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Normative hypogonadism and depression: does ‘andropause’ exist?

International Journal of Impotence Research volume 18, pages 415–422 (2006)Cite this article

Abstract

The progressive decline in testosterone level has been demonstrated in both cross-sectional and longitudinal studies, and overall at least 25% of men over the age of 70 years meet laboratory criteria for hypogonadism (i.e., testosterone deficiency). Such age-associated HPG hypofunctioning, which has been termed ‘andropause’, is thought to be responsible for a variety of symptoms experienced by elderly men, including sexual dysfunction and depression. Although, it has been difficult to establish correlations between ‘andropausal’ symptoms and plasma testosterone levels, there is some evidence that testosterone replacement leads to improvement in muscle strength, bone mineral density, and erectile dysfunction. There is little evidence of a link between HPG-axis dysfunction and depressive illness, and exogenous androgens have not been consistently shown to be antidepressant. This article reviews the relationship between androgens and depression in aging men.

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References

  1. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 2002; 87: 589–598.

    Article  CAS  PubMed  Google Scholar 

  2. Seidman SN . Testosterone deficiency and mood in aging men: pathogenic and therapeutic interactions. World J Biol Psychiatr 2003; 4: 14–20.

    Article  Google Scholar 

  3. McKinlay JB, Longcope C, Gray A . The questionable physiologic and epidemiologic basis for a male climacteric syndrome: preliminary results from the Massachusetts Male Aging Study. Maturitas 1989; 11: 103–115.

    Article  CAS  PubMed  Google Scholar 

  4. Morales A, Heaton JP, Carson CC . Andropause: a misnomer for a true clinical entity. J Urol 2000; 163: 705–712.

    Article  CAS  PubMed  Google Scholar 

  5. Morley JE . Testosterone treatment in older men: effects on the prostate. Endocr Pract 2000; 6: 218–221.

    Article  CAS  PubMed  Google Scholar 

  6. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999; 84: 1966–1972.

    CAS  PubMed  Google Scholar 

  7. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 1999; 84: 2647–2653.

    CAS  PubMed  Google Scholar 

  8. Sih R, Morley JE, Kaiser FE, Perry HM, Patrick P, Ross C . Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 1997; 82: 1661–1667.

    Article  CAS  PubMed  Google Scholar 

  9. Bakhshi V, Elliott M, Gentili A, Godschalk M, Mulligan T . Testosterone improves rehabilitation outcomes in ill older men. J Am Geriatr Soc 2000; 48: 550–553.

    Article  CAS  PubMed  Google Scholar 

  10. Hajjar RR, Kaiser FE, Morley JE . Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab 1997; 82: 3793–3796.

    Article  CAS  PubMed  Google Scholar 

  11. Schmidt PJ, Rubinow DR . Neuroregulatory role of gonadal steroids in humans. Psychopharmacol Bull 1997; 33: 219–220.

    CAS  PubMed  Google Scholar 

  12. Vermeulen A, Kaufman JM . Ageing of the hypothalamo-pituitary-testicular axis in men. Horm Res 1995; 43: 25–28.

    Article  CAS  PubMed  Google Scholar 

  13. Field AE, Colditz GA, Willett WC, Longcope C, McKinlay JB . The relation of smoking, age, relative weight, and dietary intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men. J Clin Endocrinol Metab 1994; 79: 1310–1316.

    CAS  PubMed  Google Scholar 

  14. Mulligan T, Iranmanesh A, Johnson ML, Straume M, Veldhuis JD . Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men. Am J Physiol 1997; 273 (4 Part 2): R1407–R1413.

    CAS  PubMed  Google Scholar 

  15. Luisi M, Franchi F . Double-blind group comparative study of testosterone undecanoate and mesterolone in hypogonadal male patients. J Endocrinol Invest 1980; 3: 305–308.

    Article  CAS  PubMed  Google Scholar 

  16. Burris AS, Banks SM, Carter CS, Davidson JM, Sherins RJ . A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men. J Androl 1992; 13: 297–304.

    CAS  PubMed  Google Scholar 

  17. Villareal DT, Morley JE . Trophic factors in aging. Drugs and Aging 1994; 4: 492–509.

    Article  CAS  PubMed  Google Scholar 

  18. Morley JE . Testosterone replacement in older men and women. J Gend Specif Med 2001; 4: 49–53.

    CAS  PubMed  Google Scholar 

  19. Vermeulen A . Diagnosis of partial androgen deficiency in the aging male. Ann Endocrinol (Paris) 2003; 64: 109–114.

    CAS  Google Scholar 

  20. Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. Testosterone Gel Study Group. J Clin Endocrinol Metab 2000; 85: 2839–2853.

    CAS  PubMed  Google Scholar 

  21. McNicholas TA, Dean JD, Mulder H, Carnegie C, Jones NA . A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function. BJU Int 2003; 91: 69–74.

    Article  CAS  PubMed  Google Scholar 

  22. Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004; 89: 2085–2098.

    Article  CAS  PubMed  Google Scholar 

  23. Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R . AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 2003; 88: 2673–2681.

    Article  CAS  PubMed  Google Scholar 

  24. Schmidt PJ, Berlin KL, Danaceau MA, Neeren A, Haq NA, Roca CA et al. The effects of pharmacologically induced hypogonadism on mood in healthy men. Arch Gen Psychiatr 2004; 61: 997–1004.

    Article  PubMed  Google Scholar 

  25. Araujo AB, Durante R, Feldman HA, Goldstein I, McKinlay JB . The relationship between depressive symptoms and male erectile dysfunction: cross sectional results from the Massachusetts Male Aging Study. Psychosom Med 1998; 60: 458–465.

    Article  CAS  PubMed  Google Scholar 

  26. Seidman SN, Araujo AB, Roose SP, McKinlay JB . Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men. Biol Psychiatr 2001; 50: 371–376.

    Article  CAS  Google Scholar 

  27. Lehmann DJ, Hogervorst E, Warden DR, Smith AD, Butler HT, Ragoussis J . The androgen receptor CAG repeat and serum testosterone in the risk of Alzheimer's disease in men. J Neurol Neurosurg Psychiatr 2004; 75: 163–164.

    CAS  Google Scholar 

  28. Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D . Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab 1999; 84: 573–577.

    Article  CAS  PubMed  Google Scholar 

  29. Schweiger U, Deuschle M, Weber B, Korner A, Lammers CH, Schmider J et al. Testosterone, gonadotropin, and cortisol secretion in male patients with major depression. Psychosom Med 1999; 61: 292–296.

    Article  CAS  PubMed  Google Scholar 

  30. Rupprecht R, Rupprecht C, Rupprecht M, Noder M, Schwarz W . Different reactivity of the hypothalamo-pituitary-gonadal-axis in depression and normal controls. Pharmacopsychiatry 1988; 21: 438–439.

    Article  CAS  PubMed  Google Scholar 

  31. Seidman SN, Araujo AB, Roose SP, Devanand DP, Xie S, Cooper TB et al. Low testosterone levels in elderly men with dysthymic disorder. Am J Psychiatr 2002; 159: 456–459.

    Article  PubMed  Google Scholar 

  32. Delhez M, Hansenne M, Legros JJ . Andropause and psychopathology: minor symptoms rather than pathological ones. Psychoneuroendocrinology 2003; 28: 863–874.

    Article  CAS  PubMed  Google Scholar 

  33. Booth A, Johnson DR, Granger DA . Testosterone and men's depression: the role of social behavior. J Health Soc Behav 1999; 40: 130–140.

    Article  CAS  PubMed  Google Scholar 

  34. Rubinow DR, Schmidt PJ . Androgens, brain, and behavior. Am J Psychiatr 1996; 153: 974–984.

    Article  CAS  PubMed  Google Scholar 

  35. Tricker R, Casaburi R, Storer TW, Clevenger B, Berman N, Shirazi A et al. The effects of supraphysiological doses of testosterone on angry behavior in healthy eugonadal men – a clinical research center study. J Clin Endocrinol Metab 1996; 81: 3754–3758.

    CAS  PubMed  Google Scholar 

  36. Matsumoto AM . Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle- stimulating hormone, and sperm production. J Clin Endocrinol Metab 1990; 70: 282–287.

    Article  CAS  PubMed  Google Scholar 

  37. Janowsky JS, Oviatt SK, Orwoll ES . Testosterone influences spatial cognition in older men. Behav Neurosci 1994; 108: 325–332.

    Article  CAS  PubMed  Google Scholar 

  38. Yates WR, Perry PJ, Macindoe J, Holman T, Ellingrod V . Psychosexual effects of three doses of testosterone cycling in normal men. Biol Psychiatr 1999; 45: 254–260.

    Article  CAS  Google Scholar 

  39. Su TP, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, Rubinow DR . Neuropsychiatric effects of anabolic steroids in male normal volunteers. JAMA 1993; 269: 2760–2764.

    Article  CAS  PubMed  Google Scholar 

  40. Daly RC, Su TP, Schmidt PJ, Pagliaro M, Pickar D, Rubinow DR . Neuroendocrine and behavioral effects of high-dose anabolic steroid administration in male normal volunteers. Psychoneuroendocrinology 2003; 28: 317–331.

    Article  CAS  PubMed  Google Scholar 

  41. Pope HGJ, Kouri EM, Hudson JI . Effects of supraphysiologic doses of testosterone on mood and aggression in normal men. A randomized controlled trial. Arch Gen Psychiatr 2000; 57: 133–140.

    Article  CAS  PubMed  Google Scholar 

  42. Schiavi RC, White D, Mandeli J, Levine AC . Effect of testosterone administration on sexual behavior and mood in men with erectile dysfunction. Arch Sex Behav 1997; 26: 231–241.

    Article  CAS  PubMed  Google Scholar 

  43. Benkert O, Witt W, Adam W, Leitz A . Effects of testosterone undecanoate on sexual potency and the hypothalamic-pituitary-gonadal axis of impotent males. Arch Sex Behav 1979; 8: 471–479.

    Article  CAS  PubMed  Google Scholar 

  44. O'Carroll R, Bancroft J . Testosterone therapy for low sexual interest and erectile dysfunction in men: a controlled study. Br J Psychiatr 1984; 145: 146–151.

    Article  CAS  Google Scholar 

  45. Carani C, Zini D, Baldini A, Della Casa L, Ghizzani A, Marrama P . Effect of androgen treatment in impotent men with normal and low levels of free testosterone. Arch Sex Behav 1990; 19: 223–234.

    Article  CAS  PubMed  Google Scholar 

  46. Anderson RA, Bancroft J, Wu FC . The effects of exogenous testosterone on sexuality and mood of normal men. J Clin Endocrinol Metab 1992; 75: 1503–1507.

    CAS  PubMed  Google Scholar 

  47. Seidman SN, Walsh BT . Testosterone and depression in aging men. Am J Geriatr Psychiatr 1999; 7: 18–33.

    Article  CAS  Google Scholar 

  48. Rinieris PM, Malliaras DE, Batrinos ML, Stefanis CN . Testosterone treatment of depression in two patients with Klinefelter's syndrome. Am J Psychiatr 1979; 136: 986–988.

    Article  CAS  PubMed  Google Scholar 

  49. Heuser I, Hartmann A, Oertel H . Androgen replacement in a 48, XXYY-male patient [letter]. Arch Gen Psychiatr 1999; 56: 194–195.

    Article  CAS  PubMed  Google Scholar 

  50. Ehrenreich H, Halaris A, Ruether E, Hufner M, Funke M, Kunert HJ . Psychoendocrine sequelae of chronic testosterone deficiency. J Psychiatr Res 1999; 33: 379–387.

    Article  CAS  PubMed  Google Scholar 

  51. Seidman SN, Rabkin JG . Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Disord 1998; 48: 157–161.

    Article  CAS  PubMed  Google Scholar 

  52. Rabkin JG, Wagner G, Rabkin R . A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch Gen Psychiatr 2000; 57: 141–147.

    Article  CAS  PubMed  Google Scholar 

  53. Grinspoon S, Corcoran C, Stanley T, Baaj A, Basgoz N, Klibanski A . Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocrinol Metab 2000; 85: 60–65.

    CAS  PubMed  Google Scholar 

  54. Seidman SN, Spatz E, Rizzo C, Roose SP . Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. J Clin Psychiatr 2001; 62: 406–412.

    Article  CAS  Google Scholar 

  55. Pope HGJ, Cohane GH, Kanayama G, Siegel AJ, Hudson JI . Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatr 2003; 160: 105–111.

    Article  PubMed  Google Scholar 

  56. Seidman SN, Miyazaki M, Roose SP . Intramuscular testosterone supplementation to selective serotonin reuptake inhibitor in treatment-resistant depressed men: randomized placebo-controlled clinical trial. J Clin Psychopharmacol 2005; 25: 584–588.

    Article  CAS  PubMed  Google Scholar 

  57. Rolf C, Nieschlag E . Potential adverse effects of long-term testosterone therapy. Baillieres Clin Endocrinol Metab 1998; 12: 521–534.

    Article  CAS  PubMed  Google Scholar 

  58. Seidman SN, Roose SP . The male hypothalamic-pituitary-gonadal axis: Pathogenic and therapeutic implications in psychiatry. Psychiatric Annals 2000; 30: 102–112.

    Article  Google Scholar 

  59. Meehan PJ, Saltzman LE, Sattin RW . Suicide among older United States residents: epidemiologic characteristics and trends. Am J Public Health 1991; 81: 1198–1200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Wilson IC, Prange Jr AJ, Lara PP . Methyltestosterone with imipramine in men: conversion of depression to paranoid reaction. Am J Psychiatr 1974; 131: 21–24.

    Article  CAS  PubMed  Google Scholar 

  61. Itil TM, Herrmann WM, Blasucci D, Freedman A . Male hormones in the treatment of depression: Effects of mesterolone. Prog Neuropsychopharmacol 1978; 2: 457–467.

    Article  Google Scholar 

  62. Vogel W, Klaiber EL, Broverman DM . Roles of the gonadal steroid hormones in psychiatric depression in men and women. Prog Neuro-Psychopharmacol 1978; 2: 487–503.

    Article  Google Scholar 

  63. Itil TM, Michael ST, Shapiro DM, Itil KZ . The effects of mesterolone, a male sex hormone in depressed patients (a double blind controlled study). Methods Find Exp Clin Pharmacol 1984; 6: 331–337.

    CAS  PubMed  Google Scholar 

  64. Vogel W, Klaiber EL, Broverman DM . A comparison of the antidepressant effects of a synthetic androgen (mesterolone) and amitriptyline in depressed men. J Clin Psychiatr 1985; 46: 6–8.

    CAS  Google Scholar 

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  1. Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA

    S N Seidman

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Seidman, S. Normative hypogonadism and depression: does ‘andropause’ exist?. Int J Impot Res 18, 415–422 (2006). https://doi.org/10.1038/sj.ijir.3901443

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