Stimulation of spermatogenesis and biological paternity by intranasal (low dose) gonadotropin-releasing hormone (GnRH) in a male with Kallmann's syndrome: intraindividual comparison of GnRH and gonadotropins for stimulation of spermatogenesis.
Intranasal (in) GnRH spray caused induction and maintenance of spermatogenesis and biological paternity in a 28-yr-old man with Kallmann's syndrome. Prior treatment had included GnRH analog administration, which failed to induce puberty, and testosterone (T) enanthate weekly. Prior hCG/human menopausal gonadotropin therapy had resulted in high normal serum T levels and near-normal semen quality, but during subsequent hCG therapy, spermatogenesis markedly decreased. The patient had then received 250 mg T enanthate/month for 2 yr and 7 months; it was discontinued 7 weeks before the in GnRH study began. At its start (July 1984) the subject's testis size was 7 mL, and he had azoospermia, low serum LH and FSH levels, and a serum T of 74 ng/dL (2.6 nmol/L). GnRH was administered in a dose of 200 micrograms (20-120 ng/kg were absorbed into the circulation) every 2 h, seven to nine times a day, between 0700 and 2400 h for 242 days. After 12 days of treatment, serum T had increased to 519 ng/dL (18.0 nmol/L). After 70 days, the patient's sperm count was 11.5 million/mL (4.5 mL ejaculate volume; 70% motility; 36% normal morphology); on day 185, sperm count was 31 million/mL (4 mL ejaculate volume; 54% motility; 36% normal morphology). His spouse conceived on day 162 and delivered a fullterm daughter 265 days later. The probability of paternity was 99.9994%. Our results suggest that induction and maintenance of spermatogenesis as well as fertility in hypothalamic hypogonadism can be achieved with in GnRH therapy if pituitary and testicular function are intact. Spermatogenesis induced by in GnRH has the same quality as spermatogenesis induced by hCG/human menopausal gonadotropin therapy. Patient compliance is probably the most important factor for the success of in GnRH therapy.