By: Catherine Joachin

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Catamenial Epilepsy

What is catamenial epilepsy ?

Catamenial epilepsy (CE) is a form of epilepsy in which seizures intensify around specific phases of the menstrual cycle, particularly in the perimenstrual and periovulatory phases (Reddy, 2013). This condition affects approximately 30% of women of reproductive age with epilepsy, and while more prevalent in women with temporal lobe epilepsy, they can be associated with all types of epilepsy syndrome (Joshi & Kapur, 2019).

Catamenial seizures are triggered by hormonal changes tied to the menstrual cycle. The specific pathophysiology of the disorder remains unclear, however cyclic fluctuations in the female reproductive hormones progesterone and estrogen, which regulate neuronal excitability through neuroactive properties, are believed to play a central role in the development of seizures (Mirawati et al., 2024).

Why is this important?

Catamenial epilepsy is very common, but limited research on clinical guidelines, risk assessment and treatment options has left important gaps in our understanding of the condition and in patient care (Mirawati et al., 2024). This shortcoming further impairs the quality of life of countless women, who must endure the physical burden of worsening seizures while also facing the risk of other health complications such as infertility and menstrual cycle disorders (Reddy, 2013). 

Although, the quantity of publications on catamenial epilepsy has significantly risen over the past two decades, the literature is still scare (Mirawati et al., 2024), meaning that more research is needed to improve treatment options and raise awareness about the condition.

Diagnosis and Patterns

Clinical diagnosis is based on assessing menstruation and seizure history to determine whether there is a correlation between the exacerbation of seizures and specific times of the menstrual cycle (Reddy, 2013).

Using the first day of menstrual bleeding as a reference, the menstrual cycle is divided in a menstrual phase (days – 3 to 3) ; a follicular phase (days 4 to 9); a ovulatory phase (days 10 to 16); and a luteal phase (days 17 to – 4) (Reddy, 2013).

Three clinical types of catamenial epilepsy have been identified and can be distinguished based on patterns. The clinical type with the highest incidence, perimenstrual catamenial epilepsy (C1), is characterized by greater seizure frequency in the menstrual phase of women with normal ovulatory cycles. This pattern is linked to a drop in both progesterone and estrogen levels. Next, periovulatory type (C2) seizures are linked to an increase in seizures in the ovulatory phase in normal ovulatory cycles and can be attributed to high estrogen and progesterone levels. Last, the inadequate luteal-type (C3), which is associated with higher seizure frequency during the ovulatory, luteal and menstrual phases in women with anovulatory cycles (i.e., menstrual cycles where ovaries do not release an egg), when progesterone is high but estrogen low (Reddy, 2013).

Treatment

Although there is no clear treatment for catamenial epilepsy, there are different hormonal therapy options available to women with this condition. 

Women regular menstrual cycles, may undergo intermittent treatment, which involves of taking pharmacological agents during periods of seizure exacerbation, which depending on seizure pattern refers to the perimenstrual (C1), ovulation (C2) or luteal phases (C3) (Maguire & Nevitt, 2018). For women with irregular menstrual cycles or for whom intermittent treatment is ineffective, pharmacologically stopping the menstrual cycle with synthetic hormones or sustained oral contraceptives may be considered (Maguire & Nevitt, 2018).

Pharmacological therapies can involve hormonal or non-hormonal treatments. Non-hormonal treatments include pulsed clobazam and acetazolamide while hormonal treatments include natural progesterone supplements, synthetic oral or intramuscular progesterones, allopregnanolone and gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserlin) (Maguire & Nevitt, 2018).  

Nevertheless, prolonged progesterone treatment has failed to produce significant beneficial effects despite catamenial epilepsy being a primary neurosteroid-withdrawal disorder, further underscoring the need for more research on treatment options (Joshi & Kapur, 2019).

Conclusion

Catamenial epilepsy is a menstrual cycle-linked exacerbation of seizures affecting a great number of women. This condition is thought to result from cyclic changes in progesterone, which exerts anticonvulsant properties, and estrogen, which can exacerbate seizures, at certain points along women’s menstrual cycles. While there is no cure for this condition, it can be managed using a varying form of hormonal treatments.

References

Joshi, S., & Kapur, J. (2019). Neurosteroid regulation of GABAA receptors: A role in catamenial epilepsy. Brain Research, 1703, 31–40. https://doi.org/10.1016/j.brainres.2018.02.031

Maguire, M. J., & Nevitt, S. J. (2018). Treatments for peri-menstrual seizures in catamenial epilepsy. Cochrane Database of Systematic Reviews, 2018(12). https://doi.org/10.1002/14651858.CD013225

Mirawati, D. K., Wiyono, N., Ilyas, M. F., Putra, S. E., & Hafizhan, M. (2024). Research productivity in catamenial epilepsy: A bibliometric analysis of worldwide scientific literature (1956–2022). Heliyon, 10(10), Article e31474. https://doi.org/10.1016/j.heliyon.2024.e31474
Reddy, D. S. (2013). Neuroendocrine aspects of catamenial epilepsy. Hormones and Behavior, 63(2), 254–266. https://doi.org/10.1016/j.yhbeh.2012.04.016