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Hypogonadism – Causes


The exact causes of hypogonadism in PLWHIV are unknown and the etiology is likely to be multifactorial. Possible factors leading to hypogonadism in HIV-infected individuals include:1

  • HIV infection itself
  • opportunistic infections
  • chronic debilitating illness
  • effects of cytokines on the hypothalamic-pituitary-gonadal axis
  • undernutrition2
  • pituitary dysfunction2
  • malignancy2
  • hyperprolactinemia2
  • AIDS-related lesions (rare) that disrupt the hypothalamo-pituitary axis2,3
  • inadequate adrenal androgen secretion (in females)4

In the general population, low testosterone production, indicative of hypogonadism, can stem from the administration of medications or specific disease states such as:5

  • megesterol acetate, a progestational agent used as an appetite stimulant
  • antifungals, which inhibit steroidogenesis, and/or elevation of the adrenal hormone cortisol, which is produced in abundance during chronic infections as a normal physiological defence against physical stress
  • malnutrition
  • wasting
  • concomitant illnesses
  • diseases of the hypothalamus or pituitary gland caused by:
    • cytomegalovirus
    • Cryptococcus neoformans

Although it is unclear why, the prevalence of hypogonadism in HAART-treated populations appears to be less than in untreated HIV-infected men. The prevalence of low testosterone levels in HIV-infected men has been estimated to be as high as 50%;6 however, in HIV-infected men receiving HAART, hypogonadism has been shown to be present in approximately 20% of patients.7



  1. Poretsky L, Can S, Zumoff B. Testicular dysfunction in human immunodeficiency virus-infected men. Metabolism. 1995;44:946–953.
  2. Grinspoon S. Androgen deficiency and HIV infection. Clin Infect Dis. 2005;41:1804–1805.
  3. Nieschlag E, Behre HM, Nieschlag S. Andrology: Male Reproductive Health and Dysfunction. 2010 Springer Press. 18.3.11 Infectious diseases. p352.
  4. Cooper OB, Brown TT, Dobs AS. Opiate drug use: a potential contributor to the endocrine and metabolic complications in human immunodeficiency virus disease. Clin Infect Dis. 2003;37:S132–S136.
  5. Rietschel P, Corcoran C, Stanley T, et al. Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy. Clin Infect Dis. 2000;31:1240–1244.
  6. Grinspoon S, Corcoran C, Stanley T, et al. Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome. J Clin Endocrinol Metab. 2001;86:4120–4126.
  7. Dobs AS, Dempsey MA, Ladenson PW, et al. Endocrine disorders in men infected with human immunodeficiency virus. Am J Med. 1988;84:611–616.