Introduction: The use of growth hormone (GH) treatment in GH deficiency (GHD) continues to increase. However, individual controlled trials of the efficacy and safety of GH have involved relatively few patients and yielded variable results. We seek to analyze the overall effect of GH treatment on various parameters by performing a contemporary meta-analysis of the efficacy and safety of GH administration. Methods: Meta-analysis of 48 blinded, placebo controlled, randomized clinical studies of GH treatment in GHD adults published up to June 2011 was performed. Analyzed variables included anthropomorphic measurements (waist-hip ratio (WHR), lean body mass (LBM)/fat free mass (FFM), trunk fat (TrF), total body water (TBW), fat mass (FM), and body mass index (BMI)); cardiovascular (CV) parameters (systolic/diastolic blood pressure (SBP, DBP), heart rate (HR), stroke volume (SV), LDL, HDL, total cholesterol (TChol), triglycerides (TG), apolipoprotein B (ApoB), C-reactive protein (CRP)); and diabetes parameters (fasting insulin and glucose, hemoglobin A1c (HgbA1c)). Effect sizes (ES) were used to determine significance and weighted mean differences between GH and control were used to quantify size of effect. Results: 2231 adults with growth hormone deficiency were included. Significant beneficial changes resulting from GH administration were observed in the following variables: anthropomorphic—WHR, FM, LBM, FFM, TBW; cardiovascular—LDL, HDL, TChol, ApoB, CRP; significant adverse changes were seen in diabetic parameters—fasting insulin, fasting glucose, and HgbA1c. Compared to prior meta-analyses, larger ESs were observed for LDL, HDL, total cholesterol, fasting insulin and fasting glucose levels. Conclusions: GH administration in GHD adults results in improvement in anthropomorphic parameters, as well as CV parameters, but with worsening of diabetes markers. Data on long-term safety, including on CV effects and malignancy, as well as data assessing the role of GH replacement in combination with testosterone replacement continue to be sparse.
A. S. Bates, et al., “The Effect of Hypopituitarism on Life Expectancy,” The Journal of Clinical Endocrinology & Metabolism, Vol. 84, No. 3, 1996, pp. 1169-1172. doi:10.1210/jc.81.3.1169
A. L. Barkan, et al., “Growth Hormone Therapy for Hypopituitary Adults: Time for Re-Appraisal,” Trends in Endocrinology & Metabolism, Vol. 11, No. 6, 2000, pp. 238-245. doi:10.1016/S1043-2760(00)00267-8
R. C. Cuneo, et al., “The Growth Hormone Deficiency Syndrome in Adults,” Clinical Endocrinology, Vol. 37, No. 5, 1992, pp. 387-397. doi:10.1111/j.1365-2265.1992.tb02347.x
P. B. Mark, et al., “Cardiomyopathy Induced by Performance Enhancing Drugs in a Competitive Bodybuilder,” Heart, Vol. 91, No. 7, 2005, p. 888. doi:10.1136/hrt.2004.053843
Q. E. Stevens, et al., “Aortic and Mitral Valve Thickening with Concentric Left Ventricular Hypertrophy in an Elite Bodybuilder: A Biochemical and/or Physiological Adaptation?” Cardiology, Vol. 98, No. 3, 2002, pp. 159-161. doi:10.1159/000066315
M. J. Geraci, et al., “New Onset Diabetes Associated with Bovine Growth Hormone and Testosterone Abuse in a Young Body Builder,” Human & Experimental Toxicology, Vol. 30, No. 12, 2011, pp. 2007-2012.
B. P. Brennan, et al., “Human Growth Hormone Abuse in Male Weightlifters,” American Journal on Addictions, Vol. 20, No. 1, 2011, pp. 9-13. doi:10.1111/j.1521-0391.2010.00093.x
P. V. Carroll, et al., “Growth Hormone Deficiency in Adulthood and the Effects of Growth Hormone Replacement: A Review,” The Journal of Clinical Endocrinology & Metabolism, Vol. 83, No. 2, 1998, pp. 382-395. doi:10.1210/jc.83.2.382
P. Maison, et al., “Impact of Growth Hormone (GH) Treatment on Cardiovascular Risk Factors in GH-Deficient Adults: A Metaanalysis of Blinded, Randomized, Placebo-Controlled Trials,” The Journal of Clinical Endocrinology & Metabolism, Vol. 89, No. 5, 2004, pp. 2192-2199. doi:10.1210/jc.2003-030840
P. Maison, et al., “Cardiac Effects of Growth Hormone in Adults with Growth Hormone Deficiency: A Meta-Analysis,” Circulation, Vol. 108, No. 21, 2003, pp. 2648-2652. doi:10.1161/01.CIR.0000100720.01867.1D
L. I. Arwert, et al., “The Influence of Growth Hormone (GH) Substitution on Patient-Reported Outcomes and Cognitive Functions in GH-Deficient Patients: A Meta- Analysis,” Growth Hormone & IGF Research, Vol. 15, No. 1, 2005, pp. 47-54. doi:10.1016/j.ghir.2004.11.004
W. M. Widdowson, et al., “The Effect of Growth Hormone Replacement on Exercise Capacity in Patients with GH Deficiency: A Metaanalysis,” The Journal of Clinical Endocrinology & Metabolism, Vol. 93, No. 11, 2008, pp. 4413-4417. doi:10.1210/jc.2008-1239
F. R. Sattler, et al., “Testosterone and Growth Hormone Improve Body Composition and Muscle Performance in Older Men,” The Journal of Clinical Endocrinology & Metabolism, Vol. 94, No. 6, 2009, pp. 1991-2001. doi:10.1210/jc.2008-2338
M. R. Blackman, et al., “Growth Hormone and Sex Steroid Administration in Healthy Aged Women and Men: A Randomized Controlled Trial,” The Journal of the American Medical Association, Vol. 288, No. 18, 2002, pp. 2282-2292. doi:10.1001/jama.288.18.2282
P. H. Sonksen, et al., “Consensus Guidelines for the Diagnosis and Treatment of Adults with Growth Hormone Deficiency,” Growth Hormone & IGF Research, Vol. 8, 1998, pp. 89-92.
“Consensus Guidelines for the Diagnosis and Treatment of Adults with Growth Hormone Deficiency: Summary Statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency,” The Journal of Clinical Endocrinology & Metabolism, Vol. 83, No. 2, 1998, pp. 379-381. doi:10.1210/jc.83.2.379
R. C. Cuneo, et al., “Cardiovascular Effects of Growth Hormone Treatment in Growth-Hormone-Deficient Adults: Stimulation of the Renin-Aldosterone System,” Clinical Science, Vol. 81, No. 5, 1991, pp. 587-592.
H. M. Whitehead, et al., “Growth Hormone Treatment of Adults with Growth Hormone Deficiency: Results of a 13-Month Placebo Controlled Cross-Over Study,” Clinical Endocrinology, Vol. 36, No. 1, 1992, pp. 45-52. doi:10.1111/j.1365-2265.1992.tb02901.x
R. C. Cuneo, et al., “Growth Hormone Treatment Improves Serum Lipids and Lipoproteins in Adults with Growth Hormone Deficiency,” Metabolism, Vol. 42, No. 12, 1993, pp. 1519-1523. doi:10.1016/0026-0495(93)90145-E
D. L. Russell-Jones, et al., “The Effects of Growth Hormone on Protein Metabolism in Adult Growth Hormone Deficient Patients,” Clinical Endocrinology, Vol. 38, No. 4, 1993, pp. 427-431. doi:10.1111/j.1365-2265.1993.tb00525.x
S. A. Beshyah, et al., “Cardiovascular Effects of Growth Hormone Replacement Therapy in Hypopituitary Adults,” European Journal of Endocrinology, Vol. 130, No. 5, 1994, pp. 451-458. doi:10.1530/eje.0.1300451
D. L. Russell-Jones, et al., “The Effect of Growth Hormone Replacement on Serum Lipids, Lipoproteins, Apolipoproteins and Cholesterol Precursors in Adult Growth Hormone Deficient Patients,” Clinical Endocrinology, Vol. 41, No. 3, 1994, pp. 345-350. doi:10.1111/j.1365-2265.1994.tb02555.x
S. A. Beshyah, et al., “The Effects of Short and Long-Term Growth Hormone Replacement Therapy in Hypopituitary Adults on Lipid Metabolism and Carbohydrate Tolerance,” The Journal of Clinical Endocrinology & Metabolism, Vol. 80, No. 2, 1995, pp. 356-363. doi:10.1210/jc.80.2.356
R. Nass, et al., “Effect of Growth Hormone (hGH) Replacement Therapy on Physical Work Capacity and Cardiac and Pulmonary Function in Patients with hGH Deficiency Acquired in Adulthood,” The Journal of Clinical Endocrinology & Metabolism, Vol. 80, No. 2, 1995, pp. 552-557. doi:10.1210/jc.80.2.552
R. Valcavi, et al., “Cardiac Performance and Mass in Adults with Hypopituitarism: Effects of One Year of Growth Hormone Treatment,” The Journal of Clinical Endocrinology & Metabolism, Vol. 80, No. 2, 1995, pp. 659-666. doi:10.1210/jc.80.2.659
R. H. Boger, et al., “Nitric Oxide May Mediate the Hemodynamic Effects of Recombinant Growth Hormone in Patients with Acquired Growth Hormone Deficiency. A Double-Blind, Placebo-Controlled Study,” Journal of Clinical Investigation, Vol. 98, No. 12, 1996, pp. 2706-2713. doi:10.1172/JCI119095
J. J. Chipman, et al., “The Safety Profile of GH Replacement Therapy in Adults,” Clinical Endocrinology, Vol. 46, No. 4, 1997, pp. 473-481. doi:10.1046/j.1365-2265.1997.1660984.x
E. R. Christ, et al., “The Importance of Growth Hormone in the Regulation of Erythropoiesis, Red Cell Mass, and Plasma Volume in Adults with Growth Hormone Deficiency,” The Journal of Clinical Endocrinology & Metabolism, Vol. 82, No. 9, 1997, pp. 2985-2990. doi:10.1210/jc.82.9.2985
C. M. Hwu, et al., “Growth Hormone (GH) Replacement Reduces Total Body Fat and Normalizes Insulin Sensitivity in GH-Deficient Adults: A Report of One-Year Clinical Experience. The Journal of Clinical Endocrinology & Metabolism, Vol. 82, No. 01, 1997, pp. 3285-3292. doi:10.1210/jc.82.10.3285
W. Nolte, et al., “The Effect of Recombinant Human GH Replacement Therapy on Lipoprotein(a) and Other Lipid Parameters in Adults with Acquired GH Deficiency: Results of a Double-Blind and Placebo-Controlled Trial,” European Journal of Endocrinology, Vol. 137, No. 5, 1997, pp. 459-466. doi:10.1530/eje.0.1370459
J. M. Webster, et al., “The Effect of Growth Hormone Replacement Therapy for Up to 12 Months on Lipoprotein Composition and Lipoprotein(a) in Growth Hormone-Deficient Adults,” Atherosclerosis, Vol. 133, No. 1, 1997, pp. 115-121. doi:10.1016/S0021-9150(97)00110-X
R. C. Cuneo, et al., “The Australian Multicenter Trial of Growth Hormone (GH) Treatment in GH-Deficient Adults,” The Journal of Clinical Endocrinology & Metabolism, Vol. 83, No. 1, 1998, pp. 107-116. doi:10.1210/jc.83.1.107
G. P. Leese, et al., “HDL-Cholesterol Reductions Associated with Adult Growth Hormone Replacement,” Clinical Endocrinology, Vol. 49, No. 5, 1998, pp. 673-677. doi:10.1046/j.1365-2265.1998.00597.x
D. L. Russell-Jones, et al., “Effect of Growth Hormone Treatment on Postprandial Protein Metabolism in Growth Hormone-Deficient Adults,” American Journal of Physiology, Vol. 274, 1998, pp. 1050-1056.
N. Vahl, et al., “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,” International Journal of Obesity, Vol. 22, No. 6, 1998, pp. 529-536. doi:10.1038/sj.ijo.0800618
W. Bell, et al., “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,” Annals of Human Biology, Vol. 26, No. 1, 1999, pp. 63-78. doi:10.1080/030144699282985
E. R. Christ, et al., “Effects of Growth Hormone (GH) Replacement Therapy on Very Low Density Lipoprotein Apolipoprotein B100 Kinetics in Patients with Adult GH Deficiency: A Stable Isotope Study,” The Journal of Clinical Endocrinology & Metabolism, Vol. 84, No. 1, 1999, pp. 307-316. doi:10.1210/jc.84.1.307
E. R. Christ, et al., “Growth Hormone (GH) Replacement Therapy Reduces Serum Sialic Acid Concentrations in Adults with GH-Deficiency: A Double-Blind Placebo- Controlled Study,” Clinical Endocrinology, Vol. 51, No. 2, 1999, pp. 173-179. doi:10.1046/j.1365-2265.1999.00751.x
A. M. Rosenfalck, et al., “The Effect of the Deterioration of Insulin Sensitivity on Beta-Cell Function in Growth-Hormone-Deficient Adults Following 4-Month Growth Hormone Replacement Therapy,” Growth Hormone & IGF Research, Vol. 9, No. 2, 1999, pp. 96-105. doi:10.1054/ghir.1999.0091
R. Fernholm, et al., “Growth Hormone Replacement Therapy Improves Body Composition and Increases Bone Metabolism in Elderly Patients with Pituitary Disease,” The Journal of Clinical Endocrinology & Metabolism, Vol. 85, No. 11, 2000, pp. 4104-4112. doi:10.1210/jc.85.11.4104
G. Sesmilo, et al., “Effects of Growth Hormone Administration on Inflammatory and Other Cardiovascular Risk Markers in Men with Growth Hormone Deficiency. A Randomized, Controlled Clinical Trial,” Annals of Internal Medicine, Vol. 133, No. 2, 18 2000, pp. 111-122.
S. Ezzat, et al., “Gender-Specific Responses of Lean Body Composition and Non-Gender-Specific Cardiac Function Improvement after GH Replacement in GH-Deficient Adults,” The Journal of Clinical Endocrinology & Metabolism, Vol. 87, No. 6, 2002, pp. 2725-2733. doi:10.1210/jc.87.6.2725
J. C. Smith, et al., “Effects of GH Replacement on Endothelial Function and Large-Artery Stiffness in GH-Deficient Adults: A Randomized, Double-Blind, Placebo- Controlled Study,” Clinical Endocrinology, Vol. 56, No. 4, 2002, pp. 493-501. doi:10.1046/j.1365-2265.2002.01514.x
S. B. Sneppen, et al., “Cardiac Effects of Low-Dose Growth Hormone Replacement Therapy in Growth Hormone-Deficient Adults. An 18-Month Randomised, Placebo-Controlled, Double-Blind Study,” Hormone Research, Vol. 58, No. 1, 2002, pp. 21-29.
M. Bramnert, et al., “Growth Hormone Replacement Therapy Induces Insulin Resistance by Activating the Glucose-Fatty Acid Cycle,” The Journal of Clinical Endocrinology & Metabolism, Vol. 88, No. 4, 2003, pp. 1455-1463. doi:10.1210/jc.2002-020542
W. Bell, et al., “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,” American Journal of Human Biology, Vol. 16, No. 5, 2004, pp. 533-543. doi:10.1002/ajhb.20055
K. Chihara, et al., “Adult GH Deficiency in Japanese Patients: Effects of GH Treatment in a Randomised, Placebo-Controlled Trial,” European Journal of Endocrinology, Vol. 151, No. 3, 2004, pp. 343-350. doi:10.1530/eje.0.1510343
E. R. Christ, et al., “Effects of Growth Hormone (GH) Replacement Therapy on Low-Density Lipoprotein Apo- lipoprotein B100 kinetics in Adult Patients with GH Deficiency: A Stable Isotope Study,” The Journal of Clinical Endocrinology & Metabolism, Vol. 89, No. 4, 2004, pp. 1801-1807. doi:10.1210/jc.2003-031474
T. Elgzyri, et al., “The Effects of GH Replacement Therapy on Cardiac Morphology and Function, Exercise Capacity and Serum Lipids in Elderly Patients with GH Deficiency,” Clinical Endocrinology, Vol. 61, No. 1, 2004, pp. 113-122. doi:10.1111/j.1365-2265.2004.02080.x
A. R. Hoffman, et al., “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,” The Journal of Clinical Endocrinology & Metabolism, Vol. 89, No. 5, 2004, pp. 2048-2056. doi:10.1210/jc.2003-030346
J. Bollerslev, et al., “Positive Effects of a Physiological Dose of GH on Markers of Atherogenesis: A Placebo-Controlled Study in Patients with Adult-Onset GH Deficiency,” European Journal of Endocrinology, Vol. 154, No. 4, 2006, pp. 537-543. doi:10.1530/eje.1.02125
K. Chihara, et al., “Efficacy and safety of Growth Hormone (GH) in the Treatment of Adult Japanese Patients with GH Deficiency: A Randomised, Placebo-Controlled Study,” Growth Hormone & IGF Research, Vol. 16, No. 2, 2006, pp. 132-142. doi:10.1016/j.ghir.2006.03.012
C. Beauregard, et al., “Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study,” The Journal of Clinical Endocrinology & Metabolism, Vol. 93, No. 6, 2008, pp. 2063-2071. doi:10.1210/jc.2007-2371
K. Chihara, et al., “Efficacy and Safety of Individualized Growth Hormone Treatment in Adult Japanese Patients with Growth Hormone Deficiency,” Growth Hormone & IGF Research, Vol. 18, No. 5, 2008, pp. 394-403. doi:10.1016/j.ghir.2008.02.002
A. Cittadini, et al., “Growth Hormone Deficiency in Patients with Chronic Heart Failure and Beneficial Effects of Its Correction,” The Journal of Clinical Endocrinology & Metabolism, Vol. 94, No. 9, 2009, pp. 3329-3336. doi:10.1210/jc.2009-0533
K. Chihara, et al., “Dose-Dependent Changes in Body Composition during Growth Hormone (GH) Treatment in Japanese Patients with Adult GH Deficiency: A Randomized, Placebo-Controlled Trial,” Growth Hormone & IGF Research, Vol. 20, No. 3, 2010, pp. 205-211. doi:10.1016/j.ghir.2010.01.003
P. Dutta, et al., “Effects of short Term Growth Hormone Therapy in Adult Growth Hormone Deficiency,” Journal of the Association of Physicians of India, Vol. 58, 2010, pp. 670-673.
K. K. Miller, et al., “Growth Hormone Deficiency after Treatment of Acromegaly: A Randomized, Placebo-Controlled Study of Growth Hormone Replacement,” The Journal of Clinical Endocrinology & Metabolism, Vol. 95, No. 2, 2010, pp. 567-577. doi:10.1210/jc.2009-1611
C. B. Newman, et al., “Moderate Doses of hGH (0.64 mg/d) Improve Lipids But Not Cardiovascular Function in GH-Deficient Adults with Normal Baseline Cardiac Function,” The Journal of Clinical Endocrinology & Metabolism, Vol. 96, No. 1, 2011, pp. 122-132. doi:10.1210/jc.2010-1204
C. M. Florkowski, et al., “Low-Dose Growth Hormone Replacement Lowers Plasma Leptin and Fat Stores without Affecting Body Mass Index in Adults with Growth Hormone Deficiency,” Clinical Endocrinology, Vol. 45, No. 6, 1996, pp. 769-773. doi:10.1046/j.1365-2265.1996.830895.x
S. A. Beshyah, et al., “Replacement Treatment with Biosynthetic Human Growth Hormone in Growth Hormone-Deficient Hypopituitary Adults,” Clinical Endocrinology, Vol. 42, No. 1, 1995, pp. 73-84. doi:10.1111/j.1365-2265.1995.tb02601.x
G. Johannsson, et al., “The Individual Responsiveness to Growth Hormone (GH) Treatment in GH-Deficient Adults Is Dependent on the Level of GH-Binding Protein, Body Mass Index, Age, and Gender,” The Journal of Clinical Endocrinology & Metabolism, Vol. 81, No. 4, 1996, pp. 1575-1581. doi:10.1210/jc.81.4.1575
Y. E. Snel, et al., “Energy and Macronutrient Intake in Growth Hormone-Deficient Adults: The Effect of Growth Hormone Replacement,” European Journal of Clinical Nutrition, Vol. 49, No. 7, 1995, pp. 492-500.
J. Mesa, et al., “Growth Hormone Deficiency in Adults: Effects of Replacement Therapy on Body Composition and Health-Related Quality of Life,” Medicina Clínica, Vol. 120, No. 2, 2003, pp. 41-46. doi:10.1157/13042257
L. V. Hedges, “Distribution Theory for Glass’s Estimator of Effect Size and Related Estimators,” Journal of Educational and Behavioral Statistics, Vol. 6, 1981, pp. 107-128. doi:10.3102/10769986006002107
W. Cochran, “The Combination of Estimates from Different Experiments,” Biometrics, Vol. 10, 1954, pp. 110- 129. doi:10.2307/3001666
L. Sacca, “Heart Failure as a Multiple Hormonal Deficiency Syndrome,” Circulation: Heart Failure, Vol. 2, No. 3, 2009, pp. 151-156. doi:10.1161/CIRCHEARTFAILURE.108.821892
T. Rosen, et al., “Premature Mortality Due to Cardiovascular Disease in Hypopituitarism,” The Lancet, Vol. 336, No. 8710, 1990, pp. 285-288. doi:10.1016/0140-6736(90)91812-O
W. S. Cutfield, et al., “Incidence of Diabetes Mellitus and Impaired Glucose Tolerance in Children and Adolescents Receiving Growth-Hormone Treatment,” The Lancet, Vol. 355, No. 9240, 2000, pp. 610-613. doi:10.1016/S0140-6736(99)04055-6
S. Achar, et al., “Cardiac and Metabolic Effects of Anabolic-Androgenic Steroid Abuse on Lipids, Blood Pressure, Left Ventricular Dimensions, and Rhythm,” American Journal of Cardiology, Vol. 106, No. 6, 2010, pp. 893-901. doi:10.1016/j.amjcard.2010.05.013
A. Juul, et al., “Effects of Growth Hormone Replacement Therapy on IGF-Related Parameters and on the Pituitary-Gonadal Axis in GH-Deficient Males. A Double-Blind, Placebo-Controlled Crossover Study,” Hormone Research, Vol. 49, No. 6, 1998, pp. 269-278. doi:10.1159/000023186
F. Darendeliler, et al., “Growth Hormone Increases Rate of Pubertal Maturation,” Acta Endocrinologica, Vol. 122, No. 3, 1990, pp. 414-416.
V. Y. Hayes, et al., “Recombinant Human Growth Hormone and Recombinant Human Insulin-Like Growth Factor I Diminish the Catabolic Effects of Hypogonadism in Man: Metabolic and Molecular Effects,” The Journal of Clinical Endocrinology & Metabolism, Vol. 86, No. 5, 2001, pp. 2211-2219. doi:10.1210/jc.86.5.2211
E. R. Christ, et al., “Dynamics of Lipoprotein Metabolism in Adult Growth Hormone Deficiency,” Journal of Endocrinological Investigation, Vol. 22, No. 5, 1999, pp. 16-21.
A. F. Attanasio, et al., “Prevalence of Metabolic Syndrome in Adult Hypopituitary Growth Hormone (GH)-Deficient Patients before and after GH Replacement,” The Journal of Clinical Endocrinology & Metabolism, Vol. 95, No. 1, 2010, pp. 74-81. doi:10.1210/jc.2009-1326
M. C. Cenci, et al., “Effects of 5 Years of Growth Hormone (GH) Replacement Therapy on Cardiac Parameters and Physical Performance in Adults with GH Deficiency,” Pituitary, Vol. 12, No. 4, 2009, pp. 322-329. doi:10.1007/s11102-009-0182-2
G. Sesmilo, et al., “Cardiovascular Risk Factors in Acromegaly before and after Normalization of Serum IGF-I Levels with the GH Antagonist Pegvisomant,” The Journal of Clinical Endocrinology & Metabolism, Vol. 87, No. 4, 2002, pp. 1692-1699. doi:10.1210/jc.87.4.1692
K. Caidahl, et al., “Cardiovascular and Renal Effects of Growth Hormone,” Clinical Endocrinology, Vol. 40, No. 3, 1994, pp. 393-400. doi:10.1111/j.1365-2265.1994.tb03937.x
R. C. Cuneo, et al., “Growth Hormone Treatment in Growth Hormone-Deficient Adults. II. Effects on Exercise Performance,” Journal of Applied Physiology, Vol. 70, No. 2, 1991, pp. 695-700.
J. L. Oliveira, et al., “Congenital Growth Hormone (GH) Deficiency and Atherosclerosis: Effects of GH Replacement in GH-Naive Adults,” The Journal of Clinical Endocrinology & Metabolism, Vol. 92, No. 12, 2007, pp. 4664-4670. doi:10.1210/jc.2007-1636
D. N. O’Neal, et al., “The Effect of 3 Months of Recombinant Human Growth Hormone (GH) Therapy on Insulin and Glucose-Mediated Glucose Disposal and Insulin Secretion in GH-Deficient Adults: A Minimal Model Analysis,” The Journal of Clinical Endocrinology & Metabolism, Vol. 79, No. 4, 1994, pp. 975-983. doi:10.1210/jc.79.4.975
J. U. Weaver, et al., “The Effect of Low Dose Recombinant Human Growth Hormone Replacement on Regional Fat Distribution, Insulin Sensitivity, and Cardiovascular Risk Factors in Hypopituitary Adults,” The Journal of Clinical Endocrinology & Metabolism, Vol. 80, No. 1, 1995, pp. 153-159. doi:10.1210/jc.80.1.153
J. O. Johansson, et al., “Growth Hormone-Deficient Adults Are Insulin-Resistant,” Metabolism, Vol. 44, No. 9, 1995, pp. 1126-1129. doi:10.1016/0026-0495(95)90004-7
A. F. Attanasio, et al., “Prevalence and Incidence of Diabetes Mellitus in Adult Patients on Growth Hormone Replacement for Growth Hormone Deficiency: A Surveillance Database Analysis,” The Journal of Clinical Endocrinology & Metabolism, Vol. 96, No. 7, 2011, pp. 2255-2261. doi:10.1210/jc.2011-0448
S. Neidert, et al., “Anterior Pituitary Axis Hormones and Outcome in Acute Ischaemic Stroke,” Journal of Internal Medicine, Vol. 269, No. 4, 2011, pp. 420-432. doi:10.1111/j.1365-2796.2010.02327.x
A. Selvamani, et al., “The Neurotoxic Effects of Estrogen on Ischemic Stroke in Older Female Rats Is Associated with Age-Dependent Loss of Insulin-Like Growth Factor-1,” The Journal of Neuroscience, Vol. 30, No. 20, 2010, pp. 6852-6861. doi:10.1523/JNEUROSCI.0761-10.2010
F. Pinto, et al., “Doping and Urologic Tumors,” Urologia, Vol. 77, No. 2, 2010, pp. 92-99.
C. A. Lissett, et al., “Timing of Onset of Growth Hormone Deficiency Is a Major Influence on Insulin-Like Growth Factor I Status in Adult Life,” Clinical Endocrinology, Vol. 57, No. 1, 2002, pp. 35-40. doi:10.1046/j.1365-2265.2002.01556.x
R. D. Murray, et al., “Influences on Quality of Life in GH Deficient Adults and Their Effect on Response to Treatment,” Clinical Endocrinology, Vol. 51, No. 5, 1999, pp. 565-573. doi:10.1046/j.1365-2265.1999.00838.x