Health status is related to testosterone, estrone and body fat: moving to functional hypogonadism in adult men with HIV
EUROPEAN JOURNAL OF ENDOCRINOLOGY
Authors: De Vincentis, Sara; Decaroli, Maria Chiara; Fanelli, Flaminia; Diazzi, Chiara; Mezzullo, Marco; Morini, Fabio; Bertani, Davide; Milic, Jovana; Carli, Federica; Cuomo, Gianluca; Santi, Daniele; Tartaro, Giulia; Tagliavini, Simonetta; De Santis, Maria Cristina; Roli, Laura; Trenti, Tommaso; Pagotto, Uberto; Guaraldi, Giovanni; Rochira, Vincenzo
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 <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 < 0.0001) and TT (P = 0.036), and higher E1 (P < 0.0001) and E2/TS ratio (P = 0.002). Frailty was inversely related to cFT (R-2 = 0.057, P < 0.0001) and TT (R-2 = 0.013, P = 0.043), and directly related to E1 (R-2 = 0.171, P < 0.0001), E2 (R-2 = 0.041, P = 0.004) and E2/TS ratio (R-2 = 0.104, P < 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.
MANAGEMENT OF ENDOCRINE DISEASE Rationale and current evidence for testosterone therapy in the management of obesity and its complications
EUROPEAN JOURNAL OF ENDOCRINOLOGY
Authors: Lapauw, Bruno; Kaufman, Jean-Marc
Overt hypogonadism in men adversely affects body composition and metabolic health, which generally improve upon testosterone (TS) therapy. As obese men often display lower serum TS levels, in particular when they present with the metabolic syndrome (MetS) or type 2 diabetes (T2DM), there have been claims that androgen therapy prevents or reverses obesity and improves metabolic health. This has contributed to the increase in TS prescriptions during the past two decades. In this narrative review, based on findings from larger observational studies and randomized controlled intervention trials, we evaluate whether low TS predicts or predisposes to obesity and its metabolic consequences, and whether obese men with low TS are truly hypogonadal. We further describe the mechanisms underlying the bi-directional relationships of TS levels with obesity and metabolic health, and finally assess the evidence for TS therapy in men with obesity, MetS and/or T2DM, considering efficacy, safety concerns and possible alternative approaches. It is concluded that low serum sex hormone-binding globulin and total TS levels are highly prevalent in obese men, but that only those with low free TS levels and signs or symptoms of hypogonadism should be considered androgen deficient. These alterations are reversible upon weight loss. Whether low TS is a biomarker rather than a true risk factor for metabolic disturbances remains unclear. Considering the limited number of sound TS therapy trials have shown beneficial effects, the modest amplitude of these effects, and unresolved safety issues, one cannot in the present state-of-the-art advocate TS therapy to prevent or reverse obesity-associated metabolic disturbances. Instead, the focus should remain on lifestyle measures and management of obesity-related consequences.