Maximizing the health of women with epilepsy: science and ethics in new drug development.

Issues of unique concern to women with epilepsy largely arise from gender-based physiological differences. Female sex steroid hormones may alter the expression of epilepsy and the efficacy of antiepileptic drugs (AEDs). Seizures and AEDs in turn affect the hypothalamic-pituitary axis and can adversely impact reproductive function and bone health. Maternal seizures and exposure to AEDs may compromise fetal development. At this time, women with epilepsy and their medical caretakers do not have access to all the information necessary to formulate a treatment plan that will have the least impact on reproductive and general health. In part, this is because reproductive aged women are excluded from the earliest phases of drug testing and pregnant and lactating women are excluded from all aspects of new drug development. Therefore, as new AEDs enter the marketplace, women with epilepsy must decide whether a new AED is appropriate for therapy based on very limited information. Postmarketing surveillance of gender-specific adverse effects, as with all adverse effects, depends on voluntary reporting. Only a small percentage of significant adverse events are believed to be captured by the present system. Consumers, ethicists, and some physician groups are now arguing that women should be included in all aspects of the development of drugs they will ultimately use-even pregnant and lactating women. Some of the issues of concern for women with epilepsy regarding epilepsy treatment, reproductive function and general health will be reviewed, followed by a discussion of the drug development process and how it does, and could better, address the concerns of women.