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HORMONAL EFFECTS OF GnRH AGONIST IN THE HUMAN MALE: II. TESTOSTERONE ENHANCES GONADOTROPHIN SUPPRESSION INDUCED BY GnRH AGONIST
Author(s) -
BHASIN S.,
HEBER D.,
STEINER B.,
PETERSON M.,
BLAISCH B.,
CAMPFIELD L. A.,
SWERDLOFF R. S.
Publication year - 1984
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1984.tb00066.x
Subject(s) - medicine , endocrinology , testosterone (patch) , agonist , gonadotropin releasing hormone , hormone , luteinizing hormone , stimulation , follicle stimulating hormone , receptor
SUMMARY Superactive analogues of gonadotrophin releasing hormone and testosterone, when administered together, synergistically inhibit gonadotrophin secretion and spermatogenesis in the rat. In order to determine whether testosterone also enhanced gonadotrophin suppression by GnRH agonist in the human male, two groups of four normal male volunteers first received either 10 or 100 μg of a GnRH agonist D(Nal 2 ) 6 GnRH (GnRH‐A) daily for 10 d. After at least a 50 d recovery period, the same subjects received a single injection of 200 mg of testosterone oenanthate (TE) on day 1 in addition to the same dose of GnRH‐A daily for 10 d. Serum LH, FSH and testosterone (TS) concentrations were measured dailyjust prior to the next analogue dose, and on days 1 and 10 at 0, 1, 2, 4, 6, 8, 12, 16 and 24 h after the analogue injection. Daily administration of both 10 and 100 μg 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 μg of GnRH‐A resulted in hormonal responses identical to those seen with GnRH‐A alone. Combined treatment of testosterone with 100 μg 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‐d/ml) and FSH (mean integrated responses: 20·6 ± 3·3 vs. 32·8 ± 4·2 mIU‐d/ml) responses from days 3 to 11. By day 11, all subjects receiving combined treatment (GnRH‐A 100 μg+testosterone oenanthate) 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 μg 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 μg dose respectively. We conclude that addition of a suppressive dose of testosterone to an appropriate dose of GnRN‐A significantly enhances gonadotrophin 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.