HIGH LOADING AND LOW MAINTENANCE DOSES OF A GONADOTROPIN-RELEASING-HORMONE ANTAGONIST EFFECTIVELY SUPPRESS SERUM LUTEINIZING-HORMONE, FOLLICLE-STIMULATING-HORMONE, AND TESTOSTERONE IN NORMAL MEN

The GnRH antagonist cetrorelix effectively suppresses serum LH, FSH, a nd testosterone (T) in normal men without major side-effects. However, as with other available GnRH antagonists, relatively high doses of 10 mg/day were required for sustained reduction of T levels during 1-wee k administration in normal men. Therefore, we investigated whether a s uppression of LH, FSH, and T achieved by initial high dose cetrorelix can be maintained by continued low dose injections. Sixteen young male volunteers were randomly assigned to four study groups (n = 4/group). Twelve men were injected sc with 10 mg cetrorelix at 0800 h for 5 day s, followed by injections of 2 mg/day (group I), 2 x 1 mg/day (group I I), and 1 mg/day (group III) up to the end of the 3-week injection per iod. For the control, group IV was given daily placebo injections for 3 weeks. Morning and evening blood samples were obtained daily for 4 w eeks and then at increasing time intervals up to meek 13. Initial inje ctions of 10 mg/day cetrorelix suppressed LH, FSH, and T effectively. This initial reduction of serum levels was maintained during the follo wing low dose maintenance injections in all groups. In comparison to t he initial suppression, significantly lower levels of LH, FSH, and T n ear the assay detection limits were measured during study weeks 2 and 3. The results show that compared to previous long term studies, much lower daily doses of the GnRH antagonist are sufficient for effective suppression of LH, FSH, and T after initial high loading dose injectio ns. In addition to competitive receptor blockage, other mechanisms of GnRH antagonist action, such as receptor down-regulation, appear to be involved during long term administration in men.