Gonadorelin antagonists

General information

The gonadorelin antagonists include abarelix, cetrorelix, degarelix, detirelix, ganirelix, iturelix, prazarelix, ramorelix, and teverelix.

Gonadorelin agonists suppress the release of gonadotropin after an initial surge: pituitary suppression takes up to 2 weeks to develop. Competitive antagonists at gonadorelin receptors cause immediate inhibition of gonadotropin secretion without down-regulating the receptor. This class of agents would therefore be preferable to gonadorelin agonists when a rapid clinical effect is desired, for example in controlled ovarian stimulation.

Early gonadorelin antagonists were of low potency and tended to cause histamine release [ ]. However, ganirelix and cetrorelix are better tolerated [ , ]. They do not share the lipophilic and histamine-releasing properties of earlier generation gonadorelin antagonists and neither do they lead to depot formation. There appears to be a narrow therapeutic margin in ovarian stimulation protocols. Ganirelix concentrations correlate with body weight, and it has been suggested that the dose should be adjusted to weight to maximize pregnancy rates [ ]. Adverse reactions to ganirelix are usually mild and include minor injection site reactions, mild nausea, and malaise [ ].

Adverse reactions to cetrorelix and ganirelix have been reviewed [ ]. Those most commonly reported are headache, fatigue, and injection site reactions. In the development of LHRH antagonists one problem was their ability to induce systemic histamine release; however, structural changes solved this problem [ ] and no symptoms attributed to systemic histamine release have been reported so far.