Abstracts

Rationale: The aim of the present study was to investigate possible reproductive endocrine effects of levetiracetam (LEV) compared to valproate (VPA) using human ovarian follicular cells. LEV has a broad spectrum of antiepileptic efficacy. If no reproductive endocrine problems occur, the drug may become a good alternative to VPA for many patients, especially for women in fertile age. However, recent reports from animal studies have indicated a possible reproductive endocrine effect also of LEV. Methods: Cell cultures of human granulosa cells were prepared. First, the effect of the drugs on basal and FSH-stimulated estradiol secretion was investigated at different concentrations of LEV (12, 20, 50 or 80 μg/ml) or VPA (75, 100, 250, or 350 μg/ml). Second, the effect of the drugs on CYP19 aromatase activity was studied. Results: VPA significantly and concentration-dependently decreased basal and FSH-stimulated estradiol secretion. No effects on estradiol secretion were observed for LEV. Neither VPA nor LEV had any effect on CYP19 aromatase activity under basal conditions, but both drugs reduced CYP19 aromatase activity in FSH-stimulated cells at the higher concentrations (VPA 100, 250 and 350 µg/ml; LEV 20, 50 and 80 µg/ml). Conclusions: LEV acts differently from VPA on reproductive endocrine function when studied at therapeutically relevant drug concentrations in human ovarian cells. LEV does not affect estradiol secretion, although there is an effect on CYP19 aromatase activity after gonadotropin stimulation. The clinical significance of this observation is uncertain. Our findings indicate that LEV may be a good alternative to VPA for women in fertile age with regard to possible reproductive endocrine disorders. But extrapolation from cell culture studies to the clinical situation when treating patients is difficult even when human cells are used. Caution must therefore be taken before these results can be applied in the clinic.