Epilepsy and Menopause

Menopause is marked by the involution of the ovaries and permanent cessation of menstrual cycles. Transition into menopause may vary from an abrupt to a prolonged process, which generally occurs when a woman reaches her late 40s to mid 50s. On the average, American women can expect to live another 30 years. For women with epilepsy, the inherent hormonal changes associated with menopause may have an additional impact on the quality of this phase of life.

Reproductive Hormones and Seizures

Many women with epilepsy experience changes in seizure patterns at times of hormonal fluctuations. It is known that estrogen has an excitatory effect on neurons while progesterone has an inhibitory effect.

During the menopausal process, as ovarian function ceases, estrogen levels decline, leading to the assumption that women with epilepsy may have improved seizure control. However, there is a concomitant decline in progesterone levels and thus, seizure patterns in many women with epilepsy may remain constant, or even worsen.

Antiepileptic Drugs and Aging

Doses of antiepileptic drugs (AEDs) may need reassessment as women with epilepsy age, depending on basic pharmacokinetic principles such as drug absorption and distribution, individual metabolism (primarily liver function, although small amounts of some drugs are metabolized in gut, lung, or kidney) and renal function.

Polypharmacy for conditions unrelated to the epilepsy may affect efficacy of AEDs.

Some AEDs are implicated in mineral loss from bone, resulting in osteoporosis, osteopenia, osteomalacia and fractures. Altered bone metabolism and bone density have been associated with phenytoin, carbamazepine and phenobarbital.

AEDs may influence the effectiveness of hormone replacement therapy (HRT) just as efficacy of hormonal contraception is compromised by AEDs in some women with epilepsy.

Hormone Replacement Therapy in Menopause

HRT is frequently prescribed for women with epilepsy in the menopausal years for treatment of vasomotor changes (75 percent to 85 percent of all menopausal women experience hot flashes).

HRT is considered beneficial in the prevention of osteoporosis and associated bone fractures and may be beneficial in the prevention of cardiovascular disease.

Studies are inconclusive, but HRT may increase the risk of uterine cancer and breast cancer in some populations.

HRT increases estrogen levels and may result in increased seizure activity in some women with epilepsy. Concomitant use of progesterone replacement may decrease this incidence, especially if natural progestins, rather than synthetic progestins, are used.

Therapeutic Interventions

The most appropriate treatment for seizures in women of any age is monotherapy with first-line AED appropriate for the seizure type. Interactions of AED and other medications should be considered when assessing seizure control and medication toxicity.

Assess need for HRT and individual risk factors based on medical and family history. If HRT is prescribed, consider natural progestins in combination with estrogen replacement.

Encourage appropriate lifestyle modifications to minimize risk of bone loss and osteoporosis. A high calcium diet (including calcium supplements with vitamin D), regular weight-bearing exercise and avoidance of alcohol and smoking are useful preventive measures. This is especially important if HRT is not used.

CONTACT

For additional information, contact the Women and Epilepsy Initiative of the Epilepsy Foundation at (800) 332-4050.

REFERENCES

Abassi F, Krumholz A, Kittner SJ, et al. Effects of menopause on seizures in women with epilepsy. Epilepsia. 1999;40:205-210.

Harden CL, Pulver MC, Ravdin L, et al. The effect of menopause and perimenopause on the course of epilepsy. Epilepsia. 1999;40:1402-1407.

Herzog A. Endocrine aspects of epilepsy in women. In: Pedley TA, Meldrum BS, eds. Recent Advances in Epilepsy. New York: Churchill Livingstone. 1995;221-237.

Krumholz A. Menopause and epilepsy. In: Morrell M, ed. Women with epilepsy: A handbook of health and treatment issues. Cambridge, U.K.: Cambridge University Press. In press.