Gonadal function and response to human chorionic and menopausal gonadotrophin therapy in male patients with idiopathic hypogonadotrophic hypogonadism.

OBJECTIVE

This study was designed to determine the response to therapy using human chorionic gonadotrophin (hCG) and human menopausal gonadotrophin (hMG) in males with idiopathic isolated hypogonadotrophic hypogonadism (IHH), and to compare the responses in patients presenting with and without cryptorchidism.

DESIGN

Analysis of male patients with IHH treated with hCG or combined hCG/hMG for a minimum of 6 months at St Bartholomew's Hospital. Clinical and endocrine assessment was performed in all patients prior to commencing therapy.

PATIENTS

A total of 26 males with IHH have been treated with exogenous gonadotrophins. Thirteen patients (Group 1) had cryptorchidism (unilateral in 7, bilateral in 6) at presentation, and 13 (Group 2) did not.

MEASUREMENTS

All patients had basal serum testosterone, LH and FSH determinations. An i.v. GnRH test was performed in 25 patients and an i.m. hCG stimulation test in 19. Testicular volume and serum testosterone were measured during both hCG and combined hCG/hMG therapy. Seminal analysis was performed at the start and monthly during hCG/hMG therapy.

RESULTS

Eighty-five per cent of the 13 patients in Group 1 had an olfactory defect (Kallmann's syndrome), compared with 23% of Group 2. Both groups of patients showed a subnormal response to initial i.v. GnRH and i.m. hCG testing. During hCG therapy only three patients in Group 1 and six in Group 2 achieved normal adult testosterone levels. The non-cryptorchid group achieved a higher mean testicular volume on hCG therapy than the cryptorchid group (mean (SD); 4.7 (1.8) ml vs 3.0 (1.6) ml (P < 0.02)), and for all patients there was a correlation between initial and maximal testicular volume (R = 0.69, P = 0.001). Four patients in Group 1 and five patients in Group 2 were treated with combined hCG/hMG for 6-15 months to induce fertility; only one patient in Group 1 achieved spermatogenesis, compared to all patients in Group 2 (leading to three pregnancies).

CONCLUSIONS

These data indicate that patients with idiopathic hypogonadotrophic hypogonadism (IHH) have a poor response to hCG therapy in terms of testicular growth and normalization of serum testosterone. Final testicular volume is dependent on initial testicular size. In addition, patients with IHH associated with cryptorchidism have a poor fertility potential to combined hCG/hMG therapy.