Ask the Experts - Can Topiramate Increase the Metabolism of Estrogen?
A 23-year-old female patient of mine has frequent migraines. I am starting her on topiramate prophylaxis, 25 mg daily for a week, to be titrated upward by 25 mg weekly to 100 mg. She is taking norethindrone 21 1/20 for contraception. Can topiramate increase the metabolism of estrogen? Should this patient be receiving a higher dose of estrogen? Is monitoring for breakthrough bleeding a reliable way of assessing estrogen effects? Also, could you briefly review the effect of other seizure medications on estrogen and whether adjustments in the estrogen amounts are necessary?

Randolph W. Evans, MD

Hepatic enzyme-inducing antiepileptic drugs (AEDs) reduce oral contraceptive (OC) estradiol and progestin levels by 20% to 50%. Twenty-seven percent of neurologists report oral contraceptive failures in their patients who take AEDs. Suggestions for combining oral contraceptives and AEDs or using alternative birth control are summarized in the following table.

Table. Approaches to Combining OCs and AEDs for Women With Epilepsy

Discuss contraceptive choices and the effects of enzyme-inducing AEDs (carbamazepine, phenytoin, felbamate, oxcarbazepine, phenobarbital, primidone) on OCs with all women of childbearing years who have epilepsy. This can be part of a general discussion of the risks of pregnancy and epilepsy.

When treating women with epilepsy who take OCs, continue to select AEDs according to recommended indications for epilepsy.

If AEDs are otherwise equivalent, use a nonenzyme-inducing AED (valproic acid, gabapentin, levetiracetam) for women taking OCs.

Recommend OC doses of 50 g estradiol (or mestranol equivalent) for women who take enzyme-inducing AEDs and who desire effective contraception. Obstetricians and family physicians usually prescribe the OCs. Counsel women that increased OC doses do not always protect from contraceptive failures due to AEDs, but that OC failure rates are usually lower than with barrier methods alone.

Caution women with epilepsy to monitor for breakthrough or irregular menstrual bleeding while taking OCs. Raise OC doses or switch contraceptives if irregular bleeding occurs.

Advise women who seek very high levels of contraception that they may add spermicide or barrier contraception to their OCs.

Alternative effective contraceptives include medroxyprogesterone (Depo-Provera) and IUDs. Many pregnancies have occurred with levonorgestrel implant (Norplant) combined with enzyme-inducing AEDs.

Oxcarbazepine lowers OC hormone levels, while gabapentin, vigabatrin, and tiagabine are unlikely to interfere with OCs.

Topiramate causes only mild, dose-dependent reductions in estradiol. Topiramate dose vs changes in estradiol AUC are as follows: 100 mg twice daily, 15%; 200 mg twice daily, 18%; 400 mg twice daily, 29%. There is marked individual variability in estradiol levels, however, during topiramate treatment. Changes in estradiol levels for individual patients taking topiramate 200 mg twice daily range from -48% to +29%. This suggests that most women will not have OC failures due to topiramate interactions, particularly a patient taking only topiramate 100 mg/day. Patients receiving topiramate who desire high degrees of contraceptive protection, however, may wish to add barrier contraception.