Antiepileptic drugs and hormonal contraceptives in adolescent women with epilepsy

Abstract

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 (> or =50 microg) 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.

Antiepileptic drug utilization in children from 1997–2005—a study from the Netherlands

“…Our finding that 70% of the children discontinue treatment after 9 years is in agreement with the finding that 64% of the Dutch children discontinue treatment after 5 years [19]. The reason for the significant difference in the discontinuation of treatment of boys and girls is not known, but it may possibly be due to a re-consideration in the prescribing of an AED when girls start using contraceptives since many AEDs interact with oral contraceptives [20].…”

Gender difference in acquired seizure susceptibility in adult rats after early complex febrile seizures

“…This finding may be partly interpreted on the basis of a previous study showing that estradiol and progesterone inhibit the production of IL-1 by human peripheral monocytes [35] . In addition, there is increasing evidence showing that sex hormones are associated with neuronal development, neuronal excitability, and epileptic susceptibility [36][37][38] . Since sex hormones may be infl uenced by seizures, fever, and stress, they may be involved in the gender difference of seizure susceptibility after complex FSs.…”

Managing epilepsy in women of childbearing age — Polish Society of Epileptology and Polish Gynecological Society Guidelines

“…Antiepileptic drugs can induce the cytochrome P450 family of hepatic enzymes and isoenzyme 3A4 in particular by increasing the metabolism of ethinyl estradiol (EE), and consequently decrease the effectiveness of birth control [26].…”