Growth Hormone – Hormone Replacement for the Somatopause?

Abstract

Twenty-four-hour growth hormone (GH) secretion reaches a peak at around puberty and by the age of 21 has begun to decrease. Thereafter the fall in GH secretion is progressive such that by the age of 60 most adults have total 24-hour secretion rates indistinguishable from those of hypopituitary patients with organic lesions in the pituitary gland. Patterns of GH secretion are similar to those in younger people but GH pulses are markedly reduced in amplitude. Sleep and exercise remain the major stimuli for GH secretion. The fall in GH secretion seen with ageing coincides with changes in body composition and lipid metabolism that are similar to those seen in adults with GH deficiency. In elderly subjects, although GH secretion is markedly reduced, remaining GH secretion correlates closely with body composition (particularly with lean body mass and inversely with central abdominal fat). Pioneering studies carried out by Rudman showed that GH administration to elderly subjects with low insulin-like growth factor-I levels resulted in reversal of many of the changes associated with GH deficiency, namely an increase in lean body mass and bone mineral density and a reduction in body fat and plasma cholesterol. These changes were remarkably similar to those shown a year earlier in adults with GH deficiency given GH replacement. Subsequent studies of GH replacement in elderly adults have confirmed Rudman’s initial observations but have been dominated by side effects which have led to a high number of dropouts. It is now clear that the elderly are very sensitive to GH and the doses used need to be very low, increased very slowly and tailored to the individual needs of each patient. Using this more cautious approach, recent studies have been very positive. A series of papers from Blackman’s group, presented at the US endocrine meeting in San Diego in 1999, investigated the effects of GH with or without testosterone supplements (in men) and oestrogen supplements (in women). Their results showed positive effects of GH on lean body mass, central fat, low-density lipoprotein cholesterol and aerobic capacity. In many instances there was a positive interaction between GH and hormone replacement with testosterone and oestrogen, but it appeared that GH showed the most potent anabolic effects. Clearly more studies are needed before GH replacement for the elderly becomes established. Safety issues will require close scrutiny, but the data available so far are sufficiently positive to undertake large multicentre, placebo-controlled trials, particularly looking at endpoints associated with prevention of frailty and loss of independence.

Growth Hormone Receptors in the Brain and their Potential as Therapeutic Targets in Central Nervous System Disorders

“…These behaviors include the GH effects on sleep, appetite, cognitive and memory processes as well as neuroprotective effects but also effects on pain processing pathways [7]. Most of these effects of the hormone have been confirmed by studies carried out in vitro, using various types of cells, and by studies in vivo, with a variety of experimental animal models, as well as clinical studies in humans [17,[42][43][44][45][46]. Also, in this context it is essential to consider the well-known age-related reduction in the expression and activity of the GH/IGF-1 axis [10,47].…”

Growth hormone therapy and Quality of Life: possibilities, pitfalls and mechanisms

“…By the age of 60, secretion rates over a 24-h period are often indistinguishable from those of younger hypopituitary patients (Savine & Sonksen 2000). It has been suggested that this age-related decline in somatotropic function may, like AOGHD, impact QoL, since many elderly show symptoms of GHD such as muscle atrophy, central obesity, sleep disturbances, and depression (Cummings & Merriam 1999).…”

“…This increased susceptibility reflects enhanced GH responsiveness, since the elderly require a lower dose than younger patients to induce a similar IGF-I response (Toogood & Shalet 1999). The careful titration of GH dosage to normalize IGF-I levels is therefore extremely important in the elderly in order to avoid adverse side-effects (Savine & Sonksen 2000).…”

Can Growth Hormone (GH) Accelerate Aging? Evidence from GH-Transgenic Mice

“…This was based primarily on the evidence that GH-Tg mice exhibit various histopathological lesions, including early onset of severe glomerulonephritis that could explain their reduced life span [10, 16], and that the reduced life expectancy of acromegalic patients is due to an increased incidence of cardiovascular disease, diabetes, and cancer without clear evidence for alterations in aging per se [17, 18]. Moreover, the possibility that GH may accelerate aging seemed counterintuitive in view of the well-documented decline in GH release during aging [19, 20, 21], the similarity of some of the symptoms of aging to symptoms of adult GH deficiency [22], and reports of ‘anti-aging’ effects of GH therapy in the elderly [23, 24]and in experimental animals [25]. However, various recent findings suggest that the issue of the potential ability of GH to accelerate aging should be revisited.…”