Abstract

PIP: A contraceptive approach being developed is based on analogs of the hypothalamic hormone controlling secretion of both the luteinizing hormone (LH) and the follicle stimulating hormone (FSH) from the anterior pituitary gland. This process was made possible by the isolation, determination of structure, and synthesis of this hormone in 1971. This hormone is called LH-RH/FSH-RH or gonadotropin-releasing hormone. DesHis2, desGly 10-LH-RH EA was the 1st peptide that significantly reduced LH secretion in response to LH-RH in vivo. It appeared in early tests that, for a given antagonist, inhibitory effects were improved by incorporating either the D-amino acid in the 6 position of a C-terminal ethylamide group. An improvement in antagonistic activity resulted from the repliant of L-pyroGlu by the D-pyroGlu group. In further studies in vitro activities of some LH-RH antagonists were sometimes different from in vitro potencies, but in vitro and in vivo potencies closely paralleled each other. Studies with pituitary membrane receptors and in vivo evaluation of LH-RH antagonists are studied. The inhibitory effects of modern LH-RH antagonists on gonadotropin production and ovulation in rhesus monkeys and cynomologous monkeys have been demonstrated. Clinical trials with women showed that basal levels of gonadotropins were not affected when women were given injections of D-Phe2, D-Trp3, D-Phe6-LH-RH. Other antagonists were also successful, but evaluation of side effects will have to await the completion of longterm studies. These studies so far indicate that a single administration of LH-RH antagonists can abolish the midcycle surge of LH and FSH and inhibit ovulation in most women, or induce luteolysis in others. The contraceptive effect can be exerted through 2 possible mechanisms. Some problems may be irregular bleeding and injection discomfort.