title: LHRH analogues: their clinical physiology and delivery systems.
abstract: LHRH, produced in the hypothalamus from a precursor molecule, forms an essential link between the central nervous system and the anterior pituitary gland and the control of reproduction. It is secreted in a pulsatile manner and in patients who lack the hormone it is necessary to replace LHRH in a near-physiological mode. Chronic exposure of the pituitary gonadotrophes to LHRH by infusion and to LHRH agonists leads to suppression of pituitary-gonadal function by mechanisms which involve: 1. The over-riding of pulsatile gonadotrophin release; 2. Desensitization of the gonadotrophe, particularly at the post-receptor level; 3. Inducing production of altered forms of gonadotrophin with reduced biological activity. An effective and reversible suppression of pituitary-ovarian function can be readily obtained by administering LHRH agonists by nasal spray or by slow-release depot formulations lasting 1-3 months. LHRH agonist therapy is without serious side-effects but more work is required to evaluate the role of oestrogen in maintaining bone density. Suppression of the gonadotrophe can also be obtained by the more conventional approach of receptor blockade by LHRH antagonists. These have the advantage of causing immediate pituitary suppression but higher doses are required than for agonists. LHRH antagonists suitable for clinical evaluation have only recently become available.
authors.forename: H M
authors.initials: HM
authors.lastname: Fraser
mesh_terms: D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects
chemical_list: D007987:Gonadotropin-Releasing Hormone