Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases

Abstract

Stimulatory therapy with either GnRH or gonadotropins is an effective treatment to induce spermatogenesis and achieve paternity in men with secondary hypogonadism. However, there is still uncertainty about the optimal treatment modality and schedule, the duration of treatment necessary and the influence of interfering factors such as maldescended testes. We have extended our previous series of men treated for secondary hypogonadism and now present our therapeutic experience with 42 cases. Twenty-one patients with hypothalamic disorders (11 with idiopathic hypogonadotropic hypogonadism (IHH) and 10 with Kallmann syndrome (KalS)) were treated with GnRH (group Ia) or human chorionic gonadotropin (hCG)/human menopausal gonadotropin (hMG) (group Ib), and 21 patients with hypopituitarism (group II) were treated with hCG/hMG. A total of 57 treatment courses were initiated for induction of spermatogenesis, 36 of these for the purpose of induction of pregnancy in the female partner. Bilateral testicular volumes doubled within 5-12 months of therapy. Spermatogenesis as evidenced by the appearance of sperm in the ejaculate was induced in 54/57 courses. Pregnancies occurred in 26/36 courses. Unilaterally maldescended testes did not preclude patients with IHH or KalS from gaining fertility under therapy and spermatogenesis could be successfully initiated even in some individuals with bilateral maldescended testes. In general there was a tendency for a longer duration of therapy until induction of spermatogenesis in patients with a history of bilateral cryptorchidism. However, this did not reach statistical significance. In patients with IHH or KalS treated with either hCG/hMG or GnRH there were no statistically significant differences in terms of duration to appearance of sperm or pregnancy rates. Even in KalS patients as old as 43 years spermatogenesis could be induced. In repeatedly treated patients stimulation of spermatogenesis tended to be faster while time until induction of pregnancy was significantly shorter in the second treatment course. In conclusion, GnRH or hCG/hMG are effective therapeutic modalities for patients with IHH or KalS. It remains to be determined whether highly purified urinary gonadotropin preparations or recombinant LH and FSH will provide therapeutic advantages.

Factors affecting spermatogenesis upon gonadotropin‐replacement therapy: a meta‐analytic study

“…The present literature search was finalized to sperm parameters and not to fatherhood; however, in the studies included here, pregnancy rates were not very different from those reported in other (observational) studies (L abady, 1978;Finkel et al, 1985;Mastrogiacomo et al, 1991;Okada et al, 1992;Buchter et al, 1998;Liu et al, 2009;Resorlu et al, 2009;Farhat et al, 2010). A quantitative assessment of pregnancy rate is problematic, because only a fraction of couples included in studies on spermatogenesis actually desired a pregnancy and the proportion is not always reported.…”

“…Pulsatile GnRH therapy is able to induce adult characteristics development, the achievement of normal adult sex hormone levels and spermatogenesis in HHG subjects (Delemarre- Van de Waal & Odink, 1993;Pitteloud et al, 2002;Sykiotis et al, 2010). Furthermore, GnRH therapy demonstrated to induce a pregnancy rate up to 80% (Buchter et al, 1998), without showing any difference in time to achieve pregnancy, in comparison with gonadotropin therapy (Buchter et al, 1998). However, the inconvenience of wearing a pump with a periodical release of the hormone limits its use.…”

“…Comparative studies of these different compounds in males have not yet been conducted, but the newer preparations seem to be as efficacious as the urinary derivatives in male infertility (Krausz, 2011), whereas costs are rather different, as urinary preparations are cheaper than the others. Available evidence suggests that the most important determinant of a successful response to gonadotropin therapy is baseline testis volume, with higher volume associated with a faster achievement of spermatogenesis (Burris et al, 1988a,b;Buchter et al, 1998;Liu et al, 2002Liu et al, , 2009Miyagawa et al, 2005;Ishikawa et al, 2007). In addition, an onset of HHG after completing pubertal development is associated with a better response independently from testis volume (Finkel et al, 1985;Mastrogiacomo et al, 1991;Liu et al, 2002).…”

European Consensus Statement on congenital hypogonadotropic hypogonadism—pathogenesis, diagnosis and treatment

“…[194][195][196][197][198] These therapies induce both testicular testosterone production by Leydig cells and spermatogenesis in the seminiferous tubules. [199][200][201][202] The majority of patients with CHH develop sperm in their ejaculate with longterm therapy. 149,193,196,197 Although these treatments seem to have similar fertility outcomes, [199][200][201][202] comparing their efficacy is difficult owing to the small numbers of patients studied, heterogeneity in terms of degrees of GnRH deficiency (testicular volume before treatment), prior treatment and a lack of randomized studies performed to date.…”

Maintenance of spermatogenesis in hypogonadotropic hypogonadal men with human chorionic gonadotropin alone

“…Patients with secondary hypogonadism can be effectively treated with pulsatile GnRH or hCG/hMG in order to induce spermatogenesis (14). In this study one patient received pulsatile GnRH (5 mg/120 min) and 12 patients received hCG/hMG therapy according to common clinical guidelines with 3 £ 150 IU hMG subcutaneously per week and individually adapted hCG doses ranging from 2 £ 500 to 2500 IU per week (1).…”