Gender differences in GH response to GHRHC ARG in lipodystrophic patients with HIV: a key role for body fat distribution Giulia Brigante 1,2 , Chiara Diazzi 1,2 , Anna Ansaloni 1,2 , Lucia Zirilli 1,2 , Gabriella Orlando 3 , Giovanni Guaraldi 3 and Vincenzo Rochira 1,2 1 Chair of Endocrinology and Metabolism, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy, 2 Division of Endocrinology, Integrated Department of Medicine, Endocrinology and Metabolism, and Geriatrics, Azienda USL of Modena, University of Modena and Reggio Emilia, NOCSAE of Baggiovara, Via Giardini 1355, 41126 Modena, Italy and 3 Metabolic Clinic, Infectious and Tropical Disease Unit, Department of Medical and Surgical Sciences of Mother, Child and Adult, University of Modena and Reggio Emilia, Modena, Italy Correspondence should be addressed to V Rochira Email rochira.vincenzo@unimore.it Abstract Objective: Gender influence on GH secretion in human immunodeficiency virus (HIV)-infected patients is poorly known. Design and methods: To determine the effect of gender, we compared GH response to GH-releasing hormone plus arginine (GHRHCArg), and body composition in 103 men and 97 women with HIV and lipodystrophy. The main outcomes were IGF1, basal GH, GH peak and area under the curve (AUC) after GHRHCArg, body composition, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT). Results: Men had lower GH peak and AUC than women (P!0.001). Of the study population, 21% of women and 37% of men had biochemical GH deficiency (GHD; GH peak !7.5 mg/l). VAT-to-SATratio was higher in men than in women with GHD (P!0.05). Unlike women, VAT, SAT, and trunk fat were greater in men with GHD than in men without GHD. IGF1 was significantly lower in women with GHD than in women without GHD, but not in men. At univariate analysis, BMI, trunk fat mass, VAT, and total adipose tissue were associated with GH peak and AUC in both sexes (P!0.05). BMI was the most significant predictive factor of GH peak, and AUC at multiregression analysis. Overall, abdominal fat had a less pronounced effect on GH in females than in males. Conclusions: These data demonstrate that GH response to GHRHCArg is significantly lower in HIV-infected males than females, resulting in a higher percentage of GHD in men. Adipose tissue distribution more than fat mass per se seems to account for GH gender differences and for the alteration of GH–IGF1 status in these patients. European Journal of Endocrinology (2014) 170, 685–696 Introduction Human immunodeficiency virus (HIV)-infected patients treated with highly active antiretroviral therapy (HAART) are at risk of developing several endocrine and metabolic complications (1, 2). Reduced growth hormone (GH) secretion is observed in about one-third of HIV-infected men (3, 4) on HAART and it is associated, at least in part, with HIV-related lipodystrophy (5). Furthermore, GH secretion is often impaired in HIV-infected women (6). In both sexes, GH secretion seems to be negatively associated with BMI, waist circumference, and waist-to-hip ratio (4, 6, 7). However, visceral fat is not strongly associated with GH impairment in women (8), and increased visceral adiposity does not fully explain the degree of GH deficiency (GHD) in HIV-infected patients of both sexes (6, 8, 9). GH response to GH-releasing hormone plus arginine (GHRHCArg) is impaired in HIV-infected men and women even when compared with gender-matched controls (6, 7, 8, 9). Moreover, reduced GH secretion European Journal of Endocrinology Clinical Study G Brigante and others GH–IGF1 axis in HIV: gender differences 170 :5 685–696 www.eje-online.org Ñ 2014 European Society of Endocrinology DOI: 10.1530/EJE-13-0961 Printed in Great Britain Published by Bioscientifica Ltd. Downloaded from Bioscientifica.com at 06/10/2020 04:07:56PM via free access