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Gender-Specific Responses of Lean Body Composition and Non-Gender-Specific Cardiac Function Improvement after GH Replacement in GH-Deficient Adults

Division of Endocrinology and Metabolism (S.E.), University of Toronto, Toronto, Canada M5G 2C4; Serono International S.A. (S.F., H.L., T.M., E.S.), CH-1211 Geneva 20, Switzerland; Division of Endocrinology (R.-C.G.), Cantonale Hopital Universitaire Vaudois, CH-1011 Lausanne, Switzerland; Department of Endocrinology (C.G.), King’s College School of Medicine, London WC2R 2LS, United Kingdom; Department of Endocrinology (S.M.), Montréal General Hospital, Montréal, Canada H3G 1A4; Division of Endocrinology (S.N.), St. George’s Hospital, London SW17 0RE, United Kingdom; and Section of Endocrinology (A.R.), University of Wales, Cardiff, CF10 3XQ Wales, United Kingdom

Address all correspondence and requests for reprints to: E. Svanberg, Serono International S.A, 15bis Chemin des Mines, Case postale 54, CH-1211 Geneva 20, Switzerland. E-mail: . elisabeth.svanberg{at}serono.com

Abstract

GH deficiency (GHD) in adulthood is accompanied by physical and psychological impairments. One hundred fifteen patients (67 male, 48 female) with pronounced GHD were enrolled in a randomized, double-blind, placebo-controlled study with objectives that included effects on body composition, cardiac structure, and function and safety of replacement therapy with recombinant human GH (Saizen). Sixty patients (31 male, 29 female) received GH at a dose of 0.005–0.010 mg/kg·d, and 55 patients (36 male, 19 female) received placebo for 6 months. Assessment of body composition by dual-energy x-ray absorptiometry demonstrated a treatment difference in lean body mass increase of 2.1 kg (between-group comparison, P < 0.0001), which was significantly greater among males than females (P < 0.0001) [males: GH, +3.13 kg (2.42, 3.84); placebo, +0.11 kg (-0.60, 0.82); and females: GH, +0.64 kg (-0.15, 1.44); placebo: -0.90 kg (-2.20, 0.39)] [mean change 0–6 months (95% confidence limits)] and was associated with IGF-I changes. The decrease in fat mass of 2.8 kg (between-group comparison, P < 0.0001) noted by DEXA was also evident from bioelectric impedance and anthropometric measurements. Echocardiography showed comparable improvement in left ventricular systolic function after GH treatment in both genders. End-systolic volume decreased by 4.3 ± 10.5 ml (from 35.8 ± 17.6 ml; between-group comparison, P = 0.035) and ejection fraction increased by 5.1 ± 10.0% (from 55.0 ± 11.2%; between-group comparison, P = 0.048), approaching normalcy. Diastolic function did not change as assessed by isovolumic relaxation time, early diastolic flow, diastolic flow secondary to atrial contraction, or ratio of peak mitral early diastolic and atrial contraction velocity. GH treatment was well tolerated, with adverse events primarily related to effects on fluid balance. No apparent relationship between IGF-I levels and the occurrence or severity of adverse events was identified. In conclusion, GH replacement therapy in adults with GHD demonstrated beneficial effects on lean body mass composition that was more pronounced in males than females. In contrast, cardiac function improvement appears to benefit both genders equally.

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