Hormonelle Einflüsse bei Frauen mit Epilepsie

Zusammenfassung

Bei Frauen mit Epilepsie spielen hormonelle Einflüsse eine wichtige Rolle. Durch Schwankungen der neuroaktiven Sexualsteroide während des Menstruationszyklus kommt es zur Entstehung der katamenialen Epilepsie. Östrogen wirkt dabei prokonvulsiv, Progesteron antikonvulsiv. Neben der üblichen antikonvulsiven Therapie können katameniale Anfälle mit einem GnRHAgonisten oder mit Progesteron behandelt werden.

Bei der Beratung epilepsiekranker Frauen bezüglich hormoneller Kontrazeption sind Interaktionen mit den Antiepileptika zu beachten. Aufgrund der Induktion von Zytochrom-P-450 in der Leber durch manche Antikonvulsiva (Carbamazepin, Felbamat, Phenytoin, Phenobarbital, Primidon, Oxcarbazepin, Topiramat) kommt es zu einem beschleunigten Metabolismus und damit zu einer verminderten Effektivität der Sexualsteroide. Die Fertilität ist bei Frauen mit Epilepsie reduziert.

Häufiger als in der Gesamtpopulation kommt es zu endokrinen Erkrankungen, z.B. zum PolyzystischenOvar-Syndrom (PCOS). Dies ist gekennzeichnet durch Hyperandrogenämie und ein Metabolisches Syndrom.

Als Ursachen werden sowohl die Anfälle selbst als auch medikamentöse Einflüsse diskutiert. Valproinsäure scheint dabei über den Mechanismus der Gewichtszunahme eine wichtige Rolle zu spielen. Bei Behandlung mit Valproinsäure sollten deshalb regelmäßig das Gewicht und der Menstruationszyklus kontrolliert werden. Bei Kindern von epilepsiekranken Frauen sind im Vergleich zur Gesamtpopulation häufiger angeborene Fehlbildungen wie Neuralrohrdefekte, Lippen-KieferGaumenspalten und Herzfehler zu beobachten. Ein besonders hohes Risiko ergibt sich bei Polytherapie und hohen Serumkonzentrationen der Medikamente. Durch Anfälle während der Schwangerschaft kommt es zu Fehlgeburten, Verletzungen des Feten, zu fetaler Hypoxie u./o. Azidose.

Die Teratogenität verschiedener Antiepileptika wird derzeit in einer prospektiven Studie des »European Registry of Antiepileptic Drugs and Pregnancy« (EURAP) überprüft.

Summary

Many women experience changes in seizure patterns at times of hormonal fluctuations during the menstrual cycle. These seizures are called catamenial. An increase of seizures can be observed at menarche, at ovulation and in anovulatory cycles. The exacerbation is due to the hormonal imbalance with high estrogen and low progesterone at this time.

Beside the antiepileptic drug therapy women with hormone-sensitive-seizures can be treated with progesterone or with a GnRH analogue.

Interactions between hormones and antiepileptic drugs are known. The metabolism of contraceptive hormones by the hepatic cytochrome P450 enzyme system is enhanced by some antiepileptic drugs (carbamazepine, felbamate, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate). This leads to low serum levels and reduced effectiveness of the hormonal contraception. The fertility in women with epilepsy is reduced. The prevalence of endocrine diseases is increased, especially the number of the Polycystic Ovarian Syndrome (PCOS).

The PCOS is represented by hyperandrogenism and by the metabolic syndrome. Beside multiple general etiologies the influence of epilepsy and antiepileptic drugs is known. More than other antiepileptic drugs valproate seems to promote PCOS by induced weight gain. Therefore weight and menstrual cycle should be monitored regularly in women on valproate therapy.

The risk of congenital malformations is increased in women with epilepsy compared with the general population. Often orofacial clefts, cardiac abnormalities and neural tube defects occur. Increased risk is observed under polypharmacotherapy and under high serum levels of antiepileptic drugs. Seizures during pregnancy can lead to misscarriage, trauma and fetal hypoxia and acidosis. For these women special prenatal management is recommended.

For detection of teratogenic effects of new antiepileptic drugs a prospective study of the “European Registry of Antiepileptic Drugs and Pregnancy” (EURAP) was started.

Schlüsselwörter

Epilepsie - katamenial - Fertilität - hormonelle Kontrazeptiva - Schwangerschaft

Keywords

Epilepsy - catamenial - fertility - hormonal contraception - pregnancy

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