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Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism

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Abstract

Background: Recombinant-FSH (rFSH) added to hCG at dose of 450 IU weekly is effective in inducing spermatogenesis in patients with hypogonadotropic hypogonadism (HH), but there are no data on the use of lower doses. Aim: This observational retrospective study evaluated whether 150–225 IU of rFSH weekly were able to induce spermatogenesis in HH men who failed to start it with hCG alone. Subjects and methods: Thirty-four patients with pre-pubertal onset HH (20–44 yr old) without adverse fertility factors were considered for this study. After hCG pre-treatment they received also either rFSH (Group 1) or highly purified urinary FSH (hpFSH) (Group 2) 75 IU sc 2 or 3 times weekly. Semen analysis was performed every 3 months during pre-treatment and the 1st yr of combined therapy. Patients were also invited to refer pregnancies in their partners during the subsequent 12 months. Results: Total sperm count/ejaculate did not show significant difference between 2 groups, while a significantly higher forward motility was observed in Group 1 (p<0.05). The median times to achieve sperm output thresholds (first sperm appearance, sperm concentration >1.5 or >5 mil/ml) were significantly lower in Group 1 (p<0.04, 0.03, and 0.001, respectively). A tendency to a shorter time to pregnancy was shown in partners of Group 1. Conclusions: Our data indicate that lower rFSH week dose than that so far used was able to induce potentially fertilizing sperm output in HH men previously treated with hCG. The rFSH effects are comparable to those of hpFSH but with a trend to a faster outcome achievement.

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References

  1. Matsumoto AM. Hormonal therapy of male hypogonadism. Endocrinol Metab Clin North Am 1994, 23: 857–75

    PubMed  CAS  Google Scholar 

  2. Burger HG, Baker HWG. Therapeutic considerations and results of gonadotropin treatment in male hypogonadotropic hypogonadism. Ann N Y Acad Sci 1984, 438: 447–53.

    Article  PubMed  CAS  Google Scholar 

  3. Hayes FJ, Seminara SB, Crowley WF Jr. Hypogonadotropic hypogonadism. Endocrinol Metab Clin North Am 1998, 27: 739–63.

    Article  PubMed  CAS  Google Scholar 

  4. Finkel DM, Phillips JL, Snyder PJ. Stimulation of spermatogenesis by gonadotropins in men with hypogonadotropic hypogonadism. N Engl J Med 1985, 313: 651–5.

    Article  PubMed  CAS  Google Scholar 

  5. Vicari E, Mongioì A, Calogero AE, et al. Therapy with human chorionic gonadotropin alone induces spermatogenesis in men with isolated hypogonadotrophic hypogonadism — long-term follow-up. Int J Androl 1992, 15:320–9.

    Article  PubMed  CAS  Google Scholar 

  6. Matsumoto AM, Karpas AE, Bremner WJ. Chronic human chorionic gonadotropin administration in normal men: evidence that follicle-stimulating hormone is necessary for the maintenance of quantitatively normal spermatogenesis in man. J Clin Endocrinol Metab 1986, 62: 1184–92.

    Article  PubMed  CAS  Google Scholar 

  7. Schaison G, Young J, Pholsena M, Nahoul K, Couzinet B. Failure of combined follicle-stimulating hormone-testosterone administration to initiate and/or maintain spermatogenesis in men with hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1993, 77: 1545–9.

    PubMed  CAS  Google Scholar 

  8. Okuyama A, Nakamura M, Namiki M, et al. Testicular responsiveness to long-term administration of hCG and hMG in patients with hypogonadotropic hypogonadism. Horm Res 1986, 23: 21–30.

    Article  PubMed  CAS  Google Scholar 

  9. Burgués S, Calderón MD. Subcutaneous self-administration of highly purified follicle stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotropic hypogonadism. Spanish Collaborative Group on Male ypogonadotropic Hypogonadism. Hum Reprod 1997, 12: 980–6.

    Article  PubMed  Google Scholar 

  10. Burris AS, Clark RV, Vantman DJ, Sherins RJ. A low sperm concentration does not preclude fertility in men with isolated hypogonadotropic hypogonadism after gonadotropin therapy. Fertil Steril 1988, 50: 343–7.

    PubMed  CAS  Google Scholar 

  11. Kirk JM, Savage MO, Grant DB, Bouloux PM, Besser GM. Gonadal function and response to human chorionic and menopausal gonadotrophic therapy in male patients with idiopathic hypogonadotrophic hypogonadism. Clin Endocrinol (Oxf) 1994, 41: 57–63.

    Article  CAS  Google Scholar 

  12. Büchter D, Behre HM, Kliesch S, Nieschlag E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol 1998, 139: 298–303.

    Article  PubMed  Google Scholar 

  13. European Metrodin HP Study Group. Efficacy and safety of highly purified urinary follicle-stimulating hormone with human chorionic gonadotropin for treating men with isolated hypogonadotropic hypogonadism. Fertil Steril 1998, 70: 256–62.

    Article  Google Scholar 

  14. Saal W, Happ J, Cordes U, Baum RP, Schmidt M. Subcutaneous gonadotropin therapy in male patients with hypogonadotropic hypogonadism. Fertil Steril 1991, 56: 319–24.

    PubMed  CAS  Google Scholar 

  15. Schopohl J, Mehltretter G, von Zumbusch R. Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. Fertil Steril 1991, 56: 1143–50.

    PubMed  CAS  Google Scholar 

  16. Kung AWC, Zhong YY, Lam KSL, Wang C. Induction of spermatogenesis with gonadotrophins in Chinese men with hypogonadotrophic hypogonadism. Int J Androl 1994, 17: 241–7.

    Article  PubMed  CAS  Google Scholar 

  17. Zwart-van-Rijkom JEF, Broekmans FJ, Leufkens HGM. From HMG through purified FSH preparations to recombinant FSH: a substitution study. Hum Reprod 2002, 17: 857–65.

    Article  PubMed  CAS  Google Scholar 

  18. Matorras R, Rodriguez-Escudero FJ. The use of urinary gonadotropins should be discouraged. Hum Reprod 2002, 17: 1675.

    Article  PubMed  Google Scholar 

  19. Recombinant Human FSH Product Development Group. Recombinant follicle stimulating hormone: development of the first biotechnology product for the treatment of infertility. Hum Reprod Update 1998, 4: 862–81.

    Article  Google Scholar 

  20. Driebergen A, Baer G. Quantification of the follicle stimulating hormone (follitropin alfa): is in vivo bioassay still relevant in the recombinant age? Curr Med Res Opin 2003, 19: 41–6.

    Article  PubMed  CAS  Google Scholar 

  21. Horsman G, Talbot JA, McLoughlin JD, Lambert A, Robertson WR. A biological, immunological and physiochemical comparison of the current clinical batches of the recombinant FSH preparations Gonal-F and Puregon. Hum Reprod 2000, 9: 1898–902.

    Article  Google Scholar 

  22. Kliesch S, Behre HM, Nieschlag E. Recombinant human follicle-stimulating hormone and human chorionic gonadotropin for induction of spermatogenesis in a hypogonadotropic male. Fertil Steril 1995, 63: 1326–8.

    PubMed  CAS  Google Scholar 

  23. Liu PY, Turner L, Rushford D, et al. Efficacy and safety of recombinant human follicle stimulating hormone (Gonal F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men. Hum Reprod 1999, 14: 1540–5.

    Article  PubMed  CAS  Google Scholar 

  24. Bouloux P, Warne DW, Loumaye E; FSH Study Group in Men’s Infertility. Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism. Fertil Steril 2002, 77: 270–3.

    Article  PubMed  Google Scholar 

  25. Liu PY, Gebski VJ, Turner L, Conway AJ, Wishart SM, Handelsman DJ. Predicting pregnancy and spermatogenesis by survival analysis during gonadotrophin treatment of gonadotrophin-deficient infertile men. Hum Reprod 2002, 17: 625–33.

    Article  PubMed  Google Scholar 

  26. 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.

    PubMed  CAS  Google Scholar 

  27. Warne DW, Decosterd G, Okada H, Yano Y, Koide N, Howles CM. A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. Fertil Steril 2008, Oct 20 [Epub ahead of print]; doi: 10.1016/j.fertnstert.2008.07.1720.

  28. Sinisi AA, Esposito D, Maione L, et al. Seminal anti-Müllerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism. Hum Reprod 2008, 23: 1029–34.

    Article  PubMed  CAS  Google Scholar 

  29. 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.

    Article  PubMed  CAS  Google Scholar 

  30. World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction. Cambridge: Cambridge University Press, 1992.

  31. Handelsman DJ, Turner L, Boylan LM, Conway AJ. Pharmacokinetics of human follicle-stimulating hormone in gonadotropin-deficient men. J Clin Endocrinol Metab 1995, 80: 1657–63.

    PubMed  CAS  Google Scholar 

  32. Mannaerts B, Fauser B, Lahlou N, et al. Serum hormone concentrations during treatment with multiple rising doses of recombinant folicle-stimulating hormone (Puregon) in men with hypogonadotropic hypogonadism. Fertil Steril 1996, 65: 406–10.

    PubMed  CAS  Google Scholar 

  33. Matikainen T, De Leeuw R, Mannaerts B, Huhtaniemi I. Circulating bioactive and immunoreactive recombinant human follicle-stimulating hormone (Org 32489) after administration to gonadotropin-deficient subjects. Fertil Steril 1994, 61: 62–9.

    PubMed  CAS  Google Scholar 

  34. Flack MR, Bennet AP, Froehlich J, Anasti JN, Nisula BC. Increased biological activity due to basic isoforms in recombinant human follicle-stimulating hormone produced in a human cell line. J Clin Endocrinol Metab 1994, 79: 756–60.

    PubMed  CAS  Google Scholar 

  35. Namiki M, Okuyama A, Sonoda T, Miyake A, Aono T, Matsumoto K. Down-regulation of testicular follicle-stimulating hormone receptors by human menopausal gonadotropin in infertile men. Fertil Steril 1985,44: 710–2.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine and Surgery, Endocrinology and Medical Andrology Section, Second University of Naples, Building 16, Via Pansini 5, 80131, Naples, Italy

    A. A. Sinisi MD, D. Esposito, G. Bellastella, L. Maione, V. Palumbo, A. De Bellis & A. Bellastella

  2. Department of Medical Physiopathology, “Sapienza”, University of Rome, Rome, Italy

    L. Gandini, F. Lombardo & A. Lenzi

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  1. A. A. Sinisi MD
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  2. D. Esposito
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  3. G. Bellastella
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  4. L. Maione
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  6. L. Gandini
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  7. F. Lombardo
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  8. A. De Bellis
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  10. A. Bellastella
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Correspondence to A. A. Sinisi MD.

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Sinisi, A.A., Esposito, D., Bellastella, G. et al. Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism. J Endocrinol Invest 33, 618–623 (2010). https://doi.org/10.1007/BF03346659

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