7-DAY ADMINISTRATION OF THE GONADOTROPIN-RELEASING-HORMONE ANTAGONISTCETRORELIX IN NORMAL CYCLING WOMEN

In contrast to gonadotropin-releasing hormone (GnRH) agonists, GnRH an tagonists do not show any stimulatory effect on the pituitary but thei r clinical usage was precluded by severe side effects and high dose re quirements. We report here on a 7-day treatment using the potent GnRH antagonist Cetrorelix ([Ac-D-Nal(2)(1), D-Phe(4Cl)(2), D-Pal(3)(3), D- Cit(6), D-Ala(10)]GnRH) on five women 23-33 years old. All. women were ovulatory and were studied during three consecutive cycles: a control cycle. a treatment cycle and a post-treatment control cycle. Througho ut the control cycles blood samples were obtained daily during cycle d ays 8-18 and on days 21 and 23 during the remainder of the control cyc les. On the eighth day of the treatment cycle women were hospitalized at 07.00 h for 26 h. Repeated blood samples were drawn at 15-min inter vals during the entire period. Subjects received 3 mg of Cetrorelix sc for the first time at 09.00 h on the eighth day of the cycle and dail y at 08.00 h for the following 6 days. Blood samples were obtained dai ly over a period of 25 days and every third day throughout the remaind er of the treatment cycle. Twenty-four hours after the first applicati on of Cetrorelix, luteinizing hormone (LH) and estradiol were in the s ubnormal range and remained subnormal until the end of medication. The suppressive effect of Cetrorelix compared to pretreatment values last ed at least 6 days for LH and FSH and 11 days after the last Cetroreli x injection for estradiol. An LH surge followed by postovulatory proge sterone values was found 22.6 +/- 1.4 days after the last injection. D uring application of the GnRH antagonist, LH was reduced to 16.1 +/- 0 .7%, FSH to 58.7 +/- 1.3% and estradiol to 17.9 +/- 0.4% compared to t he individual pretreatment values. The consecutive cycle after complet ion of treatment was comparable to the length of the pretreatment cycl e. No serious side effects were observed. In summary, the results of t his study give evidence of the effectiveness and safety of this new Gn RH antagonist used in low dosages for possible therapeutic application in sex-hormone-dependent diseases in women.