The long-term effects of valproic acid (VPA) on reproductive endocrine functions in women with epilepsy (WWE) were studied. Serum reproductive hormone concentrations, clinical findings and ovarian morphology were analyzed in 71 WWE who had been receiving antiepileptic drugs (AED) for a minimum of 2 years. Of the 71 WWE, polycystic ovarian syndrome (PCOS) (p = 0.011) and menstrual irregularities (p = 0.009) were found to be more prevalent in women receiving VPA treatment when compared to women on non-VPA treatment. There was no statistically significant dose or duration-related rise of risk for patients who developed PCOS and menstrual irregularities and those who were not on long-term VPA therapy. The lack of a duration-related reproductive dysfunction in this patient population may support the hypothesis of early occurring VPA-associated metabolic and endocrine changes.

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