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Andrology pp 239-261 | Cite as

The Aging Male and Late-Onset Hypogonadism

  • Claus RolfEmail author
  • Michael Zitzmann
  • Eberhard Nieschlag

Abstract

Increasing longevity in most western industrial nations and its social, medical and also economic consequences have become a growing matter of public concern. Thus during the last 100 years in Germany the mean life expectancy has nearly doubled (Fig. 14.1). This also worldwide development is largely due to improved hygiene, reduction of newborn mortality and more effective therapy and prevention of acute diseases in adult age. With larger numbers of people reaching advanced age, health problems as well as social and psychological problems of older men play an increasingly important role in clinical medicine and in research. Not only is life expectancy increasing, but altered individual life planning and effective methods of contraception will continue to delay the timepoint of starting a family until later in life, when in any event female fertility is distinctly reduced.

Keywords

Growth Hormone Erectile Dysfunction Testosterone Level Lower Urinary Tract Symptom Serum Testosterone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, Van Kerrebroeck P, Victor A, Wein A (2003) The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 61:37–49PubMedGoogle Scholar
  2. Ali ST, Shaik RN, Siddiqi NA, Siddiqi PQ (1993) Semen analysis in insulin-dependent/non-insulin-dependent diabetic men with/without neuropathy. Arch Androl 30:47–54PubMedGoogle Scholar
  3. Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI (2008) Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab 93:139–146PubMedGoogle Scholar
  4. Amin S, Zhang Y, Felson DT, Sawin CT, Hannan MT, Wilson PW, Kiel DP (2006) Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. Am J Med 119:426–433PubMedGoogle Scholar
  5. Anderson PJ, Critchley JA, Chan JC, Cockram CS, Lee ZS, Thomas GN, Tomlinson B (2001) Factor analysis of the metabolic syndrome: obesity vs. insulin resistance as the central abnormality. Int J Obesity 25:1782–1788Google Scholar
  6. Araujo AB, Esche GR, Kupelian V, O'Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB (2007) Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab 92:4241–4247PubMedGoogle Scholar
  7. Bachmann R, Happle R, Held KR, Holzgreve W, Kunze J, Rauskolb R, Rehder H, Sewig K-Fr, Schmidtke J, Wolff G, Wollersheim U, Wissenschaftlicher Beirat der Bundesärztekammer (2007) Richtlinien zur pränatalen Diagnostik von Krankheiten und Krankheitsdispositionen (http://www.bundesärztekammer.de)
  8. Bagatell CJ, Heiman JR, Matsumoto AM, Rivier JE, Bremner WJ (1994) Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men. J Clin Endocrin Metab 79:561–567Google Scholar
  9. Behre HM, Bohmeyer J, Nieschlag E (1994) Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol 40:341–349Google Scholar
  10. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM (2006) Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 91:1995–2010PubMedGoogle Scholar
  11. Bordson BL, Leonardo VS (1991) The appropriate upper age limit for semen donors: a review of the genetic effects of paternal age. Fertil Steril 56:397–401PubMedGoogle Scholar
  12. Bryant J, Loveman E, Cave C, Chase D, Milne R (2002) Endocrinology trial design: adverse event reporting in randomised controlled trials of recombinant human GH in GH-deficient adults. J Endocrinol 175:545–552PubMedGoogle Scholar
  13. Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S (2005) Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60:1451–1357PubMedGoogle Scholar
  14. Cassells HB, Haffner SM (2006) The metabolic syndrome: risk factors and management. J Cardiovasc Nurs 21:306–313PubMedGoogle Scholar
  15. Colao A, Marzullo P, Ferone D, Spiezia S, Cerbone G, Marino V, Di Sarno A, Merola B, Lombardi G (1998) Prostatic hyper-plasia: an unknown feature of acromegaly. J Clin Endocrinol Metab 83:775–779PubMedGoogle Scholar
  16. Crow JF (1997) The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci USA 94:8380–8386PubMedGoogle Scholar
  17. Dakouane M, Bicchieray L. Bergere M, Albert M, Vialard F, Selva J (2005) A histomorphometric and cytogenetic study of testis from men 29–102 years old. Fertil Steril 83:923–928PubMedGoogle Scholar
  18. de la Rochebrochard E, Thonneau P (2002) Paternal age and maternal age are risk factors for miscarriage; rersults of a multicentre European study. Hum Reprod 17:1649–1656PubMedGoogle Scholar
  19. Delhez M, Hansenne M, Legros JJ (2003) Andropause and psy-chopathology: minor symptoms rather than pathological ones. Psychoneuroendocrinology 28:863–874PubMedGoogle Scholar
  20. Dennison E, Hindmarsh P, Fall C, Kellingray S, Barker D, Phillips D, Cooper C (1999) Profiles of endogenous circulating cortisol and bone mineral density in healthy elderly men. J Clin Endocrinol Metab 84:3058–3063PubMedGoogle Scholar
  21. Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD (2003) Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol 58:710–717Google Scholar
  22. Eisenmann JC (2003) Secular trends in variables associated with the metabolic syndrome of North American children and adolescents: a review and synthesis. Am J Hum Biol 15:786–794PubMedGoogle Scholar
  23. Elliot ML (1990) Psychological aspects of sexual dysfunction in the elderly. In: Armbrecht HJ, Coe RM, Wongsurawat N (eds) Endocrine function and age. Springer, Heidelberg, pp 136–146Google Scholar
  24. Ergun-Longmire B, Mertens AC, Mitby P, Qin J, Heller G, Shi W, Yasui Y, Robison LL, Sklar CA (2006) Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab 91:3494–3498PubMedGoogle Scholar
  25. Finkel E (1998) Telomeres: keys to senescence and cancer. Lancet 351:1186PubMedGoogle Scholar
  26. Flynn MA, Weaver-Osterholtz D, Sharpe-Timms KL, Allen S, Krause G (1999) Dehydroepiandrosterone replacement in aging humans. J Clin Endocrinol Metab 84:1527–1533PubMedGoogle Scholar
  27. Francis RM (1999) The effects of testosterone on osteoporosis in men. Clin Endocrinol 50:411–414Google Scholar
  28. Frattarelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Scott RT Jr (2008) Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertil Steril 90:97–103PubMedGoogle Scholar
  29. Gallardo E, Simon C, Levy M, Guanes PP, Remohi J, Pellicer A (1996) Effect of age on sperm fertility potential: oocyte donation as a model. Fertil Steril 66:260–264PubMedGoogle Scholar
  30. Gann PH, Hennekens CH, Longcope C, Verhoek-Oftedahl W, Grodstein F, Stampfer MJ (1995) A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. Prostate 26:40–49PubMedGoogle Scholar
  31. Garfinkel D, Berner YN (1998) Antioxidants and aging: is mela-tonin a possible, practical new hope? Nutrition 14:712–713PubMedGoogle Scholar
  32. Garfinkel D, Laudon M, Nof D, Zisapel N (1995) Improvement of sleep quality in elderly people by controlled-release mela-tonin. Lancet 346:541–544PubMedGoogle Scholar
  33. Giovannucci E, Platz EA, Stampfer MJ, Chan A, Krithivas K, Kawachi I, Willett WC, Kantoff PW (1999) The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia. Urology 53:121–125PubMedGoogle Scholar
  34. Gray A, Feldman HA, McKinlay JB, Longcope C (1991) Age, and changing sex hormone levels in middle-aged men: results of the Massachusetts male aging study. J Clin Endocrinol Metab 73:1016–1025PubMedGoogle Scholar
  35. Greendale GA, Unger JB, Rowe JW, Seeman TE (1999) The relation between cortisol excretion and fractures in healthy older people: results from the MacArthur studies-Mac. J Am Geriat Soc 47:799–803PubMedGoogle Scholar
  36. Grimley Evans J, Malouf R, Huppert F, van Niekerk JK (2006) Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst 18:BCD006221Google Scholar
  37. Hajjar RR, Kaiser FE, Morley JE (1997) Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab 82:3793–3796PubMedGoogle Scholar
  38. Handelsman DJ, Staraj S (1985) Testicular size: the effects of aging, malnutritrion, and illness. J Androl 6:144–151PubMedGoogle Scholar
  39. Harkonen K, Huhtaniemi I, Makinen J, Hubler D, Irjala K, Koskenvuo M, Oettel M, Raitakari O, Saad F, Pollanen P (2003) The polymorphic androgen receptor gene CAG repeat, pituitary-testicular function and andropausal symptoms in ageing men. Int J Androl 26:187–194PubMedGoogle Scholar
  40. Harzmann R, Weckermann D, Wawroschek F (1998) Treatment of benign prostate hyperplasia. Z Arztl Fortbild Qualitatssich 92:319–324PubMedGoogle Scholar
  41. Hassan MA, Killick SR (2003) Effect of male age on fertility: evidence for the decline in male fertility with increasing age. Fertil Steril 79:1520–1527PubMedGoogle Scholar
  42. Heidenreich A, Aus G, Bolla M, Joniau S, Matveev VB, Schmid HP, Zattoni F, European Association of Urology (2008) EAU guidelines on prostate cancer. Eur Urol 53:68–80PubMedGoogle Scholar
  43. Hellstrom WJ, Overstreet JW, Sikka SC, Denne J, Ahuja S, Hoover AM, Sides GD, Cordell WH, Harrison LM, Whitaker JS (2006) Semen and sperm reference ranges for men 45 years of age and older. J Androl 27:421–428PubMedGoogle Scholar
  44. Herbert J (1995) The age of dehydroepiandrosterone. Lancet 345:1193–1194PubMedGoogle Scholar
  45. Ho KK (2007) GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol 157:695–700PubMedGoogle Scholar
  46. Holstein AF (1989) Morphological evidence for the involution of spermatogenesis during senescence. In: Holstein AF, Voigt KD, Grässlin D (eds) Reproductive biology and medicine. Diesbach Verlag, Berlin, pp 66–77Google Scholar
  47. Johnson L, Grumbles JS, Bagheri A, Petty CS (1990) Increased germ cell degeneration during postprophase of meiosis is related to increased serum follicle-stimulating hormone concentrations and reduced daily sperm production in aged men. Biol Reprod 42:281–287PubMedGoogle Scholar
  48. Kapoor D, Malkin CJ, Channer KS, Jones TH. (2005) Androgens, insulin resistance and vascular disease in men. Clin Endocrinol 63:239–250Google Scholar
  49. Kapoor D, Goodwin E, Channer KS, Jones TH (2006). Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercho-lesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 154:899–906PubMedGoogle Scholar
  50. Kaufman JM, Vermeulen A (2005) The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 26:833–876PubMedGoogle Scholar
  51. Kelleher S, Conway AJ, Handelsman DJ (2004) Blood testosterone threshold for androgen deficiency symptoms. J Clin Endocrinol Metab 89:3813–3817PubMedGoogle Scholar
  52. Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N (2007) 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 116:2694–2697PubMedGoogle Scholar
  53. Kidd SA, Eskenazi B, Wyrobek A (2001) Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 75:237–248PubMedGoogle Scholar
  54. Kirkwood TB (2008) Understanding ageing from an evolutionary perspective. J Intern Med 263:117–127PubMedGoogle Scholar
  55. Krassas GE, Perros P (2003) Thyroid disease and male reproductive function. J Endocrinol Invest 26:372–380PubMedGoogle Scholar
  56. Kühnert B, Nieschlag E (2004) Reproductive functions of the ageing male. Hum Reprod Update 10:327–339PubMedGoogle Scholar
  57. Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB (2006) Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in non-obese men. J Clin Endocrinol Metab 91:843–850PubMedGoogle Scholar
  58. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT (2004) Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 27:1036–1041PubMedGoogle Scholar
  59. Labrie F, Candas B, Dupont A, Cusan L, Gomez JL, Suburu RE, Diamond P, Levesque J, Belanger A (1999) Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial. Prostate 38:83–91PubMedGoogle Scholar
  60. Laughlin GA, Barrett-Connor E, Bergstrom J (2008) Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 93:68–75PubMedGoogle Scholar
  61. Lepor H (2004) Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. Rev Urol 6:3–10Google Scholar
  62. Levitas E, Lunenfeld E, Weisz N, Friger M, Potashnik G (2007) Relationship between age and semen parameters in men with normal sperm concentration: analysis of 6022 semen samples. Andrologia 39:45–50PubMedGoogle Scholar
  63. Liu PY, Iranmesh A, Nehra AX, Keenan DM, Veldhuis JD (2005) Mechanisms of hypoandrogenemia in healthy aging men. Endocrinol Metab Clin North Am 34:935–955PubMedGoogle Scholar
  64. Lombardi G, Di Somma C, Rota F, Colao A (2005) Associated hormonal decline in aging: is there a role for GH therapy in aging men? J Endocrinol Invest 28:99–108PubMedGoogle Scholar
  65. Lucia MS, Epstein JI, Goodman PJ, Darke AK, Reuter VE, Civantos F, Tangen CM, Parnes HL, Lippman SM, La Rosa FG, Kattan MW, Crawford ED, Ford LG, Coltman CA Jr, Thompson IM (2007) Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J Natl Cancer Inst 99:1375–1383PubMedGoogle Scholar
  66. Luetjens CM, Rolf C, Gassner P, Werny JE, Nieschlag E (2002) Sperm aneuploidy rates in younger and older men. Hum Reprod 17:1826–1832PubMedGoogle Scholar
  67. Madersbacher S, Alivizatos G, Nordling J, Sanz CR, Emberton M, de la Rosette JJ (2004) EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol 46:547–554PubMedGoogle Scholar
  68. Madersbacher S, Berger I, Ponholzer A, Marszalek M (2008) Plant extracts: sense or nonsense? Curr Opin Urol 18:16–20PubMedGoogle Scholar
  69. Mahmoud AM, Goemaere S, El-Garem Y, Van Pottelberg Y, Comhaire FH, Kaufman JM (2003) Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men. J Clin Endocrinol Metab 88:179–184PubMedGoogle Scholar
  70. Mariotti S (2002) Ageing and thyroid diseases. In: Wass JAH, Shalet SM (eds) Oxford textbook of endocrinology and diabetes. Oxford University Press, Oxford, pp 1425–1422Google Scholar
  71. McVary KT (2006) BPH: epidemiology and comorbidities. Am J Manag Care 12:122–128Google Scholar
  72. Meier C, Nguyen TV, Handelsman DJ, Schindler C, Kushnir MM, Rockwood AL, Meikle AW, Center JR, Eisman JA, Seibel MJ (2008). Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study. Arch Intern Med 14:47–54Google Scholar
  73. Michikawa Y, Mazzucchelli F, Bresolin N, Scarlato G, Attardi G (1999) Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science 286:774–779PubMedGoogle Scholar
  74. Morganti S, Ceda GP, Saccani M, Milli B, Ugolotti D, Prampolini R, Maggio M, Valenti G, Ceresini G (2007) Thyroid disease in the elderly: sex-related differences in clinical expression. J Endocrinol Invest 28:101–104Google Scholar
  75. Morley JE, Kaiser FE, Johnson LE (1990) Male sexual function. In: Cassel CK, Riesenberg DE, Sorensen LB, Walsh JR (eds) Geriatric medicine, 2nd edn. Springer, Berlin/Heidelberg/ New York/Tokyo, pp 256–270Google Scholar
  76. Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT (2005) Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 90:2618–2623PubMedGoogle Scholar
  77. Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C (2006) Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 60:762–769PubMedGoogle Scholar
  78. Neaves WB, Johnson L, Porter JC, Parker CR, Petty CS (1985) Leydig cell numbers, daily sperm production, and serum gonadotropin-levels in aging men. J Clin Endocrinol Metab 59:756–763Google Scholar
  79. Neuhouser ML, Schenk J, Song YJ, Tangen CM, Goodman PJ, Pollak M, Penson DF, Thompson IM, Kristal AR (2008) Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial. Prostate 68:1477–1486PubMedGoogle Scholar
  80. Nieschlag E, Michel E (1986) Reproductive functions in grandfathers. In: Mastroianni L, Paulsen CA (eds) Aging, reproduction, and the climacteric. Plenum, New York, pp 59–71Google Scholar
  81. Nieschlag E, Lammers U, Freischem CW, Langer K, Wickings EJ (1982) Reproductive functions in young fathers and grandfathers. J Clin Endocrinol Metab 55:676–681PubMedGoogle Scholar
  82. Nieschlag E, Brinkworth M, Rolf C, Lerchl A (2000) Fertility and fertility related problems in the ageing male. Proceedings of the 9th International Menopause Society, World Congress of the Menopause, Parthenon, LondonGoogle Scholar
  83. Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morley JE, Schulman C, Wang C, Weidner W, Wu FC (2005) Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. Int J Androl 28:125–127PubMedGoogle Scholar
  84. Nybo Andersen AM, Hansen KD, Andersen PK, Davey Smith G (2004) Advanced paternal age and risk of fetal death: a cohort study. Am J Epidemiol 160:1214–1222PubMedGoogle Scholar
  85. Pope HG Jr, Cohane GH, Kanayama G, Siegel AJ, Hudson JI (2003) Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry 160:105–111PubMedGoogle Scholar
  86. Quinn M, Babb P (2002) Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I: international comparisons. BJU Int 90:162–173PubMedGoogle Scholar
  87. Reid IR, Wattie DJ, Evans MC, Stapleton JP (1996) Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 156:1173–1177PubMedGoogle Scholar
  88. Rolf C, Nieschlag E (1998) Potential adverse effects of longterm testosterone therapy. Baillières Clin Endocrinol Metab 12:521–534PubMedGoogle Scholar
  89. Rolf C, Behre HM, Nieschlag E (1996) Reproductive parameters of older compared to younger men of infertile couples. Int J Androl 19:135–142PubMedGoogle Scholar
  90. Rolf C, Kenkel S, Nieschlag E (2002a) Age-related diesease pattern in infertile men: increasing incidence of infections in older patients. Andrologia 34:209–217PubMedGoogle Scholar
  91. Rolf C, von Eckardstein S, Koken U, Nieschlag E (2002b) Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study. Eur J Endocrinol 146:505–511PubMedGoogle Scholar
  92. Rudman D, Feller AG, Nagraj HS, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE (1990) Effects of human growth hormone in men over 60 years old. N Engl J Med 323:1–6PubMedGoogle Scholar
  93. Sartorius G, Nieschlag E (2009) Paternal age and reproduction. Hum Reprod Update epub Aug. 20Google Scholar
  94. Schlüter D (1978) Die endokrinen Organe der ÜberNeunzigjährigen. Dissertation Universität HamburgGoogle Scholar
  95. depressive symptoms in middle-aged men. Biol Psychiatry 50:371–376PubMedGoogle Scholar
  96. Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR (2006) Low serum testosterone and mortality in male veterans. Arch Intern Med 166:1660–1665PubMedGoogle Scholar
  97. Sih R, Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Ross C (1997) Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 82:1661–1667PubMedGoogle Scholar
  98. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, Dlewati A, Staley J, Santanna J, Kapoor SC, Attie MF, Haddad JG Jr, Strom BL (1999a) Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 84:1966–1972PubMedGoogle Scholar
  99. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL (1999b) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84:2647–2653PubMedGoogle Scholar
  100. Statistisches Bundesamt (Hrsg) Statistische Jahrbücher (1980– 2008) für die Bundesrepublik Deutschland. Metzler Poeschel Verlag, StuttgartGoogle Scholar
  101. Suzuki K, Ito K, Ichinose Y, Kurokawa K, Suzuki T, Imai K, Yamanaka H, Honma S (1995) Endocrine environment of benign prostatic hyperplasia: prostate size and volume are correlated with serum estrogen concentration. Scand J Urol Nephrol 29:65–68PubMedGoogle Scholar
  102. Swerdlow AJ (2006) Does growth hormone therapy increase the risk of cancer? Nat Clin Pract Endocrinol Metab 2:530–531PubMedGoogle Scholar
  103. Tarin JJ, Brines J, Cano A (1998) Long-term effects of delayed parenthood. Hum Reprod 13:2371–2376PubMedGoogle Scholar
  104. Tenover JS (1994) Androgen administration to aging men. Endocrinol Metab Clin North Am 23:878–892Google Scholar
  105. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224PubMedGoogle Scholar
  106. Tivesten A, Mellström D, Jutberger H, Fagerberg B, Lernfelt B, Orwoll E, Karlsson MK, Ljunggren O, Ohlsson C (2007) 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 50:1070–1076PubMedGoogle Scholar
  107. Umbreit K (1993) Ist eine Substitution mit Estradiol auch bei Männern angezeigt? Gyne 14:56–60Google Scholar
  108. Valtonen M, Niskanen L, Kangas AP, Koskinen T (2005) Effect of melatonin-rich night-time milk on sleep and activity in elderly institutionalized subjects. Nord J Psychiatry 59:217–221PubMedGoogle Scholar
  109. Vance ML (2003) Can growth hormone prevent aging? N Engl J Med 348:779–780PubMedGoogle Scholar
  110. Vance ML, Mauras N (1999) Growth hormone therapy in adults and children. N Engl J Med 341:1206–1216PubMedGoogle Scholar
  111. Vermeulen A, Kaufman JM (1995) Ageing of the hypothalamo-pituitary-testicular axis in men. Horm Res 43:25–28PubMedGoogle Scholar
  112. von Eckardstein A, Wu FCW (2004) Testosterone and cardiovascular diseases. In: Nieschlag E, Behre HM (eds) Testosterone: action, deficiency, substitution, 3rd edn. Cambridge University Press, Cambridge, pp 297–332Google Scholar
  113. von Mühlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R (2008) Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int 19:699–670Google Scholar
  114. Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS (1996) Testosterone replacement therapy improves mood in hypogonadal men — a clinical research center study. J Clin Endocrinol Metab 81:3578–3583PubMedGoogle Scholar
  115. Wang C, Nieschlag E, Swerdloff RS, Behre H, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC (2008) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male 1:1–8Google Scholar
  116. Webb CM, Elkington AG, Kraidly MM, Keenan N, Pennell DJ, Collins P (2008) Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease. Am J Cardiol 101:618–624PubMedGoogle Scholar
  117. Woodhouse LJ, Gupta N, Bhasin M, Singh AB, Ross R, Phillips J, Bhasin S (2004) Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men. J Clin Endocrinol Metab 89:718–726PubMedGoogle Scholar
  118. Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A, Huhtaniemi IT, Kula K, Punab M, Boonen S, Vaderschueren D, European Male Aging Study Group (2008) 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 93:2737–2745PubMedGoogle Scholar
  119. Zitzmann M (2006) Testosterone and the brain. Aging Male 9:195–199PubMedGoogle Scholar
  120. Zitzmann M, Nieschlag E (2007) 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 92:3844–3853PubMedGoogle Scholar
  121. Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E (2003) Prostate volume and growth in testosterone-substituted hypogonadal men are dependent on the CAG repeat polymorphism of the androgen receptor gene: a longitudinal pharma-cogenetic study. J Clin Endocrinol Metab 88:2049–2054PubMedGoogle Scholar
  122. Zitzmann M, Faber S, Nieschlag E (2006) Association of spe-cific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab 91:4335–4343PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Claus Rolf
    • 1
    Email author
  • Michael Zitzmann
    • 2
  • Eberhard Nieschlag
    • 2
  1. 1.St. Josef HospitalBremerhavenGermany
  2. 2.Centre of Reproductive Medicine and Andrology of the UniversityMünsterGermany

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