Sustained suppression of serum LH, FSH and testosterone and increase of high‐density lipoprotein cholesterol by daily injections of the GnRH antagonist cetrorelix over 8 days in normal men

Abstract

Recently we have shown that single dose injections of the new GnRH antagonist cetrorelix ([Ac-D-Na(2)1, D-Phe(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala]GnRH; SB-75) decrease serum LH and testosterone in a dose-dependent manner in normal men. These results prompted us to investigate the effectiveness and safety of multiple daily injections of cetrorelix in normal male volunteers. Following two control examinations 16 young men were randomly assigned to four study groups (n = 4/group). Daily doses of 0 (placebo), 2, 5, and 10 mg cetrorelix were injected subcutaneously at 0800 h for 8 days and morning and evening blood samples were obtained for 3 weeks. One day after the first cetrorelix injection, serum LH and testosterone concentrations were significantly suppressed in all treatment groups. Whereas in the 2 and 5-mg dose groups LH and testosterone showed some fluctuations, daily injections of 10 mg cetrorelix consistently suppressed LH and testosterone in all men. In addition, in this group serum FSH concentrations were significantly suppressed to subnormal values 1 day after the first injection and remained in this range up to 5 days after the last injection. A time and dose-dependent increase of high-density lipoprotein cholesterol was observed during cetrorelix-induced testosterone deprivation with a maximal increase of 0.38 +/- 0.13 mmol/l (14.8 +/- 5.1 mg/dl; mean +/- SEM) in the 10-mg dose group. In addition, parallel to suppressed testosterone the volunteers' libido was significantly reduced under the GnRH antagonist. Apart from those symptoms caused by androgen deficiency, the only adverse side-effect observed was a mild painless local erythema at the injection site that disappeared within an hour. Daily injections of 10 mg cetrorelix effectively and consistently suppress serum LH, FSH and testosterone concentrations, and therefore it has potential for treatment of sex hormone-dependent diseases and for male contraception.