Epilepsy and women

Women and epilepsy - general considerations
Men and women produce the same "sex hormones": estrogen, progesterone, and testosterone. The major differences between men and women are:
• women produce relatively more estrogen and progesterone than men
• women produce these hormones in a cyclical fashion (with significant highs and lows in progesterone and estrogen over approximately 28 days). Men have a relatively constant production of all three, but relatively more testosterone
• only women are able to experience pregnancy
• women undergo menopause

With respect to epilepsy and its treatment, it follows that there are several issues unique to women. We will attempt to answer questions and dilemmas that arise as a consequence of these differences and examine the influence these might have on:
• the menstrual cycle and its influence on the severity and frequency of seizures
• drugs used to treat epilepsy and their unique side effects in women
• fertility of women with epilepsy (how easy or difficult is it to get pregnant?)
• pregnancy (covered in a separate handout, see Epilepsy and pregnancy)

Epilepsy and the menstrual cycle
Firstly it is important to stress that the majority of women with epilepsy do NOT have more seizures during menses. But in about 30% of women there is a definite exacerbation of seizures, usually the day before or the day of menses. If a careful diary is kept and shows that more than 75% of all seizures occur in a strict and predictable way in association with the menstrual cycle, then this is accepted as "menstrual epilepsy"; the medical term for which is "catamenial epilepsy." Not all seizures in women with menstrual epilepsy will be provoked by the onset of menses; in a minority of women, the seizures occur at mid-cycle, at the time of ovulation. It is also recognized that complex partial seizures (temporal lobe epilepsy) are more likely to be associated with the diagnosis of catamenial epilepsy, as opposed to tonic clonic seizures (grand mal).

The reason for the association between the female menstrual cycle and the provocation of seizures is not known. In the laboratory, it was found that estrogen has a mild tendency to provoke a seizure, yet progesterone does the reverse and protects against seizures. The sudden rise and fall of these hormones in the 28-day cycle may be relevant. Perhaps there is mild swelling of the brain associated with the fluid retention some women experience with their menses. Most scientists agree that there is probably no single explanation and is instead a combination of many factors.

If a woman has epilepsy reliably associated with the menstrual cycle, then theoretically, one way to control the epilepsy is to manipulate the cyclical secretions of female hormones. In practice, however, this is not simple and the vast majority of women still need to rely on their usual anticonvulsant medication. Additional options, such as suppressing ovulation (the release of the egg each month) using an implant or an oral contraceptive, are decisions that need to be made on an individual basis following detailed analysis of seizure patterns and discussion between the woman, a neurologist, and perhaps an endocrinologist and/or gynecologist.

The menstrual cycle and epilepsy
The section above examined the effect a woman's menstrual cycle may have on her seizures, but to turn it around, there is increasing awareness that epilepsy itself may alter the monthly cycle of the secretion of sex hormones and influence a woman's reproductive function. For example:
• It is now known that both men and women with epilepsy are slightly less "fertile" than those without epilepsy, in other words they may have more difficulty conceiving a child.
• A seizure acutely increases the secretion of many hormones (sex hormones, thyroid, and the milk-stimulating hormone prolactin) for several hours after the event.
• Women with epilepsy have a slightly increased tendency to develop a condition called polycystic ovarian syndrome.
• Menopause may start earlier in epileptic women.

Polycystic ovarian syndrome
Polycystic ovarian syndrome is due to a subtle change is the ratio of secretion of female hormones to male hormones in a woman, and clinically there may be
(1) reduction in ovulation (less eggs produced each month) and a thickening and enlargement of the ovaries with multiple cysts in each
(2) scanty and irregular menses
(3) increased facial hair (hirsutism)

The major practical consequence for women is the degree of relative infertility. Indeed, it is estimated that about 5% of ALL women in the general population may show some signs of polycystic ovarian syndrome. In women with epilepsy, the prevalence is said to be between 10% to 25%. To put this in context, it follows that of 100 women with epilepsy, 75% to 80% will NOT show signs of polycystic ovarian syndrome. But there is an additional problem, not only does epilepsy itself increase the chance of polycystic ovarian syndrome, antiepileptic drugs may also increase the risk of developing polycystic ovarian syndrome. Not all antiepileptic drugs have this effect, some are worse than others. The antiepileptic drug most consistently studied and associated with reproductive dysfunction in women is sodium valproate (Valpro, Epilim).

Sodium valproate (VP)
Since 1986 several large trials have demonstrated the following side effects and adverse changes in the reproductive and metabolic hormones in women with epilepsy taking sodium valproate:
• Menstrual irregularity - including complete loss of the menstrual cycle (amenorrhoea)
• Features of mild excess of male hormones usually manifest as the development of excess facial hair
• Polycystic ovarian syndrome
• Weight gain

It has been hard to give accurate figures and percentages of these occurrences because in past studies women were often taking additional antiepileptic drugs, not just sodium valproate alone. But a fair estimate would be that overall about 50% of women on sodium valproate will show some or all of the above side effects to a variable degree.

It is vital that women with epilepsy recognize that the choice of anticonvulsant therapy is complex. In many instances, valproate may be the 'drug of choice,' and the risks of not treating the seizures may far out weigh the slight risk of weight gain and the changes in hormone balance listed above.

This information was written by Graham Norton FRACP, and is herewith used with permission. It was last reveiwed February 1, 2013.

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