Evaluating steroidal contraceptives: pre-clinical and clinical approaches.

Abstract

The Special Program of Research, Development and Research Training in Human Reproduction of the World Health Organization held a meeting in Geneva in February of 1987 to review the results of animal and human studies analyzing contraceptive steroids. In reviewing this data, assessment of pre-clinical toxicology and human risk would be possible. The studies reviewed included: studies on steroid exposure and breast disease, the protective factor of combined oral contraceptives (OC) (against ovarian cancer), hormonal contraceptives and cervical cancer, the relationship of gall bladder disease to OC use, congenital malformations and steroid hormone, OC use and its effect on breast milk and other topics. Basic principles on pre-clinical testing were adopted. These included: 1) the establishment of safety is a joint responsibility of experimental toxicology and clinical pharmacology. 2) Testing should include detailed analysis of the hormonal effect of new types in several animal species. 3) Species specific data should be collected. 4) Studies to detect cumulative toxicity should be performed. 5) Reproductive toxicity should concentrate on exposure throughout the embryonic period. 6) In vivo and in vitro tests should be conducted to investigate the mutagenic potential of new contraceptive steroids. 7) Long-term carcinogenicity study should be performed, preferably on the rat. 8) When new delivery systems are used to administer established steroidal contraceptives, experimental safety studies should assess potential interactions with the system and on the possibility of adverse effects of the delivery system. 9) Post-registration surveillance is on integral part of the risk assessment process.