HYPOTHALAMIC-PITUITARY-OVARIAN AXIS IN WOMEN WITH EPILEPSY

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Women with epilepsy may be at risk for reproductive health dysfunctions, including menstrual irregularity, anovulation, polycystic ovarian syndrome, and disturbances in basal and pulsatile release of gonadotropins and ovarian steroids. This study will define reproductive health risks for women with epilepsy and determine the relative mechanistic contribution of epilepsy syndrome, seizure frequency and type, and of individual antiepileptic drugs (AEDs) used in monotherapy. Pituitary and gonodal hormones, ovulatory function and ovarian morphology, and luteal phase function/adequacy will be evaluated in women with one of three distinct epilepsy syndromes: (1) idiopathic primary generalized epilepsy, in which the cerebral cortex is structurally and functionally normal; (2) symptomatic, localization related epilepsy (LRE) of temporal lobe origin, in which there is a strucutural and/or functional lesion within the temporal lobe; and (3) LRE of extratemporal lobe origin in which the epileptogenic region resides outside of the temporal lobe. These indices of reproductive function will also be evaluated according to exposure to AEDs in monotherapy that either induce, inhibit, or do not alter the hepatic mixed-function cytochrome P 450 enzyme system. Women with LRE of temporal lobe origin are hypothesized to be preferentially at risk for reproductive health dysfunctions because, given the extensive input of the mesial temporal lobe to the hypothalamus, the temporal lobe epileptogenic lesion is likely to cause hypothalamic-pituitary axis dysfunction. Women with seizures involving the temporal lobe are also at risk since these seizures are associated with pituitary hormone abnormalities. In addition, AEDs which inhibit P450 will increase steroid hormone concentrations and may predispose to reproductive dysfunctions. The effects of temporal lobe epilepsy versus AEDs will be further differentiated by evaluating reproductive function in women before and after surgical resection of a temporal lobe epileptogenic focus, after which seizures are likely to remit while AEDs are held constant. These findings will permit the clinician to select an AED which is least likely to compromise reproductive health for a given epilepsy syndrome, and will make it more likely that women with epilepsy and reproductive dysfunction are identified and appropriately treated.