Comparisons of the potential utility of LHRH agonists and antagonists for fertility control.
Prospects for the use of LHRH analogs for human fertility control have been reviewed with particular reference to two highly potent representatives. Nafarelin acetate, the LHRH agonist, has a potency about 200 X that of LHRH and is consistently effective in suppressing gonadal function in females through a desensitization of LHRH receptors in the pituitary. Such agents show promise as ovulation inhibitors for women although concern has been expressed over the dangers of unopposed estrogen or alternatively hypoestrogenemia. Although early studies indicated luteolysis in women and interceptive action in baboons it is now clear that the LHRH agonists will not be useful clinically to terminate pregnancy. Wide species differences in the male response to LHRH agonists exist. Unfortunately azoospermia has not been achieved in men. The LHRH antagonists, typified by [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]LHRH, require high doses to competitively inhibit responses to endogenous LHRH. Their advantages include a rapid induction of the hypogonadal state with apparently little species or sexual variation in response. Based on animal studies, preferable utility of the antagonists would lie in male contraception and pregnancy interception.
D000028:Abortion, Induced; D000818:Animals; D003267:Contraception; D003338:Corpus Luteum / Q000187:drug effects; D003692:Delayed-Action Preparations; D004285:Dogs; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D017274:Nafarelin; D010060:Ovulation / Q000187:drug effects; D010215:Papio; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011966:Receptors, LHRH; D013045:Species Specificity; D013076:Sperm Count / Q000187:drug effects; D013739:Testosterone / Q000097:blood
D003692:Delayed-Action Preparations; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; C043699:detirelix; D017274:Nafarelin; D007987:Gonadotropin-Releasing Hormone; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone