PULSATILE GONADOTROPIN-RELEASING-HORMONE VERSUS GONADOTROPIN TREATMENT OF HYPOTHALAMIC HYPOGONADISM IN MALES

In this study, pulsatile gonadotrophin releasing hormone (GnRH) therapy and gonadotrophin therapy were compared for male patients with idiopathic hypothalamic hypogonadism. Thirty-six patients, 19 with this condition, and 17 with Kallmann's syndrome, were included in the study. Their mean age was 21.1 +/- 3.0 years (+/- SD). They were divided into two groups of similar age, number and testicular volume. Pulsatile GnRH therapy was started with 4 mug GnRH s.c. every 2 h using a portable pump and gonadotrophin therapy with weekly i.m. injections of 3 x 2500 IU human chorionic gonadotrophin (HCG). After 8-12 weeks of HCG treatment, 150 IU human menopausal gonadotrophin (HMG) 2-4 times weekly were added and the dose of HCG reduced if necessary. Testosterone concentrations increased significantly more (P < 0.03) in the gonadotrophin group than in the GnRH group (22.5 +/- 8.1 versus 16.8 +/- 5.5 nmol/l). The rise in oestradiol levels was also significantly higher (P < 0.001) in the gonadotrophin group than in the GnRH group (150 +/- 70 versus 88 +/- 59 pmol/l). Five patients developed gynaecomastia during gonadotrophin therapy. An increased testicular volume (TV) occurred more rapidly (P < 0.001) and was significantly more pronounced (P < 0.001) after GnRH therapy (DELTATV = 8.1 +/- 2.0 ml) than with gonadotrophins (DELTATV = 4.8 +/- 1.8 ml). Sperm counts were performed in 14 patients given GnRH and in 17 patients given gonadotrophins. Ten patients given GnRH had positive sperm counts, ranging from 1.5 to 14 x 10(6) spermatozoa/ml; eight of those given gonadotrophins also developed spermatogenesis (2-26 x 10(6)/Ml). The mean time period until spermatogenesis started was significantly shorter (P < 0.02) with GnRH than with gonadotrophins (12 +/- 1.6 versus 20 +/- 2.3 months). These results show how endocrine and exocrine testicular function can be normalized by both forms of therapy. However, gonadotrophin therapy has more side-effects. Testicular growth is more pronounced with GnRH, and this therapy also initiates spermatogenesis more rapidly than gonadotrophin therapy.