Pharmacokinetic and antigenicity studies with LHRH analogues

The clinical applications of LHRH agonists cover a wide spectrum of indications, requiring single or multiple daily doses by injection, nasal spray 16,19 or other forms of administration, e. g. vaginal suppositories 14, 15, 17, 31. These treatment regimens all rely on gonadal LH receptor down-regulation and a variable degree of pituitary desensitization of FSH and LH release 18. A different regimen is sustained release from injectable microcapsules or implants30. Such formulations release agonists at a relatively constant rate, and act predominantly by pituitary desensitization, similarly to the effect of a long-term infusion of LHRH. A common characteristic of the hormonal response to treatment with all LHRH agonists is an increased gonadotrophin release during the initial phase of therapy, which gradually declines to low levels. This initial response is observed after injections, nasal spray or implant formulations. The transitory stimulation phase is followed by a decrease of the FSH and LH response to low levels during daily dosing, or during sustained release at a constant rate 20. Concomitantly, gonadal steroids decrease to uniformly low levels. During suppression, the biological response cannot be evaluated as a function of the dose.