GONADAL FUNCTION IN HUMAN IMMUNODEFICENCY VIRUS (HIV)-INFECTED MEN ASSESSED BY ISOTOPIC DILUTION-LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY (ID-LC-MS/MS) AND CHEMILUMINESCENT IMMUNOASSAY

BACKGROUND: HIV-infection is associated to premature decline of serum T. However, prevalence and biochemical characterization of hypogonadism in HIV-infected men are still to be well defined. AIM: To evaluate the gonadal status in HIV-infected men by assessing circulating total T (TT) with either ID-LC-MS/MS or CI. METHODS: Prospective, cross-sectional, observational study on HIV-infected men with ongoing Highly Active Antiretroviral Therapy (HAART). Serum TT, gonadotropins and sex hormone-binding globulin (SHBG) were measured by CI (Architect, Abbott, USA). TT was also assessed by a validated in house ID-LC-MS/MS. Free T (FT) was calculated by Vermeulen equation. Hypogonadism was defined as serum TT levels below 320 ng/dL and/or free T levels below 64 pg/ml. Statistical analysis: Parameters were not normally distributed and Mann-Whitney U test, was used to compare continuous variables. Categorical variables were compared using Chi-Square test, while correlations were performed using linear regression models. RESULTS: 316 consecutive HIV-infected men were enrolled (mean age 45.56±5.61 years; average duration of HIV-infection 16.57±10.45 years). Serum TT levels assessed by LC-MS/MS (mean 652.1+229.1 ng/dL) were significantly lower compared to CI (mean 740.2+274.7 ng/dL) (p<0.0001). As a consequence, prevalence of T deficiency was significantly higher comparing LC-MS-MS to CI (5.4% vs 3.2%, p<0.0001). 56 patients (17.8%) showed SHBG above the normal range (>71.4 nmol/L). Considering calculated FT, the prevalence of hypogonadism was 9.8% using LC-MS/MS and 7.0% using CI, with a significant difference between methodologies (p<0.0001). TT assessed with LC-MS-MS was directly related to TT assessed with CI (Beta=0.956, R2=0.913, p<0.0001), as well as FT (Beta=0.934, R2=0.873, p<0.0001). TT combined with luteinizing hormone (LH) levels was used to classify hypogonadism. By including compensated form of hypogonadism, the prevalence raised to 15.6% for TT and to 17% for FT. CONCLUSIONS: To the best of our knowledge, this is the first properly-designed prospective study aiming to investigate the gonadal status of HIV-infected men with both LC-MS/MS and CI, together with gonadotropins. Notwithstanding the strong correlation found between the two methodologies, the prevalence of hypogonadism results underestimated when CI is used compared to ID-LC-MS/MS in HIV-infected patients. In clinical practice, SHBG for calculated FT is essential for the detection of T deficiency, revealing the real prevalence of hypogonadism in this clinical setting.