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Hypogonadotropic and Hypergonadotropic Hypogonadism

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Testosterone

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Abstract

Male hypogonadism is a clinical syndrome that results from failure of the testes to produce physiological levels of testosterone and inadequate spermatogenesis due to disruption at one or more levels of the hypothalamic-pituitary-testis axis. Testosterone deficiencies arising from diseases affecting the hypothalamus/pituitary are associated with low gonadotropins (both LH and FSH) and is termed hypogonadotropic hypogonadism, whereas testicular disorders are associated usually with elevated gonadotropins and are termed hypergonadotropic hypogonadism. Diagnosis of hypogonadism can sometimes be difficult given that the symptoms and signs are nonspecific and can vary depending on age, comorbid illness, severity, and duration of hypogonadism. A thorough medical history, physical examination, and laboratory tests are required to determine the etiology.

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References

  1. Melmed S, Koenig R, Rosen C, Auchus R, Goldfine A. Williams textbook of endocrinology. 14th ed. Philadelphia, PA: Elsevier; 2019.

    Google Scholar 

  2. Lee HG, Kim CJ. Classic and backdoor pathways of androgen biosynthesis in human sexual development. Annal Pediatr Endocrinol Metabol. 2022;27(2):83–9.

    Article  Google Scholar 

  3. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95(6):2536–59.

    Article  CAS  PubMed  Google Scholar 

  4. Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92(11):4241–7.

    Article  CAS  PubMed  Google Scholar 

  5. Jayasena CN, Anderson RA, Llahana S, Barth JH, MacKenzie F, Wilkes S, Smith N, Sooriakumaran P, Minhas S, Wu FCW, Tomlinson J, Quinton R. Society for Endocrinology guidelines for testosterone replacement therapy in male hypogonadism. Clin Endocrinol. 2022;96(2):200–19.

    Article  Google Scholar 

  6. Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007;92(2):405–13.

    Article  CAS  PubMed  Google Scholar 

  7. Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, Wang C, Handelsman DJ. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol. 2010;73:382–8.

    Article  CAS  Google Scholar 

  8. Travison TG, Vesper HW, Orwoll E, Wu F, Kaufman JM, Wang Y, Lapauw B, Fiers T, Matsumoto AM, Bhasin S. 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  PubMed  PubMed Central  Google Scholar 

  9. Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F, Huhtaniemi IT. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123–35.

    Article  CAS  PubMed  Google Scholar 

  10. Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003;88(2):622–6.

    Article  CAS  PubMed  Google Scholar 

  11. Lanfranco F, Kamischke A, Zitzmann M, Nieschlag E. Klinefelter’s syndrome. Lancet. 2004;364(9430):273–83.

    Article  CAS  PubMed  Google Scholar 

  12. Groth KA, Skakkebæk A, Høst C, Gravholt CH, Bojesen A. Clinical review: Klinefelter syndrome--a clinical update. J Clin Endocrinol Metab. 2013;98(1):20–30.

    Article  CAS  PubMed  Google Scholar 

  13. Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism. 2018;86:135–44.

    Article  CAS  PubMed  Google Scholar 

  14. Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini EA, Ferlin A. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Investig. 2017;40(2):123–34.

    Article  CAS  Google Scholar 

  15. Kaleva M, Toppari J. Cryptorchidism: an indicator of testicular dysgenesis? Cell Tissue Res. 2005;322(1):167–72.

    Article  PubMed  Google Scholar 

  16. Batra NV, DeMarco RT, Bayne CE. A narrative review of the history and evidence-base for the timing of orchidopexy for cryptorchidism. J Pediatr Urol. 2021;17(2):239–45.

    Article  PubMed  Google Scholar 

  17. Imperato-McGinley J, Zhu YS. Androgens and male physiology the syndrome of 5alpha-reductase-2 deficiency. Mol Cell Endocrinol. 2002;198(1–2):51–9.

    Article  CAS  PubMed  Google Scholar 

  18. Hornig NC, Holterhus PM. Molecular basis of androgen insensitivity syndromes. Mol Cell Endocrinol. 2021;523:111146.

    Article  CAS  PubMed  Google Scholar 

  19. Gore AC, Chappell VA, Fenton SE, Flaws JA, Nadal A, Prins GS, Toppari J, Zoeller RT. EDC-2: the Endocrine Society’s second scientific statement on endocrine-disrupting chemicals. Endocr Rev. 2015;36(6):E1–e150.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fijak M, Pilatz A, Hedger MP, Nicolas N, Bhushan S, Michel V, Tung KSK, Schuppe HC, Meinhardt A. Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice? Hum Reprod Update. 2018;24(4):416–41.

    Article  CAS  PubMed  Google Scholar 

  21. Louden ED, Poch A, Kim HG, Ben-Mahmoud A, Kim SH, Layman LC. Genetics of hypogonadotropic hypogonadism-human and mouse genes, inheritance, oligogenicity, and genetic counseling. Mol Cell Endocrinol. 2021;534:111334.

    Article  CAS  PubMed  Google Scholar 

  22. Dwyer AA, Chavan NR, Lewkowitz-Shpuntoff H, Plummer L, Hayes FJ, Seminara SB, Crowley WF, Pitteloud N, Balasubramanian R. Functional hypogonadotropic hypogonadism in men: underlying neuroendocrine mechanisms and natural history. J Clin Endocrinol Metab. 2019;104(8):3403–14.

    Article  PubMed  PubMed Central  Google Scholar 

  23. El Osta R, Grandpre N, Monnin N, Hubert J, Koscinski I. Hypogonadotropic hypogonadism in men with hereditary hemochromatosis. Basic Clin Androl. 2017;27:13.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Al-Agha AE, Bawahab NS, Nagadi SA, Alghamdi SA, Felemban DA, Milyani AA. Endocrinopathies complicating transfusion-dependent hemoglobinopathy. Saudi Med J. 2020;41(2):138–43.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gubbi S, Hannah-Shmouni F, Verbalis JG, Koch CA. Hypophysitis: an update on the novel forms, diagnosis and management of disorders of pituitary inflammation. Best Pract Res Clin Endocrinol Metab. 2019;33(6):101371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chang LS, Barroso-Sousa R, Tolaney SM, Hodi FS, Kaiser UB, Min L. Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev. 2019;40(1):17–65.

    Article  PubMed  Google Scholar 

  27. Ntali G, Tsagarakis S. Traumatic brain injury induced neuroendocrine changes: acute hormonal changes of anterior pituitary function. Pituitary. 2019;22(3):283–95.

    Article  PubMed  Google Scholar 

  28. Yuen F, Nguyen BT, Swerdloff RS, Wang C. Continuing the search for a hormonal male contraceptive. Best Pract Res Clin Obstet Gynaecol. 2020;66:83–94.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Subirán N, Casis L, Irazusta J. Regulation of male fertility by the opioid system. Mol Med. 2011;17(7–8):846–53.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Tajar A, Forti G, O’Neill TW, Lee DM, Silman AJ, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Vanderschueren D, Huhtaniemi IT, Wu FC. 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  PubMed  Google Scholar 

  31. Corona G, Maseroli E, Rastrelli G, Sforza A, Forti G, Mannucci E, Maggi M. Characteristics of compensated hypogonadism in patients with sexual dysfunction. J Sex Med. 2014;11(7):1823–34.

    Article  CAS  PubMed  Google Scholar 

  32. De Vincentis S, Decaroli MC, Fanelli F, Diazzi C, Mezzullo M, Tartaro G, Tagliavini S, De Santis MC, Roli L, Milic J, Trenti T, Pagotto U, Guaraldi G, Rochira V. Primary, secondary and compensated male biochemical hypogonadism in people living with HIV (PLWH): relevance of sex hormone-binding globulin (SHBG) measurement and comparison between liquid chromatography-tandem mass spectrometry (LC-MS/MS) and chemiluminescent immunoassay for sex steroids assay. Aging Male. 2022;25(1):41–53.

    Article  PubMed  Google Scholar 

  33. Dobs AS, Dempsey MA, Ladenson PW, Polk BF. Endocrine disorders in men infected with human immunodeficiency virus. Am J Med. 1988;84(3 Pt 2):611–6.

    Article  CAS  PubMed  Google Scholar 

  34. Sinclair M, Grossmann M, Gow PJ, Angus PW. Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol. 2015;30(2):244–51.

    Article  PubMed  Google Scholar 

  35. Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N, Buring JE, Gaziano JM, Liu S. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med. 2009;361(12):1152–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang C, Jackson G, Jones TH, Matsumoto AM, Nehra A, Perelman MA, Swerdloff RS, Traish A, Zitzmann M, Cunningham G. Low testosterone associated with obesity and the metabolic syndrome contributes to sexual dysfunction and cardiovascular disease risk in men with type 2 diabetes. Diabetes Care. 2011;34(7):1669–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Corona G, Mannucci E, Petrone L, Balercia G, Paggi F, Fisher AD, Lotti F, Chiarini V, Fedele D, Forti G, Maggi M. NCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction. J Sex Med. 2007;4(4 Pt 1):1038–45.

    Article  PubMed  Google Scholar 

  38. Corona G, Monami M, Rastrelli G, Aversa A, Sforza A, Lenzi A, Forti G, Mannucci E, Maggi M. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl. 2010;34:528–40.

    Article  PubMed  Google Scholar 

  39. Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Cifelli D, Dougar D, Fluharty L, Resnick SM, Storer TW, Anton S, Basaria S, Diem SJ, Hou X, Mohler ER III, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016;374(7):611–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Resnick SM, Budoff M, Mohler ER III, Wenger NK, Cohen HJ, Schrier S, Keaveny TM, Kopperdahl D, Lee D, Cifelli D, Ellenberg SS. Lessons from the testosterone trials. Endocr Rev. 2018;39:369.

    Article  PubMed  PubMed Central  Google Scholar 

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Author notes

  1. Prativa Rajbhandari and Jerry Sanghun Han contributed equally with all other contributors.

Authors and Affiliations

  1. Division of Endocrinology, Department of Medicine, The Lundquist Institute, Harbor-UCLA Medical Center, Torrance, CA, USA

    Prativa Rajbhandari, Jerry Sanghun Han, Christina Wang & Ronald Swerdloff

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  1. Prativa Rajbhandari
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  2. Jerry Sanghun Han
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  3. Christina Wang
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  4. Ronald Swerdloff
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Corresponding author

Correspondence to Ronald Swerdloff .

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Editors and Affiliations

  1. Department of Internal Medicine - Division of Endocrinology and Metabolism, Universidade Federal de Santa Catarina, Florianopolis, Santa Catarina, Brazil

    Alexandre Hohl

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Rajbhandari, P., Han, J.S., Wang, C., Swerdloff, R. (2023). Hypogonadotropic and Hypergonadotropic Hypogonadism. In: Hohl, A. (eds) Testosterone. Springer, Cham. https://doi.org/10.1007/978-3-031-31501-5_7

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  • DOI: https://doi.org/10.1007/978-3-031-31501-5_7

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-31500-8

  • Online ISBN: 978-3-031-31501-5

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