HORMONAL EFFECTS OF GnRH AGONIST IN THE HUMAN MALE: II. TESTOSTERONE ENHANCES GONADOTROPHIN SUPPRESSION INDUCED BY GnRH AGONIST

Publisher Website
Google Scholar
Abstract
Superactive analogs of gonadotropin-releasing hormone [GnRH] and testosterone, when administered together, synergistically inhibit gonadotropin secretion and spermatogenesis in the rat. In order to determine whether testosterone also enhanced gonadotropin suppression by GnRH agonist in the human male, 2 groups of 4 normal male volunteers first received either 10 or 100 .mu.g of a GnRH agonist D(Nal2)6GnRH (GnRH-A) daily for 10 day. After at least a 50 day recovery period, the same subjects received a single injection of 200 mg of testosterone enanthate (TE) on day 1 in addition to the same dose of GnRH-A daily for 10 day. Serum LH [luteinizing hormone], FSH and testosterone (TS) concentrations were measured daily just prior to the next analog dose, and on days 1 and 10 at 0, 1, 2, 4, 6, 8, 12, 16 and 24 h after the analog injection. Daily administration of both 10 and 100 .mu.g of GnRH-A alone resulted in an early phase of stimulation followed by progressive decline in LH, FSH and testosterone to levels below baseline by day 10 despite continued administration of GnRH-A. Addition of testosterone to 10 .mu.g of GnRH-A resulted in hormonal responses identical to those seen with GnRH-A alone. Combined treatment of testosterone with 100 .mu.g of GnRH-A did not blunt the peak LH and FSH responses on day 2, but resulted in significantly lower LH (mean integrated responses: 187 .+-. 30 vs. 234 .+-. 42 mIU-day/ml) and FSH (mean integrated responses: 20.6 .+-. 3.3 vs. 32.8 .+-. 4.2 mIU-day/ml) responses from days 3 to 11. By day 11, all subjects receiving combined treatment (GnRH-A 100 .mu.g + testosterone enanthate) had undetectable serum FSH levels. In contrast, serum FSH concentrations on day 11 after treatment with GnRH-A alone were 43.6 .+-. 8.9% of control and none of the subjects had values below the limit of detection. Serum testosterone levels in the combined treatment group did not fall below baseline by day 10 in either the 10 (161.4 .+-. 48%) or the 100 .mu.g GnRH-A groups (104.6 .+-. 11.2%), while in the group receiving GnRH-A alone, testosterone levels declined to 45.6 .+-. 8.3% and 80 .+-. 18.8% with the 10 and 100 .mu.g dose, respectively. Addition of a suppressive dose of testosterone to an appropriate dose of GnRH-A significantly enhances gonadotropin suppression by GnRH-A in the human male. Combined use of testosterone and GnRH-A might be of importance in the development of a male contraceptive to achieve the desired suppression of spermatogenesis while avoiding androgen deficiency.

This publication has 14 references indexed in Scilit: