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Reproductive dysfunction in women with epilepsy

From the Department of Neurology, University of Oulu, Oulu, Finland.

Address correspondence and reprint requests to Dr. Jouko I. T. Isojärvi at Department of Neurology, University of Oulu, FIN-90014, University of Oulu, Finland.

Reproductive endocrine disorders, such as polycystic ovary syndrome (PCOS), hypothalamic amenorrhea, premature menopause, and hyperprolactinemia, are reported to be more common in women with epilepsy than in the general female population. Epilepsy itself may affect reproductive endocrine function. For example, the prevalence of PCOS appears to be high even among women with epilepsy who do not take antiepileptic drugs (AEDs). However, AEDs also induce various changes in endocrine function. The hepatic enzyme-inducing AEDs phenytoin and carbamazepine (CBZ) have been shown to increase serum levels of sex hormone-binding globulin (SHBG). This increase leads in time to a diminished estradiol:SHBG ratio and decreased bioactivity of estradiol, which may result in menstrual disorders in some women receiving long-term CBZ treatment. Enzyme-inducing AEDs also can reduce the efficacy of oral contraceptives. In women with epilepsy who are treated with valproate (VPA), especially in those who have gained weight during treatment, polycystic ovaries, hyperandrogenism, and menstrual disorders appear to be common. After the start of VPA therapy in a woman with epilepsy, the length of the menstrual cycles and body weight should be monitored. Transvaginal ultrasonography of the ovaries is indicated if the menstrual cycles are prolonged and serum testosterone levels are elevated, especially if there is associated weight gain. The endocrine effects of the new AEDs have not been widely studied. However, treatment with these agents should be considered in women who develop reproductive endocrine dysfunction during treatment with the older AEDs.

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