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hormonal problems can result in reproductive dysfunction, with the most common disorders
being polycystic ovarian syndrome (PCOS) and hypothalamic amenorrhoea1,4.

It is estimated that PCOS occurs in 20% of women with epilepsy, compared to 5% of those
without. However, this relationship is complicated by the potentially confounding effects of
AEDs, in particular valproate, which will be outlined later.

An increase in seizure frequency around the time of menstruation (catamenial epilepsy) was
first clinically documented by Gowers in 1885 but cyclical variations in seizure frequency
have been known about since antiquity and were initially attributed to the cycles of the moon.

Experimental evidence from animal studies suggests that the change in seizure frequency
during the menstrual cycle may be related to the relative oestrogen and progesterone
concentrations, with oestrogens being considered to have proconvulsant and progestogens
anticonvulsant properties, respectively5,6. Human data tend to support this hypothesis,
although there appear to be no clear differences in hormonal changes in women with and
without catamenial seizures7.

Increased seizure frequency has been reported during the follicular phase when oestrogen
concentrations are highest8. Anovulatory cycles tend to be associated with higher seizure
frequencies, in particular during times of peak oestrogen concentration9. Anovulatory cycles
tend to be associated with an increase in seizure frequency in the second half of the menstrual
cycle while ovulatory cycles can have one or two peaks in seizure frequency, at around the
time of menstruation and/or ovulation10.

There is no agreement on the degree of seizure exacerbation required to meet a definition of
catamenial epilepsy. Various authors have reported an increase in seizures perimenstrually,
however many of these studies are poorly documented, use a less than strict definition of
what seizures to include in the calculation of perimenstrual attacks and are unrepresentative
of the female population with epilepsy. Using the strict definition for catamenial epilepsy that
≥75% of seizures have to occur within four days preceding and within six days of the onset
of menstruation, Duncan et al showed that only 12.5% of 40 women met this criterion11.
However, 31 (78%) claimed that most of their seizures occurred around the time of
menstruation.

Physiological changes to gamma-aminobutyric acid A (GABAA) receptor function as a result
of progesterone and its active metabolite allopregnanolone withdrawal at the time of
menstruation provide one possible mechanism for exacerbation of seizures perimenstrually,
although other mechanisms have also been suggested12.

Other influences around the time of menstruation, such as premenstrual tension and mood
changes, may also be important and may have an effect on seizure control. For example,
premenstrual tension is more common in women with catamenial epilepsy (75%) compared
with other women with epilepsy (43%)13.

Treatment
Over the last century, many therapeutic agents have been tried with various degrees of
success. Bromides were introduced by Locock in 1857 for the treatment of catamenial and
hysterical epilepsies. By the turn of the century, it had been noted that seizure frequency
occasionally decreased at the menopause or after oopherectomy. In the 1950s acetazolamide
became available, which is advocated by some for use in catamenial epilepsy. Data, on which
this supposition is based, however are scant with conflicting views on its effectiveness14,15.