Is the somatopause an indication for growth hormone replacement?
In the normal population, a gradual and progressive fall in spontaneous growth hormone (GH) secretion occurs with increasing age and is reflected in a parallel fall in circulating insulin-like growth factor (IGF)-I, reduction in lean body mass, increase in body fat and rise in low-density lipoprotein (LDL) cholesterol. Aging is also associated with a progressive failure of body functions and particularly with an increasing lack of physical strength and mobility. Many problems of aging are attributable to the progressive loss of lean tissues and to catabolic events. This can be and often is associated with a progressive decline in independence and quality of life, leading eventually to a prolonged dependence on others, followed by a distressing process of death. By analogy with the fall in ovarian function that inevitably eventually occurs in women with increasing age, this fall in GH secretion has been termed the somatopause. In cross-sectional studies on elderly people, the amount of GH secreted spontaneously correlates well with "good risk factors" such as body composition, mobility, lipid profiles and blood pressure. The important question that these scientific facts raises is whether this fall in GH secretion with increasing years is an important physiological safety event of the normal aging process, or whether it marks the development of GH deficiency which would benefit from GH replacement. It is established that a number of the clinical features of the somatopause are shared with the syndrome of adult-onset GH deficiency and Rudman first proposed the importance of GH in maintaining health and vitality with increasing age many years ago. In 1989, GH replacement was shown to be beneficial in adults with GH deficiency, and in 1990 Rudman showed remarkably similar beneficial effects in a group of elderly men with low plasma IGF-I values, but no underlying pituitary pathology, who were administered GH. In these adults, low doses of GH increased lean body mass and bone mineral density, decreased body fat and lowered LDL cholesterol. Sleep and exercise are the two major stimuli for secretion of GH in normal people and there is evidence to indicate that the GH response to exercise is essential for developing and maintaining physical fitness. There is also some evidence to suggest that adults who continue to exercise with increasing age better maintain lean body mass and physiological GH secretion. So, is the somatopause due to lifestyle changes consequent upon indolence, too much TV and modern living? Is it better to chase our patients (and colleagues?) down to the gym three times a week or should we give them an injection of GH before they sit down with a can of lager to watch the World Cup? Should the fact that elite athletes in virtually all sports have decided from their own "clinical trials" that GH is a performance-enhancing drug, when combined with exercise, have any influence on our strategy? The long-term safety of GH replacement is clearly a matter for concern but we do now know that life without GH is poor both in quantity and quality. Is there a safe therapeutic window that allows GH replacement in the somatopause to add years to life, quality to these years, and maybe even improves the quality of death?
Savine
R
R
Department of Endocrinology, Guy's, King's and St Thomas' School of Medicine, King's College, and St Thomas' Hospital, London, UK.
Sönksen
P H
PH
D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D005260:Female; D016330:Frail Elderly; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use; D012636:Secretory Rate; D013577:Syndrome
D011994:Recombinant Proteins; D019382:Human Growth Hormone