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The anti-reproductive pharmacology of LH-RH and agonistic analogues.

LH-RH and three particular ("super") analogues were evaluated for agonistic (ovulation-induction and short-term uterotrophic properties) and postcoital contraceptive activity in rodents. Additionally, LH-RH and/or a representative analogue (D-Ala6-des Gly10-Pro9-LH-RH ethylamide) were tested for postcoital contraceptive/vaginal smear/return to fertility effects, precoital contraceptive activity, and effects on puberty in the immature female. All compounds induced ovulation and uterotrophic effects and terminated pregnancy when administered either pre- or post-implantation. LH-RH and the representative analogue, while terminating pregnancy postcoitally, produced an associated break in the characteristic leucocytic vaginal smear of pregnancy to one of cornification by day 12; at this time mating and insemination were reestablished and all rats carried to normal term. Precoitally, LH-RH administered to nembutalized (but not to unblocked) rats produced a 50% reduction in the pregnancy rate and a 38% decrease in the number of viable pups delivered. In immature rats, the representative analogue delayed puberty (i.e. vaginal canalization) and retarded the growth of the ovaries, uteri, and anterior pituitary gland. The collective data strongly support the concept that LH-RH and agonistic derivatives, in spite of their putative pro-fertility classification, are characteristically antifertility by nature. Since the latter effect appears to be the paradoxically dominant one, it is suggested that LH-RH agonism is synonymous with contraception. Furthermore, such peptides may represent a new potential approach to fertility control.