Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter July 23, 2013

Low testosterone levels may be associated with suicidal behavior in older men while high testosterone levels may be related to suicidal behavior in adolescents and young adults: a hypothesis

  • Leo Sher EMAIL logo

Abstract

Several lines of evidence suggest that there is an association between testosterone and suicidal behavior. A link between testosterone and the neurobiology of suicidal behavior may be related to: a) a direct effect of testosterone on suicidality via certain brain mechanisms; and/or b) a testosterone influence on aggression and, consequently, suicidality; and/or c) a testosterone effect on mood and, consequently, suicidality; and/or d) a testosterone effect on cognition and, consequently, suicidality. At least one study has demonstrated a relation between high levels of testosterone and suicide in young people. A significant number of studies suggest that high testosterone levels are associated with aggression in adolescents and adults. Multiple lines of evidence indicate that aggression is associated with suicidal behavior. The effect of high testosterone levels on suicidality in adolescents and young adults may be mediated by testosterone-related elevated aggression. It is also possible that, in young people, high testosterone levels are directly linked to suicidality via certain brain mechanisms. In older men, decreased testosterone levels are associated with depressive symptoms and reduced cognitive function, whereas higher blood levels of testosterone are associated with better mood and cognitive functioning. Depression and reduced cognition are associated with suicidal behavior and may mediate the effect of decreased testosterone levels on suicidality. Therefore, it is reasonable to propose that suicidal behavior in adolescents and young adults is associated with high testosterone levels, whereas suicidality in older men is associated with decreased testosterone secretion.


Corresponding author: Leo Sher, MD, Mount Sinai School of Medicine, NY, USA; and James J Peters Veterans’ Administration Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA

References

1. Brinkmann AO. Molecular mechanisms of androgen action–a historical perspective. Methods Mol Biol 2011;776:3–24.10.1007/978-1-61779-243-4_1Search in Google Scholar

2. Mainwaring WI. A soluble androgen receptor in the cytoplasm of rat prostate. J Endocrinol 1969;45:531–41.10.1677/joe.0.0450531Search in Google Scholar

3. Fang S, Anderson KM, Liao S. Receptor proteins for androgens. On the role of specific proteins in selective retention of 17-beta-hydroxy-5-alpha-androstan-3-one by rat ventral prostate in vivo and in vitro. J Biol Chem 1969;244:6584–95.10.1016/S0021-9258(18)63447-7Search in Google Scholar

4. Baulieu EE, Jung I. A prostatic cytosol receptor. Biochem Biophys Res Commun 1970;38:599–606.10.1016/0006-291X(70)90623-6Search in Google Scholar

5. Lejeune H, Habert R, Saez JM. Origin, proliferation and differentiation of Leydig cells. J Mol Endocrinol 1998;20:1–25.10.1677/jme.0.0200001Search in Google Scholar PubMed

6. Tapanainen J, Kellokumpu-Lehtinen P, Pelliniemi L, Huhtaniemi I. Age-related changes in endogenous steroids of human fetal testis during early and mid pregnancy. J Clin Endocrinol Metab 1981;52:98–102.10.1210/jcem-52-1-98Search in Google Scholar PubMed

7. Byskow AG. Differentiation of mammalian embryonic gonad. Physiol Rev 1986;66:77–112.10.1152/physrev.1986.66.1.71Search in Google Scholar PubMed

8. Aubert ML, Begeot M, Winiger BP, Morel G, Sizonenko PC, et al. Ontogeny of hypothalamic luteinizing hormone-releasing hormone (GnRH) and pituitary GnRH receptors in fetal and neonatal rats. Endocrinology 1985;116:1565–75.10.1210/endo-116-4-1565Search in Google Scholar PubMed

9. Sher L. Testosterone and suicidal behavior. Expert Rev Neurother 2012;12:25–9.10.1586/ern.12.6Search in Google Scholar PubMed

10. Tripodianakis J, Markianos M, Rouvali O, Istikoglou C. Gonadal axis hormones in psychiatric male patients after a suicide attempt. Eur Arch Psychiatry Clin Neurosci 2007;257:135–9.10.1007/s00406-006-0686-ySearch in Google Scholar PubMed

11. Markianos M, Tripodianakis J, Istikoglou C, Rouvali O, Christopoulos M, et al. Suicide attempt by jumping: a study of gonadal axis hormones in male suicide attempters versus men who fell by accident. Psychiatry Res 2009;170:82–5.10.1016/j.psychres.2008.08.001Search in Google Scholar

12. Sher L, Grunebaum MF, Sullivan GM, Burke AK, Cooper TB, et al. Testosterone levels in suicide attempters with bipolar disorder. J Psychiatr Res 2012;46:1267–71.10.1016/j.jpsychires.2012.06.016Search in Google Scholar

13. Brower KJ, Blow FC, Eliopulos GA, Beresford TP. Anabolic androgenic steroids and suicide. Am J Psychiatry 1989;146:1075.10.1176/ajp.146.8.1075aSearch in Google Scholar

14. Perez-Rodriguez MM, Lopez-Castroman J, Martinez-Vigo M, Diaz-Sastre C, Ceverino A, et al. Lack of association between testosterone and suicide attempts. Neuropsychobiology 2011;63:125–30.10.1159/000318085Search in Google Scholar

15. Butterfield MI, Stechuchak KM, Connor KM, Davidson JR, Wang C, et al. Neuroactive steroids and suicidality in posttraumatic stress disorder. Am J Psychiatry 2005;162: 380–2.10.1176/appi.ajp.162.2.380Search in Google Scholar

16. Farberow NL, Reynolds K. Dyadic crisis suicides in mental hospital patients. J Abnorm Psychol 1971;78:77–85.10.1037/h0031484Search in Google Scholar

17. Farberow NL. Personality patterns of suicidal mental hospital patients. Genet Psychol Monogr 1950;42:3–79.Search in Google Scholar

18. Morris JL Sr. Relationship of steroid levels and mode of death between suicides and sudden death victims. Unpublished Master’s thesis. Commerce, TX: East Texas State University, 1983:1–80.Search in Google Scholar

19. Roland BC, Morris JL Sr, Zelhart PF. Proposed relation of testosterone levels to male suicides and sudden deaths. Psychol Rep 1986;59:100–2.10.2466/pr0.1986.59.1.100Search in Google Scholar

20. Thiblin I, Runeson B, Rajs J. Anabolic androgenic steroids and suicide. Ann Clin Psychiatry 1999;11:223–31.10.3109/10401239909147074Search in Google Scholar

21. Ehrenkranz J, Bliss E, Sheard MH. Plasma testosterone: correlation with aggressive behavior and social dominance in man. Psychosom Med 1974;36:469–75.10.1097/00006842-197411000-00002Search in Google Scholar

22. Mattsson A, Schalling D, Olweus D, Löw H, Svensson J. Plasma testosterone, aggressive behavior, and personality dimensions in young male delinquents. J Am Acad Child Psychiatry 1980;19:476–90.10.1016/S0002-7138(09)61065-7Search in Google Scholar

23. Soler H, Vinayak P, Quadagno D. Biosocial aspects of domestic violence. Psychoneuroendocrinology 2000;25:721–39.10.1016/S0306-4530(00)00022-6Search in Google Scholar

24. Virkkunen M, Rawlings R, Tokola R, Poland RE, Guidotti A, et al. CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry 1994;51:20–27.10.1001/archpsyc.1994.03950010020003Search in Google Scholar PubMed

25. Su TP, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, et al. Neuropsychiatric effects of anabolic steroids in male normal volunteers. J Am Med Assoc 1993;269:2760–4.10.1001/jama.1993.03500210060032Search in Google Scholar

26. Pope HG Jr, Kouri EM, Hudson JI. Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial. Arch Gen Psychiatry 2000;57:133–40.10.1001/archpsyc.57.2.133Search in Google Scholar PubMed

27. Pope HG Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes. Arch Gen Psychiatry 1994;51:375–82.10.1001/archpsyc.1994.03950050035004Search in Google Scholar PubMed

28. Barzman DH, Patel A, Sonnier L, Strawn JR. Neuroendocrine aspects of pediatric aggression: can hormone measures be clinically useful? Neuropsychiatr Dis Treat 2010;6:691–7.10.2147/NDT.S5832Search in Google Scholar PubMed PubMed Central

29. Scerbo AS, Kolko DJ. Salivary testosterone and cortisol in disruptive children: relationship to aggressive, hyperactive, and internalizing behaviors. J Am Acad Child Adolesc Psychiatry 1994;33:1174–84.10.1097/00004583-199410000-00013Search in Google Scholar PubMed

30. Olweus D, Mattsson A, Schalling D, Low H. Circulating testosterone levels and aggression in adolescent males: a causal analysis. Psychosom Med 1988;50:261–72.10.1097/00006842-198805000-00004Search in Google Scholar PubMed

31. Constantino JN, Grosz D, Saenger P, Chandler DW, Nandi R, et al. Testosterone and aggression in children. J Am Acad Child Adolesc Psychiatry 1993;32:1217–22.10.1097/00004583-199311000-00015Search in Google Scholar PubMed

32. McGinnis MY. Anabolic androgenic steroids and aggression: studies using animal models. Ann NY Acad Sci 2004;1036: 399–415.10.1196/annals.1330.024Search in Google Scholar PubMed

33. Lumia AR, Thorner KM, McGinnis MY. Effects of chronically high doses of the anabolic androgenic steroid, testosterone, on intermale aggression and sexual behavior in male rats. Physiol Behav 1994;55:331–5.10.1016/0031-9384(94)90142-2Search in Google Scholar

34. Engström G, Persson B, Levander S. Temperament traits in male suicide attempters and violent offenders. Eur Psychiatry 1999;14:278–83.10.1016/S0924-9338(99)00170-4Search in Google Scholar

35. Grunebaum MF, Ramsay SR, Galfalvy HC, Ellis SP, Burke AK, et al. Correlates of suicide attempt history in bipolar disorder: a stress-diathesis perspective. Bipolar Disord 2006;8:551–7.10.1111/j.1399-5618.2006.00304.xSearch in Google Scholar PubMed

36. Sher L, Oquendo MA, Galfalvy HC, Grunebaum MF, Burke AK, et al. The relationship of aggression to suicidal behavior in depressed patients with a history of alcoholism. Addict Behav 2005;30:1144–53.10.1016/j.addbeh.2004.12.001Search in Google Scholar PubMed

37. Valenti G. The pathway of partial androgen deficiency of aging male. J Endocrinol Investig 2005;28:28–33.Search in Google Scholar

38. Araujo AB, O’Donnell AB, Brambilla DJ, Simpson WB, Longcope C, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts male aging study. J Clin Endocrinol Metabol 2004;89:5920–6.10.1210/jc.2003-031719Search in Google Scholar PubMed

39. Nardozza A, Jr., Szelbracikowski Sdos S, Nardi AC, Almeida JC. Age-related testosterone decline in a Brazilian cohort of healthy military men. Int Braz J Urol 2011;37:591–7.10.1590/S1677-55382011000500004Search in Google Scholar

40. Allan CA, McLachlan RI. Age-related changes in testosterone and the role of replacement therapy in older men. Clin Endocrinol 2004;60:653–70.10.1111/j.1365-2265.2004.02002.xSearch in Google Scholar PubMed

41. Liu CC, Wu WJ, Lee YC, Wang CJ, Ke HL, et al. The prevalence of and risk factors for androgen deficiency in aging Taiwanese men. J Sex Med 2009;6:936–46.10.1111/j.1743-6109.2008.01171.xSearch in Google Scholar PubMed

42. Amore M, Innamorati M, Costi S, Sher L, Girardi P, et al. Partial androgen deficiency, depression, and testosterone supplementation in aging men. Int J Endocrinol 2012;2012:280724.10.1155/2012/280724Search in Google Scholar PubMed PubMed Central

43. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001;86:724–31.10.1210/jcem.86.2.7219Search in Google Scholar PubMed

44. Hall SA, Esche GR, Araujo AB, Travison TG, Clark RV, et al. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metabol 2008;93:3870–7.10.1210/jc.2008-0021Search in Google Scholar PubMed PubMed Central

45. Chu LW, Tam S, Wong RL, Yik PY, Song Y, et al. Bioavailable testosterone predicts a lower risk of Alzheimer’s disease in older men. J Alzheimers Dis 2010;21:1335–45.10.3233/JAD-2010-100027Search in Google Scholar

46. Thilers PP, Macdonald SW, Herlitz A. The association between endogenous free testosterone and cognitive performance: a population-based study in 35 to 90 year-old men and women. Psychoneuroendocrinol 2006;31:565–76.10.1016/j.psyneuen.2005.12.005Search in Google Scholar PubMed

47. Barrett-Connor E, Von Mühlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab 1999;84:573–7.10.1210/jcem.84.2.5495Search in Google Scholar PubMed

48. Seidman SN, Walsh BT. Testosterone and depression in aging men. Am J Geriatr Psychiatry 1999;7:18–33.10.1097/00019442-199902000-00004Search in Google Scholar

49. Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI. Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry 2003;160:105–11.10.1176/appi.ajp.160.1.105Search in Google Scholar PubMed

50. Shores MM, Kivlahan DR, Sadak TI, Li EJ, Matsumoto AM. A randomized, double-blind, placebo-controlled study of testosterone treatment in hypogonadal older men with subthreshold depression (dysthymia or minor depression). J Clin Psychiatry 2009;70:1009–16.10.4088/JCP.08m04478Search in Google Scholar PubMed

51. Seidman SN, Orr G, Raviv G, Levi R, Roose SP, et al. Effects of testosterone replacement in middle-aged men with dysthymia: a randomized, placebo-controlled clinical trial. J Clin Psychopharmacol 2009;29:216–21.10.1097/JCP.0b013e3181a39137Search in Google Scholar PubMed

52. Ebinger M, Sievers C, Ivan D, Schneider HJ, Stalla GK. Is there a neuroendocrinological rationale for testosterone as a therapeutic option in depression? J Psychopharmacol 2009; 23:841–53.10.1177/0269881108092337Search in Google Scholar PubMed

53. Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract 2009;15:289–305.10.1097/01.pra.0000358315.88931.fcSearch in Google Scholar PubMed

54. Pope HG Jr, Katz DL. Affective and psychotic symptoms associated with anabolic steroid use. Am J Psychiatry 1988;145:487–90.10.1176/ajp.145.4.487Search in Google Scholar PubMed

55. Frye CA, Walf AA. Depression-like behavior of aged male and female mice is ameliorated with administration of testosterone or its metabolites. Physiol Behav 2009;97:266–9.10.1016/j.physbeh.2009.02.022Search in Google Scholar PubMed PubMed Central

56. Carrier N, Kabbaj M. Testosterone and imipramine have antidepressant effects in socially isolated male but not female rats. Horm Behav 2012;61:678–85.10.1016/j.yhbeh.2012.03.001Search in Google Scholar PubMed PubMed Central

57. Carrier N, Kabbaj M. Extracellular signal-regulated kinase 2 signaling in the hippocampal dentate gyrus mediates the antidepressant effects of testosterone. Biol Psychiatry 2012;71:642–51.10.1016/j.biopsych.2011.11.028Search in Google Scholar PubMed PubMed Central

58. Spence RD, Voskuhl RR. Neuroprotective effects of estrogens and androgens in CNS inflammation and neurodegeneration. Front Neuroendocrinol 2012;33:105–15.10.1016/j.yfrne.2011.12.001Search in Google Scholar PubMed PubMed Central

59. Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, et al.; Testosterone Gel Study Group. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 2000;85:2839–53.10.1210/jc.85.8.2839Search in Google Scholar

60. Bacon CG, Mittleman MA, Kawachi I, Giovannucci E, Glasser DB, et al. Sexual function in men older than 50 years of age: results from the health professionals follow-up study. Ann Intern Med 2003;139:161–8.10.7326/0003-4819-139-3-200308050-00005Search in Google Scholar PubMed

61. Nigro N, Christ-Crain M. Testosterone treatment in the aging male: myth or reality? Swiss Med Wkly 2012;19:142.10.4414/smw.2012.13539Search in Google Scholar PubMed

62. Emmelot-Vonk MH, Verhaar HJ, Nakhai Pour HR, Aleman A, Lock TM, et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. J Am Med Assoc 2008;299:39–52.10.1001/jama.2007.51Search in Google Scholar PubMed

63. Sher L. Possible link between cognitive dysfunction and suicidal behavior in individuals with alcohol use disorders. Int J Disabil Hum Dev 2007;6:149–52.10.1515/IJDHD.2007.6.2.149Search in Google Scholar

64. Jollant F, Lawrence NL, Olié E, Guillaume S, Courtet P. The suicidal mind and brain: a review of neuropsychological and neuroimaging studies. World J Biol Psychiatry 2011;12:319–39.10.3109/15622975.2011.556200Search in Google Scholar

65. Sher L, Oquendo MA, Mann JJ. Risk of suicide in mood disorders. Clin Neurosci Res 2001;1:337–44.10.1016/S1566-2772(01)00035-4Search in Google Scholar

66. Mann JJ, Apter A, Bertolote J, Beautrais A, Currier D, et al. Suicide prevention strategies: a systematic review. J Am Med Assoc 2005;294:2064–74.10.1001/jama.294.16.2064Search in Google Scholar PubMed

Received: 2013-8-10
Accepted: 2012-10-2
Published Online: 2013-07-23
Published in Print: 2013-09-01

©2013 by Walter de Gruyter Berlin Boston

Downloaded on 18.5.2024 from https://www.degruyter.com/document/doi/10.1515/ijamh-2013-0060/html
Scroll to top button