Seizures and Reproductive Function: Insights from Female Rats with Epilepsy

Objective: Chronic seizures in women can have adverse effects on reproductive function, such as polycystic ovarian syndrome, but it has been difficult to dissociate the effects of epilepsy from the role of antiepileptic drugs. To distinguish the effects of chronic seizures from medication, we used the laboratory rat, because an epileptic condition can be induced without concomitant anticonvulsant drug treatment. Methods: Adult female rats were administered the chemoconvulsant pilocarpine to initiate status epilepticus, which was decreased in severity by the anticonvulsant diazepam. These rats developed spontaneous seizures in the ensuing weeks, and are therefore termed epileptic. Controls were saline-treated rats, or animals that were injected with pilocarpine but did nor develop status epilepticus. Ovarian cyclicity and weight gain were evaluated for 2 to 3 months. Serum hormone levels were assayed from trunk blood, which was collected at the time of death. Paraformaldehyde-fixed ovaries were evaluated quantitatively. Results: Rats that had pilocarpine-induced seizures had an increased incidence of acyclicity by the end of the study, even if status epilepticus did not occur. Ovarian cysts and weight gain were significantly greater in epileptic than control rats, whether rats maintained cyclicity or not. Serum restosterone was increased in epileptic rats, but estradiol, progesterone, and prolactin were not. Interpretations: The results suggest that all epileptic condition in the rat leads to increased body weight, cystic ovaries, and increased testosterone levels. Although caution is required when comparing female rats with women, the data suggest that recurrent seizures have adverse effects, independent of antiepileptic drugs.