Growth hormone (GH) secretion declines during normal aging, resulting in lower circulating levels of insulin-like growth factor (IGF-1). Although the physiologic sequelae to decreased somatotrope function are not fully understood, many of the catabolic changes seen in normal aging, including osteopenia, muscle atrophy, and decreased exercise tolerance, may in part be caused by the decreased action of the GH-IGF-I axis. The age-related decline in the activity of the hypothalamic-somatotrope-IGF axis may thus result in catabolic diathesis leading to falls, fractures, and frailty in the elderly, a syndrome complex which has been named """"""""the somatopause"""""""". Previous work has demonstrated that GH and IGF-I decrease fat mass, increase lean body mass and nitrogen retention, and promote whole body and skeletal muscle net protein synthesis. Both GH and high dose IGF-1 increase the birthrate of remodeling osteons. However, low-dose IGF-I may directly increase osteoblastic function without increasing bone resorption, and may therefore provide a useful means to increase bone mass. Moreover, IGF-I may have mood-enhancing effects in the elderly. In order to determine the effects of prolonged GH and IGF-I therapy and to understand the endocrine mechanisms underlying their physiologic effects, three independent investigations into the physiologic role of GH and IGF-I therapy in the somatopause are proposed. In these studies, a major emphasis will be placed on understanding the interactions of estrogen/progestin hormone replacement therapy (HRT) and treatment of the somatopause. Study 1 is a year long, double-blind, randomized, placebo-controlled trial which will explore the interactions of GH, IGF-I and estrogen/progestin therapy on body composition, muscular strength, and muscle growth factor synthesis. Study II will explore endocrine mechanisms underlying the effects of GH and IGF-I therapy on fluid compartments in detail. This experiment will build upon previous studies which unexpectedly demonstrated that both hormones cause dramatic shifts of water into the intracellular space. Study III is a short term study that will examine the role of GH and IGF-1 in protein and lipid metabolism to understand the anabolic action of these hormones in elderly women. This study will help provide a mechanistic basis for the finding obtained in Study I. These studies will provide the first investigation of the interactions of hormone replacement therapies for the somatopause (GH and IGF-I) and the menopause (estrogen and progestin) and will lead to novel pharmacologic approaches for the treatment of frailty in the elderly.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Braun, Barry; Friedlander, Anne L; Pollack, Margaret et al. (2003) Five weeks of insulin-like growth factor-I treatment does not alter glucose kinetics or insulin sensitivity during a hyperglycemic clamp in older women. Metabolism 52:1182-90
Ceda, G P; Dall'Aglio, E; Salimbeni, I et al. (2002) Pituitary function in chronic heart failure in the elderly. J Endocrinol Invest 25:24-8
Friedlander, A L; Butterfield, G E; Moynihan, S et al. (2001) One year of insulin-like growth factor I treatment does not affect bone density, body composition, or psychological measures in postmenopausal women. J Clin Endocrinol Metab 86:1496-503
Taaffe, D R; Thompson, J L; Butterfield, G E et al. (2001) Recombinant human growth hormone, but not insulin-like growth factor-I, enhances central fat loss in postmenopausal women undergoing a diet and exercise program. Horm Metab Res 33:156-62
Ceda, G P; Dall'Aglio, E; Magnacavallo, A et al. (1998) The insulin-like growth factor axis and plasma lipid levels in the elderly. J Clin Endocrinol Metab 83:499-502
Thompson, J L; Butterfield, G E; Gylfadottir, U K et al. (1998) Effects of human growth hormone, insulin-like growth factor I, and diet and exercise on body composition of obese postmenopausal women. J Clin Endocrinol Metab 83:1477-84
Hoffman, A R; Lieberman, S A; Butterfield, G et al. (1997) Functional consequences of the somatopause and its treatment. Endocrine 7:73-6
Butterfield, G E; Thompson, J; Rennie, M J et al. (1997) Effect of rhGH and rhIGF-I treatment on protein utilization in elderly women. Am J Physiol 272:E94-9
Lieberman, S A; Hoffman, A R (1997) The somatopause: should growth hormone deficiency in older people Be treated? Clin Geriatr Med 13:671-84
Taaffe, D R; Jin, I H; Vu, T H et al. (1996) Lack of effect of recombinant human growth hormone (GH) on muscle morphology and GH-insulin-like growth factor expression in resistance-trained elderly men. J Clin Endocrinol Metab 81:421-5

Showing the most recent 10 out of 16 publications