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A comprehensive and individualized approach to epilepsy care is crucial for women, considering the complex interplay between reproductive hormones, seizure activity, and antiseizure medications (ASMs). Recognizing this need, a recent discussion with a leading neurologist highlighted the importance of integrating sex-specific factors into treatment plans.
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 explore these critical clinical considerations, particularly in anticipation of National Women physicians Day on February 3, 2026.
The Hormonal Landscape of Epilepsy
Fluctuations in reproductive hormones throughout a woman’s life can significantly impact seizure control. The menstrual cycle, pregnancy, and menopause all present unique challenges. This hormonal sensitivity underscores the need for neurologists to consider these biological factors when managing epilepsy in female patients.
proactive Planning: Contraception and Pregnancy
Proactive counseling regarding contraception and pregnancy planning is paramount. The interaction between ASMs and hormonal contraceptives is bidirectional, requiring careful consideration. Enzyme-inducing ASMs can reduce the effectiveness of hormonal birth control, while estrogen-containing contraceptives can alter the blood levels of certain ASMs, including lamotrigine, oxcarbazepine, and valproic acid.
Given these complexities, planned pregnancies are strongly encouraged, as they lead to improved maternal and child outcomes, especially when epilepsy and ASM use are involved.
The safety of ASMs during pregnancy remains a notable concern. While lamotrigine and levetiracetam have relatively more data demonstrating fetal safety, several ASMs carry a heightened risk of major congenital malformations and adverse neurodevelopmental outcomes, including autism.Valproate and phenobarbital are specifically cited as posing substantial risks. For many ASMs, however, sufficient data to quantify fetal risk is still lacking.
“It is significant 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,” dr. Pennell stated.
Recent Advances in Maternal and Child Outcomes
Research has significantly advanced understanding of ASM teratogenic profiles through pregnancy registries. Maintaining stable ASM blood levels throughout pregnancy is now recognized as crucial for preventing seizure worsening. Pharmacokinetic studies have mapped the timing and extent of ASM clearance changes during pregnancy, enabling evidence-based dosage adjustments during and after childbirth. Furthermore, evidence suggests that breastfeeding while on ASMs generally outweighs potential risks to the nursing infant.
Remaining Gaps and the Role of Women Physicians
Despite progress, significant gaps remain in women’s health and epilepsy research. These include comprehensive risk profiles for most ASMs, optimal vitamin supplementation regimens before and during pregnancy (even regarding folic acid dosage), and a deeper understanding of maternal mortality and obstetrical complications in women with epilepsy.
Further examination is needed to assess the impact of the perimenopausal transition on epilepsy and the potential effects of hormone replacement therapy. The influence of systemic hormonal contraception on seizure control, as well as the role of sex steroid hormones on seizure activity, mood, and anxiety throughout a woman’s life, also require further study.
Women physicians are uniquely positioned to drive progress in this area through dedicated research and advocacy. Addressing these gaps will require a concerted effort to improve care and outcomes for women with epilepsy.
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References
- Bui E. women’s Issues in Epilepsy. Continuum (Minneap Minn).2022;28(2):399-427. doi:10.1212/CON.0000000000001126
- 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
