The effect of age and sex on outcomes following isolated moderate to severe traumatic brain injury



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.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    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.

    Google Scholar 

  2. 2.

    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.

    CAS  Article  Google Scholar 

  3. 3.

    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.

    CAS  Article  Google Scholar 

  4. 4.

    Roof RL, Hall ED. Gender differences in acute CNS trauma and stroke: neuroprotective effects of estrogen and progesterone. J Neurotrauma. 2000;17:367–88.

    CAS  Article  Google Scholar 

  5. 5.

    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.

    CAS  Article  Google Scholar 

  6. 6.

    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.

    Google Scholar 

  7. 7.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Ma J, Huang S, Qin S, You C, Zeng Y. Progesterone for acute traumatic brain injury. Cochrane Database Syst Rev. 2016;12:CD008409.

    Article  PubMed  Google Scholar 

  10. 10.

    Groswasser Z, Cohen M, Keren O. Female TBI patients recover better than males. Brain Inj. 1998;12:805–8.

    CAS  Article  Google Scholar 

  11. 11.

    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.

    Article  Google Scholar 

  12. 12.

    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.

    Article  Google Scholar 

  13. 13.

    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.

    PubMed  Google Scholar 

  14. 14.

    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.

    Article  Google Scholar 

  15. 15.

    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.

    Article  Google Scholar 

  16. 16.

    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.

    Article  Google Scholar 

  17. 17.

    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.

    Article  Google Scholar 

  18. 18.

    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.

    Article  Google Scholar 

  19. 19.

    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.

    Article  Google Scholar 

  20. 20.

    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.

    Article  Google Scholar 

  21. 21.

    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.

    Article  Google Scholar 

  22. 22.

    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.

    Article  Google Scholar 

  23. 23.

    Savitsky B, Givon A, Rozenfeld M, Radomislensky I, Peleg K. Traumatic brain injury: it is all about definition. Brain Inj. 2016;30:1194–200.

    CAS  Article  Google Scholar 

  24. 24.

    Gold EB. The timing of the age at which natural menopause occurs. Obstet Gynecol Clin North Am. 2011;38(3):425–40.

    Article  Google Scholar 

  25. 25.

    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.

    CAS  Article  Google Scholar 

  26. 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.

    Article  Google Scholar 

  27. 27.

    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.

    Article  Google Scholar 

  28. 28.

    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.

    Article  Google Scholar 

  29. 29.

    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.

    Article  Google Scholar 

  30. 30.

    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.

    Article  Google Scholar 

  31. 31.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    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.

    Article  Google Scholar 

  33. 33.

    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.

    Article  Google Scholar 

  34. 34.

    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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  35. 35.

    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.

    Article  Google Scholar 

  36. 36.

    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.

    Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    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.

    Article  Google Scholar 

  38. 38.

    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.

    Article  Google Scholar 

  39. 39.

    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.

    CAS  Article  Google Scholar 

  40. 40.

    Brown CV, Rhee P, Neville AL, Sangthong B, Salim A, Demetriades D. Obesity and traumatic brain injury. J Trauma. 2006;61:572–6.

    Article  Google Scholar 

  41. 41.

    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.

    Article  Google Scholar 

  42. 42.

    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.

    Article  Google Scholar 

Download references


There was no funding associated with the development and execution of this research project.

Author information




Study design, conception, and critical revision: Zhi-Jie Hong, Katharina Mörs, Cora Schindler, Ingo Marzi, Raul Coimbra. Acquisition, analysis, and interpretation of data: Matthew Firek, Bishoy Zachary, Zhi-Jie Hong, Raul Coimbra. Literature search and drafting of manuscript: Zhi-Jie Hong, Jyh-Cherng Yu, Katharina Mörs, Cora Schindler. Final Manuscript review/editing: Raul Coimbra, Ingo Marzi.

Corresponding author

Correspondence to Raul Coimbra.

Ethics declarations

Conflict of interest

The authors do not have any conflict of interest or competing interest to report associated with this research.

Ethical approval

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.

Consent to participate


Consent for publication


Availability of data and materials

Not available publicly.

Code availability


Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation


  • Traumatic brain injury
  • Gender
  • Outcome
  • Estrogen
  • Mortality