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Cited by 93Hormonal and reproductive studiesGrowth Hormone and Insulin-like Growth FactorsNutrition and Health in Aging

NEUROENDOCRINE AGING IN MEN

Anawalt, Bradley D., Merriam, George R.·2001·Endocrinology and Metabolism Clinics of North America
DOI 10.1016/s0889-8529(05)70206-1
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Abstract

Aging is accompanied by gradual but progressive reductions in the secretion of testosterone and growth hormone in men, and by alterations in body composition and functional capacity that, to some degree, undo the effects of puberty. Preventing or reversing these changes with the use of trophic factors, including androgens, growth hormone, and growth hormone secretagogues, is an appealing prospect, but documenting the effectiveness of these interventions and their benefits and risks has proven to be a difficult undertaking that is far from complete. Small-scale clinical studies have shown that it is practicable to boost growth hormone and IGF-1 levels for periods of up to 12 months, and testosterone for up to 36 months, to reverse at least some age-related changes in body composition. Information regarding the effects of these interventions on strength, exercise capacity, and the ability to perform activities of daily living is still sparse, and additional reports from recently completed or currently ongoing clinical trials will not provide sufficient data to make firm conclusions. From the limited information currently available, androgen supplementation may be of benefit in some men aged more than 65 years, particularly in men with low serum testosterone levels (< 2 ng/mL). In this group, supplemental androgen therapy would be expected to increase lean body mass, bone mass, and possibly strength. In older men with testosterone levels between 2 and 3.5 ng/mL, some benefit might result from androgen supplementation, but it is not yet clear whether the benefits outweigh the risks. For men in this category, one might consider a 6- to 12-month trial of therapy after a full discussion and explicit consent, followed by a reassessment of the value of ongoing treatment. The even more limited data on growth hormone or growth hormone secretagogue interventions in aging do not support their general clinical use in healthy older men. Growth hormone is much more expensive than testosterone and is not covered by insurance for off-label uses. Patients who persistently seek a trial of therapy should be encouraged to enroll in a study if one is locally available. All of the growth hormone studies reported to date have focused, generally for reasons of safety, on healthy and robust groups of older subjects, men in whom the need for intervention is least compelling and in whom the functional effects of treatment may be the most difficult to observe. Phase II studies of intermediate size and duration examining prefrail groups of elderly who are at greater risk for functional loss and who stand to benefit the most from either preventive or restorative interventions are underway but are limited to the intermediate outcomes of body composition, strength, and function. Trials designed to assess clinically relevant final outcomes, such as falls, fractures, and institutionalization, are of necessity large-scale, long-term, and expensive. Support for larger phase III studies of growth hormone is unlikely to be forthcoming until the phase II studies are completed and show further promise. A multicenter clinical trial of testosterone is currently being planned under the joint sponsorship of the National Institute on Aging, the Veterans Health Administration, and industry, aimed at assessing the effects of testosterone on the risk for falls and fractures. The results of this trial and other large clinical trials should help to better define the balance of benefits and risks of trophic factor intervention in normal older men.

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Authors
Anawalt, B. D., & Merriam, G. R.
Affiliations
University of Washington (US)
Venue
Endocrinology and Metabolism Clinics of North America
Publisher
Elsevier BV
Published
2001-09
Volume
30
Issue
3
Pages
647-669
ISSN
0889-8529 (ISSN-L)
DOI
10.1016/s0889-8529(05)70206-1
OpenAlex
W151555449
Cited by
93
References
99
Citations by year
2026: 2 · 2025: 4 · 2024: 3 · 2023: 6 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 4
FWCI
0.99
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Endocrinology and Metabolism Clinics of North America (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01mh053575-05, 5r01ag010943-05)
  • National Institute on Aging (R01 AG 10943)
  • National Institute of Mental Health (R01 MH53575)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
neuroendocrine aging, male aging, testosterone, growth hormone, growth hormone secretagogues, androgen supplementation, insulin-like growth factor I, body composition, lean body mass, bone mass, strength, functional capacity, pre-frailty, older men, hormone replacement therapy, clinical trial design, off-label drug use, falls and fractures, institutionalization, cost-effectiveness, risk-benefit assessment
MeSH terms
Aging, Androgens, Humans, Male, Neurosecretory Systems, Growth Hormone, Human Growth Hormone, Hormone Replacement Therapy

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