Sommer L, Zanger K, Dyong T, Dorn C, Luckhaus J, Diedrich K, Klingmüller D. Seven-day administration of the gonadotropin-releasing hormone antagonist Cetrorelix in normal cycling women. Eur J Endocrinol 1994;131:280–5. ISSN 0804–4643
In contrast to gonadotropin-releasing hormone (GnRH) agonists, GnRH antagonists do not show any stimulatory effect on the pituitary but their clinical usage was precluded by severe side effects and high dose requirements. 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-Cit6, d-Ala10]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. Throughout the control cycles blood samples were obtained daily during cycle days 8–18 and on days 21 and 23 during the remainder of the control cycles. 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 intervals 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 daily at 08.00 h for the following 6 days. Blood samples were obtained daily over a period of 25 days and every third day throughout the remainder of the treatment cycle. Twenty-four hours after the first application of Cetrorelix, luteinizing hormone (LH) and estradiol were in the subnormal range and remained subnormal until the end of medication. The suppressive effect of Cetrorelix compared to pretreatment values lasted at least 6 days for LH and FSH and 11 days after the last Cetrorelix injection for estradiol. An LH surge followed by postovulatory progesterone values was found 22.6 ± 1.4 days after the last injection. During 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 the individual pretreatment values. The consecutive cycle after completion of treatment was comparable to the length of the pretreatment cycle. No serious side effects were observed. In summary, the results of this study give evidence of the effectiveness and safety of this new GnRH antagonist used in low dosages for possible therapeutic application in sex-hormone-dependent diseases in women.
Dietrich Klingmüller, Institut für Klinische Biochemie der Universität Bonn, Sigmund Freud Str. 25, D53105 Bonn, Germany