Induction of testicular growth and spermatogenesis by pulsatile, intravenous administration of gonadotrophin-releasing hormone in patients with hypogonadotrophic hypogonadism.

OBJECTIVE

To induce testicular growth including spermatogenesis, 38 patients with hypogonadotrophic hypogonadism were treated with long-term pulsatile GnRH administration.

PATIENTS

The group of patients comprised 17 individuals with idiopathic hypogonadotrophic hypogonadism, 11 with Kallmann's syndrome, four with multiple pituitary hormone deficiencies and six with a secondary hypogonadotrophic hypogonadism due to surgical removal of a brain tumour. Thirteen patients (seven with idiopathic hypogonadotrophic hypogonadism and six with Kallmann's syndrome) had undescended testes, of whom six had undergone surgery on both testes and four on one testis. Sixteen of the 17 had previously received androgen therapy and six others had received gonadotrophin treatment, of whom three had long-term treatment to induce testicular development, without success.

TREATMENT

GnRH was administered intravenously in a dose of 2-20 micrograms per pulse every 90 minutes. After GnRH discontinuation, hCG treatment was instituted, 1500-3000 IU (i.m.) twice weekly.

RESULTS

During treatment plasma levels of LH, FSH and testosterone increased. In 35 out of the 38 patients plasma testosterone levels increased into the normal adult range. In all patients testicular volume increased. Mean pretreatment testicular volume per patient group ranged from 2.4 to 4.8 ml and increased to 11.5-18.1 ml by the end of treatment. There was a significant difference in the achieved testicular volumes between the patients with Kallmann's syndrome and the brain tumour patients. GnRH treatment mean lasted between 46 and 75 weeks in the different groups. On hCG therapy, testicular development was either maintained or improved. Semen analysis revealed the presence of spermatogenesis in 31 out of the 38 patients (26 patients already on GnRH, and in another five patients on hCG therapy). All three patients pretreated with gonadotrophins as well as three patients with bilateral testicular surgery developed a detectable sperm count. In 19 adolescent patients with growth potential, an adequate height velocity was observed during GnRH treatment.

CONCLUSIONS

GnRH is a feasible way to induce testicular growth as well as spermatogenesis in hypogonadotrophic male patients, even in patients in whom gonadotrophin treatment has failed. After GnRH treatment, hCG alone can maintain or even improve testicular development, including spermatogenesis. GnRH treatment may also induce a physiological growth spurt in hypogonadotrophic adolescents.