Skip to main content
SpringerLink
Log in

Benefits and Risks of Testosterone Replacement in the Older Man with Hypogonadism

  • Chapter
  • First Online:
Pituitary Disorders throughout the Life Cycle

  • 312 Accesses

Abstract

The diagnosis of hypogonadism requires that both symptoms and biochemical evidence of low testosterone are present. Pathologic hypogonadism occurs secondary to organic disease of the hypothalamic-pituitary-testicular axis. Functional hypogonadism occurs with advancing age and chronic disease and often has more modest decreases in testosterone production. Diagnosis of low testosterone requires an understanding of how sex hormone-binding globulin (SHBG) levels impact the measured levels of total testosterone and the factors that impact SHBG levels including obesity and sleep apnea. Verification of true biochemical hypogonadism may require the use of free and/or bioavailable testosterone measurements. In older male patients with confirmed symptomatic hypogonadism, beside considering the benefits of testosterone replacement to the bone, muscle, and sexual function, it is also important to take into account potential risks related to cardiovascular diseases, lower urinary tract symptoms, prostate cancer, and thromboembolic disease. Standard safety monitoring should include periodic measurement of hematocrit and prostate-specific antigen.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018;103(5):1715–44.

    Article  Google Scholar 

  2. Tajar A, Forti G, O'Neill TW, Lee DM, Silman AJ, Finn JD, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metab. 2010;95(4):1810–8.

    Article  CAS  Google Scholar 

  3. 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(11):4241–7.

    Article  CAS  Google Scholar 

  4. 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(12):5920–6.

    Article  CAS  Google Scholar 

  5. Marcelli M, Mediwala SN. Male hypogonadism: a review. J Investig Med. 2020;68(2):335–56.

    Article  Google Scholar 

  6. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123–35.

    Article  CAS  Google Scholar 

  7. Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 1991;73(5):1016–25.

    Article  CAS  Google Scholar 

  8. Wu FC, 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(7):2737–45.

    Article  CAS  Google Scholar 

  9. Grossmann M, Matsumoto AM. A perspective on middle-aged and older men with functional hypogonadism: focus on holistic management. J Clin Endocrinol Metab. 2017;102(3):1067–75.

    Article  Google Scholar 

  10. Nettleship JE, Pugh PJ, Channer KS, Jones T, Jones RD. Inverse relationship between serum levels of interleukin-1beta and testosterone in men with stable coronary artery disease. Horm Metab Res. 2007;39(5):366–71.

    Article  CAS  Google Scholar 

  11. Bobjer J, Katrinaki M, Tsatsanis C, Lundberg Giwercman Y, Giwercman A. Negative association between testosterone concentration and inflammatory markers in young men: a nested cross-sectional study. PLoS One. 2013;8(4):e61466.

    Article  CAS  Google Scholar 

  12. Porte D Jr, Baskin DG, Schwartz MW. Insulin signaling in the central nervous system: a critical role in metabolic homeostasis and disease from C. elegans to humans. Diabetes. 2005;54(5):1264–76.

    Article  CAS  Google Scholar 

  13. Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev. 2006;27(1):73–100.

    Article  CAS  Google Scholar 

  14. George JT, Millar RP, Anderson RA. Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes. Neuroendocrinology. 2010;91(4):302–7.

    Article  CAS  Google Scholar 

  15. 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. 2009;70(3):455–63.

    Article  CAS  Google Scholar 

  16. 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(10):3666–72.

    Article  CAS  Google Scholar 

  17. Zakharov MN, Bhasin S, Travison TG, Xue R, Ulloor J, Vasan RS, et al. A multi-step, dynamic allosteric model of testosterone's binding to sex hormone binding globulin. Mol Cell Endocrinol. 2015;399:190–200.

    Article  CAS  Google Scholar 

  18. Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, et al. Harmonized reference ranges for circulating testosterone levels in men of four cohort studies in the United States and Europe. J Clin Endocrinol Metab. 2017;102(4):1161–73.

    Article  Google Scholar 

  19. Dalvi M, Walker BR, Strachan MW, Zammitt NN, Gibb FW. The prevalence of structural pituitary abnormalities by MRI scanning in men presenting with isolated hypogonadotrophic hypogonadism. Clin Endocrinol. 2016;84(6):858–61.

    Article  CAS  Google Scholar 

  20. Corona G, Rastrelli G, Morelli A, Sarchielli E, Cipriani S, Vignozzi L, et al. Treatment of functional hypogonadism besides pharmacological substitution. World J Mens Health. 2020;38(3):256–70.

    Article  Google Scholar 

  21. Jensterle M, Podbregar A, Goricar K, Gregoric N, Janez A. Effects of liraglutide on obesity-associated functional hypogonadism in men. Endocr Connect. 2019;8(3):195–202.

    Article  CAS  Google Scholar 

  22. Camacho EM, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol. 2013;168(3):445–55.

    Article  CAS  Google Scholar 

  23. Spitzer M, Basaria S, Travison TG, Davda MN, Paley A, Cohen B, et al. Effect of testosterone replacement on response to sildenafil citrate in men with erectile dysfunction: a parallel, randomized trial. Ann Intern Med. 2012;157(10):681–91.

    Article  Google Scholar 

  24. Buvat J, Montorsi F, Maggi M, Porst H, Kaipia A, Colson MH, et al. Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study). J Sex Med. 2011;8(1):284–93.

    Article  CAS  Google Scholar 

  25. Jannini EA, Screponi E, Carosa E, Pepe M, Lo Giudice F, Trimarchi F, et al. Lack of sexual activity from erectile dysfunction is associated with a reversible reduction in serum testosterone. Int J Androl. 1999;22(6):385–92.

    Article  CAS  Google Scholar 

  26. Qaseem A, Snow V, Denberg TD, Casey DE Jr, Forciea MA, Owens DK, et al. Hormonal testing and pharmacologic treatment of erectile dysfunction: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2009;151(9):639–49.

    Article  Google Scholar 

  27. Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, et al. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. Andrology. 2020;8(5):970–87.

    Article  Google Scholar 

  28. Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374(7):611–24.

    Article  CAS  Google Scholar 

  29. Cunningham GR, Stephens-Shields AJ, Rosen RC, Wang C, Bhasin S, Matsumoto AM, et al. Testosterone treatment and sexual function in older men with low testosterone levels. J Clin Endocrinol Metab. 2016;101(8):3096–104.

    Article  CAS  Google Scholar 

  30. Roy CN, Snyder PJ, Stephens-Shields AJ, Artz AS, Bhasin S, Cohen HJ, et al. Association of testosterone levels with anemia in older men: a controlled clinical trial. JAMA Intern Med. 2017;177(4):480–90.

    Article  Google Scholar 

  31. Snyder PJ, Kopperdahl DL, Stephens-Shields AJ, Ellenberg SS, Cauley JA, Ensrud KE, et al. Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial. JAMA Intern Med. 2017;177(4):471–9.

    Article  Google Scholar 

  32. Resnick SM, Matsumoto AM, Stephens-Shields AJ. Cognitive function after testosterone treatment. JAMA. 2017;317(22):2335–6.

    Article  Google Scholar 

  33. Barry MJ, Fowler FJ Jr, O'leary MP, Bruskewitz RC, Holtgrewe HL, Mebust WK, Cockett AT, Measurement Committee of the American Urological Association. The American urological association symptom index for benign prostatic hyperplasia. J Urol. 2017;197(2S):S189–97.

    Article  Google Scholar 

  34. Gerstenbluth RE, Maniam PN, Corty EW, Seftel AD. Prostate-specific antigen changes in hypogonadal men treated with testosterone replacement. J Androl. 2002;23(6):922–6.

    PubMed  Google Scholar 

  35. Meikle AW, Arver S, Dobs AS, Adolfsson J, Sanders SW, Middleton RG, et al. Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced testosterone transdermal system. Urology. 1997;49(2):191–6.

    Article  CAS  Google Scholar 

  36. Boyle P, Koechlin A, Bota M, d'Onofrio A, Zaridze DG, Perrin P, et al. Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis. BJU Int. 2016;118(5):731–41.

    Article  CAS  Google Scholar 

  37. Ponce OJ, Spencer-Bonilla G, Alvarez-Villalobos N, Serrano V, Singh-Ospina N, Rodriguez-Gutierrez R, et al. The efficacy and adverse events of testosterone replacement therapy in hypogonadal men: a systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Endocrinol Metab. 2018;103(5):1745–54.

    Google Scholar 

  38. Glueck CJ, Wang P. Testosterone therapy, thrombosis, thrombophilia, cardiovascular events. Metabolism. 2014;63(8):989–94.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine, The Michael E. DeBakey VA Medical Center, Houston, TX, USA

    Marco Marcelli & Sanjay Navin Mediwala

Authors
  1. Marco Marcelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sanjay Navin Mediwala
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marco Marcelli .

Editor information

Editors and Affiliations

  1. Mayo Clinic, Jacksonville, FL, USA

    Susan L. Samson

  2. Emory University School of Medicine, Atlanta, GA, USA

    Adriana G. Ioachimescu

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Marcelli, M., Mediwala, S.N. (2022). Benefits and Risks of Testosterone Replacement in the Older Man with Hypogonadism. In: Samson, S.L., Ioachimescu, A.G. (eds) Pituitary Disorders throughout the Life Cycle. Springer, Cham. https://doi.org/10.1007/978-3-030-99918-6_30

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-99918-6_30

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-99917-9

  • Online ISBN: 978-3-030-99918-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation