journal of men's health
Volume 5 , Pages S40-S45 , September 2008

The metabolic syndrome: when is testosterone treatment warranted

  • Louis Gooren, MD, PhD

      Affiliations

    • Endocrinology, Vrije Universiteit medical center, Amsterdam, The Netherlands
    • Corresponding Author InformationCorresponding author.
  • ,
  • Siegfried Meryn, MD

      Affiliations

    • Institute for Medical Education, University of Vienna, Vienna, Austria
  • ,
  • Ridwan Shabsigh, MD

      Affiliations

    • Division of Urology, Maimonides Medical Center, Columbia University, Brooklyn, NY, USA

References 

  1. Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev. 2005;26(6):833–876
  2. Araujo AB, O’Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, 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(12):5920–5926
  3. Shores MM, Moceri VM, Gruenewald DA, Brodkin KI, Matsumoto AM, Kivlahan DR. 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(12):2077–2081
  4. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR. Low serum testosterone and mortality in male veterans. Arch Intern Med. 2006;166(15):1660–1665
  5. Laughlin GA, Barrett-Connor E, Bergstrom J. Low Serum Testosterone and Mortality in Older Men. J Clin Endocrinol Metab. 2008;93(1):68–75
  6. Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, et al. Circulation. 2007;116(23):2694–2701
  7. Araujo A, Kupelian V, Page ST, Handelsman DJ, Bremner WJ, McKinlay JB. Sex steroids and all-cause mortality and cause-specific mortality in men. Arch Intern Med. 2007;167:1252–1260
  8. Mohr BA, Bhasin S, Link CL, O’Donnell AB, McKinlay JB. 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(3):443–452
  9. Rodriguez A, Muller DC, Metter EJ, Maggio M, Harman SM, Blackman MR, et al. Aging, Androgens, and the Metabolic Syndrome in a Longitudinal Study of Aging. J Clin Endocrinol Metab. 2007;92(9):3568–3572
  10. 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(4 Pt 1):1524–1527discussion 1527-8
  11. Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men. Med J Aust. 2006;185(8):424–427
  12. Kalyani RR, Dobs AS. Androgen deficiency, diabetes, and the metabolic syndrome in men. Curr Opin Endocrinol Diabetes Obes. 2007;14(3):226–234
  13. Allan CA, Strauss BJ, McLachlan RI. Body composition, metabolic syndrome and testosterone in ageing men. Int J Impot Res. 2007;19(5):448–457
  14. Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. 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(4):490–494
  15. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care. 2004;27(5):1036–1041
  16. Smith RM, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006;91:1305–1308
  17. Basaria S, Muller DC, Carducci MA, Egan J, Dobs AS. Hyperglycemia and insulin resistance in men with prostate carcinoma who receive androgen-deprivation therapy. Cancer. 2006;106(3):581–588
  18. Yialamas MA, Dwyer AA, Hanley E, Lee H, Pitteloud N, Hayes FJ. Acute Sex Steroid Withdrawal Reduces Insulin Sensitivity in Healthy Men with Idiopathic Hypogonadotropic Hypogonadism. J Clin Endocrinol Metab. 2007;92(11):4254–4259
  19. Ryan CW, Huo D, Bylow K, Demers LM, Stadler WM, Henderson TO, et al. Suppression of bone density loss and bone turnover in patients with hormone-sensitive prostate cancer and receiving zoledronic acid. BJU Int. 2007;100(1):70–75
  20. Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. Testosterone Therapy Prevents Gain in Visceral Adipose Tissue and Loss of Skeletal Muscle in Non-obese Aging Men. J Clin Endocrinol Metab. 2008;93(1):139–146
  21. Munzer T, Harman SM, Hees P, Shapiro E, Christmas C, Bellantoni MF, 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(8):3604–3610
  22. Schroeder ET, Zheng L, Ong MD, Martinez C, Flores C, Stewart Y, et al. Effects of androgen therapy on adipose tissue and metabolism in older men. J Clin Endocrinol Metab. 2004;89(10):4863–4872
  23. Svartberg J, Midtby M, Bonaa KH, Sundsfjord J, Joakimsen RM, Jorde R. The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study. Eur J Endocrinol. 2003;149(2):145–152
  24. Travison TG, Shabsigh R, Araujo AB, Kupelian V, O’Donnell AB, McKinlay JB. The natural progression and remission of erectile dysfunction: results from the Massachusetts Male Aging Study. J Urol. 2007;177(1):241–246discussion 246
  25. Isidori AM, Lenzi A. Risk factors for androgen decline in older males: lifestyle, chronic diseases and drugs. J Endocrinol Invest. 2005;28(3 Suppl):14–22
  26. Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legros JJ, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male. 2005;8(2):56–58
  27. Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legros JJ, et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. ISA, ISSAM, and EAU recommendations. Eur Urol. 2005;48(1):1–4
  28. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2006;91(6):1995–2010
  29. Saad F, Gooren LJ, Haider A, Yassin A. A Dose Response Study of Testosterone on Sexual Dysfunction and on Features of the Metabolic Syndrome Using Testosterone Gel and Parenteral Testosterone Undecanoate. J Androl. 2008;129(1):102–105
  30. Mhatre AN, Trifiro MA, Kaufman M, Kazemi-Esfarjani P, Figlewicz D, Rouleau G, et al. Reduced transcriptional regulatory competence of the androgen receptor in X-linked spinal and bulbar muscular atrophy. Nat Genet. 1993;5(2):184–188
  31. Beilin J, Ball EM, Favaloro JM, Zajac JD. Effect of the androgen receptor CAG repeat polymorphism on transcriptional activity: specificity in prostate and non-prostate cell lines. J Mol Endocrinol. 2000;25(1):85–96
  32. Albertelli MA, Scheller A, Brogley M, Robins DM. Replacing the mouse androgen receptor with human alleles demonstrates glutamine tract length-dependent effects on physiology and tumorigenesis in mice. Mol Endocrinol. 2006;20(6):1248–1260
  33. Zitzmann M, Nieschlag E. The CAG repeat polymorphism within the androgen receptor gene and maleness. Int J Androl. 2003;26(2):76–83
  34. Zeegers MP, Kiemeney LA, Nieder AM, Ostrer H. How strong is the association between CAG and GGN repeat length polymorphisms in the androgen receptor gene and prostate cancer risk?. Cancer Epidemiol Biomarkers Prev. 2004;13(11 Pt 1):1765–1771
  35. Canale D, Caglieresi C, Moschini C, Liberati CD, Macchia E, Pinchera A, et al. Androgen receptor polymorphism (CAG repeats) and androgenicity. Clin Endocrinol (Oxf). 2005;63(3):356–361
  36. Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E. Prostate volume and growth in testosterone-substituted hypogonadal men are dependent on the CAG repeat polymorphism of the androgen receptor gene: a longitudinal pharmacogenetic study. J Clin Endocrinol Metab. 2003;88(5):2049–2054
  37. Crabbe P, Bogaert V, De Bacquer D, Goemaere S, Zmierczak H, Kaufman JM. Part of the interindividual variation in serum testosterone levels in healthy men reflects differences in androgen sensitivity and feedback set point: contribution of the androgen receptor polyglutamine tract polymorphism. J Clin Endocrinol Metab. 2007;92(9):3604–3610
  38. Kelleher S, Conway AJ, Handelsman DJ. Blood testosterone threshold for androgen deficiency symptoms. J Clin Endocrinol Metab. 2004;89(8):3813–3817
  39. Zitzmann M. Mechanisms of disease: pharmacogenetics of testosterone therapy in hypogonadal men. Nat Clin Pract Urol. 2007;4(3):161–166
  40. Zitzmann M, Faber S, Nieschlag E. Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab. 2006;91(11):4335–4343
  41. O’Donnell AB, Araujo AB, McKinlay JB. The health of normally aging men: The Massachusetts Male Aging Study (1987-2004). Exp Gerontol. 2004;39(7):975–984
  42. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab. 2002;87(2):589–598
  43. Nieschlag E, Behre HM, Bouchard P, Corrales JJ, Jones TH, Stalla GK, et al. Testosterone replacement therapy: current trends and future directions. Hum Reprod Update. 2004;10(5):409–419
  44. Kshirsagar A, Seftel A, Ross L, Mohamed M, Niederberger C. Predicting hypogonadism in men based upon age, presence of erectile dysfunction, and depression. Int J Impot Res. 2006;18(1):47–51
  45. Black AM, Day AG, Morales A. The reliability of clinical and biochemical assessment in symptomatic late-onset hypogonadism: can a case be made for a 3-month therapeutic trial?. BJU Int. 2004;94(7):1066–1070

PII: S1875-6867(08)00073-0

doi: 10.1016/j.jomh.2008.03.012

journal of men's health
Volume 5 , Pages S40-S45 , September 2008