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Relationship between Low Levels of Anabolic Hormones and Mortality in Older Men
Written by Monica Mollica 09 May 2014
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.[21]
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:[22]
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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. [22]
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.
- - - Updated - - -
References:
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.
Written by Monica Mollica 09 May 2014
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.[21]
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:[22]
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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. [22]
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.
- - - Updated - - -
References:
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.