Animal toxicity studies performed for risk assessment of the once-a-month injectable contraceptive Mesigyna.
Results from toxicity studies performed for risk assessment of the combined injectable hormonal preparation Mesigyna are reviewed. Both components of Mesigyna, i.e., estradiol valerate (E2Val) and norethisterone enanthate (NET-EN), have been thoroughly investigated as individual compounds and some limited toxicity data have been obtained for the combination. Most findings which were gathered in these studies from different animal species occurred in the gonads, accessory genital and endocrine organs and can be related to the known species-specific pharmacological activity of a typical estrogen or progestin, respectively. No additional or unexpected information which might indicate a possible estrogen/progestin interaction was gained from the administration of the combined preparation to animals. Based on the results from toxicity testing, there were no objections to the long-term therapeutic use of Mesigyna 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 contraceptives into consideration. The conclusion is drawn that there is no animal model for safety assessment of sex steroids that adequately represents the human situation. Quantitative extrapolations from animal toxicity findings to humans, therefore, are not possible. Especially, the value of long-term studies and of toxicity studies on estrogen/progestin combinations is put into question. Like endocrine pharmacology studies, the toxicity studies with these steroid hormones are useful for the characterization of the possible endocrine pharmacological profile only.
Seibert
B
B
Institute for Experimental Toxicology, Schering AG, Berlin, Germany.
Günzel
P
P
D000818:Animals; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000633:toxicity*; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D006801:Humans; D007273:Injections, Intramuscular; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D012307:Risk Factors
D003271:Contraceptive Agents, Female; D003692:Delayed-Action Preparations; D004338:Drug Combinations; C418365:estradiol, norethindrone drug combination; D004958:Estradiol; C024319:norethindrone enanthate; D009640:Norethindrone