journal of men's health
Volume 5, Issue 4 , Pages 366-373 , December 2008

Can the administration of testosterone to men with late-onset hypogonadism be discontinued?

Received 1 September 2008 ,Accepted 1 September 2008.

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. Liu PY, Beilin J, Meier C, Nguyen TV, Center JR, Leedman PJ, 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(9):3599–3603
  3. Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991;73(5):1016–1025
  4. 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
  5. Mohr BA, Guay AT, O’Donnell AB, McKinlay JB. Normal, bound and nonbound testosterone levels in normally ageing men: results from the Massachusetts Male Ageing Study. Clin Endocrinol (Oxf). 2005;62(1):64–73
  6. 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
  7. Muller M, den Tonkelaar I, Thijssen JH, Grobbee DE, van der Schouw YT. Endogenous sex hormones in men aged 40-80 years. Eur J Endocrinol. 2003;149(6):583–589
  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 7-8
  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. 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
  13. 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 6
  14. 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
  15. Derby CA, Zilber S, Brambilla D, Morales KH, McKinlay JB. Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clin Endocrinol (Oxf). 2006;65(1):125–131
  16. Blouin K, Despres JP, Couillard C, Tremblay A, Prud’homme D, Bouchard C, et al. Contribution of age and declining androgen levels to features of the metabolic syndrome in men. Metabolism. 2005;54(8):1034–1040
  17. Isidori AM, Caprio M, Strollo F, Moretti C, Frajese G, Isidori A, et al. Leptin and androgens in male obesity: evidence for leptin contribution to reduced androgen levels. J Clin Endocrinol Metab. 1999;84(10):3673–3680
  18. Caprio M, Isidori AM, Carta AR, Moretti C, Dufau ML, Fabbri A. Expression of functional leptin receptors in rodent Leydig cells. Endocrinology. 1999;140(11):4939–4947
  19. Soderberg S, Olsson T, Eliasson M, Johnson O, Brismar K, Carlstrom K, et al. A strong association between biologically active testosterone and leptin in non-obese men and women is lost with increasing (central) adiposity. Int J Obes Relat Metab Disord. 2001;25(1):98–105
  20. Van Den Saffele JK, Goemaere S, De Bacquer D, Kaufman JM. Serum leptin levels in healthy ageing men: are decreased serum testosterone and increased adiposity in elderly men the consequence of leptin deficiency?. Clin Endocrinol (Oxf). 1999;51(1):81–88
  21. Pitteloud N, Hardin M, Dwyer AA, Valassi E, Yialamas M, Elahi D, et al. Increasing insulin resistance is associated with a decrease in Leydig cell testosterone secretion in men. J Clin Endocrinol Metab. 2005;90(5):2636–2641
  22. Lima N, Cavaliere H, Knobel M, Halpern A, Medeiros-Neto G. Decreased androgen levels in massively obese men may be associated with impaired function of the gonadostat. Int J Obes Relat Metab Disord. 2000;24(11):1433–1437
  23. Vermeulen A, Kaufman JM, Deslypere JP, Thomas G. Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab. 1993;76(5):1140–1146
  24. Pritchard J, Despres JP, Gagnon J, Tchernof A, Nadeau A, Tremblay A, et al. Plasma adrenal, gonadal, and conjugated steroids before and after long-term overfeeding in identical twins. J Clin Endocrinol Metab. 1998;83(9):3277–3284
  25. Vermeulen A, Kaufman JM, Giagulli VA. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metab. 1996;81(5):1821–1826
  26. Tchernof A, Labrie F, Belanger A, Prud’homme D, Bouchard C, Tremblay A, et al. Androstane-3alpha,17beta-diol glucuronide as a steroid correlate of visceral obesity in men. J Clin Endocrinol Metab. 1997;82(5):1528–1534
  27. Pritchard J, Despres JP, Gagnon J, Tchernof A, Nadeau A, Tremblay A, et al. Plasma adrenal, gonadal, and conjugated steroids following long-term exercise-induced negative energy balance in identical twins. Metabolism. 1999;48(9):1120–1127
  28. Kaukua J, Pekkarinen T, Sane T, Mustajoki P. Sex hormones and sexual function in obese men losing weight. Obes Res. 2003;11(6):689–694
  29. Niskanen L, Laaksonen DE, Punnonen K, Mustajoki P, Kaukua J, Rissanen A. Changes in sex hormone-binding globulin and testosterone during weight loss and weight maintenance in abdominally obese men with the metabolic syndrome. Diabetes Obes Metab. 2004;6(3):208–215
  30. Strain G, Zumoff B, Rosner W, Pi-Sunyer X. The relationship between serum levels of insulin and sex hormone-binding globulin in men: the effect of weight loss. J Clin Endocrinol Metab. 1994;79(4):1173–1176
  31. 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
  32. Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab. 2006;91(3):843–850
  33. Smith RMLH, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006;91:1305–1308
  34. 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
  35. Haidar A, Yassin A, Saad F, Shabsigh R. Effects of androgen deprivation on glycaemic control and on cardiovascular biochemical risk factors in men with advanced prostate cancer with diabetes. Aging Male. 2007;10(4):189–196
  36. 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
  37. 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
  38. Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab. 2008;93(1):139–146
  39. 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
  40. 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
  41. Saad F, Gooren L, Haider A, Yassin A. 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(6):353–357
  42. Saad F, Gooren LJ, Haider A, Yassin A. 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(1):102–105
  43. Page ST, Amory JK, Bowman FD, Anawalt BD, Matsumoto AM, Bremner WJ, 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(3):1502–1510
  44. Marin P, Arver S. Androgens and abdominal obesity. Baillière's Clin Endocrinol Metab. 1998;12(3):441–451
  45. Esmaillzadeh A, Mirmiran P, Azizi F. Metabolic abnormalities identified by anthropometric measures in elderly men. Am J Clin Nutr. 2006;83(1):173;Author reply: 4
  46. Svartberg J, Agledahl I, Figenschau Y, Sildnes T, Waterloo K, Jorde R. Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip. Int J Impot Res. 2008;20(4):378–387
  47. 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(1):239–243
  48. Anderson FH, Francis RM, Faulkner K. Androgen supplementation in eugonadal men with osteoporosis – effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Bone. 1996;18(2):171–177
  49. Zitzmann M, Nieschlag E. Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab. 2007;92(10):3844–3853
  50. Saad F, Gooren L, Haider A, Yassin A. Effects of testosterone gel followed by parenteral testosterone undecanoate on sexual dysfunction and on features of the metabolic syndrome. Andrologia. 2008;40:44–48
  51. Liu PY, Wishart SM, Celermajer DS, Jimenez M, Pierro ID, Conway AJ, et al. Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo-controlled clinical trial of recombinant human chorionic gonadotropin. Eur J Endocrinol. 2003;148(1):55–66
  52. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab. 2004;89(7):3313–3318
  53. Norata GD, Tibolla G, Seccomandi PM, Poletti A, Catapano AL. Dihydrotestosterone decreases tumor necrosis factor-alpha and lipopolysaccharide-induced inflammatory response in human endothelial cells. J Clin Endocrinol Metab. 2006;91(2):546–554
  54. Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63(3):280–293
  55. Kapoor D, Goodwin E, Channer KS, Jones TH. 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):899–906
  56. Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male. 2003;6(1):1–7
  57. Singh AB, Hsia S, Alaupovic P, Sinha-Hikim I, Woodhouse L, Buchanan TA, et al. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab. 2002;87(1):136–143
  58. Singh R, Artaza JN, Taylor WE, Braga M, Yuan X, Gonzalez-Cadavid NF, et al. Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology. 2006;147(1):141–154
  59. Nilsson PM. Cardiovascular risk in the metabolic syndrome: fact or fiction?. Curr Cardiol Rep. 2007;9(6):479–485
  60. 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(19):2486-97.
  61. Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288(21):2709–2716
  62. Ford ES. Prevalence of the metabolic syndrome defined by the International Diabetes Federation among adults in the U.S. Diabetes Care. 2005;28(11):2745–2749
  63. Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif W, et al. Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines. Metabolism. 2004;53(4):430–434
  64. Ulijaszek SJ, Kerr DA. Anthropometric measurement error and the assessment of nutritional status. Br J Nutr. 1999;82(3):165–177
  65. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA. 2004;292(12):1440–1446
  66. Esposito K, Giugliano F, Di Palo C, Giugliano G, Marfella R, D’Andrea F, et al. Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial. JAMA. 2004;291(24):2978–2984
  67. Almeida OP, Yeap BB, Hankey GJ, Jamrozik K, Flicker L. Low free testosterone concentration as a potentially treatable cause of depressive symptoms in older men. Arch Gen Psychiatry. 2008;65(3):283–289
  68. Brambilla DJ, O’Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol (Oxf). 2007;67(6):853–862
  69. Travison TG, Shackelton R, Araujo AB, Hall SA, Williams RE, Clark RV, et al. The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission. J Am Geriatr Soc. 2008;56(5):831–839
  70. Tsujimura A, Takada S, Matsuoka Y, Hirai T, Takao T, Miyagawa Y, et al. Is discontinuation of hormone replacement therapy possible for patients with late-onset hypogonadism?. Int J Urol. 2008;15(7):625–629
  71. Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med. 1999;16:442–443
  72. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome – a new worldwide definition. Lancet. 2005;388:1059–1062

PII: S1875-6867(08)00198-X

doi: 10.1016/j.jomh.2008.09.005

journal of men's health
Volume 5, Issue 4 , Pages 366-373 , December 2008