• Sam Haywood
  • Eric L. Laborde
  • Robert E. Brannigan


Spermatogenesis depends on an intricate interplay of hormonal factors both centrally and in the testis. Centrally, the hypothalamus releases gonadotropin-releasing hormone (GnRH), which acts on the anterior pituitary to cause secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). At the level of the testis, FSH acts on Sertoli cells to induce the maturation process in spermatogonia. LH exerts its effect on Leydig cells, stimulating production of testosterone. Effective spermatogenesis requires local testosterone concentrations to be much higher than serum concentrations. This intratesticular testosterone then acts indirectly to stimulate germ cell maturation through actions on Sertoli cells. Although endocrinopathies only account for a small minority of cases of male infertility, about 1–2%, the treatment of these conditions offers patients a strategy of directed therapy. Broad classification of endocrinopathies involves two main categories: hormonal deficiency and hormonal excess, with specific hormonal abnormalities falling under each of the above categorizations.


Male infertility Spermatogenesis Endocrinopathy Hypogonadotropic hypogonadism Hypergonadotropic hypogonadism Hyperprolactinemia Hyperthyroidism Androgen excess Estrogen excess 


  1. 1.
    Alukal J, Lamb D, Niederberger C, Makhlouf A. Spermatogenesis in the adult. In: Lipshultz L, Howards S, Niederberger C, editors. Infertility in the male. New York: Cambridge University; 2009. p. 74–89.CrossRefGoogle Scholar
  2. 2.
    Caroppo E. Male hypothalamic-pituitary-gonadal axis. In: Lipshultz L, Howards S, Niederberger C, editors. Infertility in the male. New York: Cambridge University; 2009. p. 14–28.CrossRefGoogle Scholar
  3. 3.
    Kim HH, Schlegel PN. Endocrine manipulation in male infertility. Urol Clin North Am. 2008;35:303–18.PubMedCrossRefGoogle Scholar
  4. 4.
    Sussman EM, Chudnovsky A, Niederberger CS. Hormonal evaluation of the infertile male: has it evolved? Urol Clin North Am. 2008;35:147–55.PubMedCrossRefGoogle Scholar
  5. 5.
    Coviello AD, Matsumoto AM, Bremner WJ, et al. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab. 2005;90:2595–602.PubMedCrossRefGoogle Scholar
  6. 6.
    Bouloux PM, Nieschlag E, Burger HG, et al. Induction of spermatogenesis by recombinant follicle-stimulating hormone (puregon) in hypogonadotropic azoospermic men who failed to respond to human chorionic gonadotropin alone. J Androl. 2003;24: 604–11.PubMedGoogle Scholar
  7. 7.
    Schiff JD, Ramirez ML, Bar-Chama N. Medical and surgical management male infertility. Endocrinol Metab Clin North Am. 2007;36:313–31.PubMedCrossRefGoogle Scholar
  8. 8.
    Liu PY, Baker HW, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009;94:801–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Clark ABR, Vantman D, Sherins R. A low sperm concentration does not preclude fertility in men with isolated hypogonadotropic hypogonadism after gonadotropin therapy. Fertil Steril. 1988;50: 343–7.PubMedGoogle Scholar
  10. 10.
    Miyagawa Y, Tsujimura A, Matsumiya K, et al. Outcome of gonadotropin therapy for male hypogonadotropic hypogonadism at university affiliated male infertility centers: a 30-year retrospective study. J Urol. 2005;173:2072–5.PubMedCrossRefGoogle Scholar
  11. 11.
    Farhat R, Al-Zidjali F, Alzahrani AS. Outcome of gonadotropin therapy for male infertility due to hypogonadotrophic hypogonadism. Pituitary. 2010;13(2):05–10.CrossRefGoogle Scholar
  12. 12.
    Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril. 2006;86:1664–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Ioannidou-Kadis S, Wright PJ, Neely RD, Quinton R. Complete reversal of adult-onset isolated hypogonadotropic hypogonadism with clomiphene citrate. Fertil Steril. 2006;86:1513e5–9.Google Scholar
  14. 14.
    Burge MR, Lanzi RA, Skarda ST, Eaton RP. Idiopathic hypogonadotropic hypogonadism in a male runner is reversed by clomiphene citrate. Fertil Steril. 1997;67:783–5.PubMedCrossRefGoogle Scholar
  15. 15.
    Boyle K. Nonsurgical treatment: empiric therapy. In: Lipshultz L, Howards S, Niederberger C, editors. Infertility in the male. New York: Cambridge University; 2009. p. 438–53.CrossRefGoogle Scholar
  16. 16.
    Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167:624–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Ramasamy R, Ricci JA, Palermo GD, Gosden LV, Rosenwaks Z, Schlegel PN. Successful fertility treatment for Klinefelter’s syndrome. J Urol. 2009;182:1108–13.PubMedCrossRefGoogle Scholar
  18. 18.
    Griboff SI. Semen analysis in myxedema. Fertil Steril. 1962;13: 436–43.PubMedGoogle Scholar
  19. 19.
    Meeker JD, Godfrey-Bailey L, Hauser R. Relationships between serum hormone levels and semen quality among men from an infertility clinic. J Androl. 2007;28:397–406.PubMedCrossRefGoogle Scholar
  20. 20.
    Krassas GE, Papadopoulou F, Tziomalos K, Zeginiadou T, Pontikides N. Hypothyroidism has an adverse effect on human spermatogenesis: a prospective, controlled study. Thyroid. 2008;18:1255–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Dohle GR, Smit M, Weber RF. Androgens and male fertility. World J Urol. 2003;21:341–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Turek PJ, Williams RH, Gilbaugh 3rd JH, Lipshultz LI. The reversibility of anabolic steroid-induced azoospermia. J Urol. 1995;153:1628–30.PubMedCrossRefGoogle Scholar
  23. 23.
    Menon DK. Successful treatment of anabolic steroid-induced azoospermia with human chorionic gonadotropin and human menopausal gonadotropin. Fertil Steril. 2003;79 Suppl 3: 1659–61.PubMedCrossRefGoogle Scholar
  24. 24.
    Tan RS, Vasudevan D. Use of clomiphene citrate to reverse premature andropause secondary to steroid abuse. Fertil Steril. 2003;79:203–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol. 2001;165:837–41.PubMedCrossRefGoogle Scholar
  26. 26.
    Roth MY, Amory JK, Page ST. Treatment of male infertility secondary to morbid obesity. Nat Clin Pract Endocrinol Metab. 2008;4:415–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Abalovich M, Levalle O, Hermes R, et al. Hypothalamic-pituitary-testicular axis and seminal parameters in hyperthyroid males. Thyroid. 1999;9:857–63.PubMedCrossRefGoogle Scholar
  28. 28.
    Krassas GE, Pontikides N, Deligianni V, Miras K. A prospective controlled study of the impact of hyperthyroidism on reproductive function in males. J Clin Endocrinol Metab. 2002;87:3667–71.PubMedCrossRefGoogle Scholar
  29. 29.
    Thorner MO, McNeilly AS, Hagan C, Besser GM. Long-term treatment of galactorrhoea and hypogonadism with bromocriptine. Br Med J. 1974;2:419–22.PubMedCrossRefGoogle Scholar
  30. 30.
    De Rosa M, Colao A, Di Sarno A, et al. Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine. Eur J Endocrinol. 1998;138: 286–93.PubMedCrossRefGoogle Scholar
  31. 31.
    De Rosa M, Ciccarelli A, Zarrilli S, et al. The treatment with cabergoline for 24 month normalizes the quality of seminal fluid in hyperprolactinaemic males. Clin Endocrinol (Oxf). 2006;64:307–13.CrossRefGoogle Scholar
  32. 32.
    Gillam MP, Molitch ME, Lombardi G, Colao A. Advances in the treatment of prolactinomas. Endocr Rev. 2006;27:485–534.PubMedCrossRefGoogle Scholar
  33. 33.
    Ribeiro RS, Abucham J. Recovery of persistent hypogonadism by clomiphene in males with prolactinomas under dopamine agonist treatment. Eur J Endocrinol. 2009;161:163–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Kasturi SS, Tannir J, Brannigan RE. The metabolic syndrome and male infertility. J Androl. 2008;29:251–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Sam Haywood
    • 1
  • Eric L. Laborde
    • 1
  • Robert E. Brannigan
    • 1
  1. 1.Department of UrologyNorthwestern University Feinberg School of MedicineChicagoUSA

Personalised recommendations