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Over the last decade or so one of the main areas of therapeutic research has been hormonal
manipulation. Here the aim is either to increase relative progesterone concentrations or to
convert anovulatory to ovulatory cycles16,17. In an open study of progesterone therapy in 25
women with catamenial epilepsy 72% experienced a decline in seizure frequency18. Reports
suggest that the reduced metabolite of progesterone, tetrahydroprogesterone, rather than
progesterone itself, is responsible for improved seizure control19-21, through modulation of
GABAA chloride conductance.

Other approaches have involved the intermittent use of AEDs perimenstrually. Many of the
problems of tolerance, in particular those of benzodiazepines, can be overcome using this
treatment model. In a double-blind crossover study of 20 mg clobazam versus placebo over
a predetermined ten-day period in each menstrual cycle, clobazam was found to be superior
to placebo in 14 women (78%) and completely prevented catamenial seizures in the
majority22.

With regard to therapy it should first be established whether the seizures are truly catamenial.
If so, intermittent therapy with clobazam 10 mg at night perimenstrually is the simplest and
most useful therapy for the majority of women. If this fails, it may be worth considering the
use of acetazolamide perimenstrually or increasing the dose of the AED around the time at
risk. Finally, hormonal manipulation could be considered with medroxyprogesterone or
clomiphene23. However, good evidence for the effectiveness of these therapeutic options is
lacking.

Fertility

It has been reported that women with epilepsy have reduced fertility. The potential reasons
for this are likely to be complex, and include social and economic factors. It has also been
reported that sexual arousal may be reduced in women with epilepsy. However the situation
is far from resolved, with other studies showing that when women with epilepsy marry they
have near normal fertility.

It is recognised that there is a high incidence of menstrual disorders among women with
epilepsy24. Over 35% of women with partial seizures of temporal lobe origin had anovulatory
cycles when studied over three cycles, compared to 8% of controls25. Treatment has been
tried with progesterone suppositories in the appropriate phase of the menstrual cycle26, as
well as clomiphene23, and medroxyprogesterone18, with some success.

A recent prospective study showed that women with epilepsy have an increased risk of
infertility, particularly if they are using polytherapy. Infertility was least (7.1%) for those
with no AED exposure and higher (P = 0.001) for those with AED exposure (31.8% with one
AED, 40.7% with two AEDs and 60.3% with three or more AEDs). In this study women with
epilepsy exposed to phenobarbital had significant risk of infertility, but no such trend was
observed for valproate or other AEDs27.

Particular emphasis has been placed on valproate. In 1993, Isojarvi reported that polycystic
ovaries and hyperandrogenism are frequently detected in women on valproate28.
Subsequently they reported that these abnormalities are more common in women on valproate
who gain weight29, especially if this is during pubertal maturation30. However, their initial
study was retrospectively based in a selected population and did not concentrate on clinical
endocrine status. More recently, studies have been conflicting, reporting both significant
associations between valproate and PCOS and reporting no significant associations. Betts et
al have shown that women who had taken valproate for at least a year were more likely to