initiative. Menopause (New York, NY). 2012;19:616–21.
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The authors do not have any conflict of interest or competing interest to report associated with this research.
The current study was reviewed by the Riverside University Health System Institutional Review Board (protocol # 1636962) and it was deemed exempt from informed consent as it uses only deidentified data from a national administrative data base.
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Hong, Z., Firek, M., Zachary, B. et al. The effect of age and sex on outcomes following isolated moderate to severe traumatic brain injury. Eur J Trauma Emerg Surg (2020). https://doi.org/10.1007/s00068-020-01491-1
- Traumatic brain injury