Improvement of the Metabolic Syndrome and of Non-alcoholic Liver Steatosis upon Treatment of Hypogonadal Elderly Men with Parenteral Testosterone Undecanoate

Abstract

This is a study of a cohort of 117 men aged between 34–69 years, with plasma testosterone levels between 5.9–12.1 nmol/L (N>14.0 nmol/L) who were treated with administration of testosterone undecanoate for 1 year as the sole intervention. There was a remarkable improvement of body weight, BMI and waist size along with an improvement of lipid profiles. Liver fat is highly significantly and linearly correlated with all components of the metabolic syndrome. Hepatic inflammation secondary to liver steatosis is a potential contributor to the low-grade inflammation associated with the metabolic syndrome. Elevations of liver enzymes are associated with higher CRP concentrations. Levels of ALT (GPT) AST (GOT) and CRP had decreased significantly after one year of testosterone treatment. At baseline 74/117 met the criteria of the metabolic syndrome as defined by the NCEP and after one year of testosterone treatment this number had declined to 42/117.

Key words

testosterone - metabolic syndrome - liver steatosis - aging

References

• 1 Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) . Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III).  Jama. 2001;  285 2486-2497
• 2 Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications.  Endocr Rev. 2005;  26 833-876
• 3 Araujo AB, O’Donnell AB, Brambilla DJ. et al . Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study.  J Clin Endocrinol Metab. 2004;  89 5920-5926
• 4 Liu PY, Beilin J, Meier C. et al . Age-related changes in serum testosterone and sex hormone binding globulin in Australian men: longitudinal analyses of two geographically separate regional cohorts.  J Clin Endocrinol Metab. 2007;  92 3599-3603
• 5 Shores MM, Moceri VM, Gruenewald DA. et al . Low testosterone is associated with decreased function and increased mortality risk: a preliminary study of men in a geriatric rehabilitation unit.  J Am Geriatr Soc. 2004;  52 2077-2081
• 6 Shores MM, Matsumoto AM, Sloan KL. et al . Low serum testoster-one and mortality in male veterans.  Arch Intern Med. 2006;  166 1660-1665
• 7 Laughlin GA, Barrett-Connor E, Bergstrom J. Low Serum Testosterone and Mortality in Older Men.  J Clin Endocrinol Metab. 2008;  93 68-75
• 8 Khaw KT, Dowsett M, Folkerd E. et al . Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study.  Circulation. 2007;  116 2694-2701
• 9 Araujo A, Kupelian V, Page ST. et al . Sex steroids and all-cause mortality and cause-specific mortality in men.  Arch Intern Med. 2007;  167 1252-1260
• 10 Mohr BA, Bhasin S, Link CL. et al . The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study.  Eur J Endocrinol. 2006;  155 443-452
• 11 Rodriguez A, Muller DC, Metter EJ. et al . Aging, androgens, and the metabolic syndrome in a longitudinal study of aging.  J Clin Endocrinol Metab. 2007;  92 3568-3572
• 12 Kaplan SA, Meehan AG, Shah A. The age related decrease in testosterone is significantly exacerbated in obese men with the metabolic syndrome. What are the implications for the relatively high incidence of erectile dysfunction observed in these men?.  J Urol. 2006;  176 1524-1527 , ; discussion 1527–1528
• 13 Allan CA, Strauss BJ, Burger HG. et al . The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men.  Med J Aust. 2006;  185 424-427
• 14 Kalyani RR, Dobs AS. Androgen deficiency, diabetes, and the metabolic syndrome in men.  Current opinion in endocrinology, diabetes, and obesity. 2007;  14 226-234
• 15 Allan CA, Strauss BJ, MacLachlan RI. Body composition, metabolic syndrome and testosterone in ageing men.  Int J Impot Res. 2007;  19 448-457
• 16 Stellato RK, Feldman HA, Hamdy O. et al . Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study.  Diabetes Care. 2000;  23 490-494
• 17 Laaksonen DE, Niskanen L, Punnonen K. et al . Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men.  Diabetes Care. 2004;  27 1036-1041
• 18 Smith RM LH, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer.  J Clin Endocrinol Metab. 2006;  91 1305-1308
• 19 Basaria S, Muller DC, Carducci MA. et al . Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy.  Cancer. 2006;  106 581-588
• 20 Yialamas MA, Dwyer AA, Hanley E. et al . Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism.  J Clin Endocrinol Metab. 2007;  92 4254-4259
• 21 Rector RS, Thyfault JP, Wei Y. et al . Non-alcoholic fatty liver disease and the metabolic syndrome: An update.  World J Gastroenterol. 2008;  14 185-192
• 22 Musso G, Gambino R, Bo S. et al . Should nonalcoholic fatty liver disease be included in the definition of metabolic syndrome? A cross-sectional comparison with Adult Treatment Panel III criteria in nonobese nondiabetic subjects.  Diabetes Care. 2008;  31 562-568
• 23 Kotronen A, Westerbacka J, Bergholm R. et al . Liver fat in the metabolic syndrome.  The Journal of clinical endocrinology and metabolism. 2007;  92 3490-3497
• 24 Kerner A, Avizohar O, Sella R. et al . Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome.  Arterioscler Thromb Vasc Biol. 2005;  25 193-197
• 25 Allan CA, Strauss BJ, Burger HG. et al . Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in non-obese aging men.  J Clin Endocrinol Metab. 2007; 
• 26 Munzer T, Harman SM, Hees P. et al . Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men.  J Clin Endocrinol Metab. 2001;  86 3604-3610
• 27 Schroeder ET, Zheng L, Ong MD. et al . Effects of androgen therapy on adipose tissue and metabolism in older men.  J Clin Endocrinol Metab. 2004;  89 4863-4872
• 28 Esmaillzadeh A, Mirmiran P, Azizi F. Metabolic abnormalities identified by anthropometric measures in elderly men.  Am J Clin Nutr. 2006;  83 173 , author reply 173–174
• 29 Allan CA, Strauss BJ, Burger HG. et al . Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men.  J Clin Endocrinol Metab. 2008;  93 139-146
• 30 Marin P, Oden B, Bjorntorp P. Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens.  J Clin Endocrinol Metab. 1995;  80 239-243
• 31 Page ST, Amory JK, Bowman FD. et al . Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T.  J Clin Endocrinol Metab. 2005;  90 1502-1510
• 32 Saad F, Gooren L, Haider A. et al . An exploratory study of the effects of 12 month administration of the novel long-acting testosterone undecanoate on measures of sexual function and the metabolic syndrome.  Arch Androl. 2007;  53 353-357
• 33 Yassin AS, Saad F. Erectile dysfunction, metabolic syndrome, hypogonadism are intertwined.  J Urol. 2007;  177 288
• 34 Saad F, Gooren L, Haider A. et al . Effects of testosterone gel followed by parenteral testosterone undecanoate on sexual dysfunction and on features of the metabolic syndrome.  Andrologia. 2008;  40 44-48
• 35 Saad F, Gooren LJ, Haider A. et al . A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate.  J Androl. 2008;  29 102-105
• 36 Pitteloud N, Hardin M, Dwyer AA. et al . Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men.  J Clin Endocrinol Metab. 2005;  90 2636-2641
• 37 Svartberg J, Agledahl I, Figenschau Y. et al . Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip.  Int J Impot Res. 2008;  20 378-387

Correspondence