Hypogonadism in HIV-infected males
- Morris Schambelan, MD
Morris Schambelan, MD
- Professor Emeritus of Medicine
- University of California San Francisco
- Melissa Weinberg, MD
Melissa Weinberg, MD
- Assistant Clinical Professor of Medicine
- University of California, San Francisco
Hypogonadism was recognized as being relatively common early in the HIV epidemic. Low levels of testosterone in HIV-infected men may be associated with a variety of symptoms and signs including weight loss, muscle wasting, low bone mineral density, and decreased libido .
This topic will address hypogonadism in HIV-infected men. Issues related to sex hormones in HIV-infected women, such as menstrual irregularities, fertility, and pregnancy are found elsewhere. (See "HIV and women" and "Prenatal evaluation and intrapartum management of the HIV-infected woman in resource-rich settings" and "Antiretroviral treatment of pregnant HIV-infected women and antiretroviral prophylaxis of their infants in resource-rich settings".)
The general management and treatment of AIDS-associated tissue wasting is discussed in detail elsewhere. General information about hypogonadism in HIV-uninfected patients, testosterone replacement therapy, and patient monitoring are found in other selected topics. (See "Clinical features and diagnosis of male hypogonadism" and "Testosterone treatment of male hypogonadism" and "Treatment of osteoporosis in men".)
Testosterone is produced by the Leydig cells of the testes under stimulation of leuteinizing hormone (LH), which is secreted by the pituitary gland. Both LH and follicle-stimulating hormone (FSH) are required for the maturation of spermatozoa. Testosterone, in turn, inhibits gonadotropin secretion. Failure of the testes to produce physiological levels of testosterone results in the syndrome of hypogonadism.
Primary versus secondary hypogonadism — Hypogonadism can result from disease of the testes (primary hypogonadism) or disease of the pituitary or hypothalamus (secondary hypogonadism). Differentiation of the two types of hypogonadism has implications for patient evaluation and therapeutic interventions. (See 'How to distinguish between primary and secondary hypogonadism?' below.)
- Wanke CA, Silva M, Knox TA, et al. Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis 2000; 31:803.
- Dobs AS, Dempsey MA, Ladenson PW, Polk BF. Endocrine disorders in men infected with human immunodeficiency virus. Am J Med 1988; 84:611.
- Arver S, Sinha-Hikim I, Beall G, et al. Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss. J Androl 1999; 20:611.
- Cooley TP. Non-AIDS-defining cancer in HIV-infected people. Hematol Oncol Clin North Am 2003; 17:889.
- Etzel JV, Brocavich JM, Torre M. Endocrine complications associated with human immunodeficiency virus infection. Clin Pharm 1992; 11:705.
- Raffi F, Brisseau JM, Planchon B, et al. Endocrine function in 98 HIV-infected patients: a prospective study. AIDS 1991; 5:729.
- Christeff N, Gharakhanian S, Thobie N, et al. Evidence for changes in adrenal and testicular steroids during HIV infection. J Acquir Immune Defic Syndr 1992; 5:841.
- Dobs AS, Few WL 3rd, Blackman MR, et al. Serum hormones in men with human immunodeficiency virus-associated wasting. J Clin Endocrinol Metab 1996; 81:4108.
- Dubé MP, Parker RA, Mulligan K, et al. Effects of potent antiretroviral therapy on free testosterone levels and fat-free mass in men in a prospective, randomized trial: A5005s, a substudy of AIDS Clinical Trials Group Study 384. Clin Infect Dis 2007; 45:120.
- Collazos J, Martinez E, Mayo J, Ibarra S. Sexual hormones in HIV-infected patients: the influence of antiretroviral therapy. AIDS 2002; 16:934.
- Rochira V, Diazzi C, Santi D, et al. Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study. Andrology 2015; 3:298.
- Araujo AB, O'Donnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2004; 89:5920.
- Klein RS, Lo Y, Santoro N, Dobs AS. Androgen levels in older men who have or who are at risk of acquiring HIV infection. Clin Infect Dis 2005; 41:1794.
- Grossmann M, Gianatti EJ, Zajac JD. Testosterone and type 2 diabetes. Curr Opin Endocrinol Diabetes Obes 2010; 17:247.
- Zitzmann M. Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol 2009; 5:673.
- Misra M, Papakostas GI, Klibanski A. Effects of psychiatric disorders and psychotropic medications on prolactin and bone metabolism. J Clin Psychiatry 2004; 65:1607.
- 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 Suppl 2:S132.
- Bliesener N, Albrecht S, Schwager A, et al. Plasma testosterone and sexual function in men receiving buprenorphine maintenance for opioid dependence. J Clin Endocrinol Metab 2005; 90:203.
- Collazos J. Sexual dysfunction in the highly active antiretroviral therapy era. AIDS Rev 2007; 9:237.
- George J, Ganesh HK, Acharya S, et al. Bone mineral density and disorders of mineral metabolism in chronic liver disease. World J Gastroenterol 2009; 15:3516.
- Bannister P, Handley T, Chapman C, Losowsky MS. Hypogonadism in chronic liver disease: impaired release of luteinising hormone. Br Med J (Clin Res Ed) 1986; 293:1191.
- Bhasin S, Cunningham GR, Hayes FJ, et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95:2536.
- Dobs A. Role of testosterone in maintaining lean body mass and bone density in HIV-infected patients. Int J Impot Res 2003; 15 Suppl 4:S21.
- Tindall B, Forde S, Goldstein D, et al. Sexual dysfunction in advanced HIV disease. AIDS Care 1994; 6:105.
- 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.
- Martin ME, Benassayag C, Amiel C, et al. Alterations in the concentrations and binding properties of sex steroid binding protein and corticosteroid-binding globulin in HIV+patients. J Endocrinol Invest 1992; 15:597.
- de Ronde W, van der Schouw YT, Pols HA, et al. Calculation of bioavailable and free testosterone in men: a comparison of 5 published algorithms. Clin Chem 2006; 52:1777.
- Rosner W, Auchus RJ, Azziz R, et al. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007; 92:405.
- Lo JC, Schambelan M. Reproductive function in human immunodeficiency virus infection. J Clin Endocrinol Metab 2001; 86:2338.
- Sekar V, Lefebvre E, De Marez T, et al. Effect of repeated doses of darunavir plus low-dose ritonavir on the pharmacokinetics of sildenafil in healthy male subjects: phase I randomized, open-label, two-way crossover study. Clin Drug Investig 2008; 28:479.
- 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.
- Mulligan K, Zackin R, Von Roenn JH, et al. Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with human immunodeficiency virus-associated weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. J Clin Endocrinol Metab 2007; 92:563.
- Ebeling PR. Clinical practice. Osteoporosis in men. N Engl J Med 2008; 358:1474.
- Fairfield WP, Finkelstein JS, Klibanski A, Grinspoon SK. Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome. J Clin Endocrinol Metab 2001; 86:2020.
- Kong A, Edmonds P. Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. Lancet Infect Dis 2002; 2:692.
- Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363:109.
- Bhatia R, Murphy AB, Raper JL, et al. Testosterone replacement therapy among HIV-infected men in the CFAR Network of Integrated Clinical Systems. AIDS 2015; 29:77.
- Primary versus secondary hypogonadism
- RISK FACTORS
- Liver disease
- CLINICAL PRESENTATION
- General approach
- Free testosterone versus total testosterone levels
- Caveats about when to test serum testosterone
- How to distinguish between primary and secondary hypogonadism?
- DIFFERENTIAL DIAGNOSIS
- INDICATIONS FOR TESTOSTERONE TREATMENT
- Patients with low libido and/or hypogonadal symptoms
- - Clinical trial data
- Patients with low bone mineral density
- - Clinical trial data
- Patients with weight loss and low lean body mass
- DRUG FORMULATION AND DOSING
- DURATION OF THERAPY
- ADVERSE EVENTS
- CAUTIONS REGARDING TESTOSTERONE THERAPY
- Caution regarding unintentional drug transfer
- Male infertility
- PATIENT MONITORING
- SUMMARY AND RECOMMENDATIONS