Hypogonadism and liver fibrosis in HIV-infected patients

Abstract

Purpose Hypogonadism 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. Methods We 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. Results Hypogonadism 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. Conclusion Overt 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.

Impact of hypogonadism on bone mineral density and vertebral fractures in HIV-infected men

“…Moreover, Jing et al [ 40 ] showed that FSH increase was associated with higher risk of osteoporosis/osteopenia in type 2 diabetic men. We previously showed that elevated SHBG levels are very common in HIV-infected men [ 18 , 41 ] and might represent the primum movens of the compensated form of hypogonadism in these patients. In fact, an increase in SHBG would lower the amount of free testosterone and oestradiol, with subsequent compensatory increase in LH production from the pituitary gland, which is able to maintain the testicular production of testosterone.…”

New perspectives in functional hypogonadotropic hypogonadism: beyond late onset hypogonadism

“…In HIV-infected men, hypogonadism is caused by an impairment of the HPG-A, resulting in secondary hypogonadism rather than primitive testicular failure. However, very frequently an increase in SHBG levels can coexist in HIV-infected men, such that the determination of free testosterone is of paramount importance, as total testosterone levels may not reveal the condition of FHH ( 94 , 95 ).…”

Risk factors on testicular function in adolescents

“…HIV infection can cause a significant deterioration in the reproductive capacity [ 177 , 178 ] as well as its treatment [ 179 ]. Not infrequently, it may cause a reduction in testosterone levels [ 180 ]. Pubertal onset can also be delayed in untreated HIV infection [ 181 ], though new treatments may have benefits [ 182 ].…”