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Are declining testosterone levels a major risk factor for ill-health in aging men?

International Journal of Impotence Research volume 21, pages 24–36 (2009)Cite this article

Abstract

As men grow older, testosterone levels fall, with a steeper decline in unbound or free testosterone compared with total testosterone concentrations. Lower testosterone levels have been associated with poorer cognitive function, and with impaired general and sexual health in aging men. Recently, lower testosterone levels have been linked with metabolic syndrome and type II diabetes, both conditions associated with cardiovascular disease, and shown to predict higher overall and cardiovascular-related mortality in middle-aged and older men. However, reverse causation has to be considered, as systemic illness may result in reduced testosterone levels. Thus, the strength of these associations and the likely direction of causation need to be carefully considered. Furthermore, these conditions may overlap, for example aging, lower testosterone levels, erectile dysfunction and cardiovascular disease are interrelated. Cross-sectional and longitudinal observational studies may be informative. However, ultimately randomized controlled trials of testosterone therapy are needed to clarify its role in the maintenance of general and sexual health in aging men. Testosterone therapy should be considered in hypogonadal men who meet rigorous criteria for the diagnosis of androgen deficiency. Additional consideration should be given to designing and testing interventions that may prevent or ameliorate the age-related decline in testosterone levels in men.

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References

  1. Bhasin S . Testicular disorders. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR (eds). Williams Textbook of Endocrinology, 11th edn. Saunders, Elsevier: Philadelphia, 2008; 645–699.

    Google Scholar 

  2. Jones ME, Boon WC, McInnes K, Maffei L, Carani C, Simpson ER . Recognizing rare disorders: aromatase deficiency. Nat Clin Pract Endocrinol Metab 2007; 3: 414–421.

    Article  CAS  PubMed  Google Scholar 

  3. Rahman F, Christian HC . Non-classical actions of testosterone: an update. Trends Endocrinol Metab 2007; 18: 371–378.

    Article  CAS  PubMed  Google Scholar 

  4. Achermann JC, Hughes IA . Disorders of sex development. In: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR (eds). Williams Textbook of Endocrinology, 11th edn. Saunders, Elsevier: Philadelphia, 2008; 783–848.

    Google Scholar 

  5. Ferrini RL, Barrett-Connor E . Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 1998; 147: 750–754.

    Article  CAS  PubMed  Google Scholar 

  6. 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: 145–152.

    Article  CAS  PubMed  Google Scholar 

  7. Muller M, den Tonkellar I, Thijssen JHH, Grobbee DE, van der Schouw YT . Endogenous sex hormones in men aged 40–80 years. Eur J Endocrinol 2003; 149: 583–589.

    Article  CAS  PubMed  Google Scholar 

  8. Litman HJ, Bhasin S, Link CL, Araujo AB, McKinlay JB . Serum androgen levels in black, Hispanic, and white men. J Clin Endocrinol Metab 2006; 91: 4326–4334.

    Article  CAS  PubMed  Google Scholar 

  9. Morley JE, Kaiser FE, Perry HM, Patrick P, Morley PMK, Stauber PM et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism 1997; 46: 410–413.

    Article  CAS  PubMed  Google Scholar 

  10. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR . Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 2001; 86: 724–731.

    Article  CAS  PubMed  Google Scholar 

  11. 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: 589–598.

    Article  CAS  PubMed  Google Scholar 

  12. 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: 3599–3603.

    Article  CAS  PubMed  Google Scholar 

  13. Orwoll E, Lambert LC, Marshall LM, Phipps K, Blank J, Barrett-Connor E et al. Testosterone and estradiol in older men. J Clin Endocrinol Metab 2006; 91: 1336–1344.

    Article  CAS  PubMed  Google Scholar 

  14. Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SAP, Jamrozik K et al. In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health In Men Study. Eur J Endocrinol 2007; 156: 585–594.

    Article  CAS  PubMed  Google Scholar 

  15. Eriksson AL, Lorentzon M, Mellstrom D, Vandenput L, Swanson C, Andersson N et al. SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density. J Clin Endocrinol Metab 2006; 91: 5029–5037.

    Article  CAS  PubMed  Google Scholar 

  16. Kaufman JM, Vermeulen A . The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26: 833–876.

    Article  CAS  PubMed  Google Scholar 

  17. 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: 1821–1826.

    CAS  PubMed  Google Scholar 

  18. Leifke E, Goreno V, Wichers C, von zur Muhlen A, von Buren E, Brabant G . Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone binding globulin levels in men: cross-sectional data from a healthy male cohort. Clin Endocrinol 2000; 53: 689–695.

    Article  CAS  Google Scholar 

  19. Wu FCW, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW et al. Hypothalamic–pituitary–testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: The European Male Aging Study. J Clin Endocrinol Metab 2008; 93: 2737–2745.

    Article  CAS  PubMed  Google Scholar 

  20. Veldhuis JD . Aging and hormones of the hypothalamo–pituitary axis: gonadotropic axis in men and somatotropic axes in men and women. Ageing Res Rev 2008; 7: 189–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM . Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab 2002; 87: 5001–5007.

    Article  CAS  PubMed  Google Scholar 

  22. Barrett-Connor E, Goodman-Gruen D, Patay B . Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999; 84: 3681–3685.

    CAS  PubMed  Google Scholar 

  23. Yaffe K, Lui L-Y, Zmuda J, Cauley J . Sex hormones and cognitive function in older men. J Am Geriatr Soc 2002; 50: 707–712.

    Article  PubMed  Google Scholar 

  24. Thilers PP, MacDonald SWS, Herlitz A . The association between endogenous free testosterone and cognitive performance: a population-based study in 35–90 year-old men and women. Psychoneuroendocrinology 2006; 31: 565–576.

    Article  CAS  PubMed  Google Scholar 

  25. Muller M, Aleman A, Grobbee DE, de Haan EHF, van der Schouw YT . Endogenous sex hormone levels and cognitive function in aging men. Neurology 2005; 64: 866–871.

    Article  CAS  PubMed  Google Scholar 

  26. Yeap BB, Almeida OP, Hyde Z, Chubb SAP, Hankey GJ, Jamrozik K et al. Higher serum free testosterone is associated with better cognitive function in older men, whilst total testosterone is not. The Health In Men Study. Clin Endocrinol 2008; 68: 404–412.

    CAS  Google Scholar 

  27. Hogervorst E, Bandelow S, Combrinck M, Smith AD . Low free testosterone is an independent risk factor for Alzheimer's disease. Exp Gerontol 2004; 39: 1633–1639.

    Article  CAS  PubMed  Google Scholar 

  28. Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM et al. Free testosterone and risk for Alzheimer disease in older men. Neurology 2004; 62: 188–193.

    Article  CAS  PubMed  Google Scholar 

  29. Fonda SJ, Bertrand R, O’Donnell A, Longcope C, McKinlay JB . Age, hormones, and cognitive functioning among middle-aged and elderly men: cross-sectional evidence from the Massachusetts Male Aging Study. J Gerontol A Biol Sci Med Sci 2005; 60: 385–390.

    Article  PubMed  Google Scholar 

  30. Yonker JE, Eriksson E, Nilsson L-G, Herlitz A . Negative association of testosterone on spatial visualisation in 35 to 80 year old men. Cortex 2006; 42: 376–386.

    Article  PubMed  Google Scholar 

  31. Martin DM, Wittert G, Burns NR, Haren MT, Sugarman R . Testosterone and cognitive function in ageing men: data from the Florey Adelaide Male Ageing Study (FAMAS). Maturitas 2007; 57: 182–194.

    Article  CAS  PubMed  Google Scholar 

  32. Burkhardt MS, Foster JK, Clarnette RM, Chubb SAP, Bruce DG, Drummond PD et al. Interaction between testosterone and apolipoprotein E ɛ4 status on cognition in healthy older men. J Clin Endocrinol Metab 2006; 91: 1168–1172.

    Article  CAS  PubMed  Google Scholar 

  33. Cherrier MM, Rose AL, Higano C . The effects of combined androgen blockade on cognitive function during the first cycle of intermittent androgen suppression in patients with prostate cancer. J Urol 2003; 170: 1808–1811.

    Article  CAS  PubMed  Google Scholar 

  34. Salminen EK, Portin RI, Koskinen A, Helenius H, Nurmi M . Associations between serum testosterone fall and cognitive function in prostate cancer patients. Clin Cancer Res 2004; 10: 7575–7582.

    Article  CAS  PubMed  Google Scholar 

  35. Almeida OP, Waterreus A, Spry N, Flicker L, Martins RN . One year follow-up study of the association between chemical castration, sex hormones, beta-amyloid, memory and depression in men. Psychoneuroendocrinology 2004; 29: 1071–1081.

    Article  CAS  PubMed  Google Scholar 

  36. Hogervorst E, Bandelow S, Moffat SD . Increasing testosterone levels and effects on cognitive functions in elderly men and women: a review. Curr Drug Targets CNS Neurol Disord 2005; 4: 531–540.

    Article  CAS  PubMed  Google Scholar 

  37. Beauchet O . Testosterone and cognitive function: current clinical evidence of a relationship. Eur J Endocrinol 2006; 155: 773–781.

    Article  CAS  PubMed  Google Scholar 

  38. Cherrier MM, Anawalt BD, Herbst KL, Amory JK, Craft S, Matsumoto AM et al. Cognitive effects of short-term manipulation of serum sex steroids in healthy young men. J Clin Endocrinol Metab 2002; 87: 3090–3096.

    Article  CAS  PubMed  Google Scholar 

  39. Maki PM, Ernst M, London ED, Mordecai KL, Perschler P, Durso SC et al. Intramuscular testosterone treatment in elderly men: evidence of memory decline and altered brain function. J Clin Endocrinol Metab 2007; 92: 4107–4114.

    Article  CAS  PubMed  Google Scholar 

  40. Lu PH, Masterman DA, Mulnard R, Cotman C, Miller B, Yaffe K et al. Effects of testosterone on cognition and mood in male patients with mild Alzheimer disease and healthy elderly men. Arch Neurol 2006; 63: 177–185.

    Article  PubMed  Google Scholar 

  41. Cherrier MM, Craft S, Matsumoto AH . Cognitive changes associated with supplementation of testosterone or dihydrotestosterone in mildly hypogonadal men: a preliminary report. J Androl 2003; 24: 568–576.

    Article  CAS  PubMed  Google Scholar 

  42. Cherrier MM, Matsumoto AM, Amory JK, Asthana S, Bremner W, Peskind ER et al. Testosterone improves spatial memory in men with Alzheimer disease and mild cognitive impairment. Neurology 2005; 64: 2063–2068.

    Article  CAS  PubMed  Google Scholar 

  43. Cherrier MM, Matsumoto AM, Amory JK, Ahmed S, Bremner W, Perkind ER et al. The role of aromatisation in testosterone supplementation: effects on cognition in older men. Neurology 2005; 64: 290–296.

    Article  CAS  PubMed  Google Scholar 

  44. Karagiannis A, Harsoulis F . Gonadal dysfunction in systemic diseases. Eur J Endocrinol 2005; 152: 501–513.

    Article  CAS  PubMed  Google Scholar 

  45. Hijazi RA, Cunningham GR . Andropause: is androgen replacement therapy indicated for the aging male? Annu Rev Med 2005; 56: 117–137.

    Article  CAS  PubMed  Google Scholar 

  46. Morley JE, Haren MT, Kim M-J, Kevorkian R, Perry HM . Testosterone, aging and quality of life. J Endocrinol Invest 2005; 28 (Suppl 3): 76–80.

    CAS  PubMed  Google Scholar 

  47. Haren MT, Kim MJ, Tariq SH, Wittert GA, Morley JE . Andropause: a quality-of-life issue in older males. Med Clin N Am 2006; 90: 1005–1023.

    Article  CAS  PubMed  Google Scholar 

  48. Finas D, Bals-Pratsch M, Sandmann J, Eichenauer R, Jocham D, Diedrich K et al. Quality of life in elderly men with androgen deficiency. Andrologia 2006; 38: 48–53.

    Article  CAS  PubMed  Google Scholar 

  49. Perry PJ, Lund BC, Arndt S, Holman T, Bever-Stille KA, Paulsen J et al. Bioavailable testosterone as a correlate of cognition, psychological status, quality of life, and sexual function in aging males: implications for testosterone replacement therapy. Ann Clin Psychiatry 2001; 13: 75–80.

    Article  CAS  PubMed  Google Scholar 

  50. Potosky AL, Reeve BB, Clegg LX, Hoffman RM, Stephenson RA, Albertsen PC et al. Quality of life following localized prostate cancer treated initially with androgen deprivation therapy or no therapy. J Natl Cancer Inst 2002; 94: 430–437.

    Article  PubMed  Google Scholar 

  51. Basaria S, Lieb J, Tang AM, DeWeese T, Carducci M, Eisenberger M et al. Long-term effects of androgen deprivation therapy in prostate cancer patients. Clin Endocrinol 2002; 56: 779–786.

    Article  CAS  Google Scholar 

  52. Dacal K, Sereika SM, Greenspan SL . Quality of life in prostate cancer patients taking androgen deprivation therapy. J Am Geriatr Soc 2006; 54: 85–90.

    Article  PubMed  Google Scholar 

  53. Spry NA, Kristjanson L, Hooton B, Hayden L, Neerhut G, Gurney H et al. Adverse effects to quality of life arising from treatment can recover with intermittent androgen suppression in men with prostate cancer. Eur J Cancer 2006; 42: 1083–1092.

    Article  CAS  PubMed  Google Scholar 

  54. Baumgartner RN, Waters DL, Gallagher D, Morley JE, Garry PJ . Predictors of skeletal muscle mass in elderly men and women. Mech Ageing Dev 1999; 107: 123–136.

    Article  CAS  PubMed  Google Scholar 

  55. Iannuzzi-Sucich M, Prestwood KM, Kenny AM . Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. J Gerontol A Biol Sci Med Sci 2002; 57: M772–M777.

    Article  PubMed  Google Scholar 

  56. Schaap LA, Pluijm SMF, Smit JH, van Schoor NM, Visser M, Gooren LJG et al. The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clin Endocrinol 2005; 63: 152–160.

    Article  CAS  Google Scholar 

  57. O’Donnell AB, Travison TG, Harris SS, Tenover JL, McKinlay JB . Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2006; 91: 425–431.

    Article  PubMed  CAS  Google Scholar 

  58. Orwoll E, Lambert LC, Marshall LM, Blank J, Barrett-Connor E, Cauley J et al. Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med 2006; 166: 2124–2131.

    Article  PubMed  Google Scholar 

  59. Fink HA, Ewing SK, Ensrud KE, Barrett-Connor E, Taylor BC, Cauley JA et al. Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. J Clin Endocrinol Metab 2006; 91: 3908–3915.

    Article  CAS  PubMed  Google Scholar 

  60. Meier C, Nguyen TV, Handelsman DJ, Schindler C, Kushnir MM, Rockwood AL et al. Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study. Arch Intern Med 2008; 168: 47–54.

    Article  CAS  PubMed  Google Scholar 

  61. Ferrucci L, Maggio M, Bandinelli S, Basaria S, Lauretani F, Ble A et al. Low testosterone levels and the risk of anemia in older men and women. Arch Intern Med 2006; 166: 1380–1388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Penninx BWJH, Pahor M, Cesari M, Corsi AM, Woodman RC, Bandinelli S et al. Anemia is associated with disability and decreased physical performance and muscle strength in the elderly. J Am Geriatr Soc 2004; 52: 719–724.

    Article  PubMed  Google Scholar 

  63. Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C . Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 2006; 60: 762–769.

    Article  CAS  PubMed  Google Scholar 

  64. Gruenewald DA, Matsumoto AM . Testosterone supplementation therapy for older men: potential benefits and risks. J Am Geriatr Soc 2003; 51: 101–115.

    Article  PubMed  Google Scholar 

  65. Liverman CT, Blazer DG editors Testosterone and Aging: Clinical Research Directions. Institute of Medicine. The National Academies Press: Washington, DC, 2004.

    Google Scholar 

  66. 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 2005; 63: 280–293.

    Article  CAS  Google Scholar 

  67. Tracz MJ, Sideras K, Bolona ER, Haddad RM, Kennedy CC, Uraga MV et al. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. J Clin Endocrinol Metab 2006; 91: 2011–2016.

    Article  CAS  PubMed  Google Scholar 

  68. 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: 378–387.

    Article  CAS  PubMed  Google Scholar 

  69. Emmelot-Vonk MH, Verhaar HJJ, Nakhai Pour HR, Aleman A, Lock TMTW, Bosch JLHR et al. Effect of testosterone supplementation on functional mobility, cognition, and other parameters in older men: a randomized controlled trial. JAMA 2008; 299: 39–52.

    CAS  PubMed  Google Scholar 

  70. Behre HM, Heinemann L, Morales A, Pexman-Fieth C . Rationale, design and methods of the ESPRIT study: energy, sexual desire and body PropoRtions with AndroGel, Testosterone 1% gel therapy, in hypogonadal men. Aging Male 2008; 11: 101–106.

    Article  CAS  PubMed  Google Scholar 

  71. 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: 5920–5926.

    Article  CAS  PubMed  Google Scholar 

  72. Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab 2007; 92: 4241–4247.

    Article  CAS  PubMed  Google Scholar 

  73. Travison TG, Morley JE, Araujo AB, O’Donnell AB, McKinlay JB . The relationship between libido and testosterone levels in aging men. J Clin Endocrinol Metab 2006; 91: 2509–2513.

    Article  CAS  PubMed  Google Scholar 

  74. Morley JE, Perry HM, Kevorkian RT, Patrick P . Comparison of screening questionnaires for the diagnosis of hypogonadism. Maturitas 2006; 53: 424–429.

    Article  PubMed  Google Scholar 

  75. Beutel ME, Wiltink J, Hauck EW, Auch D, Behre HM, Brahler E et al. Correlations between hormones, physical, and affective parameters in aging urologic outpatients. Eur Urol 2005; 47: 749–755.

    Article  CAS  PubMed  Google Scholar 

  76. 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: 4335–4343.

    Article  CAS  PubMed  Google Scholar 

  77. Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB . Incidence of erectile dysfunction in men 40–69 years old: longitudinal results from the Massachusetts Male Aging Study. J Urol 2000; 163: 460–463.

    Article  CAS  PubMed  Google Scholar 

  78. Lyngdorf P, Hemmingsen L . Epidemiology of erectile dysfunction and its risk factors: a practise-based study in Denmark. Int J Impot Res 2004; 16: 105–111.

    Article  CAS  PubMed  Google Scholar 

  79. Holden CA, McLachlan RI, Pitts M, Cumming R, Wittert G, Agius PA et al. Men in Australia Telephone Survey (MATeS): a national survey of the reproductive health and concerns of middle-aged and older Australian men. Lancet 2005; 366: 218–224.

    Article  PubMed  Google Scholar 

  80. Ahn TY, Park JK, Lee SW, Hong JH, Park NC, Kim JJ et al. Prevalence and risk factors for erectile dysfunction in Korean men: results of an epidemiological study. J Sex Med 2007; 4: 1269–1276.

    Article  PubMed  Google Scholar 

  81. Selvin E, Burnett AL, Platz EA . Prevalence and risk factors for erectile dysfunction in the US. Am J Med 2007; 120: 151–157.

    Article  PubMed  Google Scholar 

  82. Chew KK, Stuckey B, Bremner A, Earle C, Jamrozik K . Male erectile dysfunction: its prevalence in Western Australia and associated sociodemographic factors. J Sex Med 2008; 5: 60–69.

    Article  PubMed  Google Scholar 

  83. Ahn HS, Park CM, Lee SW . The clinical relevance of sex hormone levels and sexual activity in the ageing male. BJU Int 2002; 89: 526–530.

    Article  CAS  PubMed  Google Scholar 

  84. Basar MM, Aydin G, Mert HC, Keles I, Caglayan O, Orkun S et al. Relationship between serum sex steroids and aging male symptoms score and International Index of Erectile Function. Urology 2005; 66: 597–601.

    Article  PubMed  Google Scholar 

  85. Kupelian V, Shabsigh R, Travison TG, Page ST, Araujo AB, McKinlay JB . Is there a relationship between sex hormones and erectile dysfunction? Results from the Massachusetts Male Aging Study. J Urol 2006; 176: 2584–2588.

    Article  CAS  PubMed  Google Scholar 

  86. Chiang HS, Hwang TI, Hsui YS, Lin YC, Chen HE, Chen GC et al. Transdermal testosterone gel increases serum testosterone levels in hypogonadal men in Taiwan with improvements in sexual function. Int J Impot Res 2007; 19: 411–417.

    Article  CAS  PubMed  Google Scholar 

  87. Allan CA, Forbes EA, Strauss BJG, McLachlan RI . Testosterone therapy increases sexual desire in ageing men with low-normal testosterone levels and symptoms of androgen deficiency. Int J Impot Res 2008; 20: 396–401.

    Article  CAS  PubMed  Google Scholar 

  88. Isidori AM, Giannetta E, Gianfrilli D, Greco EA, Bonifacio V, Aversa A et al. Effects of testosterone on sexual function in men: results of a meta-analysis. Clin Endocrinol 2005; 63: 381–394.

    Article  CAS  Google Scholar 

  89. Swerdloff RS, Wang C . Androgens and the ageing male. Best Pract Res Clin Endocrinol Metab 2004; 18: 349–362.

    Article  CAS  PubMed  Google Scholar 

  90. Krause W, Mueller U, Mazur A . Testosterone supplementation in the aging male: which questions have been answered? Aging Male 2005; 8: 31–38.

    Article  CAS  PubMed  Google Scholar 

  91. Aversa A, Isidori AM, De Martino MU, Caprio M, Fabbrini E, Rochietti-March M et al. Androgens and penile erection: evidence for a direct relationship between free testosterone and cavernous vasodilation in men with erectile dysfunction. Clin Endocrinol 2000; 53: 517–522.

    Article  CAS  Google Scholar 

  92. Traish AM, Guay AT . Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 2006; 3: 382–407.

    Article  CAS  PubMed  Google Scholar 

  93. Greco EA, Spera G, Aversa A . Combining testosterone and PDE5 inhibitors in erectile dysfunction: basic rationale and clinical evidences. Eur Urol 2006; 50: 940–947.

    Article  CAS  PubMed  Google Scholar 

  94. Aversa A, Isidori AM, Greco EA, Giannetta E, Gianfrilli D, Spera E et al. Hormonal supplementation and erectile dysfunction. Eur Urol 2004; 45: 535–538.

    Article  CAS  PubMed  Google Scholar 

  95. Shabsigh R . Testosterone therapy in erectile dysfunction and hypogonadism. J Sex Med 2005; 2: 785–792.

    Article  CAS  PubMed  Google Scholar 

  96. Kloner RA . Erectile dysfunction as a predictor of cardiovascular disease. Int J Impot Res 2008; 20: 460–465.

    Article  CAS  PubMed  Google Scholar 

  97. Esposito K, Giugliano F, Martedi E, Feola G, Marfella R, D’Armiento M et al. High proportions of erectile dysfunction in men with the metabolic syndrome. Diabetes Care 2005; 28: 1201–1203.

    Article  PubMed  Google Scholar 

  98. Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA . Erectile dysfunction and subsequent cardiovascular disease. JAMA 2005; 294: 2996–3002.

    Article  CAS  PubMed  Google Scholar 

  99. Grover SA, Lowensteyn I, Kaouache M, Marchand S, Coupal L, deCarolis E et al. The prevalence of erectile dysfunction in the primary care setting. Arch Intern Med 2006; 166: 213–219.

    Article  PubMed  Google Scholar 

  100. Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT . Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 2005; 90: 2618–2623.

    Article  CAS  PubMed  Google Scholar 

  101. Chubb SAP, Hyde Z, Almeida OP, Flicker L, Norman PE, Jamrozik K et al. Lower sex hormone binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men. The Health In Men Study. Eur J Endocrinol 2008; 158: 785–792.

    Article  CAS  PubMed  Google Scholar 

  102. 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: 843–850.

    Article  CAS  PubMed  Google Scholar 

  103. Ding EL, Song Y, Malik VS, Liu S . Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2006; 295: 1288–1299.

    Article  CAS  PubMed  Google Scholar 

  104. Selvin E, Feinleib M, Zhang L, Rohrmann S, Rifai N, Nelson WG et al. Androgens and diabetes in men: results from the Third National Health and Nutrition Examination Survey (NHANES III). Diabetes Care 2007; 30: 234–238.

    Article  CAS  PubMed  Google Scholar 

  105. Oh J-Y, Barrett-Connor E, Wedick NM, Wingard DL . Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care 2002; 25: 55–60.

    Article  CAS  PubMed  Google Scholar 

  106. 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: 1036–1041.

    Article  CAS  PubMed  Google Scholar 

  107. Grossmann M, Thomas MC, Panagiotopoulos S, Sharpe K, Macisaac RJ, Clarke S et al. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J Clin Endocrinol Metab 2008; 93: 1834–1840.

    Article  CAS  PubMed  Google Scholar 

  108. van den Beld AW, Bots ML, Janssen JA, Pols HA, Lamberts SW, Grobbee DE . Endogenous hormones and carotid atherosclerosis in elderly men. Am J Epidemiol 2003; 157: 25–31.

    Article  CAS  PubMed  Google Scholar 

  109. Makinen J, Jarvisalo MJ, Pollanen P, Perheentupa A, Irjala K, Koskenvuo M et al. Increased carotid atherosclerosis in andropausal middle-aged men. J Am Coll Cardiol 2005; 45: 1603–1608.

    Article  PubMed  CAS  Google Scholar 

  110. Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW, van der Schouw YT . Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 2004; 109: 2074–2079.

    Article  CAS  PubMed  Google Scholar 

  111. Tivesten A, Mellstrom D, Jutberger H, Fagerberg B, Lernfelt B, Orwoll E et al. Low serum testosterone and high serum estradiol associate with lower extremity peripheral arterial disease in elderly men. The MrOS Study in Sweden. J Am Coll Cardiol 2007; 50: 1070–1076.

    Article  CAS  PubMed  Google Scholar 

  112. Hak AE, Witteman JCM, de Jong FH, Geerlings MI, Hofman A, Pols HAP . Low levels of endogenous androgens increase the risk of atherosclerosis in elderly men: the Rotterdam study. J Clin Endocrinol Metab 2002; 87: 3632–3639.

    Article  CAS  PubMed  Google Scholar 

  113. Kapoor D, Clarke S, Channer KS, Jones TH . Erectile dysfunction is associated with low bioactive testosterone levels and visceral adiposity in men with type 2 diabetes. Int J Androl 2007; 30: 500–507.

    Article  CAS  PubMed  Google Scholar 

  114. Ma RC-W, So W-Y, Yang X, Yu LW-L, Kong AP-S, Ko GT-C et al. Erectile dysfunction predicts coronary heart disease in type 2 diabetes. J Am Coll Cardiol 2008; 51: 2045–2050.

    Article  PubMed  Google Scholar 

  115. Giagulli VA, Kaufman JM, Vermeulen A . Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 1994; 79: 997–1000.

    CAS  PubMed  Google Scholar 

  116. 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: 2636–2641.

    Article  CAS  PubMed  Google Scholar 

  117. Allan CA, Strauss BJG, McLachlan RI . Body composition, metabolic syndrome and testosterone in ageing men. Int J Impot Res 2007; 19: 448–457.

    Article  CAS  PubMed  Google Scholar 

  118. Allan CA, Strauss BJG, 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: 139–146.

    Article  CAS  PubMed  Google Scholar 

  119. Liu PY, Death AK, Handelsman DJ . Androgens and cardiovascular disease. Endocr Rev 2003; 24: 313–340.

    Article  CAS  PubMed  Google Scholar 

  120. Allan CA, McLachlan RI . Age-related changes in testosterone and the role of replacement therapy in older men. Clin Endocrinol 2004; 60: 653–670.

    Article  CAS  Google Scholar 

  121. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR . Low serum testosterone and mortality in male veterans. Arch Intern Med 2006; 166: 1660–1665.

    Article  CAS  PubMed  Google Scholar 

  122. Khaw K-T, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R 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.

    Article  CAS  PubMed  Google Scholar 

  123. Laughlin GA, Barrett-Connor E, Bergstrom J . Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 2008; 93: 68–75.

    Article  CAS  PubMed  Google Scholar 

  124. Smith GD, Ben-Shlomo Y, Beswick A, Yarnell J, Lightman S, Elwood P . Cortisol, testosterone and coronary heart disease. Prospective evidence from the Caerphilly study. Circulation 2005; 112: 332–340.

    Article  CAS  PubMed  Google Scholar 

  125. Araujo AB, Kupelian V, Page ST, Handelsman DJ, Bremner WJ, McKinlay JB . Sex steroids and all-cause and cause-specific mortality in men. Arch Intern Med 2007; 167: 1252–1260.

    Article  CAS  PubMed  Google Scholar 

  126. Arnlov J, Pencina MJ, Amin S, Nam BH, Benjamin EJ, Murabito JM et al. Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med 2006; 145: 176–184.

    Article  CAS  PubMed  Google Scholar 

  127. Er F, Michels G, Gassanov N, Rivero F, Hoppe UC . Testosterone induces cytoprotection by activating ATP-sensitive K+ channels in the cardiac mitochondrial inner membrane. Circulation 2004; 110: 3100–3107.

    Article  CAS  PubMed  Google Scholar 

  128. Nettleship JE, Jones TH, Channer KS, Jones RD . Physiological testosterone replacement therapy attenuates fatty streak formation and improves high-density lipoprotein cholesterol in the Tfm mouse. Circulation 2007; 116: 2427–2434.

    Article  CAS  PubMed  Google Scholar 

  129. Nieschlag E . Testosterone therapy comes of age: new options for hypogonadal men. Clin Endocrinol 2006; 65: 275–281.

    Article  CAS  Google Scholar 

  130. Seftel A . Testosterone replacement therapy for male hypogonadism: part III. Pharmacologic and clinical profiles, monitoring, safety issues, and potential future agents. Int J Impot Res 2007; 19: 2–24.

    Article  CAS  PubMed  Google Scholar 

  131. Rhoden EL, Morgentaler A . Risks of testosterone replacement therapy and recommendations for monitoring. N Engl J Med 2004; 350: 482–492.

    Article  CAS  PubMed  Google Scholar 

  132. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL et al. Adverse events associated with testosterone replacement therapy in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol 2005; 60A: 1451–1457.

    Article  CAS  Google Scholar 

  133. Endogenous Hormones and Prostate Cancer Collaborative Group. Endogenous sex hormones and prostate cancer: a collaborative analysis of 18 prospective studies. J Natl Cancer Inst 2008; 100: 170–183.

    Article  CAS  Google Scholar 

  134. Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. JAMA 2006; 296: 2351–2361.

    Article  CAS  PubMed  Google Scholar 

  135. Conway AJ, Handelsman DJ, Lording DW, Stuckey B, Zajac JD . Use, misuse and abuse of androgens. The Endocrine Society of Australia consensus guidelines for androgen prescribing. Med J Aust 2000; 172: 220–224.

    CAS  PubMed  Google Scholar 

  136. 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. J Androl 2006; 27: 135–137.

    Article  CAS  PubMed  Google Scholar 

  137. 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: 1995–2010.

    Article  CAS  PubMed  Google Scholar 

  138. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H . Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society Position Statement. J Clin Endocrinol Metab 2007; 92: 405–413.

    Article  CAS  PubMed  Google Scholar 

  139. Wheeler MJ, Barnes SC . Measurement of testosterone in the diagnosis of hypogonadism in the ageing male. Clin Endocrinol 2008; 69: 515–525.

    Article  CAS  Google Scholar 

  140. 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: 831–839.

    Article  PubMed  PubMed Central  Google Scholar 

  141. Yeap BB . The role of testosterone in older men: recent advances and future directions. Expert Rev Endocrinol Metab 2008; 3: 415–418.

    Article  PubMed  Google Scholar 

  142. Travison TG, Araujo AB, O’Donnell AB, Kupelian V, McKinlay JB . A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab 2007; 92: 196–202.

    Article  CAS  PubMed  Google Scholar 

  143. Andersson AM, Jensen TK, Juul A, Petersen JH, Jorgensen T, Skakkebaek NE . Secular decline in male testosterone and sex hormone binding globulin serum levels in Danish population surveys. J Clin Endocrinol Metab 2007; 92: 4696–4705.

    Article  CAS  PubMed  Google Scholar 

  144. Svartberg J, von Muhlen D, Sundsfjord J, Jorde R . Waist circumference and testosterone levels in community dwelling men. The Tromso study. Eur J Epidemiol 2004; 9: 657–663.

    Google Scholar 

  145. Travison TG, Araujo AB, Kupelian V, O’Donnell AB, McKinlay JB . The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metab 2007; 92: 549–555.

    Article  CAS  PubMed  Google Scholar 

  146. Mohr BA, Bhasin S, 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: 443–452.

    Article  CAS  PubMed  Google Scholar 

  147. Allen NE, Appleby PN, Davey GK, Key TJ . Lifestyle and nutritional determinants of bioavailable androgens and related hormones in British men. Cancer Causes Control 2002; 13: 353–363.

    Article  PubMed  Google Scholar 

  148. Wu AH, Whittemore AS, Kolonel LN, John EM, Gallagher RP, West DW et al. Serum androgens and sex-hormone binding globulins in relation to lifestyle factors in older African-American, white, and Asian men in the United States and Canada. Cancer Epidemiol Biomarkers Prev 1995; 4: 735–741.

    CAS  PubMed  Google Scholar 

  149. Wong SYS, Chan DCC, Hong A, Woo J . Prevalence of and risk factors for androgen deficiency in middle-aged men in Hong Kong. Metabolism 2006; 55: 1488–1494.

    Article  CAS  PubMed  Google Scholar 

  150. Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K et al. Healthier lifestyle predicts higher circulating testosterone in older men. The Health In Men Study. Clin Endocrinol 2008; doi 10.1111/j.1365-2265.2008.03372.x.

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  1. School of Medicine and Pharmacology, University of Western Australia, WA, Australia

    B B Yeap

  2. Department of Endocrinology and Diabetes, Fremantle Hospital, WA, Australia

    B B Yeap

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The author has received a speaker's honorarium from Bayer Healthcare for presenting at an educational meeting.

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Yeap, B. Are declining testosterone levels a major risk factor for ill-health in aging men?. Int J Impot Res 21, 24–36 (2009). https://doi.org/10.1038/ijir.2008.60

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