ANIMAL TOXICITY STUDIES PERFORMED FOR RISK ASSESSMENT OF THE ONCE-A-MONTH INJECTABLE CONTRACEPTIVE MESIGYNA(R)

Results from toxicity studies performed for risk assessment of the com bined injectable hormonal preparation Mesigyna(R) are reviewed. Both c omponents of Mesigyna(R), i.e., estradiol valerate (E(2)Va1) and noret histerone enanthate (NET-EN), have been thoroughly investigated as ind ividual compounds and some limited toxicity data have been obtained fo r the combination. Most findings which were gathered in these studies from different animal species occurred in the gonads, accessory genita l and endocrine organs and can be related to the known species-specifi c pharmacological activity of a typical estrogen or progestin, respect ively. No additional or unexpected information which might indicate a possible estrogen/progestin interaction was gained from the administra tion of the combined preparation to animals. Based on the results from toxicity testing, there were no objections to the long-term therapeut ic use of Mesigyna(R) for hormonal contraception. The predictive value of the effects (including the tumorigenicity) observed in the common laboratory animals with regard to human safety is critically discussed , taking the vast amount of previous experience with hormonal contrace ptives into consideration. The conclusion is drawn that there is no an imal model for safety assessment of sex steroids that adequately repre sents the human situation. Quantitative extrapolations from animal tox icity findings to humans, therefore, are not possible. Especially, the value of long-term studies and of toxicity studies on estrogen/proges tin combinations is put into question. Like endocrine pharmacology stu dies, the toxicity studies with these steroid hormones are useful for the characterization of the possible endocrine pharmacological profile only.