Prevalence of Hypogonadism among Men with Weight Loss Related to Human Immunodeficiency Virus Infection Who Were Receiving Highly Active Antiretroviral Therapy

Rietschel, Petra; Corcoran, Colleen; Stanley, Takara L.; Basgoz, Nesli; Klibanski, Anne; Grinspoon, Steven

doi:10.1086/317457

Cited by 150 publications

(124 citation statements)

References 25 publications

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“…Median tPSA levels were low in our study, possibly reflecting comparatively younger age at PCa diagnosis, a higher prevalence of hypogonadism in HIV+ men (20%) [16], or an alternate biological relationship between PCa and PSA in the presence of HIV. Two American studies reported similar PSA ranges in HIV+ men to that reported here [17,18] and previous studies have shown lower latest PSA levels when PCa is present in HIV+ compared to -men prior to diagnosis [1].…”

Section: Discussioncontrasting

confidence: 59%

Predictive Value of Prostate Specific Antigen in a European HIV-positive Cohort: Does One Size Fit All?

Shepherd¹,

Borges²,

Ravn³

et al. 2015

Antiviral Therapy

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Background: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. Methods: A nested case control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total PSA. Results: 61 HIV+ men were included with a median 6 (IQR 2-9) years follow-up. Levels of tPSA increased by 13.7% per year (95% CI 10.3, 17.3) in cases, but was stable in controls (-0.4%; 95% CI -2.5, 1.7). Elevated PSA was associated with higher odds of PCa at first (OR for twofold higher 4.7; 95% CI 1.7, 12.9; P<0.01) and last sample (8.1; 95% CI 1.1, 58.9; P=0.04). A similar relationship was seen between fPSA and PCa. Testosterone and SHBG level were not associated with PCa. tPSA level >4 ng/ml had 99% specificity and 38% sensitivity. The optimal PSA cutoff was 1.5 ng/ml overall (specificity =84%, sensitivity =81%). Conclusions: PSA was highly predictive of PCa in HIV+ men; however, the commonly used PSA>4 ng/ml to indicate high PCa risk was not sensitive in our population and use of the lower cutoff of PSA>1.5 ng/ml warrants consideration.Recent studies have consistently found a lower incidence of prostate cancer (PCa) in HIV+ than HIV-men in the combination antiretroviral therapy (cART) era [1-3], independently of screening patterns for prostate specific antigen (PSA). However, the frequency of PCa diagnoses in HIV+ men increased significantly from 2001 to 2005, attributed to ageing of the HIV+ population due to availability of effective treatment [4,5]. As a result, PCa screening, detection and treatment are likely to become an integral component of future HIV care [6].Men at high risk of PCa are generally identified through elevated PSA tests (PSA≥4.0 ng/ml [7,8]), an abnormal digital rectal exam (or both) and a biopsy [9]. Despite two large trials, the benefit of PSA testing as a

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Section: Discussioncontrasting

confidence: 59%

Predictive Value of Prostate Specific Antigen in a European HIV-positive Cohort: Does One Size Fit All?

Shepherd¹,

Borges²,

Ravn³

et al. 2015

Antiviral Therapy

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“…No entanto, hipogonadismo também tem sido relatado em pacientes com controle da replicação viral e dos níveis de células CD4 (19). Estudos recentes apontaram prevalência de hipogonadismo de cerca de 20% mesmo após a introdução da terapia antirretroviral altamente ativa (HAART) (20). Crum e cols.…”

Section: Disfunção Gonadal Na Infecção Pelo Hiv/aidsunclassified

Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids

Ponte

Gurgel

Montenegro

2009

Arq Bras Endocrinol Metab

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RESUMOA disfunção do eixo gonadotrófico é frequentemente observada em pacientes infectados pelo HIV. A patogênese é multifatorial e está relacionada à duração da infecção pelo HIV, aos efeitos citopáticos diretos do vírus, ao uso de drogas gonadotóxicas, às infecções oportunistas, às neo plasias, à desnutrição, entre outros fatores. Em homens, a redução dos níveis de testosterona está associada à perda de massa e de força muscular, à redução da densidade mineral óssea, à lipodistrofia, à depressão, à astenia, à fadiga e à disfunção sexual. Em pacientes infectados pelo HIV com hipogonadismo, inúmeros estudos têm comprovado os efeitos benéficos da reposição de testosterona sobre o perfil metabólico e a distribuição da gordura corporal, com aumento da massa corporal magra, além de promover melhora da qualidade de vida, reduzir a perda de mas sa óssea e reduzir os índices de depressão. Assim, esta revisão teve como objetivo trazer uma breve atualização sobre o presente tema, abordando dados epidemiológicos, mecanismos fisio patológicos e estratégias terapêuticas para as principais anormalidades do eixo gonadotrófico masculino associadas à infecção pelo HIV e ao seu tratamento. ABSTRACTGonadotrophic axis dysfunction is commonly observed in HIVinfected patients. The pathogen esis is multifactorial and related to duration of HIV infection, direct cytopathic effects of viruses, use of drugs, opportunistic infections, malignancies, and malnutrition, among other factors. In men, reduced levels of testosterone is associated with loss of muscle mass and strength, de creased bone mineral density, lipodystrophy, depression, asthenia, fatigue and sexual dysfunc tion. In HIVinfected patients with hypogonadism, numerous studies have shown the beneficial effects of testosterone replacement on the metabolic profile and distribution of body fat, with increased body mass weight, and promote better quality of life, reduce the bone mass loss and the rates of depression. Thus, this review aimed to present a brief update of epidemiologic data, pathophysiology aspects and treatment strategies for the major abnormalities of male gonado trophic axis associated with HIV infection and its treatment. Arq Bras Endocrinol Metab. 2009;53(8):983-8

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“…At baseline, hypogonadism was mostly associated with low or normal gonadotropin levels, indicating a disturbance of the HPG axis. In previous studies, androgen deficiency in HIV-positive men has been associated with low CD4 cell counts, a more advanced stage of disease and weight loss [16][17][18]. In our study, cART was associated with an increase in gonadotropin levels in patients who developed lipoatrophy (P 5 0.005 for LH; P 5 0.06 for FSH), but not in negative controls (P 5 0.2 for LH; P 5 0.9 for FSH).…”

Section: Discussionmentioning

confidence: 95%

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

Wunder¹,

Fux

Bersinger³

et al. 2008

HIV Medicine

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ObjectivesWe compared androgen and gonadotropin values in HIV-infected men who did and did not develop lipoatrophy on combination antiretroviral therapy (cART). MethodsFrom a population of 136 treatment-naïve male Caucasians under successful zidovudine/ lamivudine-based cART, the 10 patients developing lipoatrophy (cases) were compared with 87 randomly chosen controls. Plasma levels of free testosterone (fT), dehydroepiandrosterone (DHEA), follicle-stimulating hormone and luteinizing hormone (LH) were measured at baseline and after 2 years of cART. ResultsAt baseline, 60% of the cases and 71% of the controls showed abnormally low fT values. LH levels were normal or low in 67 and 94% of the patients, respectively, indicating a disturbance of the hypothalamic-pituitary-gonadal axis. fT levels did not significantly change after 2 years of cART. Cases showed a significant increase in LH levels, while controls showed a significant increase in DHEA levels. In a multivariate logistic regression model, lipoatrophy was associated with higher baseline DHEA levels (P 5 0.04), an increase in LH levels during cART (P 5 0.001), a lower body mass index and greater age. ConclusionsHypogonadism is present in the majority of HIV-infected patients. The development of cART-related lipoatrophy is associated with an increase in LH and a lack of increase in DHEA levels. 427The lipodystrophy syndrome represents a well-known adverse effect of cART consisting of fat redistribution abnormalities, insulin resistance and dyslipidaemia [4,5]. Lipodystrophy includes central lipohypertrophy and peripheral lipoatrophy. The latter has been associated with the toxic effects of nucleoside reverse transcriptase inhibitors (NRTIs) on mitochondria [6][7][8] and cART-related dysregulation of the expression of cytokines and cytokine receptors, and there are some reports of genetic predispositions, based on single nucleotide polymorphisms, to cART-related lipoatrophy [6,[9][10][11][12]. We showed in a previous study that there is no association between changes in leptin levels and the development of lipoatrophy [13]. In this study, we evaluated the association between sex hormone levels and the development of lipoatrophy in HIV-infected men treated with cART. Materials and methodsThe Swiss HIV Cohort Study (SHCS; www.shcs.ch) prospectively follows HIV-infected adults. Every 6 months, clinical data are collected and blood plasma samples are drawn, analysed and stored at À 80 1C for future research. Study designWe performed a nested case-control study in HIV-infected, antiretroviral therapy-naïve Caucasian men who were successfully treated with zidovudine (ZDV)-and lamivudine (3TC)-based cART for a minimum of 2 years. Patients with acute opportunistic infections, uncontrolled AIDSdefining illnesses, diabetes mellitus, androgen treatment or a change in cART during the study period were excluded. Cases developing lipoatrophy and negative controls were identified and serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), free testoste...

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Prevalence of Hypogonadism among Men with Weight Loss Related to Human Immunodeficiency Virus Infection Who Were Receiving Highly Active Antiretroviral Therapy

Cited by 150 publications

References 25 publications

Predictive Value of Prostate Specific Antigen in a European HIV-positive Cohort: Does One Size Fit All?

Predictive Value of Prostate Specific Antigen in a European HIV-positive Cohort: Does One Size Fit All?

Disfunção do eixo gonadotrófico em homens com infecção pelo HIV/Aids

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

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