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Should a Varicocele Be Repaired in Non-infertile Patients with Hypogonadism?

  • Taha Abo-Almagd Abdel-Meguid HamodaEmail author
Chapter

Abstract

Varicocele is a common condition that has been traditionally linked to impaired spermatogenesis and infertility. More recently, however, there is a growing evidence that varicocele may also jeopardize Leydig cell function with consequential impairment of testosterone biosynthesis and hypogonadism, which could be reversed with varicocelectomy. The pathophysiology of varicocele-induced Leydig cell ultrastructural and functional alterations and impaired steroidogenesis is still illusive, and several mechanisms have been proposed. While testicular hyperthermia theory prevails, the pathophysiology is more likely multifactorial.

Several contemporary studies confirmed improvements of androgen levels after repair of varicocele which were found to be inversely correlating to baseline serum testosterone levels, with higher response in baseline hypogonadal men compared to eugonadals.

Very few studies have examined the association between varicocele and hypogonadism symptoms, such as erectile dysfunction (ED), hypoactive sexual drive, as well as premature ejaculation (PE), to report improvements of these sexual functions after varicocelectomy. However, these studies have several flaws and the hypothesis of improvement of sexual symptoms after varicocelectomy is still lacking good evidence.

The majority of studies supporting varicocele-hypogonadism relationship have primarily focused on infertile men, while evidence addressing varicocele-hypogonadism linkage among fertile men is still lacking. Thus, proposing varicocelectomy as a treatment of biochemical or symptomatic hypogonadism among fertile men should not be considered as a standard of care in the routine practice and should be only contemplated on an experimental basis.

Keywords

Androgen Hypogonadism Infertility Leydig cell Testicle Testosterone Varicocele Varicocelectomy Sexual dysfunction Spermatogenesis 

References

  1. 1.
    Masson P, Brannigan RE. The varicocele. Urol Clin North Am. 2014;41(1):129–44.CrossRefGoogle Scholar
  2. 2.
    Meacham RB, Townsend RR, Rademacher D, Drose JA. The incidence of varicoceles in the general population when evaluated by physical examination, gray scale sonography and color Doppler sonography. J Urol. 1994;151:1535–8.CrossRefGoogle Scholar
  3. 3.
    The influence of varicocele on parameters of fertility in a large group of men presenting in infertility clinics. World Health Organization. Fertil Steril. 1992;57:1289–93.CrossRefGoogle Scholar
  4. 4.
    Gat Y, Bachar GN, Zukerman Z, et al. Varicocele: a bilateral disease. Fertil Steril. 2004;81:424–9.CrossRefGoogle Scholar
  5. 5.
    Raman JD, Walmsley K, Goldstein M. Inheritance of varicoceles. Urology. 2005;65:1186–9.CrossRefGoogle Scholar
  6. 6.
    Schlegel PN, Goldstein M. Alternate indications for varicocele repair: non-obstructive azoospermia, pain, androgen deficiency and progressive testicular dysfunction. Fertil Steril. 2011;96(6):1288–93.CrossRefGoogle Scholar
  7. 7.
    Hayden RP, Tanrikut C. Testosterone and Varicocele. Urol Clin North Am. 2016;43(2):223–32.CrossRefGoogle Scholar
  8. 8.
    Kim KH, Lee JY, Kang DH, Lee H, Seo JT, et al. Impact of surgical varicocele repair on pregnancy rate in subfertile men with clinical varicocele and impaired semen quality: a meta-analysis of randomized clinical trials. Korean J Urol. 2013;54:703–9.CrossRefGoogle Scholar
  9. 9.
    Agarwal A, Deepinder F, Cocuzza M, et al. Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology. 2007;70:532–8.CrossRefGoogle Scholar
  10. 10.
    Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does varicocele repair improve male infertility? An evidence-based perspective from a randomized, controlled trial. Eur Urol. 2011;59:455–61.CrossRefGoogle Scholar
  11. 11.
    Ficarra V, Cerruto MA, Liguori G, et al. Treatment of varicocele in subfertile men: the Cochrane review—a contrary opinion. Eur Urol. 2006;49:258–63.CrossRefGoogle Scholar
  12. 12.
    Goldstein M, Gilbert BR, Dicker AP, et al. Microsurgical inguinal varicocelectomy with delivery of the testis: an artery and lymphatic sparing technique. J Urol. 1992;148:1808–11.CrossRefGoogle Scholar
  13. 13.
    Li F, Yue H, Yamaguchi K, et al. Effect of surgical repair on testosterone production in infertile men with varicocele: a meta-analysis. Int J Urol. 2012;19(2):149–54.CrossRefGoogle Scholar
  14. 14.
    Chen X, Yang D, Lin G, Bao J, Wang J, Tan W. Efficacy of varicocelectomy in the treatment of hypogonadism in subfertile males with clinical varicocele: a meta-analysis. Andrologia. 2017;49(10).CrossRefGoogle Scholar
  15. 15.
    Pastuszak AW, Wang R. Varicocele and testicular function. Asian J Androl. 2015;17(4):659–67.CrossRefGoogle Scholar
  16. 16.
    Dahl EV, Herrick JF. A vascular mechanism for maintaining testicular temperature by counter-current exchange. Surg Gynecol Obstet. 1959;108:697–705.Google Scholar
  17. 17.
    Zorgniotti AW, Macleod J. Studies in temperature, human semen quality, and varicocele. Fertil Steril. 1973;24:854–63.CrossRefGoogle Scholar
  18. 18.
    Mieusset R, Bujan L, Mondinat C, Mansat A, Pontonnier F, et al. Association of scrotal hyperthermia with impaired spermatogenesis in infertile men. Fertil Steril. 1987;48:1006–11.CrossRefGoogle Scholar
  19. 19.
    Goldstein M, Eid JF. Elevation of intratesticular and scrotal skin surface temperature in men with varicocele. J Urol. 1989;142:743–5.CrossRefGoogle Scholar
  20. 20.
    Yin Y, Hawkins KL, DeWolf WC, Morgentaler A. Heat stress causes testicular germ cell apoptosis in adult mice. J Androl. 1997;18:159–65.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Shiraishi K, Takihara H, Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol. 2010;28:359–64.CrossRefGoogle Scholar
  22. 22.
    Hassanin AM, Ahmed HH, Kaddah AN. A global view of the pathophysiology of varicocele. Andrology. 2018;6:654.  https://doi.org/10.1111/andr.12511. [Epub ahead of print.CrossRefGoogle Scholar
  23. 23.
    Allamaneni SS, Naughton CK, Sharma RK, Thomas AJ Jr, Agarwal A. Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertil Steril. 2004;82:1684–6.CrossRefGoogle Scholar
  24. 24.
    Hendin BN, Kolettis PN, Sharma RK, Thomas AJ Jr, Agarwal A. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. J Urol. 1999;161:1831–4.CrossRefGoogle Scholar
  25. 25.
    Gilbert BR, Witkin SS, Goldstein M. Correlation of sperm-bound immunoglobulins with impaired semen analysis in infertile men with varicoceles. Fertil Steril. 1989;52:469–73.CrossRefGoogle Scholar
  26. 26.
    Fujisawa M, Yoshida S, Matsumoto O, Kojima K, Kamidono S. Deoxyribonucleic acid polymerase activity in the testes of infertile men with varicocele. Fertil Steril. 1988;50:795–800.CrossRefGoogle Scholar
  27. 27.
    Simsek F, Turkeri L, Cevik I, Bircan K, Akdas A. Role of apoptosis in testicular tissue damage caused by varicocele. Arch Esp Urol. 1998;51:947–50.PubMedGoogle Scholar
  28. 28.
    Ando S, Giacchetto C, Colpi G, et al. Physiopathologic aspects of Leydig cell function in varicocele patients. J Androl. 1984;5(3):163–70.CrossRefGoogle Scholar
  29. 29.
    Ando S, Giacchetto C, Beraldi E, et al. Progesterone, 17-OH-progesterone, androstenedione and testosterone plasma levels in spermatic venous blood of normal men and varicocele patients. Horm Metab Res. 1985;17(2):99–103.CrossRefGoogle Scholar
  30. 30.
    Scholler R, Nahoul K, Castanier M, et al. Testicular secretion of conjugated and unconjugated steroids in normal adults and in patients with varicocele. Baseline levels and time-course response to hCG administration. J Steroid Biochem. 1984;20(1):203–15.CrossRefGoogle Scholar
  31. 31.
    Sirvent JJ, Bernat R, Navarro MA, Rodriguez Tolra J, Guspi R, et al. Leydig cell in idiopathic varicocele. Eur Urol. 1990;17:257–61.CrossRefGoogle Scholar
  32. 32.
    Francavilla S, Bruno B, Martini M, et al. Quantitative evaluation of Leydig cells in testicular biopsies of men with varicocele. Arch Androl. 1986;16(2):111–7.CrossRefGoogle Scholar
  33. 33.
    Weiss DB, Rodrigues-Rigau L, Smith KD, et al. Leydig cell density and function and their relation to gonadotropins in infertile oligospermic men with varicocele. Isr J Med Sci. 1979;15(7):556–63.PubMedGoogle Scholar
  34. 34.
    Rajfer J, Turner TT, Rivera F, et al. Inhibition of testicular testosterone biosynthesis following experimental varicocele in rats. Biol Reprod. 1987;36(4):933–7.CrossRefGoogle Scholar
  35. 35.
    Zheng Y, Zhang X, Zhou J, et al. Effects on the ipsilateral testis during progression of experimental varicocele in rat. Med Sci Monit. 2008;14(6):BR122–6.PubMedGoogle Scholar
  36. 36.
    Ozturk MI, Koca O, Keles MO, et al. The impact of unilateral experimental rat varicocele model on testicular histopathology, Leydig cell counts, and intratesticular testosterone levels of both testes. Urol J. 2013;10(3):973–80.PubMedGoogle Scholar
  37. 37.
    Shafik A, Wali MA, Abdel Azis YE, et al. Experimental model of varicocele. Eur Urol. 1989; 16(4):298–303.CrossRefGoogle Scholar
  38. 38.
    Ghosh PK, York JP. Changes in testicular testosterone and acid and alkaline phosphatase activity in testis and accessory sex organs after induction of varicocele in noble rats. J Surg Res. 1994;56(3):271–6.CrossRefGoogle Scholar
  39. 39.
    Luo D-Y, Yang G, Liu J-J, et al. Effects of varicocele on testosterone, apoptosis and expression of StAR mRNA in rat Leydig cells. Asian J Androl. 2011;13(2):287–91.CrossRefGoogle Scholar
  40. 40.
    Diemer T, Allen JA, Hales KH, et al. Reactive oxygen disrupts mitochondria in MA-10 tumor Leydig cells and inhibits steroidogenic acute regulatory (StAR) protein and steroidogenesis. Endocrinology. 2003;144(7):2882–91.CrossRefGoogle Scholar
  41. 41.
    Rodriguez-Rigau LJ, Weiss DB, Zukerman Z, et al. A possible mechanism for the detrimental effect of varicocele on testicular function in man. Fertil Steril. 1978;30(5):577–85.CrossRefGoogle Scholar
  42. 42.
    Shabana W, Teleb M, Dawod T, et al. Predictors of improvement in semen parameters after varicocelectomy for male subfertility: a prospective study. Can Urol Assoc J. 2015;9(9–10):E579–82.CrossRefGoogle Scholar
  43. 43.
    Hudson RW, Perez-Marrero RA, Crawford VA, et al. Hormonal parameters of men with varicoceles before and after varicocelectomy. Fertil Steril. 1985;43(6):905–10.CrossRefGoogle Scholar
  44. 44.
    Sweeney TE, Rozum JS, Gore RW. Alteration of testicular microvascular pressures during venous pressure elevation. Am J Phys. 1995;269(1):H37–45.Google Scholar
  45. 45.
    Pasqualini T, Chemes H, Coco R, et al. Testicular function in varicocele. Int J Androl. 1980;3(6):679–91.CrossRefGoogle Scholar
  46. 46.
    Stocco DM, Wells J, Clark BJ. The effects of hydrogen peroxide on steroidogenesis in mouse Leydig tumor cells. Endocrinology. 1993;133(6):2827–32.CrossRefGoogle Scholar
  47. 47.
    Pirke KM, Vogt HJ, Sintermann R, et al. Testosterone in peripheral plasma, spermatic vein and in testicular tissue under basal conditions and after HCG stimulation in patients with varicocele. Andrologia. 1983;15(6):637–41.CrossRefGoogle Scholar
  48. 48.
    Comhaire F, Vermeulen A. Plasma testosterone in patients with varicocele and sexual inadequacy. J Clin Endocrinol Metab. 1975;40:824–9.CrossRefGoogle Scholar
  49. 49.
    Mehta A, Goldstein M. Microsurgical varicocelectomy: a review. Asian J Androl. 2013;15:56–60.CrossRefGoogle Scholar
  50. 50.
    Andó S, Giacchetto C, Beraldi E, Panno ML, Carpino A, et al. Testosterone and dihydrotestosterone seminal plasma levels in varicocele patients. Andrologia. 1983;15:374–9.CrossRefGoogle Scholar
  51. 51.
    Younes AK. Low plasma testosterone in varicocele patients with impotence and male infertility. Arch Androl. 2000;45:187–95.CrossRefGoogle Scholar
  52. 52.
    Hudson RW, Hayes KA, Crawford VA, McKay DE. Seminal plasma testosterone and dihydrotestosterone levels in men with varicoceles. Int J Androl. 1983;6:135–42.CrossRefGoogle Scholar
  53. 53.
    Swerdloff RS, Walsh PC. Pituitary and gonadal hormones in patients with varicocele. Fertil Steril. 1975;26:1006–12.CrossRefGoogle Scholar
  54. 54.
    Su LM, Goldstein M, Schlegel PN. The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles. J Urol. 1995;154:1752–5.CrossRefGoogle Scholar
  55. 55.
    Tanrikut C, Choi J, Lee R, Benjamin J, Mulhall J, et al. Varicocele is a risk factor for androgen deficiency. Fertil Steril. 2007;88:S386.Google Scholar
  56. 56.
    Tanrikut C, Goldstein M, Rosoff JS, Lee RK, Nelson CJ, et al. Varicocele as a risk factor for androgen deficiency and effect of repair. BJU Int. 2011;108:1480–4.CrossRefGoogle Scholar
  57. 57.
    Hsiao W, Rosoff JS, Pale JR, Greenwood EA, Goldstein M. Older age is associated with similar improvements in semen parameters and testosterone after subinguinal microsurgical varicocelectomy. J Urol. 2011;185:620–5.CrossRefGoogle Scholar
  58. 58.
    Hsiao W, Rosoff JS, Pale JR, Powell JL, Goldstein M. Varicocelectomy is associated with increases in serum testosterone independent of clinical grade. Urology. 2013;81:1213–7.CrossRefGoogle Scholar
  59. 59.
    Di Bisceglie C, Bertagna A, Baldi M, Lanfranco F, Tagliabue M, et al. Varicocele sclerotherapy improves serum inhibin B levels and seminal parameters. Int J Androl. 2007;30:531–6.CrossRefGoogle Scholar
  60. 60.
    Abdel-Meguid TA, Farsi HM, Al-Sayyad A, Tayib A, Mosli HA, et al. Effects of varicocele on serum testosterone and changes of testosterone after varicocelectomy: a prospective controlled study. Urology. 2014;84:1081–7.CrossRefGoogle Scholar
  61. 61.
    Ahmed A, Abdel-Aziz A, Maarouf A, et al. The impact of varicocelectomy on premature ejaculation in varicocele patients. Andrologia. 2015;47(3):276–81.CrossRefGoogle Scholar
  62. 62.
    Pierik FH, Abdesselam SA, Vreeburg JT, et al. Increased serum inhibin B levels after varicocele treatment. Clin Endocrinol. 2001;54(6):775–80.CrossRefGoogle Scholar
  63. 63.
    Rodriguez Peña M, Alescio L, Russell A, et al. Predictors of improved seminal parameters and fertility after varicocele repair in young adults. Andrologia. 2009;41(5):277–81.CrossRefGoogle Scholar
  64. 64.
    Resorlu B, Kara C, Sahin E, et al. The significance of age on success of surgery for patients with varicocele. Int Urol Nephrol. 2010;42(2):351–6.CrossRefGoogle Scholar
  65. 65.
    Younes AK. Improvement of sexual activity, pregnancy rate, and low plasma testosterone after bilateral varicocelectomy in impotence and male infertility patients. Arch Androl. 2003;49:219–28.CrossRefGoogle Scholar
  66. 66.
    Zohdy W, Ghazi S, Arafa M. Impact of varicocelectomy on gonadal and erectile functions in men with hypogonadism and infertility. J Sex Med. 2011;8:885–93.CrossRefGoogle Scholar
  67. 67.
    Sathya Srini V, Belur Veerachari S. Does varicocelectomy improve gonadal function in men with hypogonadism and infertility? Analysis of a prospective study. Int J Endocrinol. 2011;2011:916380.CrossRefGoogle Scholar
  68. 68.
    Najari BB, Introna L, Paduch DA. Improvements in patient reported sexual function after microsurgical varicocelectomy. Urology. 2016;16:30194–7.Google Scholar
  69. 69.
    Lotti F, Corona G, Mancini M, et al. The association between varicocele, premature ejaculation and prostatitis symptoms: possible mechanisms. J Sex Med. 2009;6:2878–87.CrossRefGoogle Scholar
  70. 70.
    Wan X, Wang H, Ji Z. Microsurgical varicocelectomy for clinical varicocele: a review for potential new indications. Andrologia. 2017;49:e12827.CrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Urology, Faculty of MedicineKing Abdulaziz UniversityJeddahSaudi Arabia
  2. 2.Department of Urology, Faculty of MedicineMinia UniversityEl-MiniaEgypt

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