Multiple Hormonal Deficiencies in Anabolic Hormones in Frail Older Women

Reduced levels of anabolic hormones can contribute to aging and frailty. Most studies that have investigated this focused on the relationship between individual hormones and specific age-associated diseases. An interesting study in older women aged 70-79 years sought to examine the associations of individual anabolic hormonal deficiencies of free testosterone, IGF-1 and DHEA, and to assess their combined effects as well.[1]

The odds of frailty for deficiency in each hormone individually, as well as for a count of all three hormones, was calculated. It was found that for each hormone, those with the deficiency were more likely to be frail than those without the deficiency, although this did not achieve statistical significance (free T: odds ratio 2.03; IGF-1: odds ratio 1.82; DHEAS: odds ratio 1.68). In contrast, those with two or three deficiencies had a very high likelihood of being frail with an odds ratio of 2.79, i.e. almost three times as likely of being frail.

 Importance of diagnosing and treating multiple hormonal deficiencies

Both pre-frail and frail older women tend to have lower levels of anabolic hormones and are more likely to have deficiencies in multiple hormones than aged-matched non-frail women. The aggregate burden of hormonal deficiencies is an independent predictor of frailty, and the hormonal burden is more strongly associated with frailty than the type of hormonal deficiency.[1]

Interestingly, the hormones investigated in this study, testosterone, IGF-1 and DHEA, are from three distinctly regulated hormonal axes that in younger individuals fail simultaneously only in rare cases of pituitary dysfunction. Furthermore, IGF-1 and T have different receptors, each present in muscle, and a DHEAS receptor has never been cloned. However, there may be a biological link among these hormones beyond their individual axes, as muscle IGF-1 production is affected by T and DHEAS in part acts through its conversion to androgens.[2]

Other studies confirm this by showing that in elderly women over 66 years of age, even after adjusting for age, anthropometric measurements and physical activity, leg maximal muscle power correlated directly and similarly with IGF-1 and DHEA(S) levels. It was found that in healthy elderly women, lower values for maximal leg muscle power are related to lower circulating levels of both DHEAS and IGF-I.[3]

These findings underscore the importance of investigating all major hormones, and correcting deficiencies if present.[4-10] Given the known mechanisms of testosterone and GH/IGF-1 in building muscle (and possibly also DHEA in elderly) it is reasonable that age-related low levels of anabolic hormones contribute over time to sarcopenia and frailty.[2, 4, 5, 7, 10, 11] Thus, multiple small effects in aggregate can lead to adverse loss of muscle and disability. In this scenario, if replacement was to occur, it would require lower doses of multiple anabolic hormones [12]. In addition, multiple anabolic hormone replacement might also have beneficial synergistic effects.[13, 14]

References: 

  1. 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.
  2. Morley, J.E., M.J. Kim, and M.T. Haren, Frailty and hormones. Rev Endocr Metab Disord, 2005. 6(2): p. 101-8.
  3. Kostka, T., et al., Leg extensor power and dehydroepiandrosterone sulfate, insulin-like growth factor-I and testosterone in healthy active elderly people. Eur J Appl Physiol, 2000. 82(1-2): p. 83-90.
  4. Bross, R., M. Javanbakht, and S. Bhasin, Anabolic interventions for aging-associated sarcopenia. J Clin Endocrinol Metab, 1999. 84(10): p. 3420-30.
  5. Morley, J.E., Anabolic steroids and frailty. J Am Med Dir Assoc, 2010. 11(8): p. 533-6.
  6. Villareal, D.T. and J.O. Holloszy, DHEA enhances effects of weight training on muscle mass and strength in elderly women and men. Am J Physiol Endocrinol Metab, 2006. 291(5): p. E1003-8.
  7. McIntire, K.L. and A.R. Hoffman, The endocrine system and sarcopenia: potential therapeutic benefits. Curr Aging Sci, 2011. 4(3): p. 298-305.
  8. 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.
  9. Sayer, A.A., et al., New horizons in the pathogenesis, diagnosis and management of sarcopenia. Age Ageing, 2013. 42(2): p. 145-50.
  10. Burks, T.N. and R.D. Cohn, One size may not fit all: anti-aging therapies and sarcopenia. Aging (Albany NY), 2011. 3(12): p. 1142-53.
  11. Maggio, M., et al., The hormonal pathway to frailty in older men. J Endocrinol Invest, 2005. 28(11 Suppl Proceedings): p. 15-9.
  12. Giannoulis, M.G., et al., Hormone replacement therapy and physical function in healthy older men. Time to talk hormones? Endocr Rev, 2012. 33(3): p. 314-77.
  13. Sattler, F., et al., Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial. J Gerontol A Biol Sci Med Sci, 2011. 66(1): p. 122-9.
  14. Sattler, F.R., et al., Testosterone and growth hormone improve body composition and muscle performance in older men. J Clin Endocrinol Metab, 2009. 94(6): p. 1991-2001.

 

Last modified on Saturday, 10 May 2014 18:40
Monica Mollica

Medical Writer & Nutritionist

MSc in Nutrition

University of Stockholm & Karolinska Institute, Sweden 

   Baylor University, TX, USA

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