Dtsch Med Wochenschr 2012; 137(41): 2117-2122
DOI: 10.1055/s-0032-1305332
Übersicht | Review article
Urologie, Geriatrie
© Georg Thieme Verlag KG Stuttgart · New York

Testosteron im Alter – ein Update

Testosterone in old age – an up-date
A. Hilbert-Walter
1   Klinik für Innere Medizin 2 – Geriatrie des Klinikums Nürnberg, Nürnberg
,
R. Büttner
2   Innere Medizin, Krankenhaus Bogen
,
C. Sieber
1   Klinik für Innere Medizin 2 – Geriatrie des Klinikums Nürnberg, Nürnberg
3   Institut für Biomedizin des Alterns, Friedrich-Alexander-Universität Erlangen-Nürnberg
,
C. Bollheimer
3   Institut für Biomedizin des Alterns, Friedrich-Alexander-Universität Erlangen-Nürnberg
› Author Affiliations
Further Information

Publication History

18 April 2012

17 July 2012

Publication Date:
02 October 2012 (online)

Zusammenfassung

Eine der Menopause vergleichbare Andropause gibt es nicht. Beim Mann kommt es mit zunehmendem Alter allenfalls zu einem graduellen Abfall der Testosteronproduktion. Da nach den Schwellenwerten aktueller Leitlinien ein Androgendefizit bei einem Großteil der über 80-jährigen Männer vorläge, wirft dies insbesondere in der Geriatrie die Frage nach therapeutischen Konsequenzen auf. In zahlreichen Studien korrelierten niedrige Testosteronwerte mit einem erhöhten Mortalitäts- und Morbiditätsrisiko. Ein Kausalitätsgefüge für diese Assoziation konnte bislang jedoch nicht belegt werden, sodass praktisch-klinische Schlussfolgerungen verfrüht sind. Dem im Alter von über 60 Jahren neu festgestellten Adrogendefizit wird bei gleichzeitigem Vorliegen bestimmter Symptome ein Krankheitswert als sogenannter Late-onset-Hypogonadismus (LOH) beigemessen. Die für die Diagnose notwendigen Symptome waren bislang weit gefasst. Auf dem Boden aktuellster Forschungsarbeiten (EMAS-Studie) muss der LOH jedoch eingeschränkt als sexualanamnestisch akzentuiertes Syndrom mit für die Geriatrie nachgeordneter Relevanz gesehen werden. In Assoziationsstudien findet sich ein vager Zusammenhang zwischen Androgendefizit und Gebrechlichkeit (Frailty) bzw. dem assoziierten geriatrischen Syndrom der Sarkopenie, d. h. einer Abnahme von Muskelmasse und Muskelkraft. Therapeutische Ansätze, Sarkopenie durch Testosteronsupplementation zu behandeln, zeigten nur eingeschränkten Erfolg. Mehr noch: Aufgrund des erhöhten Auftretens kardiovaskulärer Ereignisse unter Testosteronsupplementation in der TOM-Studie muss bei der Verordnung von Testosteron aktuell zu besonderer Vorsicht geraten und beim älteren Mann mit kardiovaskulärer Anamnese für ein Moratorium der Testosterongabe plädiert werden.

Abstract

Contrasting the relatively abrupt hormonal changes during female menopause, male reproductive function gradually declines during aging. This leads to the formal diagnosis of androgen deficiency in many apparently healthy 80-year-old men, when conventional thresholds are applied, and consequently to the question of androgen substitution in geriatric medicine. Although many clinical studies have documented a correlation between low plasma testosterone levels and mortality a clear causal relationship – which would imply immanent substitution therapy – has not been demonstrated. With this in mind, the diagnosis of late-onset hypogonadism (LOH) should only be made when testosterone-deficiency related symptoms concur with low testosterone levels. Which exact symptoms justify the diagnosis of LOH, however, is not sharply defined. Using criteria defined in the recent EMAS study, LOH might even be an over-diagnosed entity without huge relevance in geriatrics. Low testosterone levels are associated with frailty, but testosterone supplementation has only shown limited effects on age-related sarcopenia. Moreover: the increased incidence of cardiovascular events in the TOM study should be a caveat and lead to a moratorium for uncritical testosterone supplementation in aging men with cardiovascular diseases.

 
  • Literatur

  • 1 Araujo AB, Dixon JM, Suarez EA et al. Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011; 96: 3007-3019
  • 2 Atkinson RA, Srinivas-Shankar U, Roberts SA et al. Effects of testosterone on skeletal muscle architecture in intermediate-frail and frail elderly men. J Gerontol A Biol Sci Med Sci 2010; 65: 1215-1219
  • 3 Basaria S, Coviello AD, Travison TG et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363: 109-122
  • 4 Bhasin S, Cunningham GR, Hayes FJ et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010; 95: 2536-2559
  • 5 Bischoff-Ferrari HA, Orav EJ, Dawson-Hughes B. Additive benefit of higher testosterone levels and vitamin D plus calcium supplementation in regard to fall risk reduction among older men and women. Osteoporos Int 2008; 19: 1307-1314
  • 6 Brambilla DJ, Matsumoto AM, Araujo AB et al. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab 2009; 94: 907-913
  • 7 Cattabiani C, Basaria S, Ceda GP et al. Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men. J Endocrinol Invest 2012; 35: 104-120
  • 8 Cawthon PM, Ensrud KE, Laughlin GA et al. Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metab 2009; 94: 3806-3815
  • 9 Corona G, Monami M, Rastrelli G et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl 2011; 34: 528-540
  • 10 Corona G, Rastrelli G, Vignozzi L et al. Testosterone, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab 2011; 25: 337-353
  • 11 Falahati-Nini A, Riggs BL, Atkinson EJ et al. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 2000; 106: 1553-1560
  • 12 Fernández-Balsells MM, Murad MH, Lane M et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010; 95: 2560-2575
  • 13 Fink HA, Ewing SK, Ensrud KE 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
  • 14 Fried LP, Tangen CM, Walston J et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001; 56: 146-156
  • 15 Gray A, Feldman HA, McKinlay JB et al. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991; 73: 1016-1025
  • 16 Harman SM, Metter EJ, Tobin JD et al. Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001; 86: 724-731
  • 17 Huhtaniemi I, Forti G. Male late-onset hypogonadism: pathogenesis, diagnosis and treatment. Nat Rev Urol 2011; 8: 335-344
  • 18 Hyde Z, Flicker L, Almeida OP et al. Low free testosterone predicts frailty in older men: the health in men study. J Clin Endocrinol Metab 2010; 95: 3165-3172
  • 19 Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26: 833-876
  • 20 Kenny AM, Kleppinger A, Annis K et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc 2010; 58: 1134-1143
  • 21 Krasnoff JB, Basaria S, Pencina MJ et al. Free testosterone levels are associated with mobility limitation and physical performance in community-dwelling men: the Framingham Offspring Study. J Clin Endocrinol Metab 2010; 95: 2790-2799
  • 22 Mellström D, Vandenput L, Mallmin H et al. Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Miner Res 2008; 23: 1552-1560
  • 23 Mohr BA, Bhasin S, Kupelian V et al. Testosterone, sex hormone-binding globulin, and frailty in older men. J Am Geriatr Soc 2007; 55: 548-555
  • 24 Ruige JB, Mahmoud AM, De Bacquer D et al. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart 2011; 97: 870-875
  • 25 Saad F, Aversa A, Isidori AM et al. Testosterone as potential effective therapy in treatment of obesity in men with testosterone deficiency: a review. Curr Diabetes Rev 2012; 8: 131-143
  • 26 Sattler F, Bhasin S, He J et al. Testosterone threshold levels and lean tissue mass targets needed to enhance skeletal muscle strength and function: the HORMA trial. J Gerontol A Biol Sci Med Sci 2011; 66: 122-129
  • 27 Schatzl G, Madersbacher S, Temml C et al. Serum androgen levels in men: impact of health status and age. Urology 2003; 61: 629-633
  • 28 Seftel AD, Miner MM, Kloner RA et al. Office evaluation of male sexual dysfunction. Urol Clin North Am 2007; 34: 463-482
  • 29 Shelton JB, Rajfer J. Androgen deficiency in aging and metabolically challenged men. Urol Clin North Am 2012; 39: 63-75
  • 30 Shores MM, Matsumoto AM, Sloan KL et al. Low serum testosterone and mortality in male veterans. Arch Intern Med 2006; 166: 1660-1665
  • 31 Shores MM, Moceri VM, Gruenewald DA et al. Low testosterone is associated with decreased function and increased mortality risk: a preliminary study of men in a geriatric rehabilitation unit. J Am Geriatr Soc 2004; 52: 2077-2081
  • 32 Srinivas-Shankar U, Roberts SA, Connolly MJ et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. J Clin Endocrinol Metab 2010; 95: 639-650
  • 33 Tivesten A, Vandenput L, Labrie F et al. Low serum testosterone and estradiol predict mortality in elderly men. J Clin Endocrinol Metab 2009; 94: 2482-2488
  • 34 Tracz MJ, Sideras K, Boloña ER 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
  • 35 Travison TG, Basaria S, Storer TW et al. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci 2011; 66: 1090-1099
  • 36 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
  • 37 Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666-3672
  • 38 Vikan T, Schirmer H, Njølstad I et al. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the Tromsø Study. Eur J Endocrinol 2009; 161: 435-442
  • 39 Wang C, Nieschlag E, Swerdloff R et al. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol 2008; 159: 507-514
  • 40 Wu FC, Tajar A, Beynon JM et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010; 363: 123-135
  • 41 Zitzmann M. Die Therapie des Hypogonadismus des Mannes. Internist (Berl.) 2008; 49: 559-569