Document Type : Original Article

Authors

1 Vallabhbhai Patel Chest Institute, New Delhi, India

2 Pt. B.D. Sharma PGIMS, University in Rohtak, Rohtak, India

3 Department of Biochemistry, Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India

Abstract

Background: One intriguing aspect of stroke is its higher incidence in men as compared to women. Endogenous sex hormones, testosterone and estradiol, may be responsible for this difference. This research aims to study serum testosterone and estradiol levels in men with acute ischemic stroke (AIS) and to correlate these levels with National Institutes of Health Stroke Scale (NIHSS) score and infarct size in computed tomography (CT).
Methods: 100 male patients with AIS and 100 age-matched controls were included in this case-control study. Patients with hemorrhagic stroke, taking hormonal preparations, or suffering from chronic illnesses like tuberculosis (TB), cancer, etc. were excluded. Complete history was obtained including presence of established risk factors and physical examination was done in cases and controls with informed written consent. Severity of stroke in cases was assessed by the NIHSS. CT scan of brain was performed within 72 hours of patient’s admission to hospital. The infarct size was measured in centimeters as the largest visible diameter of the infarct on CT scan. Fasting blood samples were obtained for routine investigations and estimating estradiol and testosterone levels.
Results: Mean total testosterone level in cases (223.30 ± 143.44 ng/dl) was significantly lower than that of controls (515.34 ± 172.11 ng/dl) (P < 0.001), while estradiol levels had no significant statistical difference (P = 0.260). A significant inverse correlation was found between total testosterone levels and stroke severity (r = -0.581, P < 0.001) and also, total testosterone levels and infarct size (r = -0.557, P < 0.001). Estradiol levels in patients had no significant correlation with stroke severity (P = 0.618) or infarct size (P = 0.463).
Conclusion: Low testosterone levels are associated with increased stroke severity and infarct size in men. Further studies are required to establish whether low testosterone is a cause or effect of ischemic stroke and also to explore the potential benefits of testosterone supplementation in men with AIS.

Keywords

  1. Indian Council for Medical Research. Stroke. In: Assessment of the burden of non-communicable diseases: Final project report. New Delhi, India: Indian Council of Medical Research; 2004. p. 18-22.
  2. World Health Organization. World Health Statistics 2009 [Online]. [cited 2009]; Available from: URL: https://apps.who.int/iris/bitstream/handle/10665/44078/9789241563819_eng.pdf?sequence=1&isAllowed=y
  3. Kumar S, Taylor F. Stroke in India - Fact-sheet (Updated 2012). South Asian Center for Chronic Diseases 2012 [Online]. [cited 2012]; Available from: URL: https://www.researchgate.net/publication/264116605_Stroke_in_India_-_Fact-sheet_Updated_2012
  4. Sacco RL, Kasner SE, Broderick JP, Caplan LR, Connors JJ, Culebras A, et al. An updated definition of stroke for the 21st century: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013; 44(7): 2064-89.
  5. Jeppesen LL, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS, Winther K. Decreased serum testosterone in men with acute ischemic stroke. Arterioscler Thromb Vasc Biol 1996; 16(6): 749-54.
  6. Zeller T, Schnabel RB, Appelbaum S, Ojeda F, Berisha F, Schulte-Steinberg B, et al. Low testosterone levels are predictive for incident atrial fibrillation and ischaemic stroke in men, but protective in women - results from the FINRISK study. Eur J Prev Cardiol 2018; 25(11): 1133-9.
  7. Yeap BB, Hyde Z, Almeida OP, Norman PE, Chubb SA, Jamrozik K, et al. Lower testosterone levels predict incident stroke and transient ischemic attack in older men. J Clin Endocrinol Metab 2009; 94(7): 2353-9.
  8. Hollander M, Koudstaal PJ, Bots ML, Grobbee DE, Hofman A, Breteler MM. Incidence, risk, and case fatality of first ever stroke in the elderly population. The Rotterdam Study. J Neurol Neurosurg Psychiatry 2003; 74(3): 317-21.
  9. Srinath R, Gottesman RF, Hill GS, Carson KA, Dobs A. Association between endogenous testosterone and cerebrovascular disease in the ARIC Study (Atherosclerosis Risk in Communities). Stroke 2016; 47(11): 2682-8.
  10. Shores MM, Matsumoto AM. Testosterone, aging and survival: biomarker or deficiency. Curr Opin Endocrinol Diabetes Obes 2014; 21(3): 209-16.
  11. Abbott RD, Launer LJ, Rodriguez BL, Ross GW, Wilson PW, Masaki KH, et al. Serum estradiol and risk of stroke in elderly men. Neurology 2007; 68(8): 563-8.
  12. Zirkin BR, Tenover JL. Aging and declining testosterone: past, present, and hopes for the future. J Androl 2012; 33(6): 1111-8.
  13. Van Pottelbergh I, Braeckman L, De Bacquer D, De Backer G, Kaufman JM. Differential contribution of testosterone and estradiol in the determination of cholesterol and lipoprotein profile in healthy middle-aged men. Atherosclerosis 2003; 166(1): 95-102.
  14. Agledahl I, Skjaerpe PA, Hansen JB, Svartberg J. Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: The Tromso study. Nutr Metab Cardiovasc Dis 2008; 18(4): 256-62.
  15. Francomano D, Bruzziches R, Natali M, Aversa A, Spera G. Cardiovascular effect of testosterone replacement therapy in aging male. Acta Biomed 2010; 81(Suppl 1): 101-6.
  16. Saad F, Gooren LJ, Haider A, Yassin A. A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate. J Androl 2008; 29(1): 102-5.
  17. Cheng J, Alkayed NJ, Hurn PD. Deleterious effects of dihydrotestosterone on cerebral ischemic injury. J Cereb Blood Flow Metab 2007; 27(9): 1553-62.
  18. Yang SH, Perez E, Cutright J, Liu R, He Z, Day AL, et al. Testosterone increases neurotoxicity of glutamate in vitro and ischemia-reperfusion injury in an animal model. J Appl Physiol (1985) 2002; 92(1): 195-201.
  19. Pugh PJ, Channer KS, Parry H, Downes T, Jone TH. Bio-available testosterone levels fall acutely following myocardial infarction in men: association with fibrinolytic factors. Endocr Res 2002; 28(3): 161-73.
  20. Ahlbom E, Grandison L, Bonfoco E, Zhivotovsky B, Ceccatelli S. Androgen treatment of neonatal rats decreases susceptibility of cerebellar granule neurons to oxidative stress in vitro. Eur J Neurosci 1999; 11(4): 1285-91.
  21. Ahlbom E, Prins GS, Ceccatelli S. Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism. Brain Res 2001; 892(2): 255-62.
  22. Gu F, Hata R, Toku K, Yang L, Ma YJ, Maeda N, et al. Testosterone up-regulates aquaporin-4 expression in cultured astrocytes. J Neurosci Res 2003; 72(6): 709-15.
  23. Woolf PD, Hamill RW, McDonald JV, Lee LA, Kelly M. Transient hypogonadotropic hypogonadism caused by critical illness. J Clin Endocrinol Metab 1985; 60(3): 444-50.