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

Abstract

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/T ratio. Patients with MM had lower cFT (p<0.0001) and TT (p=0.036), and higher E1 (p<0.0001) and E2/T ratio (p=0.002). Frailty was inversely related to cFT (R2=0.057, p<0.0001) and TT (R2=0.013, p=0.043), and directly related to E1 (R2=0.171, p<0.0001), E2 (R2=0.041, p=0.004) and E2/T ratio (R2=0.104, p<0.0001). Conclusions. Lower TT and cFT, higher E1, E2/T 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.

HIV and Sexual Dysfunction in Men

“…In the pre-HAART era, hypogonadism was mainly related to end-stage AIDS and poor general conditions, in conjunction with opportunistic infection [117]. In the HAART-era, hypogonadism with inappropriately low or normal LH levels (secondary hypogonadism) affects a conspicuous percentage of young to middle-aged patients and has been associated with altered body composition, virus-infection per se and HAART, and could be considered an overall expression of premature aging and patients' increased frailty [79,118].…”

The Prevalence of Hypogonadism and the Effectiveness of Androgen Administration on Body Composition in HIV-Infected Men: A Meta-Analysis

“…Indeed, an impairment of the hypothalamic-pituitary-gonadal axis is frequently reported in HIV populations, although there is a highly variable incidence, depending on both the criteria used to diagnose hypogonadism and the clinical characteristics of patients enrolled [3]. Despite this heterogeneous picture, the well-known age-related decline in testosterone (Te) serum levels seems anticipated in HIV patients [4,5]. This progressive decline could be due either to a direct viral action on glandular tissue, or to the HAART-related sequelae, although the exact pathogenic mechanism remains to be elucidated [4,5].…”

“…Despite this heterogeneous picture, the well-known age-related decline in testosterone (Te) serum levels seems anticipated in HIV patients [4,5]. This progressive decline could be due either to a direct viral action on glandular tissue, or to the HAART-related sequelae, although the exact pathogenic mechanism remains to be elucidated [4,5]. Moreover, available studies assessing the prevalence of hypogonadism in HIV-infected patients reported very variable percentages, leaving open the question of the real interconnection between hypogonadism and HIV [3].…”

“…The relevance of hypogonadism in HIV settings has progressively increased in recent years, since it has been suggested as a marker of poor health status and frailty in the general population [6,7] and in HIV subjects [5,8]. Te and each related derivative compound (such as anabolic-androgenic steroids) [9] are used and, in terms of androgen anabolic properties, an involvement of Te reduction in HIV-related changes in body composition has been investigated [10].…”

Hypogonadism and liver fibrosis in HIV-infected patients

“…Interestingly, patients in this group were more frequently obese, and it is well known that obesity is among the most frequent cause of secondary/normogonadotropic hypogonadism [26]. Focusing on the known body fat redistribution due to HIV-induced lipodystrophy, the relationship between body fat (not necessarily obesity) and gonadal status was recently evaluated by De Vincentis and colleagues [27]. They found that cFT and TT were inversely related, whereas oestradiol was directly related to total body and visceral fat, and therefore hypothesized that these findings could depend on an increase of testosterone aromatization, similarly to what happens in obese hypogonadal men of general population.…”