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If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. Reprints and Permissions. Bian, A. Association between sarcopenia and levels of growth hormone and insulin-like growth factor-1 in the elderly.
BMC Musculoskelet Disord 21, Download citation. Received : 04 November Accepted : 25 March Published : 07 April Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Abstract Background Age-related sarcopenia is a serious global health issue in elderly individuals and for the community as it induces disability and significant economic burden.
Background Sarcopenia is an important global public health issue in the elderly due to the serious physical and psychological problems induced by this disease.
Patient and public involvement The study design was motivated by the elderly patients having to cope with sarcopenia and the subsequent lower quality of life.
Results A total of elderly participants, including males and females, were enrolled in this study. The frequency of sarcopenia According to the diagnostic criteria of the AWGS for sarcopenia, the frequency of sarcopenia in the study population was Moreover, observations of GH-deficient children 33 , 83 and, more recently, adults 33 , 46 treated with rhGH have not revealed any increase in the incidence of neoplasia.
Of note, however, are several epidemiologic studies in which higher endogenous levels of circulating IGF-I preceded increased incidence rates of prostate 54 , 55 , breast 53 , and colon 56 , 57 cancers. The above data remain associative and equivocal, with no clear evidence of a causal link, although basic studies have provided plausible mechanisms by which IGF-I could accelerate the growth of malignant cells 84 , To date, no prospective, placebo-controlled trials large enough to clearly define the risk of neoplasia have been completed for rhGH replacement in elderly people.
Thus, this risk remains a legitimate concern, but one that is largely theoretical and unproved. The authors' trial was too small and of insufficient duration to elucidate the cancer question.
Also of theoretical concern is the potential for stimulation by rhGH, of benign prostatic hyperplasia BPH In our study, use of a structured standardized questionnaire 87 revealed no evidence of worsening of BPH symptoms in any of the active hormone groups, and mean serum prostate-specific antigen levels decreased slightly, but significantly, in the GH-treated men and were unchanged in the other groups.
Several studies have reported that rhGH treatment increased the frequencies of headaches in adult GHD patients and of benign intracranial hypertension with papilledema in children 88 , In the authors' study, there was not a significant increase in headache symptoms in the rhGH-treated participants, nor were changes detected in the optic fundi during monthly opthalmoscopic examinations. Gynecomastia due to conversion of T to estrogens is a known complication of T treatment 90 , but has also been reported in rhGH-treated men A final concern with regard to rhGH therapy in humans is the theoretical, but intriguing, possibility that it may actually accelerate, rather than retard, the aging process Observations of mice transgenic for overexpression of GH have shown a shortened life span and a number of physiologic and anatomic changes suggestive of accelerated aging 92 , Consistent with the latter observation, dwarf mice with a genetic deficiency of either pituitary GH secretion 94 or GH receptors 95 have a prolonged life span, compared with their wild-type counterparts.
Another possible mechanism is suggested by the finding that DNA damage to human peripheral blood lymphocytes in vitro by bleomycin oxidative stress is amplified by GH and IGF-I upregulation of p53 protein expression In contrast to these observations in rodents is the observation that pathologic GH deficiency in humans is associated with increased mortality Whether rhGH supplementation in elderly people will promote anti-aging or pro-aging effects may be better answered by future clinical studies in which restoration of GH and IGF-I homeostasis is achieved by more physiologic treatment paradigms, such as the use of GH secretagogues.
Although most adverse effects of rhGH treatment appear to be dose dependent, it is unknown whether, and to what extent, use of lower doses of rhGH would eliminate or reduce beneficial effects. In studies in older men reported in an abstract , few or no adverse effects of low-dose rhGH and an additive effect of T to rhGH similar to that reported in our study 58 were observed.
However, middle-aged and older adult participants in the studies using lower doses of rhGH generally demonstrated smaller improvements in body composition and no data regarding physical or psychologic function fitness, strength, improved activities of daily living, quality of life were reported. Furthermore, because soft tissue adverse effects are seldom observed in children or young adults treated with relatively high doses of rhGH 33 , it is likely that aging increases susceptibility to these adverse effects, a conclusion also suggested by previous investigators The clinical usefulness of any therapeutic intervention depends in part on the relationship of benefits to risks, which will depend on the population age, sex, type and severity of illness, and so forth in which it is assessed, the doses and regimen employed, the severity of adverse effects encountered, and other factors.
The possible use of hormone replacement therapies to reduce risks of age-related problems such as sarcopenia, osteoporosis, cardiovascular disease, dementia, or the combined loss of functions characteristic of frailty deserve special scrutiny in this regard. Moreover, rhGH injections have been prescribed for large numbers of middle-aged and older persons, despite the absence of Food and Drug Administration approval for this use and scant data regarding efficacy or long-term safety of rhGH treatment in this population.
In addition, a plethora of products alleged to increase endogenous GH secretion, but of uncertain efficacy, are being advertised to the general public. Shortly after the publication of the authors' report on GH and sex steroid effects in elderly people 58 , a counterresponse was published by the American Association of Anti-Aging Medicine A4M The latter claimed that prior studies of rhGH in adults have established the effectiveness and safety of rhGH to treat the somatopause in otherwise healthy persons.
They further asserted that the adverse effects observed in the authors' study were due to use of higher doses of rhGH than commonly employed by anti-aging medicine physicians, and that patients given lower doses maintain beneficial effects, while experiencing little or no adverse consequences of treatment.
The A4M document cited eight recently published research studies in support of their claims. Men administered rhGH gained an average of 8. Moreover, that study was discontinued after 1 year due to the accumulation of adverse events in the rhGH-treated men 43 , a fact not mentioned in the A4M critique. In the other seven studies cited by the A4M , — , patients had pituitary disease and positive criteria for adult GHD, with profound GH deficiency, in most cases, based on provocative testing with insulin, growth hormone-releasing hormone, glucagon, or arginine.
Such tests are generally not conducted by anti-aging medicine doctors nor are the criteria for rhGH treatment in most anti-aging clinics well defined. Second, the patients in the reports cited were mainly middle-aged mean of 44 to 51 years, depending on the study , whereas the participants in our study averaged To assert that conclusions based on results obtained in a younger hypopituitary patient population can be generalized to an older somatopausal population is potentially misleading.
In fact, in one of the studies cited, the results of treatment in a subset of adult GHD patients older than age 60, compared with younger groups, showed more frequent adverse effects and, importantly, smaller improvements in LBM and body fat mass, which beneficial changes failed to reach statistical significance The differences between adult GHD and the somatopause are important.
It is clear that the great majority of healthy people in their 40s and 50s, without pituitary disease, have physiologically reduced levels of GH secretion and circulating IGF-I that remain in the normal range, and distinctly higher than the corresponding levels in patients with adult GHD.
It is only in the mids to 70s that substantial numbers but not all of otherwise healthy people begin to exhibit significantly decreased levels of GH and IGF-I 1—6. Another issue is dose regimen. However, the doses shown to be effective in adult GHD patients in all but one of the studies cited ranged from 5 to Moreover, in the authors' trial, IGF-I levels were only restored to the normal youthful range and did not exceed the upper limits of normal.
In addition, in the majority of the cited reports, significant incidences of the same adverse effects fluid retention, joint pain, carpal tunnel, glucose intolerance, and diabetes reported by the authors in their study were also seen.
The single apparent exception to the above was an uncontrolled open-label trial in adult GHD patients in which rhGH doses from 1. In the authors' study, although both men and women given rhGH increased LBM and decreased fat mass, only the men treated with both rhGH and T demonstrated improvements in muscle strength and VO 2 max, and these were small changes unlikely to be of clinical significance.
We contend that such changes in body composition are, per se, only cosmetic however attractive they may be and cannot justify the use of rhGH unless accompanied by true physiologic and functional changes. Although rhGH administration has improved indices of QOL in some but not other studies of aged adult GHD patients, to date there are no reports of similar benefits in healthy somatopausal individuals.
Because of the absence of placebo controls in most of the studies cited by the A4M, a placebo effect cannot be discounted. Finally, there is a legitimate question with regard to serious adverse effects especially cancer occurring over the long term, which cannot be evaluated in studies of 2—3 years or less or conducted in relatively small numbers fewer than of patients. Thus, determination of the true efficacy, safety, and clinical utility of rhGH supplementation in healthy aged individuals will require successful, properly controlled studies of sufficient size and duration before claims of clinical efficacy for rhGH in elderly persons can be substantiated.
Given the above considerations, we conclude that, while rhGH treatment for middle-aged patients with proven pathological pituitary GH deficiency appears to be effective and safe, there is considerable reason for caution with regard to employing rhGH intervention as a means of reducing or delaying the effects of aging.
We thus recommend that, until such studies have been reported and an optimal regimen has been developed, treatment of healthy elderly men and women with rhGH, or agents that augment GH and IGF-I levels, should be confined to properly controlled research studies. Decision Editor: James R. Smith, PhD. Age-related changes in the twenty-four hour spontaneous secretion of growth hormone in normal individuals. J Clin Endocrinol Metab.
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