Objectives/Methods: To induce testicular growth and spermatogenesis, 11 patients with idiopathic hypogonadotropic hypogonadism were treated with long-term subcutaneous pulsatile gonadotropin-releasing hormone (GnRH) administration. Three patients had a history of undescended testes. Patients who did not respond to therapy with a sufficient increase in serum testosterone or spermatogenesis were offered additional injections with hCG or, after discontinuation of GnRH, either combined therapy with hCG and hMG or recombinant FSH. Results: During treatment testicular volume and serum levels of FSH, LH and testosterone increased. Semen analysis revealed the presence of spermatogenesis in 9 of the 11 patients (8 on GnRH alone and in 1 when hCG/hMG was subsequently instituted), and 7 pregnancies have resulted thus far. Conclusion: Pulsatile GnRH therapy is a well-tolerated and effective therapy for the induction of spermatogenesis in some men with idiopathic hypogonadotropic hypogonadism. It appears that a significant fraction of them should be treated for a minimum of 1–2 years to maximize testicular growth and achieve spermatogenesis. Cryptorchidism was a negative prognostic factor.

Keywords:
Idiopathic hypogonadotropic hypogonadism, Gonadotropin-releasing hormone, Gonadotropins, Cryptorchidism
1.
Naftolin F, Harris GW: Effect of purified luteinizing hormone releasing factor on normal and hypogonadotrophic anosmic men. Nature 1971;232:496–497.
2.
Knobil E: On the control of gonadotropin secretion in the rhesus monkey. Recent Prog Horm Res 1974;30:1–46.
3.
Crowley WF, Filicori M, Spratt D, Santore NF: The physiology of gonadotropin-releasing hormone (GnRH) in men and women. Recent Prog Horm Res 1985;41:473–531.
4.
Sokol RZ, Swerdloff RS: Practical considerations in the use of androgen therapy; in Santen RJ, Swerdloff RS (eds): Male Reproductive Dysfunction. New York, Dekker, 1986, pp 211–226.
5.
Arver S, Dobs AS, Meikle AW, Allen RP, Sanders SW, Mazer MA: Improvement of sexual function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system. J Urol 1996;155:1604–1608.
6.
Spratt DI, Hoffman AR, Crowey WF Jr: Hypogonadotropic hypogonadism and its treatment; in Santen RJ, Swerdloff RS (eds): Male Reproductive Dysfunction. New York, Dekker, 1986, pp 227–249.
7.
World Health Organisation: WHO Laboratory Manual for the Examination of Human Semen and Semen-Cervical Mucus Interaction. Cambridge, Cambridge University Press, 1987.
8.
Stanhope R, Brook CGD, Pringle PJ, et al: Induction of puberty by pulsatile gonadotropin releasing hormone. Lancet 1987;ii:552–555.
9.
Hoffman AR, Crowley WF: Induction of puberty in men by long-term pulsatile administration of low-dose gonadotropin-releasing hormone. N Engl J Med 1982;307:1237–1241.
10.
Krabbe S, Skakkebæk NE: Gonadotropin-releasing hormone (LH-RH) and human chorionic gonadotropin in the treatment of two boys with hypogonadotropic hypogonadism. Acta Paediatr Scand 1977;66:361–365.
11.
Rabin D, McNeil LW: Long term therapy with luteinizing hormone-releasing hormone in isolated gonadotropin deficiency: Failure of therapeutic response. J Clin Endocrinol Metab 1981;52:557–561.
12.
Morris DV, Adeniyi-Jones R, Wheeler M, et al: The treatment of hypogonadotropic hypogonadism in men by the pulsatile infusion of luteinizing hormone-releasing hormone. Clin Endocrinol 1984;21:189–200.
13.
Schopohl J, Mehltretter G, von Zumbusch R, Eversmann T, von Werder K: Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. Fertil Steril 1991;56:1143–1150.
14.
Liu L, Banks SM, Barnes KM, et al: 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 Endocrinol Metab 1988;67:1140–1145.
15.
Aulitzki W, Frick J, Galvan G: Pulsatile-gonadotropin-releasing hormone treatment of male hypogonadotropic hypogonadism. Fertil Steril 1988;50:480–486.
16.
Spratt DI, Crowley WF, Butler JP, Hoffman AR, Conn PM, Badger TM: Pituitary luteinizing hormone responses to intravenous and subcutaneous administration of gonadotropin-releasing hormone in men. J Clin Endocrinol Metab 1985;61:890–895.
17.
Koivisto VA, Felig P: Alteration in insulin absorption and in blood glucose control associated with varying insulin injection sites in diabetic patients. Ann Intern 1980;92:59–61.
18.
Spratt DI, Carr DB, Merriam GR, Scully RE, Rao PN, Crowley WF Jr: The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: Clinical and laboratory correlations. J Clin Endocrinol Metab 1987;64:283–291.
19.
Boyar RM, Finkelstein RW, Witkin M, Sheldon K, Weitzman E, Hellman L, et al: Studies of endocrine function in ‘isolated’ gonadotropin deficiency. J Clin Endocrinol Metab 1973;36:64–72.
20.
Boyar RM, Wu RHK, Kapan S, Hellman L, Weitzman ED, Finkelstein JW: Clinical and laboratory heterogeneity in idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1976;43:1268–1275.
21.
Spratt DI, Finkelstein JS, O’dea LSL, Badger TM, Narasimha R, Campbell JD, Crowley WF: Long-term administration of gonadotropin-releasing hormone in men with idiopathic hypogonadotropic hypogonadism. Ann Intern Med 1986;105:848–855.
22.
Delemarre-Van de Waal HA: Induction of testicular growth and spermatogenesis by pulsatile, intravenous administration of gonadotropin-releasing hormone in patients with hypogonadotropic hypogonadism. Clin Endocrinol 1993;38:473–480.
23.
Finkel DM, Phillips JL, Snyder PJ: Stimulation of spermatogenesis by gonadotropins in men with hypogonadotropic hypogonadism. N Engl J Med 1985;313:651–655.
24.
Ley SB, Leonard JM: Male hypogonadotropic hypogonadism: Factors influencing response to human chorionic gonadotropin and human menopausal gonadotropin, including prior exogenous androgens. J Clin Endocrinol Metab 1985;61:746–752.
25.
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. Eur J Endocrinol 1998;139:298–303.
26.
Hedinger C: Über den Zeitpunkt frühest erkennbarer Hodenveränderungen beim Kryptorchismus des Kleinkindes. Verh Dtsch Ges Pathol 1971;55:172–175.
27.
Mengel W, Hienz HA, Sippe WG, Hecker WC: Studies on cryptorchidism: A comparison of histological findings in the germinative epithelium before and after the second year of life. J Pediatr Surg 1974;9:445–450.
28.
Evain-Brion D, Gendrel D, Bozzola M, Job JC: Diagnosis of Kallmann’s syndrome in early infancy. Acta Paediatr Scand 1982;71:937–940.
29.
Weiss J, Axelrod L, Whitcomb RW, Harris PE, Crowley WF, Jameson JL: Hypogonadism caused by a single amino acid substitution in the β-subunit of luteinizing hormone. N Engl J Med 1992;326:179–183.
30.
Bain J, Duthie M, Keene J: Relationship of seminal plasma testosterone and dihydrotestosterone to sperm count and motility in man. Arch Androl 1979;2:35–39.
31.
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;50:343–347.
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2002
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