Endocrine Abstracts

Managing epilepsy in women is complicated by effects of sex steroids on seizures, antiepileptic drug (AED)- oral contraceptive (OCs) interactions, AED associated bone disease, reproductive endocrine disorders such as polycystic ovary syndrome (PCOS) and by the teratogenic and adverse developmental effects of some AEDs.

Approximately 30% of women with epilepsy (WWE) have catamenial seizure patterns with seizures occurring with the ovulatory estrogen surge and the late luteal drop in progesterone. Estrogen is proconvulsant and progesterone is anticonvulsant. Hormone treatment trials for catamenial seizures are underway.

Anovulatory cycles and a PCOS phenotype are associated with epilepsy and taking AEDs. Seizures and epileptiform discharges disrupt hypothalamic and pituitary hormones. An effective and widely used AED, valproate (VPA), is associated with a PCOS phenotype that is most prevalent in young women. VPA stimulates testosterone and insulin synthesis and release and inhibits VPA metabolism. In some WWE, VPA is associated with weight gain, hyperandrogenism, anovulatory cycles, and polycystic ovaries. These symptoms appear to resolve when VPA is discontinued.

WWE epilepsy have a 3 fold higher risk for hip fractures and 2 fold higher risk for all fractures. AEDs that induce the cytochrome P450 system, especially phenytoin, are associated with bone loss. Possible mechanisms include catabolism of vitamin D with hypocalcemia and secondary hyperparathyroidism, direct effects on bone cells, resistance to PTH, calcitonin deficiency, and impaired calcium absorption.

The treatment of WWE has been hampered by the lack of definitive data regarding comparative teratogenicity of the various AEDs. Pregnancy registries indicate that phenobarbital, VPA, and topiramate have significant teratogenic effects, while carbamazepine and lamotrigine have more favourable profiles. Phenobarbital and VPA may also have adverse effects on neurodevelopmental outcome. Data from pregnancy registries will better define the teratogenic and developmental effects of the older and newer AEDs.