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Die Therapie des Hypogonadismus des Mannes

Therapy of male hypogonadism

  • Schwerpunkt: Hormontherapie
  • Published:
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Zusammenfassung

Der Hypogonadismus (Testosterondefizit) des Mannes ist eine der häufigsten, aber auch unterdiagnostiziertesten Endokrinopathien. Diese klinische Entität präsentiert sich in unterschiedlichen klinischen Bildern, die entscheidend für Diagnose und mögliche Therapie sind. Manifestationen in Form von Störungen der Stimmung, der kognitiven Fähigkeiten und der sexuellen Funktion sind ebenso möglich wie eine Umverteilung der Körperzusammensetzung mit Verlust der Muskelmasse und einer Zunahme viszeraler Fettdepots. Desgleichen wird der Hypogonadismus des Mannes häufig von einer Osteopenie/Osteoporose und milden bis funktionellen Anämie begleitet. Auch gibt es deutliche Hinweise darauf, dass ein Testosteronmangel mit dem metabolischen Syndrom und insbesondere der Insulinresistenz assoziiert sein kann. Βei älteren Männern weisen die Symptome eines Androgendefizits häufig ein anderes Profil auf als bei jüngeren Männern, insbesondere da häufig Ko-Morbiditäten mit ähnlichen klinischen Symptomen vorliegen. Im vorliegenden Beitrag werden diagnostische Pfade zum Hypogonadismus des Mannes vorgestellt. Verschiedene Optionen der Therapie sowie deren Überwachung werden beleuchtet und Perspektiven der endokrinologischen Andrologie diskutiert. So sind in den letzten Jahren neue Testosteronersatzmodalitäten eingeführt worden, die kurzwirksame transdermale Gele und langwirksame Depotinjektionen einschließen.

Abstract

One of the most frequent, but also most undiagnosed, endocrinopathies is male hypogonadism (testosterone deficiency). Understanding the variety of clinical pictures male hypogonadism exhibits is pivotal for diagnosis and putative treatment. There can be disturbances of mood and cognitive abilities as well as sexual functions. Further on, a decrease in muscle mass and strength, an accumulation of body fat and osteopenia/osteoporosis as well as anemia might be observed. There are indications that insulin sensitivity is mitigated in a state of androgen depletion, especially due to an inverse association of testosterone to the metabolic syndrome. In older men, symptoms of androgen deficiency may feature a differential profile due to accompanying co-morbidities. Restoring serum testosterone levels by substitution therapy can markedly attenuate, if not relieve, the clinical picture of hypogonadism. New treatment modalities have been introduced, including short-acting transdermal as well as long-acting depot preparations. Herewith, the diagnostic pathways to describe or exclude male hypogonadism and as well as various options of initiation and surveillance of testosterone substitution therapy are elucidated. Future perspectives of andrology regarding metabolic and pharmacogenetic aspects are discussed.

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Literatur

  1. Allan CA, Strauss BJ, Burger HG et al. (2008) Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in non-obese aging men. J Clin Endocrinol Metab 93: 139–146

    Article  PubMed  CAS  Google Scholar 

  2. Amin S, Zhang Y, Felson DT et al. (2006) Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. Am J Med 119: 426–433

    Article  PubMed  CAS  Google Scholar 

  3. Bagchus WM, Hust R, Maris F et al. (2003) Important effect of food on the bioavailability of oral testosterone undecanoate. Pharmacotherapy 23: 319–325

    Article  PubMed  CAS  Google Scholar 

  4. Benito M, Vasilic B, Wehrli FW et al. (2005) Effect of testosterone replacement on trabecular architecture in hypogonadal men. J Bone Miner Res 20: 1785–1791

    Article  PubMed  CAS  Google Scholar 

  5. Berger AP, Deibl M, Steiner H et al. (2005) Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk. Prostate 64: 240–245

    Article  PubMed  Google Scholar 

  6. Bhasin S, Woodhouse L, Casaburi R et al. (2001) Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 281: E1172–E1181

    PubMed  CAS  Google Scholar 

  7. Calof OM, Singh AB, Lee ML et al. (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: 1451–1457

    PubMed  Google Scholar 

  8. Canale D, Caglieresi C, Moschini C et al. (2005) Androgen receptor polymorphism (CAG repeats) and androgenicity. Clin Endocrinol (Oxf) 63: 356–361

    Google Scholar 

  9. Cherrier MM, Asthana S, Plymate S et al. (2001) Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology 57: 80–88

    Article  PubMed  CAS  Google Scholar 

  10. Crabbe P, Bogaert V, De Bacquer D et al. (2007) 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 92: 3604–3610

    Article  PubMed  CAS  Google Scholar 

  11. Deansley R, Parkes AS (1938) Further experiments on the administration of hormones by the subcutaneous implantation of tablets. Lancet II: 606–608

    Article  Google Scholar 

  12. Dobs AS, Meikle AW, Arver S et al. (1999) Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab 84: 3469–3478

    Article  PubMed  CAS  Google Scholar 

  13. Hiort O, Zitzmann M (2004) Androgen receptor: pathophysiology. In: Nieschlag E, Behre HM (eds) Testosterone – action, deficiency, substitution, 3rd edn. Cambridge University Press, UK, pp 93–124

  14. Kamischke A, Nieschlag E (2004) Progress towards hormonal male contraception. Trends Pharmacol Sci 25: 49–57

    Article  PubMed  CAS  Google Scholar 

  15. Kapoor D, Goodwin E, Channer KS, Jones TH (2006) Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 154: 899–906

    Article  PubMed  CAS  Google Scholar 

  16. Kapoor D, Malkin CJ, Channer KS, Jones TH (2005) Androgens, insulin resistance and vascular disease in men. Clin Endocrinol (Oxf) 63: 239–250

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  18. Kupelian V, Page ST, Araujo AB et al. (2006) 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 91: 843–850

    Article  PubMed  CAS  Google Scholar 

  19. Laaksonen DE, Niskanen L, Punnonen K et al. (2005) The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study. J Clin Endocrinol Metab 90: 712–719

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  21. Malkin CJ, Pugh PJ, Jones RD et al. (2004) The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 89: 3313–3318

    Article  PubMed  CAS  Google Scholar 

  22. McMahon CN, Smith CJ, Shabsigh R (2006) Treating erectile dysfunction when PDE5 inhibitors fail. Br Med J 332: 589–592

    Article  Google Scholar 

  23. Min JK, Williams KA, Okwuosa TM et al. (2006) Prediction of coronary heart disease by erectile dysfunction in men referred for nuclear stress testing. Arch Intern Med 166: 201–206

    Article  PubMed  Google Scholar 

  24. Morales A, Schulman CC, Tostain J, Wu FCW (2006) Testosterone Deficiency Syndrome (TDS) needs to be named appropriately–the importance of accurate terminology. Eur Urol 50: 407–409

    Article  PubMed  Google Scholar 

  25. Muller M, Beld AW van den, Bots ML et al. (2004) Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 109: 2074–2079

    Article  PubMed  CAS  Google Scholar 

  26. Nieschlag E (2006) Testosterone treatment comes of age: new options for hypogonadal men. Clin Endocrinol (Oxf) 65: 275–281

    Google Scholar 

  27. Nieschlag E, Swerdloff R, Behre HM et al. (2005) Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. Int J Androl 28: 125–127

    Article  PubMed  CAS  Google Scholar 

  28. Parker S, Armitage M (1999) Experience with transdermal testosterone replacement therapy for hypogonadal men. Clin Endocrinol (Oxf) 50: 57–62

    Google Scholar 

  29. Pitteloud N, Mootha VK, Dwyer AA et al. (2005) Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 28: 1636–1642

    Article  PubMed  CAS  Google Scholar 

  30. Pope HG Jr, Cohane GH, Kanayama G et al. (2003) Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry 160: 105–111

    Article  PubMed  Google Scholar 

  31. Saad F, Gooren LJ, Haider A, Yassin A (2008) A dose-response study of testosterone on sexual dysfunction and features of the metabolic syndrome using testosterone gel and parenteral testosterone undecanoate. J Androl 29: 102–105

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  34. Singh R, Artaza JN, Taylor WE et al. (2003) Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 144: 5081–5088

    Article  PubMed  CAS  Google Scholar 

  35. Snyder PJ, Peachey H, Hannoush P et al. (1999) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84: 2647–2653

    Article  PubMed  CAS  Google Scholar 

  36. Thompson IM, Tangen CM, Goodman PJ et al. (2005) Erectile dysfunction and subsequent cardiovascular disease. JAMA 294: 2996–3002

    Article  PubMed  CAS  Google Scholar 

  37. Wang C, Cunningham G, Dobs A et al. (2004) Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 89: 2085–2098

    Article  PubMed  CAS  Google Scholar 

  38. Woodhouse LJ, Gupta N, Bhasin M et al. (2004) Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men. J Clin Endocrinol Metab 89: 718–726

    Article  PubMed  CAS  Google Scholar 

  39. Zhang XH, Filippi S, Morelli A et al. (2006) Testosterone restores diabetes-induced erectile dysfunction and sildenafil responsiveness in two distinct animal models of chemical diabetes. J Sex Med 3: 253–264

    Article  PubMed  CAS  Google Scholar 

  40. Zitzmann M, Weckesser M, Schober O, Nieschlag E (2001) Changes in cerebral glucose metabolism and visuospatial capability in hypogonadal males under testosterone substitution therapy. Exp Clin Endocrinol Diabetes 109: 302–304

    Article  PubMed  CAS  Google Scholar 

  41. Zitzmann M, Brune M, Vieth V, Nieschlag E (2002) Monitoring bone density in hypogonadal men by quantitative phalangeal ultrasound. Bone 31: 422–429

    Article  PubMed  CAS  Google Scholar 

  42. Zitzmann M, Junker R, Kamischke A, Nieschlag E (2002) Contraceptive steroids influence the hemostatic activation state in healthy men. J Androl 23: 503–511

    PubMed  CAS  Google Scholar 

  43. 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 pharmacogenetic study. J Clin Endocrinol Metab 88: 2049–2054

    Article  PubMed  CAS  Google Scholar 

  44. Zitzmann M, Gromoll J, Eckardstein A von, Nieschlag E (2003) The CAG repeat polymorphism in the androgen receptor gene modulates body fat mass and serum concentrations of leptin and insulin in men. Diabetologia 46: 31–39

    PubMed  CAS  Google Scholar 

  45. Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E (2004) X-chromosome inactivation patterns and androgen receptor functionality influence phenotype and social characteristics as well as pharmacogenetics of testosterone therapy in Klinefelter patients. J Clin Endocrinol Metab 89: 6208–6217

    Article  PubMed  CAS  Google Scholar 

  46. Zitzmann M, Nieschlag E (2004) Androgens and erythropoiesis. In: Nieschlag E, Behre HM (eds) Testosterone – action, deficiency, substitution, 3rd edn. Cambridge University Press, UK, pp 283–296

  47. Zitzmann M, Ezgimen H, Nieschlag E (2005) Fertility induction in 83 men with secondary hypogonadism: confounders and predictors. Int J Androl 2005 28: 42

    Google Scholar 

  48. Zitzmann M, Faber S, Nieschlag E (2006) Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab 91: 4335–4343

    Article  PubMed  CAS  Google Scholar 

  49. 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: 3844–3853

    Article  PubMed  CAS  Google Scholar 

  50. Zitzmann M (2007) Mechanisms of disease: pharmacogenetics of testosterone therapy in hypogonadal men. Nat Clin Pract Urol 4: 161–166

    Article  PubMed  CAS  Google Scholar 

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  1. WHO Collaborating Center for Male Reproduction, Institut für Reproduktionsmedizin der Universitätskliniken Münster, Domagkstraße 11, 48149, Münster, Deutschland

    M. Zitzmann

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Zitzmann, M. Die Therapie des Hypogonadismus des Mannes. Internist 49, 559–569 (2008). https://doi.org/10.1007/s00108-008-2108-x

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