Doses of growth hormone in adults with growth hormone deficiency are now lower than previously. However, it is not clear they are as effective as higher doses. The objective of this meta-analysis was to assess efficacy of low to moderate dose (LD) GH replacement on standard endpoints of GH compared to higher doses.
A meta-analysis was carried out using PubMed, Cochrane and Embase databases from 1960 to 9/23/12. Three reviewers identified randomized double-blind, placebo-controlled trials of 6 months duration. Of 173 publications, 28 representing 22 trials (591 GH-treated patients and 562 placebo) were included. Data were independently extracted by three reviewers. Endpoints were analyzed if ≥4 studies per dose group reported baseline and 6 month data.
Mean lean body mass (LBM) increased by 2.61 kg in GH-treated subjects versus 0.04 in the placebo group (P < 0.0001). Fat mass (FM) was reduced by −2.19 kg versus 0.31 (GH vs. placebo) (P = 0.0002). Changes in LBM and FM were dose-related (P = 0.02 and 0.007, respectively), high dose (HD) being more effective than low dose (LBM P = 0.03 and FM P = 0.04). In contrast, treatment with GH reduced total cholesterol −0.38 mmol/L versus. 0.01 (placebo) (P < 0.0001), and low density lipoprotein cholesterol (LDL-C) −0.42 mmol/L versus −0.1 (P = 0.0009), but there were no differences between LD and HD GH.
LDs of hGH improve total- and LDL-C, and body composition. Higher doses are more effective on body composition, but not lipids.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Salomon F, Cuneo RC, Hesp R, Sonksen PH (1989) The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med 321:1797–1803
de Boer H, Blok GJ, van der Veen EA (1995) Clinical aspects of growth hormone deficiency in adults. Endocr Rev 16:63–86
Rabkin MT, Frantz AG (1966) Hypopituitarism: a study of growth hormone and other endocrine functions. Ann Intern Med 64:1197–1207
Giustina A, Barkan A, Chanson P, Grossman A, Hoffman A, Ghigo E, Casanueva F, Colao A, Lamberts S, Sheppard M, Melmed S (2008) Guidelines for the treatment of growth hormone excess and growth hormone deficiency in adults. J Endocrinol Invest 31:820–838
Appelman-Dijkstra NM, Claessen KM, Roelfsema F, Pereira AM, Biermasz NR (2013) Long-term effects of recombinant human GH replacement in adults with GH deficiency: a systematic review. Eur J Endocrinol 169:R1–R14
Gasco V, Prodam F, Grottoli S, Marzullo P, Longobardi S, Ghigo E, Aimaretti G (2013) GH therapy in adult GH deficiency: a review of treatment schedules and the evidence for low starting doses. Eur J Endocrinol 168:R55–R66
Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML (2011) Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 96:1587–1609
Newman CB, Frisch K, Rosenzweig B, Roubenoff R, Rey M, Kidder T, Kong Y, Pursnani A, Sedlis S, Schwartzbard A, Kleinberg D (2010) Moderate doses of hGH (0.64 mg/d) improve lipids but not cardiovascular function in GH-deficient adults with normal baseline cardiac function. J Clin Endocrinol 96:122–132
Maison P, Griffin S, Nicoue-Beglah M, Haddad N, Balkau B, Chanson P (2004) Impact of growth hormone (GH) treatment on cardiovascular risk factors in GH-deficient adults: a metaanalysis of blinded, randomized, placebo-controlled trials. J Clin Endocrinol Metab 89:2192–2199
Chung YS, Lee HC, Hwang SK, Paik IK, Lee JH, Huh KB (1994) Growth hormone replacement therapy in adults with growth hormone deficiency; thrice weekly low dose administration. J Korean Med Sci 9:169–178
Rosen T, Bengtsson BA (1990) Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 336:285–288
Bates AS, Van’t Hoff W, Jones PJ, Clayton RN (1996) The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 81:1169–1172
Tomlinson JW, Holden N, Hills RK, Wheatley K, Clayton RN, Bates AS, Sheppard MC, Stewart PM (2001) Association between premature mortality and hypopituitarism. West Midlands Prospective Hypopituitary Study Group. Lancet 357:425–431
Bulow B, Hagmar L, Eskilsson J, Erfurth EM (2000) Hypopituitary females have a high incidence of cardiovascular morbidity and an increased prevalence of cardiovascular risk factors. J Clin Endocrinol Metab 85:574–584
Carmichael JD, Danoff A, Milani D, Roubenoff R, Lesser ML, Livote E, Reitz RE, Ferris S, Kleinberg DL (2006) GH peak response to GHRH-arginine: relationship to insulin resistance and other cardiovascular risk factors in a population of adults aged 50–90. Clin Endocrinol (Oxf) 65:169–177
Whitehead HM, Boreham C, McIlrath EM, Sheridan B, Kennedy L, Atkinson AB, Hadden DR (1992) Growth hormone treatment of adults with growth hormone deficiency: results of a 13-month placebo controlled cross-over study. Clin Endocrinol 36:45–52
Webster JM, Stewart M, al Maskari M, Osman I, Kendall-Taylor P, Mitcheson J, Laker MF (1997) The effect of growth hormone replacement therapy for up to 12 months on lipoprotein composition and lipoprotein(a) in growth hormone-deficient adults. Atherosclerosis 133:115–121
Vahl N, Jorgensen JO, Hansen TB, Klausen IB, Jurik AG, Hagen C, Christiansen JS (1998) The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study. Int J ObesRelat Metab Disord 22:529–536
Elgzyri T, Castenfors J, Hagg E, Backman C, Thoren M, Bramnert M (2004) The effects of GH replacement therapy on cardiac morphology and function, exercise capacity and serum lipids in elderly patients with GH deficiency. ClinEndocrinol(Oxf) 61:113–122
Colao A, Di Somma C, Cuocolo A, Spinelli L, Tedesco N, Pivonello R, Bonaduce D, Salvatore M, Lombardi G (2001) Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency. J Clin Endocrinol Metab 86:1874–1881
Gillberg P, Bramnert M, Thoren M, Werner S, Johannsson G (2001) Commencing growth hormone replacement in adults with a fixed low dose. Effects on serum lipoproteins, glucose metabolism, body composition, and cardiovascular function. Growth Horm IGF Res 11:273–281
Binnerts A, Swart GR, Wilson JHP, Hoogerbrugge N, Pols HAP, Birkenhager JC, Lamberts SWJ (1992) The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol 37:79–87
Cuneo RC, Salomon F, Watts GF, Hesp R, Sonksen PH (1993) Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency. Metabolism 42:1519–1523
Weaver JU, Monson JP, Noonan K, John WG, Edwards A, Evans KA, Cunningham J (1995) The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults. J Clin Endocrinol Metab 80:153–159
Burman P, Johansson AG, Siegbahn A, Vessby B, Karlsson FA (1997) Growth hormone (GH)-deficient men are more responsive to GH replacement therapy than women. J Clin Endocrinol Metab 82:550–555
Christopher M, Hew FL, Oakley M, Rantzau C, Alford F (1998) Defects of insulin action and skeletal muscle glucose metabolism in growth hormone-deficient adults persist after 24 months of recombinant human growth hormone therapy. J Clin Endocrinol Metab 83:1668–1681
Russell-Jones DL, Watts GF, Weissberger A, Naoumova R, Myers J, Thompson GR, Sonksen PH (1994) The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients. Clin Endocrinol (Oxf) 41:345–350
Beshyah SA, Henderson A, Niththyananthan R, Skinner E, Anyaoku V, Richmond W, Sharp P, Johnston DG (1995) The effects of short and long term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance. J Clin Endocrinol Metab 80:356–363
Cuneo RC, Judd S, Wallace JD, Perry-Keene D, Burger H, Lim-Tio S, Strauss B, Stockigt J, Topliss D, Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages S, Cheung NW, Hurley D (1998) The Australian multicenter trial of growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 83:107–116
Attanasio AF, Lamberts SWJ, Matranga AMC, Birkett MA, Bates PC, Valk NK, Hilsted J, Bengtsson BA, Strasburger CJ, The Adult Growth Hormone Deficiency Study G (1997) Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. J Clin Endocrinol Metab 82:82–88
Caidahl K, Eden S, Bengtsson BA (1994) Cardiovascular and renal effects of growth hormone. Clin Endocrinol 40:393–400
Valcavi R, Gaddi O, Zini M, Iavicoli M, Mellino U, Portioli I (1995) Cardiac performance and mass in adults with hypopituitarism: effects of one year of growth hormone treatment. J Clin Endocrinol Metab 80:659–666
Moller N, Jorgensen JO (2009) Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 30:152–177
Moller J, Jorgensen JO, Moller N, Christiansen JS, Weeke J (1992) Effects of growth hormone administration on fuel oxidation and thyroid function in normal man. Metab Clin Exp 41:728–731
Gravholt CH, Schmitz O, Simonsen L, Bulow J, Christiansen JS, Moller N (1999) Effects of a physiological GH pulse on interstitial glycerol in abdominal and femoral adipose tissue. Am J Physiol 277:E848–E854
Thomas JD, Monson JP (2009) Adult GH deficiency throughout lifetime. Eur J Endocrinol 161(Suppl 1):S97–S106
Johannsson G, Oscarsson J, Rosen T, Wiklund O, Olsson G, Wilhelmsen L, Bengtsson BA (1995) Effects of 1 year of growth hormone therapy on serum lipoprotein levels in growth hormone-deficient adults. Influence of gender and Apo(a) and ApoE phenotypes. Arterioscler Thromb Vasc Biol 15:2142–2150
Beauregard C, Utz AL, Schaub AE, Nachtigall L, Biller BM, Miller KK, Klibanski A (2008) Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 93:2063–2071
Bell W, Davies JS, Evans WD, Scanlon MF (1999) Strength and its relationship to changes in fat-free mass, total body potassium, total body water and IGF-1 in adults with growth hormone deficiency: effect of treatment with growth hormone. Ann Hum Biol 26:63–78
Bell W, Davies JS, Evans WD, Scanlon MF, Mullen R (2004) Somatic characteristics and cardiovascular risk factors in growth hormone deficiency: a randomized, double-blind, placebo-controlled study of the effect of treatment with recombinant human growth hormone. Am J Hum Biol 16:533–543
Johannsson G, Bengtsson BA, Andersson B, Isgaard J, Caidahl K (1996) Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults. Preliminary data in a small group of patients. Clin Endocrinol (Oxf) 45:305–314
Beshyah SA, Shahi M, Skinner E, Sharp P, Foale R, Johnston DG (1994) Cardiovascular effects of growth hormone replacement therapy in hypopituitary adults. Eur J Endocrinol 130:451–458
Beshyah SA, Freemantle C, Shahi M, Anyaoku V, Merson S, Lynch S, Skinner E, Sharp P, Foale R, Johnston DG (1995) Replacement treatment with biosynthetic human growth hormone in growth hormone-deficient hypopituitary adults. Clin Endocrinol 42:73–84
Chihara K, Kato Y, Shimatsu A, Tanaka T, Kohno H (2008) Efficacy and safety of individualized growth hormone treatment in adult Japanese patients with growth hormone deficiency. Growth Horm IGF Res 18:394–403
Cuneo RC, Salomon F, Wilmshurst P, Byrne C, Wiles CM, Hesp R, Sonksen PH (1991) Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system. Clin Sci (Lond) 81:587–592
Daugaard JR, Bramnert M, Manhem P, Endre T, Groop LC, Lofman M, Richter EA (1999) Effect of 6 months of GH treatment on myosin heavy chain composition in GH-deficient patients. Eur J Endocrinol 141:342–349
Eden S, Wiklund O, Oscarsson J, Rosen T, Bengtsson BA (1993) Growth hormone treatment of growth hormone-deficient adults results in a marked increase in Lp(a) and HDL cholesterol concentrations. Arterioscler Thromb 13:296–301
Fernholm R, Bramnert M, Hagg E, Hilding A, Baylink DJ, Mohan S, Thoren M (2000) Growth hormone replacement therapy improves body composition and increases bone metabolism in elderly patients with pituitary disease. J Clin Endocrinol Metab 85:4104–4112
Ezzat S, Fear S, Gaillard RC, Gayle C, Landy H, Marcovitz S, Mattioni T, Nussey S, Rees A, Svanberg E (2002) Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults. J Clin Endocrinol Metab 87:2725–2733
Hoffman AR, Kuntze JE, Baptista J, Baum HB, Baumann GP, Biller BM, Clark RV, Cook D, Inzucchi SE, Kleinberg D, Klibanski A, Phillips LS, Ridgway EC, Robbins RJ, Schlechte J, Sharma M, Thorner MO, Vance ML (2004) 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. J Clin Endocrinol Metab 89:2048–2056
Hwu CM, Kwok CF, Lai TY, Shih KC, Lee TS, Hsiao LC, Lee SH, Fang VS, Ho LT (1997) Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: a report of one-year clinical experience. J Clin Endocrinol Metab 82:3285–3292
Nass R, Huber RM, Klauss V, Muller OA, Schopohl J, Strasburger CJ (1995) Effect of growth hormone (hGH) replacement therapy on physical work capacity and cardiac and pulmonary function in patients with hGH deficiency acquired in adulthood. J Clin Endocrinol Metab 80:552–557
Soares CN, Musolino NR, Cunha Neto M, Caires MA, Rosenthal MC, Camargo CP, Bronstein MD (1999) Impact of recombinant human growth hormone (RH-GH) treatment on psychiatric, neuropsychological and clinical profiles of GH deficient adults. A placebo-controlled trial. Arq Neuropsiquiatr 57:182–189
Verhelst J, Abs R, Vandeweghe M, Mockel J, Legros JJ, Copinschi G, Mahler C, Velkeniers B, Vanhaelst L, van Aelst A, de Rijdt D, Stevenaert A, Beckers A (1997) Two years of replacement therapy in adults with growth hormone deficiency. Clin Endocrinol (Oxf) 47:485–494
Wallymahmed ME, Foy P, Shaw D, Hutcheon R, Edwards RH, MacFarlane IA (1997) Quality of life, body composition and muscle strength in adult growth hormone deficiency: the influence of growth hormone replacement therapy for up to 3 years. Clin Endocrinol (Oxf) 47:439–446
We thank Beatriz Mitrzyk, Harvey Kushner, Maryjo Dixon, Erin Mack and Heather Levitt for their assistance in preparing the manuscript. We also thank Katalin Frisch, MD, who worked on this concept early on. Supported in part by Novo Nordisk which provided funds to do library research and statistical analysis.
Conflict of interest
C.B.N. and J.D.C. have nothing to declare. D.L.K. has received consulting fees from Novo Nordisk.
About this article
Cite this article
Newman, C.B., Carmichael, J.D. & Kleinberg, D.L. Effects of low dose versus high dose human growth hormone on body composition and lipids in adults with GH deficiency: a meta-analysis of placebo-controlled randomized trials. Pituitary 18, 297–305 (2015). https://doi.org/10.1007/s11102-014-0571-z
- Growth hormone
- GH deficient adults
- Body composition