Testosterone and Depression

Yıl 2010, Cilt: 2 Sayı: 4, 457 - 472, 01.12.2010

Şükrü Kartalcı

Öz

Androgens have various effects on human body and mood. Testosterone, a hormone mainly secreted from testes and adrenals, is one of the most potent androgens. Multiple studies have found that testosterone plays a role in regulating sexual activity, libido, social behaviors, aggression, cognitive functions, sleep control and well-being in men and women. Testosterone deficiency in hypogonadic or elderly men leads to neuropsychiatric problems, such as fatigue, loss of libido, irritability, insomnia and depressive mood. Testosterone replacement therapy consistently reverses these sequel in men. On the other hand, hyperandrogenic states in women are related to aggression and antisocial behavior, which might lead to depressive mood. Low testosterone levels may also result in depression among oophorectomized women. Because of such effects, a relationship between testosterone and depression has long been an issue of speculation, but yet very few studies have addressed this relation. Along with clinical studies, experimental and epidemiological studies show that testosterone is related to depression in men and women. But studies of testosterone concentrations in depression have yielded inconsistent results reporting low as well as high testosterone levels associated with depression. In this article, the physiological and psychological effects of testosterone and evidence regarding its relationship to depressive disorders and possible gender differences have been reviewed.

Anahtar Kelimeler

Testosterone, Depression, Androgen, Gender

Testosteron ve Depresyon

Öz

Androjenler, insanda beden ve duygudurum üzerinde çok çeşitli etkilere sahiptir. Testis ve adrenallerden salgılanan testosteron insan bedenindeki en güçlü androjenlerden biridir. Testosteronun erkeklerde ve kadınlarda cinsel aktivite, libido, sosyal davranışlar, saldırganlık, bilişsel işlevler, uyku kontrolü ve iyilik halinin düzenlenmesinde rol oynadığı bilinmektedir. Hipogonadal ya da yaşlı erkeklerdeki testosteron yetmezliği yorgunluk, libido azalması, çabuk sinirlenme, uykusuzluk ve depresyon gibi nöropsikiyatrik problemlere yol açmaktadır. Testosteron yerine koyma tedavisi bu bozuklukları tutarlı bir şekilde tersine çevirmektedir. Bunun dışında yüksek testosteron düzeyleri de depresyona yol açabilmektedir. Kadınlarda aşırı androjen düzeyleri, depresif duygudurum, sinirlilik ve antisosyal davranışlarla ilişkilendiirlmiştir. Ooferektomi yapılmış kadınlardaki düşük testosteron düzeyleri de depresyona neden olabilir. Bu bildirimlerden dolayı testosteron ve depresyon arasında bir ilişki olabileceği uzun zamandan beri düşünülmekle birlikte şu ana kadar bu konuyu araştıran çok az sayıda çalışma yapılmıştır. Klinik çalışmalar gibi, deneysel ve epidemiyolojik çalışmalarda testosteronun erkek ve kadınlarda depresyonla ilişkili olduğunu göstermektedir. Fakat depresyonda testosteron konsantrasyonlarının araştırıldığı klinik çalışmalar çelişkili sonuçlar ortaya koymuş, hem düşük hem de yüksek testosteron düzeylerinin depresyonla ilişkili olduğu bulunmuştur. Bu makalede testosteronun fizyolojik ve psikolojik etkileri ve depresif bozukluklarla ilişkisi ve olası cinsiyet farklılıkları ele alınıp değerlendirilmiştir.

Anahtar Kelimeler

Testosteron, Depresyon, Androjen, Cinsiyet

Kaynakça

• Morley JE. Testosterone and behavior. Clin Geriatr Med 2003; 19:605-616.
• Brown-Sequard CE. The effects produced on man by subcutaneous injections of a liquid obtained from the testicles of animals. Lancet 1889; 2:105-107.
• 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.
• Seidman SN. Testosterone deficiency and mood in aging men: Pathogenic and therapeutic interactions.World J Biol Psychiatry 2003; 4:14-20.
• Rohr UD. The impact of testosterone imbalance on depression and women's health. Maturitas 2002; 41(Suppl 1):25-46.
• Stoffel-Wagner B. Neurosteroid metabolism in the human brain. Eur J Endocrinol 2001; 145:669-679.
• Kartalcı Ş, Eşel E. Nörosteroidler: psikofarmakolojik ve davranışsal etkileri. Klinik Psikofarmakoloji Bülteni 2004; 14:38-49
• Rupprecht R, Holsboer F. Neuroactive steroids: mechanisms of action and neuropsychopharmacological perspectives. Trends Neurosci 1999; 22:410-416.
• Paul SM, Purdy RH. Neuroactive steroids. FASEB J 1992; 6:2311-2322.
• McEwen BS. Non-genomic and genomic effects of steroids on neural activity. Trends Pharmacol Sci 1991; 12:141-147.
• Ramirez VD, Zheng J. Membrane sex-steroid receptors in the brain. Front Neuroendocrinol 1996; 17:402-439.
• Weinbauer GE, Gromoll J, Simoni M. Physiology of the testicular function. In: Andrology. Male Reproductive Health and Dysfunction (Eds E Nieschlag, H Behre): Berlin, Germany, Springer Verlag, 1998.
• Wallen K, Eisler JA, Tannenbaum PL, Nagell KM, Mann DR. Antide (Nal-Lys GnRH antagonist) suppression of pituitary-testicular function and sexual behavior in group-living rhesus monkeys. Physiol Behav 1991; 50:429-435.
• 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.
• Bagatell CJ, Heiman JR, Rivier JE, Bremner WJ. Effects of endogenous testosterone and estradiol on sexual behavior in normal young men. J Clin Endocrinol Metab 1994; 78:711-716.
• Steiner M, Dunn E, Born L. Hormones and mood: from menarche to menopause and beyond. J Affect Disord 2003; 74: 67-83.
• Burger H, Hailes J, Nelson J, Menelaus M. Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. Br Med J (Clin Res Ed) 1987; 294:936-937.
• Gouras GK, Xu H, Gross RS, Greenfield JP, Hai B, Wang R et al. Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Proc Natl Acad Sci USA 2000; 97:1202-1205.
• Morley JE, Kaiser F, Raum WJ, Perry HM 3rd, Flood JF, Jensen J et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA 1997; 94:7537-7542.
• Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999; 84:3681-3685.
• Janowsky JS, Oviatt SK, Orwoll ES. Testosterone influences spatial cognition in older men.Behav Neurosci 1994; 108:325-332.
• Janowsky JS, Chavez B, Orwoll E. Sex steroids modify working memory. J Cogn Neurosci 2000; 12:407-414.
• Cherrier MM, Asthana S, Plymate S, Baker L, Matsumoto AM, Peskind E et al. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology 2001; 57:80-88.
• Wolf OT, Preut R, Hellhammer DH, Kudielka BM, Schürmeyer TH, Kirschbaum C. Testosterone and cognition in elderly men: a single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory. Biol Psychiatry 2000; 47:650-654.
• Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G 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; 85:2839-2853.
• 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.
• Zitzmann M. Testosterone and the brain. Aging Male 2006; 9:195-199.
• Delhez M, Hansenne M, Legros JJ. Andropause and psychopathology: Minor symptoms rather than pathological ones. Psychoneuroendocrinology 2003; 28:863- 874.
• Yesavage JA, Davidson J, Widrow L, Berger PA. Plasma testosterone levels, depression, sexuality and age. Biol Psychiatry 1985;20:222–225.
• Lunenfeld B, Nieschlag E. Testosterone therapy in the aging male. Aging Male 2007; 10:139-153.
• Amiaz R, Seidman SN. Testosterone and depression in men. Curr Opin Endocrinol Diabetes Obes 2008; 15:278-283.
• 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.
• 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; 84:573-577.
• Carnahan RM, Perry PJ. Depression in aging men: The role of testosterone. Drugs Aging 2004; 21:361-376.
• Vermeulen A. Diagnosis of partial androgen deficiency in the aging male. Ann Endocrinol 2003; 64:109-114.
• Morales A, Heaton JP, Carson CC. Andropause: a misnomer for a true clinical entity. J Urol 2000; 163:705-712.
• Margolese HC. The male menopause and mood: Testosterone decline and depression in the aging male - is there a link? J Geriatr Psychiatry Neurol 2000; 13:93-101.
• Sachar EJ, Halpern F, Rosenfeld RS, Galligher TF, Hellman L. Plasma and urinary testosterone levels in depressed men. Arch Gen Psychiatry 1973; 28:15-18.
• Seidman SN, Walsh BT. Testosterone and depression in aging men. Am J Geriatr Psychiatry 1999; 7:18-33.
• 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.
• McIntyre RS, Mancini D, Eisfeld BS, Soczynska JK, Grupp L, Konarski JZ et al. Calculated bioavailable testosterone levels and depression in middle-aged men. Psychoneuroendocrinology 2006; 31:1029-1035.
• 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 Psychiatry 2002; 159:456-459.
• Rubin RT, Poland RE, Lesser IM. Neuroendocrine aspects of primary endogenous depression. VIII. Pituitary-gonadal axis activity in male patients and matched control subjects. Psychoneuroendocrinology 1989; 14:217-229.
• Schweiger U, Deuschle M, Weber B, Körner A, Lammers CH, Schmider J et al Testosterone, gonadotropin, and cortisol secretion in male patients with major depression. Psychosom Med 1999; 61:292-296.
• Amsterdam JD, Winokur A, Caroff S, Snyder P. Gonadotropin release after administration of GnRH in depressed patients and healthy volunteers. J Affect Disord 1981; 3:367-380.
• Levitt AJ, Joffe RT. Total and free testosterone in depressed men. Acta Psychiatr Scand 1988; 77:346-348.
• Davies RH, Harris B, Thomas DR, Cook N, Read G, Riad-Fahmy D. Salivary testosterone levels and major depressive illness in men. Br J Psychiatry 1992; 161:629-632.
• Rubin RT, Poland RE, Lesser IM. Neuroendocrine aspects of primary endogenous depression VIII. Pituitary-gonadal axis activity in male patients and matched control subjects. Psychoneuroendocrinology 1989; 14:217-229.
• Rivier C, Vale W. Influence of corticotrophin-releasing factor on reproductive functions in the rat. Endocrinology 1984; 114:914–921.
• Rivier C, Rivest S. Effect of stress on the activity of the hypothalamic-pituitary- gonadal axis: Peripheral and central mechanisms. Biol Reprod 1991; 45:523-532.
• Seidman SN. Neuroendocrinology of mood disorders. In: Textbook of Mood Disorders. (Eds DJ Stein, AF Schatz-berg, DJ Kupfer): . Washington DC, American Psychiatric Press, 2005.
• Altschule MD, Tillotson KJ. The use of testosterone in the treatment of depressions. N Engl J Med 1948; 239:1036-1038.
• Rinieris PM, Malliaras DE, Batrinos ML, Stefanis CN. Testosterone treatment of depression in two patients with Klinefelter's syndrome. Am J Psychiatry 1979; 136:986-988.
• Heuser I, Hartmann A, Oertel H. Androgen replacement in a 48, XXYY-male patient. Arch Gen Psychiatry 1999; 56:194-195.
• Ehrenreich H, Halaris A, Ruether E, Hüfner M, Funke M, Kunert HJ. Psychoendocrine sequelae of chronic testosterone deficiency. J Psychiatr Res 1999; 33:379-387.
• Seidman SN, Rabkin JG. Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Disord 1998; 48:157-161.
• Rabkin JG, Wagner GJ, Rabkin R. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Arch Gen Psychiatry 2000; 57:141-147.
• 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.
• 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 Psychiatry 2001; 62:406-412.
• 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; 160:105-111.
• Orengo CA, Fullerton L, Kunik ME. Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy. J Geriatr Psychiatry Neurol 2005; 18:20-24.
• 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.
• Perry PJ, Yates WR, Williams RD, Andersen AE, MacIndoe JH, Lund BC et al. Testosterone therapy in late-life major depression in males. J Clin Psychiatry 2002; 63:1096-1101.
• Shamlian NT, Cole MG. Androgen treatment of depressive symptoms in older men: a systematic review of feasibility and effectiveness. Can J Psychiatry 2006; 51:295-299.
• Kanayama G, Amiaz R, Seidman S, Pope HG Jr. Testosterone supplementation for depressed men: Current research and suggested treatment guidelines. Exp Clin Psychopharmacol 2007; 15:529-538.
• Booth A, Dabbs J. Testosterone and men’s marriages. Social Forces 1993; 72:463-477.
• Booth A, Johnson DR, Granger DA. Testosterone and men's depression: the role of social behavior. J Health Soc Behav 1999; 40:130-140.
• Angold A, Costello EJ, Erkanli A, Worthman CM. Pubertal changes in hormone levels and depression in girls. Psychol Med 1999; 29:1043-1053.
• Fava M. New approaches to the treatment of refractors depression. J Clin Psychiatry 2000; 61:26-32.
• Morisson MF. Androgens in the elderly: will androgens replacement therapy improve mood, cognition, and quality of life in aging men and women. Psychopharmacol Bull 1998; 33:293-296.
• Burger H, Davis S. Should women treated with testosterone? Clin Endocrinol 1998; 49:159-160.
• Yonkers KA. Women and Depression: Who is at risk? Am J Obstetrics Gynecol 1998; 69:98-101.
• Sands R, Studd J. Exogeneous androgens in postmenopausal women. Am J Med 1995; 98:76-79.
• Davies S, Tran J. Testosterone influences libido and well being in women. Trends Endocrinol Metab 2001; 12:33-37.
• Guzick DS, Hoeger K. Sex hormones and hysterectomies. New Engl J Med 2000; 343:730-1
• Rowe T, Sasse V. Androgens and premenstrual symptoms—the response to therapy. In: Hormones and Behaviour (Eds L Denneerstein, I Frazer):160-165. Elsevier, New York, 1986.
• Burnet RB, Radden HS, Easterbrook EG, McKinnon RA. Premenstrual syndrome and spironolactone. Aust NZJ Obstet Gynaecol 1991; 31:366-368.
• Dougherty DM, Bjork JM, Moeller, FG, Swann AC. The influence of menstrual-cycle phase on the relationship between testosterone and aggression. Physiol Behav 1997; 62: 431-435.
• Bloch M, Schmidt PJ, Su TP, Tobin MB, Rubinow,DR. Pituitary–adrenal hormones and testosterone across the menstrual cycle in women with premenstrual syndrome and controls. Biol Psychiatry 1998; 43:897-903.
• Steiner M. Female-specific mood disorders. Clin Obstet Gynecol 1992; 35:599-611.
• Eriksson E, Sundblad C, Landen M, Steiner M. Behavioural effects of androgens in women. In: Mood Disorders in Women. (Eds M Steiner, KA Yonkers, E Eriksson): 233- 246. Martin Dunitz, London, 2000.
• Eriksson E, Sundblad C, Lisjo P, Modigh K, Andersch B. Serum levels of androgens are higher in women with premenstrual irritability and dysphoria than in controls. Psychoneuroendocrinology 1992; 17:195-204.