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Objective  Hypogonadism is common in HIV-infected men. The relationship between health status, sex steroids and body composition is poorly known in HIV. The aim was to investigate the association between health status (comorbidities/frailty), body composition, and gonadal function in young-to-middle-aged HIV-infected men.    Design  Prospective, cross-sectional, observational study.    Methods  HIV-infected men aged  &lt; 50 years and ongoing Highly Active Antiretroviral Therapy were enrolled. Serum total testosterone (TT), estradiol (E2), estrone (E1) were measured by liquid chromatography-tandem mass spectrometry, LH and FSH by immunoassay. Free testosterone (cFT) was calculated by Vermeulen equation. Body composition was assessed by dual-energy X-ray absorptiometry and abdominal CT scan. Multimorbidity (MM) and frailty were defined as ≥3 comorbidities and by a 37-item index, respectively.    Results  A total of 316 HIV-infected men aged 45.3 ± 5.3 years were enrolled. Body fat parameters were inversely related to cFT and TT, and directly related to E1 and E2/testosterone (TS) ratio. Patients with MM had lower cFT ( P  &lt; 0.0001) and TT ( P  = 0.036), and higher E1 ( P  &lt; 0.0001) and E2/TS ratio ( P  = 0.002). Frailty was inversely related to cFT (R 2  = 0.057,  P  &lt; 0.0001) and TT (R 2  = 0.013,  P  = 0.043), and directly related to E1 (R 2  = 0.171,  P  &lt; 0.0001), E2 (R 2  = 0.041,  P  = 0.004) and E2/TS ratio (R 2  = 0.104,  P  &lt; 0.0001).    Conclusions  Lower TT and cFT, higher E1, E2/TS ratio and visceral fat were independently associated to poor health status and frailty, being possible hallmarks of unhealthy conditions in adult HIV-infected men. Overall, MM, frailty and body fat mass are strictly associated to each other and to sex steroids, concurring together to functional male hypogonadism in HIV.

Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV