Treatment of Women With Epilepsy

Alison M. Pack, MD, Martha J. Morrell, MD

Disclosures

Semin Neurol. 2002;22(3) 

In This Article

Catamenial Seizures and Possible Treatments

Many women with epilepsy have seizures that cluster around the menstrual cycle. In studies of seizure patterns across ovulatory and anovulatory cycles, reproducible seizure patterns emerge.

Gonadotropin-releasing hormone (GnRH) secreted from the hypothalamus stimulates the release of the pituitary gonadotropin, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The formation of the ovarian follicle is stimulated by FSH, and during the follicular phase, or first half of the menstrual cycle, estrogen is the predominant ovarian sex hormone. In ovulatory cycles, a midcycle LH surge triggers ovulation and transforms the follicle into the corpus luteum, which secretes progesterone throughout the second, or luteal, phase of the cycle. If fertilization does not occur, the follicle involutes, progesterone secretion stops, and the uterine lining is shed. During anovulatory cycles, there is no midcycle surge of LH, estrogen remains high throughout the cycle, and progesterone remains low.

Hormone-mediated seizure patterns differ between ovulatory and anovulatory cycles. During ovulatory cycles, most seizures occur approximately 3 days before onset of menstrual flow and persist for about 6 days. These seizures appear to be triggered by the perimenstrual progesterone withdrawal.[17] Seizures may also occur at ovulation, precipitated by the estrogen surge. In contrast to the perimenstrual and ovulatory seizures in ovulatory cycles, seizures in anovulatory cycles are more frequent and dispersed, perhaps because estrogen remains relatively high and progesterone relatively low.

The first-line treatment for catamenial seizures, as for any seizure type, is the most effective AED in monotherapy. In addition, there may be a role for adjunctive therapy including carbonic anhydrase inhibitors or hormonal therapy. Acetazolamide (Diamox) may be helpful as adjunctive therapy for catamenial seizures, although this not a labeled indication. Acetazolamide is a weak carbonic anhydrase inhibitor with mild diuretic actions and anticonvulsant properties that may be related to a mild, transient metabolic acidosis. The usual dosage is 250 to 1000 mg in two divided doses. As tolerance to the anticonvulsant properties of the drug develops, intermittent therapy (10 to 14 days surrounding the time of seizure vulnerability) may be preferable. Acetazolamide should not be used in pregnant women.

Progesterones and antiestrogens have also been studied as antiepileptic agents in the treatment of hormone-associated seizures. Although synthetic oral progestins overall have not been helpful,[18] parenteral medroxyprogesterone (Depo-Provera) given in large enough doses to cause amenorrhea has been associated with a reported reduction in seizure frequency in some women. Natural progesterone is available as extract of soy in suppository and lozenge form and may be given over the initial luteal phase of the cycle as 100 to 200 mg three to four times a day with an average dose of 600 mg to achieve a serum level of 5 to 25 ng/mL.[19,20] Other alternatives are Prometrium 100-mg capsules and a progesterone topical cream. Progesterone therapy should be avoided during or in anticipation of a pregnancy and in the absence of contraception. Antiestrogens, such as clomiphene, have been reported to reduce seizures in women with intractable partial epilepsy. However, these medications have been associated with potentially significant side effects such as hot flashes, polycystic ovaries, and unplanned pregnancy.[19] Many antiestrogens are presently under development, and some may eventually have a role in treatment of hormone-sensitive seizures.

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