Hypogonadism in the HIV-Infected Man

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Key points

  • Hypogonadism is common and occurs prematurely in human immunodeficiency virus (HIV)-infected men, the prevalence being around 25% in young to middle-aged men with HIV.

  • Hypogonadotropic hypogonadism due to hypothalamic-pituitary dysfunction is more frequent than primary hypergonadotropic hypogonadism in HIV-infected men.

  • Signs and symptoms of hypogonadism become less specific in men with HIV because of the overlap with signs and symptoms of the HIV infection and do not help in ruling out the

Epidemiology

The reported prevalence of hypogonadism among HIV-infected men varies depending on both the definition and the type of T measurement used and study dates. Since the introduction of HAART, HIV-infected men are living longer and their health status has improved in accordance with the changed spectrum of comorbidities.5, 6 For that reason, prevalence data of male hypogonadism are reported here according to the pre-HAART and post-HAART periods.

Pathogenesis of male hypogonadism in men with HIV

The pathogenesis of hypogonadism in HIV-infected men remains unclear. Hypothesis on the underlying causes and mechanisms have been provided based on some well-recognized pathophysiologic phenomena, but their cause-effect relationships need to be substantiated by further evidence.40 The authors provide the state of the art on known risk factors and predictor of T deficiency, as well as on pathophysiologic issues that contribute the genesis of hypogonadism in men with HIV infection.

Diagnosis

The diagnostic approach to male hypogonadism in HIV-infected patients should be based on a medical interview to obtain information on both patient’s health status and symptoms and on clinical examination, as in the general population.50 All these information should be thereafter integrated with and substantiated by biochemical testing.18, 50, 65

Treatment

Decision making concerning the selection of candidate for T replacement is difficult because the interpretation of signs, symptoms, and serum T levels is complex in HIV-infected men. Treatment should be started in all patients with severe T deficiency (total T<100 ng/dL or free T<30 ng/dL). Patients with slightly decreased serum T levels could be monitored and a wait-and-see approach might lead T prescription, especially if a progressive further decrease in T level occurs. Borderline low serum

Current controversies

The best way for the diagnosis of male hypogonadism in men with HIV remains to be precisely defined (see previous paragraph for details).

Screening of male hypogonadism is not recommended in the general population. Due to the elevated prevalence of hypogonadism among HIV-infected men, screening for T deficiency might be useful to identify patients who need replacement treatment. However, if the difficulties in making the diagnosis, the risk of overtreating patients who do not need T replacement,

Summary

The management of male hypogonadism needs a multidisciplinary approach involving both the specialist in HIV medicine and the endocrinologist (or andrologist). Based on extensive clinical experience in the management of endocrine disease in patients with HIV infection, the authors organized this multidisciplinary evaluation by providing endocrinological outpatients service directly within the clinic of infectious disease where patients are referred to. This or other similar kind of

Acknowledgments

The authors are indebted to Giulia Brigante, MD, PhD, and Chiara Diazzi, MD, PhD, for their help in searching the literature for useful resources and for their continuous support in the clinical management of HIV-infected patients. They thank Chiara Diazzi, MD, PhD, for technical support in painting digital pictures.

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References (90)

  • V. Roulet et al.

    Susceptibility of human testis to human immunodeficiency virus-1 infection in situ and in vitro

    Am J Pathol

    (2006)
  • P. Wasserman et al.

    Low sex hormone-binding globulin and testosterone levels in association with erectile dysfunction among human immunodeficiency virus-infected men receiving testosterone and oxandrolone

    J Sex Med

    (2008)
  • G. Corona et al.

    Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes

    Best Pract Res Clin Endocrinol Metab

    (2013)
  • J.J. Lefrere et al.

    Hypogonadism in AIDS

    AIDS

    (1988)
  • D.E. Sellmeyer et al.

    Endocrine and metabolic disturbances in human immunodeficiency virus infection and the acquired immune deficiency syndrome

    Endocr Rev

    (1996)
  • S. Grinspoon et al.

    Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial

    Ann Intern Med

    (1998)
  • F.J. Palella et al.

    Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators

    N Engl J Med

    (1998)
  • Available at:...
  • T.S. Croxson et al.

    Changes in the hypothalamic-pituitary-gonadal axis in human immunodeficiency virus-infected homosexual men

    J Clin Endocrinol Metab

    (1989)
  • J.M. Villette et al.

    Circadian variations in plasma levels of hypophyseal, adrenocortical and testicular hormones in men infected with human immunodeficiency virus

    J Clin Endocrinol Metab

    (1990)
  • F. Raffi et al.

    Endocrine function in 98 HIV-infected patients: a prospective study

    AIDS

    (1991)
  • G. Wagner et al.

    Illness stage, concurrent medications, and other correlates of low testosterone in men with HIV illness

    J Acquir Immune Defic Syndr Hum Retrovirol

    (1995)
  • S. Grinspoon et al.

    Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting

    J Clin Endocrinol Metab

    (1996)
  • S. Arver et al.

    Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss

    J Androl

    (1999)
  • A. Laudat et al.

    Changes in systemic gonadal and adrenal steroids in asymptomatic human immunodeficiency virus-infected men: relationship with the CD4 cell counts

    Eur J Endocrinol

    (1995)
  • J.A. Merenich et al.

    Evidence of endocrine involvement early in the course of human immunodeficiency virus infection

    J Clin Endocrinol Metab

    (1990)
  • A.S. Dobs et al.

    Serum hormones in men with human immunodeficiency virus-associated wasting

    J Clin Endocrinol Metab

    (1996)
  • W. Rosner et al.

    Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement

    J Clin Endocrinol Metab

    (2007)
  • S. Bhasin et al.

    Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline

    J Clin Endocrinol Metab

    (2010)
  • Berger D, Muurahainen N, Wittert H, et al. Hypogonadism and wasting in the era of HAART in HIV-infected patients....
  • P. Rietschel 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)
  • Fisher A, Desyatnik M, Baaj A. The prevalence of hypogonadism in HIV infected patients receiving HAART. XIII...
  • N.F. Crum-Cianflone et al.

    Erectile dysfunction and hypogonadism among men with HIV

    AIDS Patient Care STDS

    (2007)
  • V. Rochira et al.

    Premature decline of serum total testosterone in HIV-infected men in the HAART-era

    PLoS One

    (2011)
  • J. Pepe et al.

    The combination of FRAX and Ageing Male Symptoms scale better identifies treated HIV males at risk for major fracture

    Clin Endocrinol (Oxf)

    (2012)
  • A.K. Monroe et al.

    Testosterone and Abnormal Glucose Metabolism in an Inner-City Cohort

    J Mens Health

    (2012)
  • K. Sunchatawirul et al.

    Hypogonadism among HIV-infected men in Thailand

    Int J STD AIDS

    (2012)
  • G. Blick

    Optimal diagnostic measures and thresholds for hypogonadism in men with HIV/AIDS: comparison between 2 transdermal testosterone replacement therapy gels

    Postgrad Med

    (2013)
  • A.K. Monroe et al.

    Morning free and total testosterone in HIV-infected men: implications for the assessment of hypogonadism

    AIDS Res Ther

    (2014)
  • M.P. Dubé 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)
  • J. Collazos et al.

    Has prolactin a role in the hypogonadal status of HIV-infected patients?

    J Int Assoc Physicians AIDS Care

    (2009)
  • R.S. Klein et al.

    Androgen levels in older men who have or who are at risk of acquiring HIV infection

    Clin Infect Dis

    (2005)
  • D.M. Wunder et al.

    Androgen and gonadotropin patterns differ in HIV-1-infected men who develop lipoatrophy during antiretroviral therapy: a case-control study

    HIV Med

    (2008)
  • M. Amini Lari et al.

    Depression, testosterone concentration, sexual dysfunction and methadone use among men with hypogonadism and HIV infection

    AIDS Behav

    (2012)
  • A.B. Araujo 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)
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      Estrogens strongly inhibit the secretion of gonadotropins (Rochira et al., 2000, 2006), acting at both hypothalamus and pituitary levels, thus an over-expression of aromatase can lead to hypogonadotropic hypogonadism through the increased production of estrogens (Rochira & Carani, 2017; Rochira et al., 2006) (Table 2). Therefore, the excess of body fat (and especially visceral fat) that characterizes obesity and/or the alterations of body fat distribution such as in obesity (Cohen, 2001; Kelly & Jones, 2015; Russell & Grossmann, 2019) and in the Human Immunodeficiency Virus (HIV)-related lipodystrophy (Rochira & Guaraldi, 2014) is associated to over-expression of aromatase and increased production of estrogens, this latter leading to inhibition of gonadotropins incretion (Rochira & Guaraldi, 2014; Rochira et al., 2000, 2006). Many drugs can determine the onset of hypogonadism through both central and/or testicular impairment (Table 2).

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      Approximately 25% of HIV+ patients experience dysfunction of the hypothalamic-pituitary-gonadal (HPG; e.g., hypogonadism) and/or hypothalamic-pituitary-adrenal (HPA) axes (e.g., elevated basal corticosterone with adrenal insufficiency in response to HPA activation; Chrousos and Zapanti, 2014; George and Bhangoo, 2013; Gomes et al., 2017; Lachâtre et al., 2017; Mirza et al., 2018; Wong et al., 2017). In the era of combined antiretroviral therapy, HPG and HPA disruption typically involve dysfunction within the CNS, rather than dysfunction at peripheral steroid sources such as the gonads or adrenals (Bons et al., 2013; Chrousos and Zapanti, 2014; Freda and Bilezikian, 1999; Rochira and Guaraldi, 2014; Mirza et al., 2018). In support, others have found evidence of neurosteroidogenic dysregulation in post-mortem HIV+ brain tissue, cultured human fetal neurons, and the brains of cats infected with feline immunodeficiency virus (Maingat et al., 2013).

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    Disclosure: The authors have nothing to disclose.

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