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      Hypogonadotropic hypogonadism in human immunodeficiency virus-infected men: uncommonly low testosterone levels

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          Abstract

          Hypogonadotropic hypogonadism (HH) is common and occurs prematurely in HIV-infected men. However, HH with very low testosterone has not been described. Three men with normal pubertal development and HIV1 diagnosis at the ages of 22, 34 and 35 years. All complained of decreased libido, anejaculation and erectile dysfunction thirteen years, six months and one year after HIV diagnosis, respectively. Two had depressive syndrome and two were treated with antiretroviral therapy. Laboratory tests revealed isolated HH in all. Sellar and head CT scans were normal and all had normal CD4 count. They started testosterone replacement therapy, with symptoms improvement. Causes of HH in HIV-infected men include undernutrition, severe illness, drugs, pituitary dysfunction and comorbidities. Despite having none of these conditions (except two that were treated with low-dose psychotropics), our patients had HH with uncommonly low testosterone. This suggests that a different mechanism contributes to severe HH in HIV-infected men.

          Learning points:
          • The pathogenesis of hypogonadotropic hypogonadism in HIV-infected men is multifactorial and androgen deficiency is more often a consequence of secondary hypogonadism than primary hypogonadism.

          • Causes of hypogonadotropic hypogonadism in HIV-infected men include undernutrition, severe illness, drugs (psychotropics, opiates, megestrol acetate or steroids), pituitary dysfunction (tumor, hyperprolactinemia), an AIDS-related lesion (very rarely) and comorbid conditions, such as antibody to hepatitis C virus seropositivity and injection drug use.

          • Highly active antiretroviral therapy (HAART), particularly protease inhibitor therapy has been associated with sexual dysfunction in men, but the causal nature of this relation has not been clearly established.

          • Hypogonadotropic hypogonadism with uncommonly low testosterone levels are not usually associated with the conditions referred and this suggests that a different mechanism could contribute to severe hypogonadotropic hypogonadism in HIV-infected men.

          • Screening for hypogonadism in all HIV-infected men might help to understand its etiology.

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          Most cited references8

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          Hypogonadism in the HIV-infected man.

          Androgen deficiency occurs frequently in men with human immunodeficiency virus (HIV) infection. Antiretroviral treatments had reduced the prevalence of male hypogonadism. The pathogenesis of testosterone (T) deficiency in HIV is multifactorial. Several mechanisms have been proposed; among them, drugs, fat redistribution, and a poor health status could explain the mechanism leading to gonadotropins inhibition and hypogonadotropic hypogonadism. The diagnosis of hypogonadism in HIV-infected men should be made based on clinical symptoms and a specific workup including T measurement. The interpretation of the results of biochemical testing is more difficult in men with HIV due to several confounding factors. T treatment should be offered to HIV-infected men with documented clinical hypogonadism and symptoms, especially if they are losing lean mass.
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            Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study.

            Men with human immunodeficiency virus (HIV) infection are often hypogonadal and develop several HIV-associated non-acquired immunodeficiency syndrome (AIDS) (HANA) conditions that impair overall health status. No studies explored the relationship between health status and serum testosterone (T) in HIV-infected men. This study aims to investigate the association between total serum T and HANA, multimorbidity, and frailty in a large cohort of 1359 HIV-infected men and to explore the relationship between patients' overall health status and serum T. Among biochemical and hormonal measurement performed the main are serum total T, free triiodothyronine (fT3), and luteinizing hormone. Other outcome measurements include anthropometry, assessment of comorbidities and disabilities, overall health status defined as the number of HANA and by the 38-item multimorbidity frailty index, anthropometry, and bone mineral density. The cumulative relative risk of comorbidities is increased in HIV-infected men with hypogonadism (p < 0.001) and hypogonadism is associated with several comorbidities. The prevalence of hypogonadism increases progressively with the increase of the number of comorbidities. Frailty index is inversely related to serum total T (age-adjusted r = 0.298, r(2) = 0.089, p < 0.0001). Serum fT3 levels are significantly lower in hypogonadal than eugonadal men (p = 0.022). This suggests that low serum T could be considered a sensitive marker of frailty and poor health status and that the latter might induce hypogonadism. The more HIV-infected men are frail the more they are hypogonadal. This suggests that hypogonadism might be a naturally occurring condition in unhealthy HIV-infected men and raises concern about the safety of T treatment. In conclusion, low serum T is associated with multimorbidity, HANA, and frailty in HIV-infected men and this association seems to be bidirectional. Given the wide attitude to offer T treatment to HIV-infected men, caution is needed when prescribing T to HIV-infected male patients, especially if the patient is unhealthy or frail.
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              Testicular dysfunction in human immunodeficiency virus-infected men.

              This review pertains to gonadal function in men with human immunodeficiency virus (HIV) infection, who often exhibit clinical and biochemical evidence of hypogonadism. Hypogonadotropic hypogonadism appears to be the most commonly encountered abnormality, although complete anterior pituitary insufficiency and primary gonadal failure have been reported. Levels of sex hormone-binding globulin (SHBG) are either unchanged or increased. Plasma levels of estrogens, progesterone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and prolactin vary. Pathologically, except for involvement by opportunistic infections, no significant abnormality in the hypothalamic-pituitary area has been described, but evidence of orchitis is commonly present. The cause(s) of these abnormalities remains unclear. The possible factors leading to hypogonadism in HIV-infected men include HIV infection itself, opportunistic infections, chronic debilitating illness, and effects of cytokines on the hypothalamic-pituitary-gonadal axis. Further studies are needed to clarify the cause(s) of testicular dysfunction in HIV-infected men and its clinical significance, treatment, relevance to the progression of HIV infection, and influence on the immune system.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                06 September 2017
                2017
                : 2017
                : 17-0104
                Affiliations
                [1 ]Endocrinology , Diabetes and Metabolism Department, Hospital de Santa Maria, Lisbon, Portugal
                [2 ]Endocrinology Department , Hospital Beatriz Ângelo, Lisbon, Portugal
                [3 ]Infectious Diseases Department , Hospital de Santa Maria, Lisbon, Portugal
                Author notes
                Correspondence should be addressed to A C Gomes; Email: anarcgomes@ 123456gmail.com
                Article
                EDM170104
                10.1530/EDM-17-0104
                5592708
                48c50f2d-4cfc-411c-be88-3a560cc9093f
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

                History
                : 27 July 2017
                : 4 August 2017
                Categories
                Unique/Unexpected Symptoms or Presentations of a Disease

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