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Antiepileptic drugs and hormonal contraceptives in adolescent women with epilepsy

From the Department of Pediatrics and Neurology, Pediatric Comprehensive Epilepsy Program, Medical College of Wisconsin, Children’s Hospital of Wisconsin, Milwaukee, Wisconsin.

Address correspondence and reprint requests to Dr. Mary L Zupanc, Children’s Hospital of Wisconsin, 900 West Wisconsin Avenue, PO Box 1997, Milwaukee, WI 53201-1997; email: mzupanc{at}mcw.edu

Both estrogen and progesterone influence seizure activity in women with epilepsy, with estrogen generally demonstrating proconvulsant and progesterone anticonvulsant effects. Women with epilepsy exhibit a variety of endocrine disturbances, probably due to a combination of factors, including the epilepsy syndrome and the effect of interictal and ictal epileptic discharges in the brain. The direct effects of some antiepileptic drugs (AEDs) further increase this risk, apparently related to a specific drug’s effect on hepatic microsomal enzymes of the cytochrome P-450 system. AEDs that induce hepatic microsomal enzymes also interact with hormonal contraception to increase estrogen’s metabolism and progesterone’s protein binding, decreasing concentrations of both hormones and thus reducing contraceptive efficacy. Some evidence indicates that concurrent use of hormonal contraceptives and lamotrigine significantly decreases the plasma concentration of lamotrigine, suggesting that close monitoring is warranted. Nevertheless, hormonal contraception confers comparable or superior efficacy compared with such other contraceptives as the intrauterine device and barrier methods and remains an appropriate option in women with epilepsy. Importantly, concurrent use of hormonal contraception and AEDs does not adversely affect seizure control. Careful patient management, including the use of increased estrogen doses (50 µg) in patients receiving enzyme-inducing AEDs, may further minimize the risk for unintended pregnancy. Special considerations in women of childbearing age include decreased compliance and disease prevention. Although adequate seizure control is the critical requirement of an AED, the potential for interactions with hormonal contraception and the increased risk for endocrine disturbances caused by drugs that alter hepatic microsomal enzymes suggest additional potential advantages for AED treatment that does not affect these enzymes. Both the constellation of physicians treating women with epilepsy and the patients themselves have a poor understanding of the spectrum of reproductive health issues involved, and increased awareness is needed to improve patient management.

Publication of this supplement was supported by an educational grant from UCB Pharma Inc. The sponsor has provided the author with an honorarium for her participation in this project, plus she has received other honoraria from the sponsor during her career.