Gonadotrophinreleasing hormone antagonists SED14 1523 SEDA24 504 SEDA25 521

Competitive gonadorelin receptor antagonists inhibit gonadotrophin secretion without the initial flare seen with gonadorelin agonists, and without receptor down-regulation. Potential applications include treatment of prostate cancer and prevention of premature LH surges in in vitro fertilization.

Skin Injection sites reactions (pain, itching, redness, swelling, or bruising) are common. In 226 women randomized to subcutaneous ganirelix and 111 to triptorelin there were local symptoms in 12% of those given ganirelix 1 hour after injection and 4.6% still had symptoms after 24 hours (22C). In another study of ovarian stimulation there were moderate local reactions in 12% of 197 women treated with ganirelix (23C).

Teratogenicity Of 232 infants conceived after ovarian stimulation using cetrorelix seven had major malformations and six had minor malformations; this rate was similar to that in the general population (31C). Mental development was normal during 2 years of follow-up. After the use of combined ganirelix and follicle-stimulating hormone in 68 pregnancies, one child had Beckwith-Wiedemann syndrome (exophthalmos and macroglossia); five had minor malformations, including torticollis, asymmetrical head shape, nevus, skin tags, talipes, pyloric stenosis, and sacral sinus (32C). Although the numbers were too small to definitely exclude an increase in malformations, the rate of both major and minor defects was consistent with expected values.

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