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Causes of primary hypogonadism in males

Peter J Snyder, MD
Section Editor
Alvin M Matsumoto, MD
Deputy Editor
Kathryn A Martin, MD


Hypogonadism in a man refers to a decrease in one or both of the two major functions of the testes: sperm production and testosterone production. These abnormalities usually result from disease of the testes (primary hypogonadism) or disease of the pituitary or hypothalamus (secondary hypogonadism). In occasional cases, however, a defect in the ability to respond to testosterone is the cause of hypogonadism. (See "Diagnosis and treatment of disorders of the androgen receptor" and "Steroid 5-alpha-reductase 2 deficiency".)

The distinction between primary and secondary hypogonadism is made by measurement of the serum concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH):

The patient has primary hypogonadism if the serum testosterone concentration and the sperm count are below normal and the serum LH and FSH concentrations are above normal

The patient has secondary hypogonadism if the serum testosterone concentration and the sperm count are subnormal and the serum LH and FSH concentrations are normal or reduced

Primary hypogonadism differs from secondary hypogonadism in two ways:

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Literature review current through: Oct 2017. | This topic last updated: Apr 18, 2017.
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  1. Schwartz ID, Root AW. The Klinefelter syndrome of testicular dysgenesis. Endocrinol Metab Clin North Am 1991; 20:153.
  2. Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab 2003; 88:622.
  3. Paulsen CA, Gordon DL, Carpenter RW, et al. Klinefelter's syndrome and its variants: a hormonal and chromosomal study. Recent Prog Horm Res 1968; 24:321.
  4. Wang C, Baker HW, Burger HG, et al. Hormonal studies in Klinefelter's syndrome. Clin Endocrinol (Oxf) 1975; 4:399.
  5. Ferlin A, Zuccarello D, Zuccarello B, et al. Genetic alterations associated with cryptorchidism. JAMA 2008; 300:2271.
  6. Bender BG, Linden MG, Robinson A. Neuropsychological impairment in 42 adolescents with sex chromosome abnormalities. Am J Med Genet 1993; 48:169.
  7. Simm PJ, Zacharin MR. The psychosocial impact of Klinefelter syndrome--a 10 year review. J Pediatr Endocrinol Metab 2006; 19:499.
  8. Ross JL, Roeltgen JP, Stefanatos G, et al. Cognitive and motor development during childhood in boys with early Klinefelter's Syndrome. Am J Medical Genetics 2008; 146A:708.
  9. Bojesen A, Juul S, Birkebaek NH, Gravholt CH. Morbidity in Klinefelter syndrome: a Danish register study based on hospital discharge diagnoses. J Clin Endocrinol Metab 2006; 91:1254.
  10. Case records of the Massachusetts General Hospital. Case 44-1965. N Engl J Med 1965; 273:816.
  11. Völkl TM, Langer T, Aigner T, et al. Klinefelter syndrome and mediastinal germ cell tumors. Am J Med Genet A 2006; 140:471.
  12. Weiss JR, Moysich KB, Swede H. Epidemiology of male breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14:20.
  13. Swerdlow AJ, Schoemaker MJ, Higgins CD, et al. Cancer incidence and mortality in men with Klinefelter syndrome: a cohort study. J Natl Cancer Inst 2005; 97:1204.
  14. Campbell WA, Newton MS, Price WH. Hypostatic leg ulceration and Klinefelter's syndrome. J Mental Deficiency Res 1988; 24:115.
  15. Scofield RH, Bruner GR, Namjou B, et al. Klinefelter's syndrome (47,XXY) in male systemic lupus erythematosus patients: support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 2008; 58:2511.
  16. Geffner ME, Kaplan SA, Bersche N, et al. Insulin resistance in Klinefelter syndrome. J Pediatr Endocrinol 1987; 2:173.
  17. Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E. X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J Clin Endocrinol Metab 2004; 89:6208.
  18. Zinn AR, Ramos P, Elder FF, et al. Androgen receptor CAGn repeat length influences phenotype of 47,XXY (Klinefelter) syndrome. J Clin Endocrinol Metab 2005; 90:5041.
  19. Ramasamy R, Ricci JA, Palermo GD, et al. Successful fertility treatment for Klinefelter's syndrome. J Urol 2009; 182:1108.
  20. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter's syndrome. Lancet 2004; 364:273.
  21. Simpson JL. Male pseudohermaphroditism: genetics and clinical delineation. Hum Genet 1978; 44:1.
  22. Foresta C, Moro E, Garolla A, et al. Y chromosome microdeletions in cryptorchidism and idiopathic infertility. J Clin Endocrinol Metab 1999; 84:3660.
  23. Tapanainen JS, Aittomäki K, Min J, et al. Men homozygous for an inactivating mutation of the follicle-stimulating hormone (FSH) receptor gene present variable suppression of spermatogenesis and fertility. Nat Genet 1997; 15:205.
  24. Simoni M, Gromoll J, Höppner W, et al. Mutational analysis of the follicle-stimulating hormone (FSH) receptor in normal and infertile men: identification and characterization of two discrete FSH receptor isoforms. J Clin Endocrinol Metab 1999; 84:751.
  25. Latronico AC, Anasti J, Arnhold IJ, et al. Brief report: testicular and ovarian resistance to luteinizing hormone caused by inactivating mutations of the luteinizing hormone-receptor gene. N Engl J Med 1996; 334:507.
  26. Harper P, Penny R, Foley TP Jr, et al. Gonadal function in males with myotonic dystrophy. J Clin Endocrinol Metab 1972; 35:852.
  27. Beard CM, Benson RC Jr, Kelalis PP, et al. The incidence and outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974. Mayo Clin Proc 1977; 52:3.
  28. Aiman J, Brenner PF, MacDonald PC. Androgen and estrogen production in elderly men with gynecomastia and testicular atrophy after mumps orchitis. J Clin Endocrinol Metab 1980; 50:380.
  29. Brauner R, Czernichow P, Cramer P, et al. Leydig-cell function in children after direct testicular irradiation for acute lymphoblastic leukemia. N Engl J Med 1983; 309:25.
  30. Shapiro E, Kinsella TJ, Makuch RW, et al. Effects of fractionated irradiation of endocrine aspects of testicular function. J Clin Oncol 1985; 3:1232.
  31. Handelsman DJ, Turtle JR. Testicular damage after radioactive iodine (I-131) therapy for thyroid cancer. Clin Endocrinol (Oxf) 1983; 18:465.
  32. Qureshi MS, Pennington JH, Goldsmith HJ, Cox PE. Cyclophosphamide therapy and sterility. Lancet 1972; 2:1290.
  33. Watson AR, Rance CP, Bain J. Long term effects of cyclophosphamide on testicular function. Br Med J (Clin Res Ed) 1985; 291:1457.
  34. Friedman NM, Plymate SR. Leydig cell dysfunction and gynaecomastia in adult males treated with alkylating agents. Clin Endocrinol (Oxf) 1980; 12:553.
  35. Lampe H, Horwich A, Norman A, et al. Fertility after chemotherapy for testicular germ cell cancers. J Clin Oncol 1997; 15:239.
  36. Danesi R, La Rocca RV, Cooper MR, et al. Clinical and experimental evidence of inhibition of testosterone production by suramin. J Clin Endocrinol Metab 1996; 81:2238.
  37. Pont A, Williams PL, Azhar S, et al. Ketoconazole blocks testosterone synthesis. Arch Intern Med 1982; 142:2137.
  38. Odell WD. Testosterone treatment of men treated with glucocorticoids. Arch Intern Med 1996; 156:1133.
  39. Whorton D, Krauss RM, Marshall S, Milby TH. Infertility in male pesticide workers. Lancet 1977; 2:1259.
  40. Lantz GD, Cunningham GR, Huckins C, Lipshultz LI. Recovery from severe oligospermia after exposure to dibromochloropropane. Fertil Steril 1981; 35:46.
  41. Schemo DJ. U.S. pesticide kills foreign fruit pickers' hopes. http://www.nytimes.com/1995/12/06/world/us-pesticide-kills-foreign-fruit-pickers-hopes.html?pagewanted=all&src=pm (Accessed on July 26, 2012).
  42. Thomas WE, Cooper MJ, Crane GA, et al. Testicular exocrine malfunction after torsion. Lancet 1984; 2:1357.
  43. Shulman S. Antisperm antibodies and subfertility? Fertil Steril 1994; 62:1283.
  44. Uibo R, Aavik E, Peterson P, et al. Autoantibodies to cytochrome P450 enzymes P450scc, P450c17, and P450c21 in autoimmune polyglandular disease types I and II and in isolated Addison's disease. J Clin Endocrinol Metab 1994; 78:323.
  45. Baker HW, Burger HG, de Kretser DM, et al. A study of the endocrine manifestations of hepatic cirrhosis. Q J Med 1976; 45:145.
  46. Van Thiel DH, Lester R, Sherins RJ. Hypogonadism in alcoholic liver disease: evidence for a double defect. Gastroenterology 1974; 67:1188.
  47. Guéchot J, Chazouillères O, Loria A, et al. Effect of liver transplantation on sex-hormone disorders in male patients with alcohol-induced or post-viral hepatitis advanced liver disease. J Hepatol 1994; 20:426.
  48. Gordon GG, Altman K, Southren AL, et al. Effect of alcohol (ethanol) administration on sex-hormone metabolism in normal men. N Engl J Med 1976; 295:793.
  49. Holdsworth S, Atkins RC, de Kretser DM. The pituitary-testicular axis in men with chronic renal failure. N Engl J Med 1977; 296:1245.
  50. Lim VS, Fang VS. Gonadal dysfunction in uremic men. A study of the hypothalamo-pituitary-testicular axis before and after renal transplantation. Am J Med 1975; 58:655.
  51. Poretsky L, Can S, Zumoff B. Testicular dysfunction in human immunodeficiency virus-infected men. Metabolism 1995; 44:946.