The anabolic hormones testosterone, IGF-1 and DHEA (a pre-hormone) are receiving more and more attention by health professionals because the anabolic-catabolic imbalance that favors catabolism is a key factor in accelerated physical deterioration aging.[1, 2] Anabolic impairment can speed up the age-related decline in muscle mass and physical performance, increase in fat mass, development of insulin resistance, cardiovascular risk factors, metabolic syndrome and diabetes, conditions that in turn affect mortality.[3-18]
Interestingly, low levels of multiple anabolic hormones, rather than a single one, has a stronger association with age related muscle loss and the frailty syndrome. [19, 20] In men with chronic heart failure, deficiency of more than one anabolic hormone identifies patients with higher mortality rates.
An interesting study sought to investigate the relationship between parallel deficiency of several anabolic hormones and mortality in a general population of older men, regardless of coexisting disease:
Testosterone, IGF-1, DHEA-S, and health parameters were evaluated in a representative sample of 410 men aged 65 years and older. A total of 126 men died during the 6-year follow-up.
Thresholds for lowest-quartile definitions were:
bioavailable testosterone 70 ng/dL or below
IGF-1 63.9 ng/mL or below
DHEA(S) 50 microg/dL or below
Men were divided into 4 groups: no hormone in the lowest quartile range (reference) and 1, 2, and 3 hormones in the lowest quartiles.
Compared with men with levels of all 3 hormones above the lowest quartiles, having 1, 2, and 3 hormones in the lowest quartile was associated with an increased risk of death by 47%, 85% and 229% respectively.
In the fully adjusted analysis, only men with 3 anabolic hormone deficiencies had a significant 244%, almost a 2.5-fold, increase in mortality.
This study shows that the risk of death increases progressively with the number of anabolic hormone deficiencies, and becomes close to 2.5 times higher when 3 anabolic hormones are in the low range, compared with no anabolic hormone in the low range. 
Independent of age and several confounding factors (obesity, inflammatory status, physical activity, caloric and alcohol intake, smoking, and pre-existing diseases), low circulating levels of the anabolic hormones testosterone, IGF-1, and DHEA(S) were an independent predictor of mortality during 6 years of follow-up in older men. On the contrary, blood levels of each of these hormones considered separately were much less associated with mortality.
Thus, the age-associated decline in anabolic hormone levels is a strong independent predictor of mortality in older men. Having multiple hormonal deficiencies rather than a deficiency in a single anabolic hormone, is a robust biomarker of health status and risk of death in older persons. This underscores the importance of monitoring and correcting all hormonal deficiencies, and not just focusing on a single hormone.
- Anker, S.D., et al., Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation, 1997. 96(2): p. 526-34.
- Debigare, R., et al., Catabolic/anabolic balance and muscle wasting in patients with COPD. Chest, 2003. 124(1): p. 83-9.
- Kelly, D.M. and T.H. Jones, Testosterone: a vascular hormone in health and disease. J Endocrinol, 2013. 217(3): p. R47-71.
- Kelly, D.M. and T.H. Jones, Testosterone: a metabolic hormone in health and disease. J Endocrinol, 2013. 217(3): p. R25-45.
- Stenholm, S., et al., Anabolic and catabolic biomarkers as predictors of muscle strength decline: the InCHIANTI study. Rejuvenation Res, 2010. 13(1): p. 3-11.
- O'Donnell, A.B., et al., Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab, 2006. 91(2): p. 425-31.
- Corona, G., et al., Testosterone, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab, 2011. 25(2): p. 337-53.
- Kovacheva, E.L., et al., Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways. Endocrinology, 2010. 151(2): p. 628-38.
- Dillon, E.L., et al., Hormone treatment and muscle anabolism during aging: androgens. Clin Nutr, 2010. 29(6): p. 697-700.
- Boyanov, M.A., Z. Boneva, and V.G. Christov, Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male, 2003. 6(1): p. 1-7.
- Bhasin, S., Testosterone supplementation for aging-associated sarcopenia. J Gerontol A Biol Sci Med Sci, 2003. 58(11): p. 1002-8.
- Kapoor, D., et al., Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol, 2006. 154(6): p. 899-906.
- Traish, A.M., et al., The dark side of testosterone deficiency: III. Cardiovascular disease. J Androl, 2009. 30(5): p. 477-94.
- Traish, A.M., F. Saad, and A. Guay, The dark side of testosterone deficiency: II. Type 2 diabetes and insulin resistance. J Androl, 2009. 30(1): p. 23-32.
- Traish, A.M., et al., The dark side of testosterone deficiency: I. Metabolic syndrome and erectile dysfunction. J Androl, 2009. 30(1): p. 10-22.
- Cappola, A.R., Q.L. Xue, and L.P. Fried, Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women's Health and Aging studies. J Gerontol A Biol Sci Med Sci, 2009. 64(2): p. 243-8.
- Anagnostis, P., et al., Clinical review: The pathogenetic role of cortisol in the metabolic syndrome: a hypothesis. J Clin Endocrinol Metab, 2009. 94(8): p. 2692-701.
- Bross, R., M. Javanbakht, and S. Bhasin, Anabolic interventions for aging-associated sarcopenia. J Clin Endocrinol Metab, 1999. 84(10): p. 3420-30.
- Leng, S.X., et al., Serum levels of insulin-like growth factor-I (IGF-I) and dehydroepiandrosterone sulfate (DHEA-S), and their relationships with serum interleukin-6, in the geriatric syndrome of frailty. Aging Clin Exp Res, 2004. 16(2): p. 153-7.
- Maggio, M., et al., The hormonal pathway to frailty in older men. J Endocrinol Invest, 2005. 28(11 Suppl Proceedings): p. 15-9.
- Jankowska, E.A., et al., Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation, 2006. 114(17): p. 1829-37.
- Maggio, M., et al., Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study. Arch Intern Med, 2007. 167(20): p. 2249-54.
Medical Writer & Nutritionist
University of Stockholm & Karolinska Institute, Sweden
Baylor University, TX, USA
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