The central nervous system is highly sensitive to the fluctuating levels of hormones that govern the menstrual cycle. For many women with epilepsy, the menstrual cycle significantly influences seizure frequency. This recognized phenomenon highlights a complex interplay between reproductive hormones and neuronal excitability. Hormonal shifts can alter the brain’s susceptibility to seizures, leading to seizure clusters predictably linked to specific phases of the monthly cycle.
Defining Catamenial Epilepsy
Catamenial epilepsy (CE) describes a pattern of seizure exacerbation that occurs specifically during certain phases of the menstrual cycle. The term “catamenia” is derived from the Greek word for “monthly.” This is not a separate disease but a subtype of epilepsy where the timing of seizures is influenced by hormonal changes. Approximately one-third of women with epilepsy experience this pattern. Diagnosis requires the average daily seizure frequency to increase by at least twofold during a specific phase of the menstrual cycle.
The Role of Estrogen and Progesterone
The underlying mechanism of Catamenial epilepsy is rooted in the opposing actions of the two primary sex hormones, estrogen and progesterone, on the brain’s seizure threshold. Estrogen is considered pro-convulsant, increasing neuronal excitability and lowering the seizure threshold. Estradiol, the most potent form of estrogen, increases excitatory input in brain regions like the hippocampus.
In contrast, progesterone and its metabolite, allopregnanolone, are anti-convulsant, stabilizing brain activity. Allopregnanolone acts as a positive modulator of the GABA-A receptor, the brain’s primary inhibitory neurotransmitter system. The presence of progesterone raises the seizure threshold, offering a protective effect against neuronal hyperexcitability.
Seizure exacerbation occurs when the balance shifts toward a high estrogen-to-progesterone ratio or during rapid progesterone withdrawal. The sharp decline in progesterone levels is a potent trigger for seizures due to the sudden withdrawal of its stabilizing effects. This hormonal fluctuation can alter the expression of GABA-A receptor subunits, making them less responsive to natural inhibitors. This correlation between predictable hormone peaks and troughs and increased seizure vulnerability demonstrates the brain’s influence by the reproductive endocrine system.
Identifying the Different Seizure Patterns
Clinicians classify Catamenial epilepsy into three distinct patterns based on when the seizure frequency is highest during the menstrual cycle.
Perimenstrual (Type 1)
This pattern is associated with a seizure increase during the days immediately preceding and including the first few days of menstruation (typically days -3 to +3). This exacerbation is triggered by the simultaneous rapid decline of both estrogen and progesterone from their luteal phase highs.
Periovulatory (Type 2)
Seizures increase around the time of ovulation (typically days 10 to 13 of the cycle). This occurs because estrogen levels peak just before ovulation while progesterone levels remain low, creating a high estrogen-to-progesterone ratio.
Luteal Phase (Type 3)
This pattern is observed in women who have inadequate or anovulatory cycles. Seizures are elevated throughout the entire second half of the cycle, as progesterone levels fail to rise sufficiently to provide anti-convulsant protection.
Accurate diagnosis hinges on the careful tracking of both seizure occurrence and the menstrual cycle over at least two months, often utilizing a seizure diary. This detailed tracking is essential for tailoring treatment, as the strategy depends on identifying the exact hormonal trigger.
Targeted Treatment Strategies
Treatment for Catamenial epilepsy is highly individualized, focusing on stabilizing the hormonal environment or adjusting anti-epileptic drugs (AEDs) to cover periods of greatest risk. For women with predictable cycles, an intermittent approach targets specific vulnerable days. This involves pulse dosing, where the standard AED dose is temporarily increased, or adding a short-acting benzodiazepine like clobazam during the high-risk phase.
Hormonal interventions are used, particularly for the Perimenstrual (Type 1) pattern. Supplemental natural progesterone can be administered during the late luteal phase to prevent the sharp hormonal withdrawal. For women with irregular cycles or non-response to intermittent treatments, the goal may be to suppress the menstrual cycle entirely. This is done using synthetic hormones, such as depot-medroxyprogesterone acetate or sustained oral contraceptives, which stabilize hormone levels and eliminate cyclical fluctuations.