Anti-epileptic drugs and hormonal treatments.

OPINION STATEMENT: Epilepsy and the medications used in its treatment are known to affect the menstrual cycle, aspects of contraception, and bone health in women. Adolescence is an important time to review the diagnosis of both epilepsy and the epilepsy syndrome because of the implications and decisions, which should be made regarding antiepileptic drug (AED) treatment. In girls, once they are on AED therapy, seizure free, and driving, it becomes difficult to change therapy because of the risk of breakthrough seizures and the fact that the new AED may not be as effective as the first. So a treatment choice made in adolescence is often life-long. Therefore, women need to be started on an AED that currently appears to be the most suitable for their seizure type, has a low teratogenic risk, and hopefully does not interact with contraception. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Nonenzyme-inducing AEDs (valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine, and zonisamide) do not show any interactions with the combined oral contraceptive. There are interactions between the combined oral contraceptive and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages >200 mg/day], oxcarbazepine, eslicarbazepine and perampanel [dosages >12 mg/day]) and lamotrigine. Women taking enzyme inducing AEDs should be encouraged to use a method of contraception that is unaffected by their epilepsy medication. Interactions between AEDs and other hormonal therapies are less well studied. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis, and osteomalacia. No studies have been undertaken looking at preventative therapies for these comorbidities. This article will concentrate on current contraceptive treatment options in patients taking AEDs.

Managing epilepsy in women of childbearing age.

Epilepsy affects the menstrual cycle, aspects of contraception, fertility, pregnancy and bone health in women. It is common for seizure frequency to vary throughout the menstrual cycle. In ovulatory cycles, two peaks can be seen around the time of ovulation and in the few days before menstruation. In anovulatory cycles, there is an increase in seizures during the second half of the menstrual cycle. There is also an increase in polycystic ovaries and hyperandrogenism associated with valproate therapy. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Non-enzyme-inducing antiepileptic drugs (AEDs) [valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine and zonisamide] do not show any interactions with the combined oral contraceptive (OC). There are interactions between the combined OC and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages>200 mg/day], oxcarbazepine) and lamotrigine. Pre-conception counselling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be informed about issues relating to the future pregnancy, including methods and consequences of prenatal screening, fertility, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labour, breast feeding and care of a child. During pregnancy, the lowest effective dose of the most appropriate AED should be used, aiming for monotherapy where possible. Recent pregnancy databases have suggested that valproate is significantly more teratogenic than carbamazepine, and the combination of valproate and lamotrigine is particularly teratogenic. Most pregnancies in women with epilepsy are without complications, and the majority of infants are delivered healthy with no increased risk of obstetric complications in women. There is no medical reason why a woman with epilepsy cannot breastfeed her child. The AED concentration profiled in breast milk follows the plasma concentration curve. The total amount of drug transferred to infants via breast milk is usually much smaller than the amount transferred via the placenta during pregnancy. However, as drug elimination mechanisms are not fully developed in early infancy, repeated administration of a drug such as lamotrigine via breast milk may lead to accumulation in the infant. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis and osteomalacia. No studies have been undertaken looking at preventative therapies for these co-morbidities.