Hormonal effects of GnRH agonist in the human male: an approach to male contraception using combined androgen and GnRH agonist treatment.

Observations that hypophysectomized men demonstrate predictable azoospermia have led to attempts to suppress gonadotropin secretion with drugs for contraceptive purposes. Testosterone enanthate, given on a weekly or bimonthly basis, failed to predictably induce azoospermia in men. Treatment with agonist analogs of GnRH significantly suppressed spermatogenesis, but led to concomitant decline in serum testosterone concentrations. To prevent GnRH agonist induced changes in libido and potency we tested regimens employing daily subcutaneous injections of 200 micrograms of D(Nal2)6GnRH in combination with 200 mg testosterone enanthate every 2 weeks. This regiment led to 86% decline in mean sperm count over the 16-week treatment period, but azoospermia was not achieved in any subject. Basal or 24 h integrated serum LH or 24 h urinary LH concentrations were not significantly suppressed by combined treatment. In order to assess whether constant infusion of GnRH agonist will lead to greater suppression of gonadal function than its intermittent administration, we administered either 20 or 200 micrograms of D(Nal2)6GnRH to 2 groups of normal male volunteers for 28 days either by single daily injection or by constant subcutaneous infusion. Serum testosterone, LH and FSH responses were not significantly different between the two modes of agonist delivery either at 20 or 200 micrograms dose. Marked decrease in serum testosterone and sperm counts in these studies occurred in the face of little or no change in immunoreactive LH, indicating that the antigonadal actions of GnRH agonist in the human male cannot be fully explained on the basis of downregulation of pituitary LH secretion alone. GnRH agonist treatment however, led to marked decrease in bioassayable LH concentrations suggesting secretion of a molecularly altered LH species with diminished biologic activity.