Women Physicians Day 2026: Sex-Specific Clinical Considerations in Women With Epilepsy

Women with epilepsy can face unique clinical considerations related to interactions among reproductive hormones, seizure activity, and antiseizure medications (ASMs) across the lifespan. Advances in understanding these relationships have informed best practices for managing fertility, pregnancy, and menopause, although ASM use during pregnancy has been associated with an increased risk of major congenital malformations. Therefore, care for women with epilepsy may require a comprehensive approach that accounts for sex- and gender-related influences throughout life.^1,2

In recognition of National Women Physicians Day, held February 3, 2026, NeurologyLive^® spoke with Page B. Pennell, MD, FAES, FAAN, FANA, the Henry B. Higman Professor of Neurology at the University of Pittsburgh School of Medicine, to further explore the clinical importance of integrating sex-specific factors into epilepsy care. She emphasized how fluctuations in reproductive hormones can influence seizure patterns across key life stages, including puberty, the reproductive years, perimenopause, and pregnancy, with catamenial epilepsy serving as an example.

Pennell also highlighted the need for proactive counseling around contraception and pregnancy planning, particularly given bidirectional interactions between ASMs and hormonal contraceptives, as well as differing teratogenic risk profiles among available ASMs. Additionally, she underscored the role of clinician-led research and advocacy in advancing care, noting persistent gaps in data related to ASM safety profiles, optimal vitamin supplementation, maternal outcomes, and the effects of hormonal transitions and therapies on seizure control.

NeurologyLive: What are the most important considerations when caring for women with neurological conditions across different life stages?

Page B. Pennell, MD, FAES, FAAN, FANA: Care for adolescent girls and women with epilepsy should include consideration of a few sex-specific factors:

Seizures may vary with changes in women reproductive sex steroid hormones, leading to some instability during puberty and perimenopause, times that are both marked by irregular hormone cycling. During the reproductive years, approximately 1/3 of women with uncontrolled seizure notice a catamenial pattern, with increased seizures in sync with their menstrual cycles. The most common catamenial pattern is to have increased seizures perimenstrually.

It is essential that care includes strategies and discussions to decrease the likelihood of unplanned pregnancies. Planned pregnancies have better maternal and child outcomes, especially in the setting of epilepsy and use of ASMs. The neurology provider should consider interactions with systemic hormonal contraceptives (e.g. birth control pills) and the ASMs they prescribe. Enzyme-inducing ASMs can lower the efficacy of hormonal contraceptives, and estrogen-containing contraceptives can lower some ASM blood levels (lamotrigine, oxcarbazepine, valproic acid).

There are very few ASMs which have adequate data demonstrating fetal safety when used during pregnancy (lamotrigine and levetiracetam). There are a few which have a particularly high teratogenic risk for major congenital malformations and adverse neurodevelopmental outcomes, including autism (e.g., valproate and phenobarbital). There are many more ASMs for which we do not have adequate data to quantify the fetal risk. It is important to be on the safest ASM going into a planned pregnancy balanced against the ASM types and doses needed for the best maternal seizure control.

What additional research has improved maternal and child outcomes for women with epilepsy?

Although we have gained knowledge about teratogenic profiles for some ASMs from pregnancy registries, we have also learned that it is important to keep an individual woman’s ASM blood level stable during pregnancy to prevent seizure worsening. Pharmacokinetic studies have identified the time course and extent of clearance changes for many ASMs. Recent published literature has also provided evidence-based guidance about how to adjust doses of several ASMs during pregnancy and postpartum. Literature has also provided evidence that the benefit of breastfeeding on ASMs outweighs any potential risks to the nursing baby.

What gaps still exist in women’s health and epilepsy, and how can women physicians help drive progress in this area?

We still have many gaps, starting with risk profiles for most of our ASMs. Other areas that need further research are to determine the best supplemental vitamin regimen to begin prior to conception and continuing during pregnancy. Even for folic acid, we have mixed data and recommendations about the best daily dose periconceptionally and through pregnancy.

More research is needed to determine maternal mortality and obstetrical complications during pregnancy in women with epilepsy, as well as the factors that can be addressed through different care pathways. Additional studies are needed to better understand the course of epilepsy during the perimenopausal transition and whether different hormone replacement therapy regimens can worsen or improve seizures. The effects of systemic hormonal contraception on seizure control, as well as the role of sex steroid hormones and their neuroactive steroid metabolites on seizure activity, mood, and anxiety during pregnancy, postpartum, and the nonpregnant state, also require further investigation.

Transcript edited for clarity. Click here for more of our coverage on epilepsy.

REFERENCES
1. Bui E. Women's Issues in Epilepsy. Continuum (Minneap Minn). 2022;28(2):399-427. doi:10.1212/CON.0000000000001126
2. Hophing L, Kyriakopoulos P, Bui E. Sex and gender differences in epilepsy. Int Rev Neurobiol. 2022;164:235-276. doi:10.1016/bs.irn.2022.06.012