Relative values of recombinant growth hormone and growth hormone secretagogues in clinical practice

摘要

Empirical and scientific evidence suggest that functional deterioration of tissues and organs during aging is causally related, at least in part to decrements in anabolic hormones and/or their activities. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) are examples of potent anabolic hormones with ubiquitous effects. Their circulating concentrations decrease in parallel with progressive senescence of the mind and body. This relationship may have some degree of causality because in a landmark clinical trial, hGH administration to elderly men changed their body composition to a more youthful type. Basically, lean body mass increased and abdominal fat decreased. These observations were sensationalized by the media; consequently, a market in hGH replacement for aging arose as the cornerstone of a larger field of "anti-aging" medicine that grew logarithmically during the 1990s. Although efficacy and safety of GH administration to healthy adults as a means to oppose the progressive physical and mental deterioration of aging has not been proven, the hormone is widely prescribed for this "off label" use. The objective of increasing GH and IGF-1 can be achieved pharmacologically by two means, including administration of exogenous, synthetic hormone or by stimulating endogenous production and secretion of GH from the pituitary gland. Thus, the purpose of this article is to review the basis for using hGH "replacement" therapy in aging and also to compare the relative benefits of achieving this objective by administration of exogenous hGH or GH secretagogues. Other than the landmark report of hGH effects on body composition that was published in 1990, most support for hGH administration to aging adults as a means to sustain health and vitality is extrapolated from data in which younger adults with pathologic growth hormone deficiency (GHD) were administered hGH replacement. Before treatment, these individuals experienced higher than normal incidences of morbidity and mortality. Furthermore, the intrinsic diseases that they experienced were similar to those in the elderly, but they occurred at younger ages than are typically expected. The hGH replacement relieved these problems. However, unlike aging individuals, the pituitary glands of GHD individuals are incapable of producing and secreting GH. Thus, administration of exogenous GH is the only practical means to treat them. In contrast, the pituitaries of aging individuals remain responsive to stimulation by GH secretagogues. Also, factors contributing to the age-related decrease in GH secretion are, for the most part, extrapituitary. Because of these facts, GH secretagogues could provide an alternative to exogenous hormone administration and potentially be used instead of hGH to increase endogenous GH secretion in aging. Such application could have the practical advantage of providing a means to test the hypothesis that a functional decrease in GH neurosecretory activity contributes to senescence.