Large doses of stimulatory analogues of luteinizing hormone-releasing hormone (LH-RH) caused paradoxical antifertility effects. These effects are being utilized for the possible development of contraceptive methods. Several inhibitory analogues of LH-RH have been tested in men and women and shown to be active. The synthetic approach based on inhibitory analogues of LH-RH has been proven to be feasible for development of new methods of birth control. Continued research and testing along these lines may lead to the development of contraceptives based on inhibitory analogues of LH-RH that could be conveniently applied as a nasal spray and could be free of undesirable side effects.
PIP: The available literature on luteinizing hormone-releasing hormone (LH-RH) agonists and antagonists is reviewed in view of their possible uses for contraception. Cyclical contraception (i.e., ovulation suppression) is best achieved by using the inhibitory analogs of LH-RH (i.e., LH-RH blocking agents); however, the possibilities for a precoital contraceptive based on the paradoxical antifertility effects of large doses of agonistic analogs are also discussed. A variety of recent studies have demonstrated that prolonged treatment with large doses of LH-RH and its long-acting, superactive stimulatory analogs cause impairment of reproductive functions. For example, in female rats a delay in vaginal opening was detected using D-Leu6-HL-RH EA or D-Trp6-LH-RH on days 30-40 and inhibition of ovarian and uterine weight. In addition, recent clinical studies indicated that superactive LH-RH analogs can also exert antifertility effects in humans when used in relatively large doses or when given by repeated administration. It is suggested that replacement or deletion of 1 or more amino acids in LH-RH might result in analogs possessing features requisite for effective binding but lacking requisites that are necessary for functional effect (i.e., stimulation of LH and follicle stimulating hormone FSH, release). This type of approach to making synthetic antagonistic peptides related to LH-RH that strongly block LH and FSH release and ovulation is feasible. New birth control methods would be based on the blockade of the ovulatory midcycle peak of LH. Inhibitory analogs of LH-RH may also be useful for treating precocious puberty, endometriosis, and menopausal symptoms. Contraceptives based on inhibitory analogs of LH-RH may be administered via nasal sprays without undue side effects.