Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism--diagnostic and therapeutic aspects

Abstract

Background: Puberty is the result of reactivation of the gonadotropin releasing hormone (GnRH) pulse generator resulting in an increasing release of GnRH by the hypothalamus, which stimulates the gonadotropic cells of the pituitary to synthesize and secrete LH and FSH. Hypogonadotropic hypogonadism (HH) is often the result of GnRH deficiency. The clinical picture is characterized by the absence of pubertal development and infertility. It is difficult to differentiate HH from delayed puberty since low gonadotropin and low testosterone levels are found in both conditions. We hypothesized that long-term GnRH administration may differentiate between the two conditions by a difference in the increase of gonadotropins, the idea being that in normal delayed puberty the pituitary of the patient has been primed with GnRH during the fetal and early postnatal period. Patients: Seventeen adolescents suspected of having hypogonadotropic hypogonadisn were treated with pulsatile GnRH for 7 days. At the present time, the diagnosis of these patients is known and the results of the long-term GnRH stimulation have been evaluated according to the present diagnosis. Results:The results show that the increase in gonadotropins following GnRH treatment is similar in both conditions. Therefore, at a prepubertal age a normal delayed puberty cannot be distinguished from hypogonadotropic hypogonadism using long-term GnRH stimulation. Long-term pulsatile GnRH treatment is a physiological therapy for the induction of puberty. Unlike testosterone it has the advantage of stimulation of testicular growth and fertility, as well as virilization, in males. We have treated 68 male patients with HH with pulsatile GnRH. The results show testicular growth and virilization in all the patients and spermatogenesis in 58 patients. Wearing a portable pump is cumbersome. However, the patients were very motivated and adapted very easily to this inconvenience. When spermatogenesis had developed, GnRH treatment was changed to human chorionic gonadotropin (hCG) administration 1-2 times per week intramuscularly or subcutaneously. During hCG therapy spermatogenesis was maintained or even improved. At least ten patients fathered children. Conclusion: Pulsatile GnRH cannot distinguish between a normal delayed puberty and a hypothalamic defect in still prepubertal patients. Pulsatile GnRH offers an appropriate way to initiate testicular growth including virilization and fertility in males with hypogonadotropic hypogonadism.

Human Chorionic Gonadotropin Modulates Prostate Cancer Cell Survival after Irradiation or HMG CoA Reductase Inhibitor Treatment

“…hCG is a clinically used growth factor in the treatment of delayed puberty in adolescents (Delemarre-van de Waal, 2004;Soliman et al, 2005). Previous in vitro studies using hCG have demonstrated that this growth factor can radiosensitize mammary carcinoma cells, although no mechanistic analyses as to the mode of cell killing were performed (PondTor et al, 2002).…”

Outcome of gonadotropin therapy for male infertility due to hypogonadotrophic hypogonadism

“…The pulsatile nature of this secretion is critical for the testicular response and spermatogenesis [3,[15][16][17]. Continuous chronic administration of GnRH induces secondary infertility due to loss of this pulsatile secretion [18,19].…”

“…The management of male infertility in cases of HH is complex due to the difficulty in imitating the normal physiological secretion of gonadotropins [1,14]. While using GnRH-injecting pumps is one technique in which GnRH is injected subcutaneously in a pulsatile nature [14,15], the availability and expertise with these pumps are limited to a few specialized centers [1,13]. Furthermore, the success rate with this relatively cumbersome method is moderate [1,12].…”

Inducing puberty

“…However, the response of gonadotropins to an acute challenge of GnRH can be difficult to interpret, since in the pre-pubertal state the pituitary, although intact, will not or hardly respond, similar to the situation in hypogonadotropic hypogonadism (7). Repetitive administration of GnRH intravenously does increase gonadotropin levels in patients in a pre-pubertal and hypogonadotropic state.…”