Endocrine Care – HGH, The Human Growth Hormone

Growth Hormone (GH) Replacement Therapy in Adult-Onset GH Deficiency: Effects on Body Composition in Men and Women in a Double-Blind, Randomized, Placebo-Controlled Trial

Adult GH Deficiency (AGHD) is characterized by an altered body composition, an atherogenic lipid profile, decreased exercise capacity, and diminished quality of life. We performed a randomized, double-blind, placebo-controlled, multicenter study in 166 subjects with AGHD to assess the effects of GH on these outcomes. GH was initiated at 0.0125 mg/kg·d, increased to 0.025 mg/kg·d as tolerated, or decreased to 0.00625 mg/kg·d for 12 months. Primary measures of efficacy included body composition, strength and endurance, and quality of life. Additional parameters included serum IGF-I concentrations, serum lipids, and bone mineral density.

After 12 months, 79% of subjects remained on GH 0.0125 mg/kg·d, whereas 21% received 0.00625 mg/kg·d. GH-treated men and women demonstrated significant decreases in total body and trunk fat and increases in lean body mass over baseline. In GH-treated men, mean IGF-I sd scores exceeded age-adjusted normal ranges, whereas similar doses produced a smaller response in women. GH treatment was associated with significant improvements in total cholesterol and low-density lipoprotein (P < 0.05 for all). No significant treatment effects were observed in strength and endurance, quality of life, or bone mineral density. GH treatment was generally well tolerated. Subjects with AGHD should receive individualized GH therapy to maintain IGF-I between the mean value and +2 sd and improve body composition and cardiovascular risk factors.

GH IS REQUIRED for normal growth and metabolic homeostasis in children. However, GH secretion occurs throughout life and is known to have profound effects on anabolism, lipolysis, and carbohydrate metabolism. Individuals who develop adult GH deficiency (AGHD) secondary to pituitary or hypothalamic disease exhibit abnormal body composition, characterized by a significant increase in fat mass, particularly visceral fat, and a decrease in lean body mass (1, 2, 3, 4, 5, 6). Many have diminished strength and exercise capacity that may improve with GH therapy (7, 8). Adults with AGHD also demonstrate altered lipid metabolism, increased incidence of cardiovascular disease, and diminished quality of life (9, 10, 11, 12). Reduced life expectancy secondary to increased cerebrovascular and cardiovascular disease has also been reported in patients with hypopituitarism (13). Adults with AGHD experience feelings of social isolation, decreased energy, and an overall poorer quality of life when compared with controls (11, 14, 15, 16). Bone mineral density (BMD) is also reduced in these subjects (6), resulting in a 3-fold increase in bone fracture rate (17).

Short-term GH replacement therapy in adults has been associated with beneficial effects on body composition, fat distribution, and quality of life (2, 18, 19). Improvements in bone mineral content and BMD are not apparent until GH has been administered for at least 18 months (20, 21). In general, studies of GH therapy in subjects with AGHD have been relatively small, nonrandomized, or uncontrolled. Moreover, potential differences in the ability of men and women to respond to GH have not been adequately examined in most of these studies.

This large multicenter, randomized, placebo-controlled study explored the effects of GH treatment on body composition and physical performance. The primary end points were a decrease in percentage of body fat, an increase in muscle strength, and improved quality of life. The anticipated reduction in cardiovascular risk emerged as the most compelling reason to examine the impact of GH replacement therapy in adults with GHD.