Desensitization of gonadotropin-releasing response following vaginal consecutive administration of leuprolide in rats.

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Abstract
The vaginal absorption of a potent LHRH analog (leuprolide), and the gonadotropins (luteinizing hormone and FSH)-releasing response after continuous vaginal and s.c. administration of the analog to rats were determined by radioimmunoassay. A marked suppressive effect on the gonadotropin-releasing response along with long-lasting serum levels of leuprolide were paradoxically observed after consecutive 3-d [day] vaginal administration of the analog at doses of 1 .mu.g/kg or greater. Pituitary function recovered progressively with cessation of the treatment but was not complete 4 d after cessation. Continuous vaginal and s.c. infusion resulted in an almost complete inhibition of both gonadotropins response. Effective desensitization of the pituitary gonadotropin response is apparently elicited by continuous administration of leuprolide and the vaginal administration resulting in prolonged serum levels of the analog could be preferable as a self-administration method for medical treatments such as anti-tumor therapy and birth control.

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