Hypogonadism and liver fibrosis in HIV-infected patients

E Quiros-Roldan,L C Pezzaioli,C Carriero,F Castelli,E Focà,S Paghera,M Degli Antoni,M Properzi,A Ferlin,T Porcelli

doi:10.1007/s40618-021-01512-9

Abstract

PurposeHypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis.MethodsWe performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores.ResultsHypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores.ConclusionOvert and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

Highlights

Hypogonadism is a clinical syndrome characterized by low testosterone (T) plasma levels with symptoms and signs of low androgen action, caused by alteration of the hypothalamus–pituitary-testis axis (HPT) at one or more stages [1, 2]
Compensated hypogonadism, which represents another frequent finding in both, general population and HIV-infected men complaining of sexual dysfunction, can be diagnosed by luteinizing hormone (LH) determination, since it is characterized by normal T levels and high LH [8,9,10]
Androgen actions are mediated by free T (FT), which represents only 1–3% of total T, being the large part bound to albumin and sex-hormone binding protein (SHBG), both produced by the liver

Summary

Introduction

Hypogonadism is a clinical syndrome characterized by low testosterone (T) plasma levels with symptoms and signs of low androgen action, caused by alteration of the hypothalamus–pituitary-testis axis (HPT) at one or more stages [1, 2]. Sexual symptoms, such as decreased libido and erectile dysfunction, are considered the most specific manifestations, but many other conditions and co-morbidities are associated with hypogonadism, for example osteoporosis, increased fat/lean mass, cardiovascular diseases, sarcopenia, asthenia, and depression [3]. Methods that directly measure FT are inaccurate; the best approach is represented by its calculation (calculated FT, cFT) after determination of SHBG and albumin using formulae, as the Vermeulen one (http://www.issam.ch/freetesto.htmwww.issam.ch/freetesto.htm)

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