Evidence-Based Andrology: The Importance of Controlled Clinical Trials

  • E. Leifke
  • E. Nieschlag
Conference paper
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 2/1996)


The concept of evidence-based medicine has emerged over the past decades, and, by virtue of its pervasive influence, is becoming a “constitutional amendment” in all fields of clinical practice. Personal authority and skills born of experience are no longer the major determining factors when therapeutic decisions must be made. In addition to pathophysiological rationales and professional expertise, clinical practice should be based on properly designed studies and applied statistics, summarized under the term of outcome research (Evidence-Based Medicine Working Group 1992). While widely regarded as an oddity in medicine up to the 1960s, today the controlled, prospective, randomized — and if possible — double-blind clinical trial is accepted as the most reliable method of proving the effectiveness of diagnostic and therapeutic strategies. No drug, no surgical therapy, and not even a diagnostic test should enter or remain in clinical practice without evidence and outcome research-based confirmation of their benefits.


Pregnancy Rate Male Infertility Infertility Treatment Cervical Mucus Obstructive Azoospermia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bals-Pratsch M, Knuth UA, Hönigl W, Klein HM, Bergmann M, Nieschlag E (1989) Pulsatile GnRH-therapy in oligozoospermic men does not improve seminal parameters despite decreased FSH levels. Clin Endocrinol (Oxf) 30:549–560.CrossRefGoogle Scholar
  2. Bals-Pratsch M, Dören M, Karbowski B, Schneider HPG, Nieschlag E (1992) Cyclic corticoid immunosuppression is unsuccessful in the treatment of sperm antibody-related male infertility: a controlled study. Hum Reprod 7:99–104.PubMedGoogle Scholar
  3. Evidence-based Medicine Working Group (1992) Evidence-based medicine: a new approach to teaching the practice of medicine. JAMA 268:2420–2425.CrossRefGoogle Scholar
  4. Glezerman M, Lunenfeld E, Potashnik G, Huleihel M, Soffer Y, Segal S (1993) Efficacy of kallikrein in the treatment of oligozoospermia and as-thenozoospermia: a double-blind trial. Fertil Steril 60:1052–1056.PubMedGoogle Scholar
  5. Gotzsche PC (1994) Is there logic in the placebo? Lancet 344:925–926.PubMedCrossRefGoogle Scholar
  6. Haas G, Manganiello P (1987) A double-blind, placebo-controlled study of the use of methylprednisolone in infertile men with sperm-associated immunoglobulins. Fertil Steril 47:295–301.PubMedGoogle Scholar
  7. Hendry WF, Stedronska J, Parslow J, Hughes L (1981) The results of intermittent high dose steroid therapy for male infertility due to antisperm antibodies. Fertil Steril 36:351–355.PubMedGoogle Scholar
  8. Hendry W, Hughes L, Scammell G, Pryor J, Hargreave T (1990) Comparison of prednisolone and placebo in subfertile men with antibodies to spermatozoa. Lancet 335:85–88.PubMedCrossRefGoogle Scholar
  9. Hirsch AV, Mills C, Bekir J, Dean N, Yovich JL, Tan SL (1994) Factors influencing the outcome of in vitro fertilization with epididymal spermatozoa in irreversible obstructive azoospermia. Hum Reprod 9:1710–1716.Google Scholar
  10. Howards SS (1995) Treatment of male infertility. N Engl J Med 2:312–317.CrossRefGoogle Scholar
  11. Hull M, Glazener C, Kelley N, Conway D, Foster P, Hinton R, Coulson C, Lambert P, Watt E, Desai K (1985) Population studies of causes, treatment and outcome of infertility. Br Med J 291:1693–1697.CrossRefGoogle Scholar
  12. Jager S, Kremer J, van Slochteren-Draaisma T (1979) Presence of sperm agglutination antibodies in infertile men and inhibition of in vitro sperm penetration into cervical mucus. Int J Androl 2:117–130.CrossRefGoogle Scholar
  13. Jager S, Kremer J, Kuiken J, van Slochteren-Draaisma T (1980) Immunoglobulin class of antispermatozoal antibodies from infertile men and inhibition of in vitro sperm penetration into cervical mucus. Andrology 3:1–14.CrossRefGoogle Scholar
  14. Johnson AG (1994) Surgery as a placebo. Lancet 344:1140–1142.PubMedCrossRefGoogle Scholar
  15. Keck C, Behre HM, Jockenhövel F, Nieschlag E (1994) Ineffectiveness of kallikrein in treatment of idiopathic male infertility: a double-blind, randomized, placebo-controlled trial. Hum Reprod 9:325–329.PubMedGoogle Scholar
  16. Kleijnen J, de Craen AJM, van Everdingen J, Krol L (1994) Placebo effect in double-blind clinical trials: a review of interactions with medications. Lancet 344:1347–1351.PubMedCrossRefGoogle Scholar
  17. Kliesch S, Behre HM, Nieschlag E (1994) High efficacy of gonadotropin or pulsatile GnRH treatment in hypogonadotropic hypogonadal men. Eur J Endocr 131:347–354.CrossRefGoogle Scholar
  18. Knuth UA, Hönigl W, Bals-Pratsch M, Schleicher G, Nieschlag E (1987) Treatment of severe oligozoospermia with hCG/hMG. A placebo-controlled double blind trial. J Clin Endocrinol Metab 65:1081–1087.PubMedCrossRefGoogle Scholar
  19. Leidl W, Prinzen R, Schill WB, Fritz H (1975) The effect of kallikrein on motility and metabolism of spermatozoa in vitro. In: Haberland GL, Rohen JW, Schirren C, Huber P (eds) Kininogenases. Kallikrein 2. Schattauer, Stuttgart, pp 33–40.Google Scholar
  20. Liu L, Banks SM, Barnes KM, Sherins RJ (1988) Two-year comparison of testicular responses to pulsatile gonadotropin-releasing hormone and exogenous gonadotropins from the inception of therapy in men with isolated.hypogonadotropic hypogonadism. J Clin Endoc Metabol 67:1140–1145.CrossRefGoogle Scholar
  21. Micic S, Bila S, Nic V, Sulovic V (1985) Treatment of men with oligoasthenozoospermia and asthenozoospermia with kallikrein. Acta Eur Fertil 16:51–54.PubMedGoogle Scholar
  22. Micic S, Tulic C, Dotlic R (1990) Kallikrein therapy of infertile men with varicocele and impaired sperm motility. Andrologia 22:179–183.PubMedCrossRefGoogle Scholar
  23. Nieschlag E (1993) Current therapy: care for the infertile male. Clin Endocrinol (Oxf) 38:123–133.CrossRefGoogle Scholar
  24. Nieschlag E (1994) Clinical relevance and irrelevance of molecular and cellular research on the testis in molecular and cellular endocrinology of the testis. In: Verhoeven G, Habenicht UF (eds) Molecular and cellular endocrinology of the testis. Springer, Berlin Heidelberg New York, pp 273–292 (Ernst Schering Research Foundation Workshop, Suppl 1).Google Scholar
  25. Nieschlag E, Behre HM (1992) Male Infertility due to testicular dysfunction. In: Drife JO, Templeton AA (eds) Infertility. Proceedings of the 25th study group of the Royal College of Obstetricians and Gynaecologists. Springer, Berlin Heidelberg New York, pp 65–80.Google Scholar
  26. Nieschlag E, Wickings EJ, Mauss J (1979) Endocrine testicular function in vivo and in vitro in infertile men. Acta Endocrinol (Copenh) 90:544–551.Google Scholar
  27. Nieschlag E, Hertle L, Fischedick A, Behre HM (1995) Treatment of varicocele: counselling as effective as occlusion of the vena spermatica. Hum Reprod 10 (2):347–353.PubMedGoogle Scholar
  28. Olive DL (1986) Analysis of clinical fertility trials: a methodologic review. Fertil Steril 45:157–171.PubMedGoogle Scholar
  29. Peck C, Coleman G (1991) Implications for placebo theory for clinical research and practice in pain management. Theor Med 12:247–270.PubMedCrossRefGoogle Scholar
  30. Pocock SJ (1983) Clinical trials: a practical approach. Wiley, New York.Google Scholar
  31. Purvis K, Christiansen E (1993) Infection in the male reproductive tract. Impact, diagnosis and treatment in relation to male infertility. Int J Androl 16:1–13.PubMedCrossRefGoogle Scholar
  32. Rolf C, Behre HM, Nieschlag E (1996) Tamoxifen bei männlicher Infertilität. Analyse einer fragwürdigen Therapie. Dtsch Med Wochenschr 121:33–39.PubMedCrossRefGoogle Scholar
  33. Sato H (1980) Studies on the components of kallikrein-kinin system and treatment of male infertility. Keio J Med 29:19–38.PubMedCrossRefGoogle Scholar
  34. Schäfer M, Brühl P, Jankowski (1989) Aktuelle Diagnostik und Therapie des Maldeszensus testis. Klin Padiatr 201:452–457.CrossRefGoogle Scholar
  35. Schill WB (1979) Treatment of idiopathic oligozoospermia by kallikrein: results of a double-blind study. Arch Androl 2:163–170.PubMedCrossRefGoogle Scholar
  36. Schill WB (1986) Medical treatment of male infertility. In: Insler V, Lunenfeld B (eds) Infertility: male and female. Churchill Livingstone, Edinburgh, pp 533–573.Google Scholar
  37. Schopohl J, Mehltretter G, von Zumbusch R, Eversman T, von Werder K (1991) Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. Fertil Steril 56:1143–1150.PubMedGoogle Scholar
  38. Scottish Infertility Group, Hargreave T, Kyle K, Baxby K, Rogers A, Scott R, Tolley D, Abel D, Orr T, Elton R (1984) Randomized trial of mesterolone versus vitamin C for male infertility Br J Urol 56:740–744.PubMedCrossRefGoogle Scholar
  39. Shulman JF, Shulman S (1982) Methylprednisolone treatment of immunologic infertility in the male. Fertil Steril 38:591–599.PubMedGoogle Scholar
  40. Steiner R, Hofmann N, Hartmann R, Kaufmann R (1981) Kallikrein-enhanced human sperm motility in different media and cervical mucus measured with Laser-Doppler-spectroscopy. In: Haberland GL, Rohen J (eds) Kininogenases. Kallikrein 5. Schattauer, Stuttgart, pp 17–26.Google Scholar
  41. Takihara H, Sakatoku J, Cockett ATK (1991) The pathophysiology of varicocele in male infertility. Fertil Steril 55:861–868.PubMedGoogle Scholar
  42. Tournaye H, Camus M, Goosens A, Liu J, Nagy P, Silber S, Van Steirteghem AC, Devroey P (1995) Recent concepts in the management of infertility because of non-obstructive azoospermia. Hum Reprod 10 [Suppl 1]:115–119.PubMedCrossRefGoogle Scholar
  43. Tulloch WS (1952) Consideration of sterility factors in light of subsequent pregnancies: subfertility in the male. Edinb Med J 59:29.Google Scholar
  44. Vandekerckhove P, O’Donavan PA, Lilford RJ, Harada TW (1993) Infertility treatment: from cookery to science. The epidemiology of randomized controlled trials. Br J Obstet Gynaecol 100:1005–1036.PubMedCrossRefGoogle Scholar
  45. Vessey M, Doll R, Peto R, Johnson B, Wiggins P (1976) A long-term follow up study of women using different methods of contraception — an interim report. J Biosoc Sci 8:373–427.PubMedCrossRefGoogle Scholar
  46. Wagner ROF, Warsch F (1984) Pulsatile LHRH therapy of “slow pulsing oligospermia”: indirect evidence for a hypothalamic origin of the disorder. Acta Endocrinol (Copenh) 105 [Suppl 264]:142–145.Google Scholar
  47. Weinbauer GF, Nieschlag E (1993) Hormonal control of spermatogenesis. In: De Kretser D (ed) Molecular biology of the male reproductive system. Academic, New York, p 99.Google Scholar
  48. WHO Task Force on the Diagnosis and Treatment of Infertility (1989) Mesterolone and idiopathic male infertility: a double-blind study. Int J Androl 12:254–264.CrossRefGoogle Scholar
  49. WHO (1992a) The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril 57:1289–1293.Google Scholar
  50. WHO Special Programme of Research, Development and Research Training in Human Reproduction, Task Force on the Prevention and Management of Infertility (1992b) A double-blind trial of clomiphene citrate for the treatment of idiopathic male infertility. Int J Androl 15:299–307.CrossRefGoogle Scholar
  51. Yanushpolski ET, Politch JA, Hill JA, Anderson DJ (1995) Antibiotic therapy and leukocytospermia: a prospective randomized controlled study. Fertil Steril 63:142–147.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • E. Leifke
  • E. Nieschlag

There are no affiliations available

Personalised recommendations