Gender difference in the response of growth hormone (GH)-deficient adults to GH therapy

Abstract

While individual hypopituitary patients undoubtedly benefit from growth hormone (GH) therapy, there is considerable variability in the response to treatment. Given the expense, possible lack of benefit, and potential risks associated with long-term therapy, we sought to identify characteristics potentially associated with a favorable response to GH replacement. Twelve GH-deficient adults (seven men and five women aged 35.4 ± 2.5 years, mean ± SEM) participated in a 12-month open study of GH replacement (0.125 IU/kg/wk for 4 weeks and 0.25 IU/kg/wk thereafter) designed to examine the impact of GH on body composition, lipid profile, and psychological well-being. Using bioelectrical impedance analysis (BIA), there was a reduction in body fat (BF) and an increase in lean body mass (LBM) and total body water (TBW) ( P < .05) following 12 months of GH treatment. In addition, there was a significant improvement in psychological well-being as indicated by a decrease in the Nottingham Health Profile (NHP) score ( P < .05) and a decrease in both total cholesterol ( P = .005) and low-density lipoprotein (LDL) cholesterol ( P < .03). GH therapy was associated with an increase in fasting plasma glucose ( P = .008) and hemoglobin A 1c (HbA 1c ( P = .06). When analyzed by gender, the beneficial effect of GH was greater in men versus women for the increment in insulin-like growth factor-1 ([IGF-1] 375 ± 59 v 148 ± 73 μg/L, mean ± SEM), increase in LBM (6.8 ± 2.5 v −0.06 ± 1.6 kg), reduction in BF (5.6 ± 1.6 v 1.0 ± 1.9 kg), and increase in TBW (5.0 ± 1.6 v 0.14 ± 1.29 L) ( P < .05). HbA 1c increased significantly in women ( P < .05). The beneficial effect of GH tended to be greatest in those with the most significant abnormality in baseline values ( P < .05). The duration of hypopituitarism showed an indirect correlation with the change in total cholesterol ( P < .005). Baseline IGF-1 levels correlated directly with changes in TBW ( P < .05). These data indicate that men with GH deficiency appear more responsive to GH therapy than women with respect to the increase in IGF-1 levels and improvement in body composition. In general, patients with the most significant abnormality in baseline values, the highest IGF-1 levels, and the shortest duration of hypopituitarism respond best. With long-term GH therapy, careful monitoring of glucose tolerance is indicated.