Dose effects of the gonadotropin-releasing hormone antagonist, Nal-Glu, combined with testosterone enanthate on gonadotropin levels in normal men.
OBJECTIVE
To test the hypothesis that over a 4-week treatment period, Nal-Glu GnRH antagonist ([AcD2Nal1, D4ClPhe2, D3Pal3, Arg5, DGlu6 [AA], DAla10] GnRH) at a dose of 200 micrograms/kg per day SC would suppress levels of immunologically active and biologically active LH and FSH more completely than a dose of 100 micrograms/kg per day.


METHODS
Placebo controlled clinical study.


METHODS
A university community.


METHODS
Thirty normal male volunteers.


METHODS
We administered Nal-Glu at doses of 0, 100, and 200 micrograms/kg body weight per day in combination with T enanthate, 50 mg IM weekly, to separate groups of men (9 or 10 men per group) for 4 weeks.


RESULTS
Serum levels of immunologically active and biologically active gonadotropins were suppressed similarly in both groups of men who received Nal-Glu; this suppression was significantly greater than in the men who received placebo + T. Local side effects were more severe in the Nal-Glu 200 micrograms/kg per day group.


CONCLUSIONS
Administration of Nal-Glu in combination with T suppresses gonadotropins more completely than does T alone, but at doses > 100 micrograms/kg, gonadotropins are not suppressed additionally with larger doses of Nal-Glu. Subjects experienced greater local discomfort and side effects with the higher dosage. These findings suggest that dosages of Nal-Glu of > 100 micrograms/kg per day may have no advantage over the 100-micrograms/kg dose in a male contraceptive regimen.
Bagatell
C J
CJ
University of Washington School of Medicine, Seattle, USA.
Rivier
J E
JE
Bremner
W J
WJ
D000328:Adult; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D015200:Fluoroimmunoassay; D007987:Gonadotropin-Releasing Hormone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006062:Gonadotropins / Q000097:blood*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011863:Radioimmunoassay; D013739:Testosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
D006062:Gonadotropins; C057805:LHRH, N-Ac-2-Nal(1)-4-Cl-Phe(2)-3-Pal(3)-Arg(5)-Glu(6)-AlaNH2(10)-; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; C004648:testosterone enanthate; D007986:Luteinizing Hormone