Teratogenic screening methods and their application to contraceptive products.

Abstract

ABSTRACT After an analysis of the basic principles of teratogenic drug testing and the complexity of factors involved in the production of congenital malformations, the following topics are considered: the mechanisms of the teratogenic action the role of the placenta in drug transfer the choice of an animal model for teratogenic testing of hormonal sex steroids the influence of oral contraceptives upon various phases of reproduction. To compete with the various mechanisms which control the normal intrauterine development, multiple conditions have to be fulfilled. Such a situation occurs only occasionally in humans. Much data are available but little knowledge exists regarding the teratogenic mechanisms and the precise role of the placenta in drug teratogenicity. Great differences of reactions to drugs exist among various species. They can be related to differences in the enzymatic systems involved in the metabolic turnover of a drug, but in many cases no explanation is yet available. It seems that preliminary screening of sex steroids could be done in rodents. This can contribute to the selection of interesting therapeutical agents and may aid in discovering potential side effects. Since the maintenance of pregnancy in rodents requires functioning ovaries, while in women and in primates the placenta takes over very early the hormonal control of pregnancy, it is suggested to use primates for the safety evaluation of contraceptive drugs. The results obtained in these species are likely to have good predictive value. Oral contraceptives have no mutagenic effects, they do not produce chromosomal aberrations and seem to be devoid of teratogenic action. Experimental and clinical data suggest that oral contraceptives have no adverse effects on the perinatal and postnatal development.