Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism.

OBJECTIVE: To compare pulsatile gonadotropin-releasing hormone (GnRH) therapy with gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. DESIGN: Prospective study. Patients had free choice between the two forms of therapy. SETTING: Patients were treated on an outpatient basis in our department. PATIENTS: Eighteen patients of matched age (mean +/- SD] age: 21.1 +/- 3.0 years and 23.6 +/- 7.3 years) and similar testicular volume were treated in each group. INTERVENTIONS: Pulsatile GnRH therapy was started with 4 micrograms GnRH subcutaneously every 2 hours using a portable pump and gonadotropin therapy with 3 x 2,500 IU human chorionic gonadotropin (hCG) weekly injected intramuscularly. After 8 to 12 weeks of hCG treatment, 150 IU human menopausal gonadotropin two to four times weekly were added. RESULTS: Testosterone (T) and estradiol (E2) levels increased significantly higher (T: P less than 0.03; E2; P less than 0.001) in the gonadotropin group than in the GnRH group (T: 22.5 +/- 8.1 versus 16.8 +/- 5.5 nmol/L; E2: 150 +/- 70 versus 88. +/- 59 pmol/L). Five patients developed gynecomastia during gonadotropin therapy. The rise of testicular volume was significantly more pronounced (P less than 0.001) in the GnRH group (delta testicular volume = 8.1 +/- 2.0 mL) than in the gonadotropin group (delta testicular volume = 4.8 +/- 1.8 mL). Ten patients of the GnRH and 8 of the gonadotropin group had positive sperm counts, ranging from 1.5 to 26 x 10(6) spermatozoa/mL. The latter was achieved more rapidly in the GnRH group (12 +/- 1.6 versus 20 +/- 2.3 months: P less than 0.02). CONCLUSIONS: Endocrine and exocrine testicular function can be normalized by both forms of therapy. Gonadotropin therapy has more side effects. Gonadotropin-releasing hormone leads to a higher testicular volume and a more rapid initiation of spermatogenesis compared with gonadotropin therapy.