Abstracts

There is increasing concern about the effects of antiepileptic drugs on female reproductive function. Long-term valproate (VPA) treatment has been associated with hyperandrogenism and polycystic ovaries in women, while enzyme-inducing drugs seem to reduce biologically active sex steroid hormone levels. If devoid of endocrine effects, levetiracetam (LEV) may be a good alternative in women with epilepsy. However, it has recently been shown that also LEV may affect ovarian morphology in rats after long-term treatment (Epilepsia 2004; 45: suppl 7: 129-130). The aim of the present study was to investigate the effects of LEV in comparison with VPA and phenytoin (PHT) on basal and gonadotropin-stimulated steroid secretion in porcine ovarian follicular cells. Medium sized ovarian follicles were obtained from prepubertal pig ovaries. Theca and granulosa cells were collected and co-cultured in one well to resemble follicles in vivo. Drugs were added to control and gonadotropin-stimulated cultures in the following concentrations: LEV: 0, 20, 50, 80 ug/ml. VPA: 0, 100, 250, 350 ug/ml. PHT: 0, 15, 25, 35 ug/ml. The cells were exposed to the drug for 48 hours. Both LEV and VPA in all doses used caused a significant increase in basal testosterone secretion (37.9, 80.4, 94.6 and 95,6 ng testosterone/ml after exposure to 0, 20, 50 and 80 ug/ml LEV; and 26.3, 76.0, 86.0 and 99,2 ng testosterone/ml after exposure to 0, 100, 250 and 350 ug/ml VPA). In LH-stimulated cells, however, only VPA, but not LEV increased testosterone secretion. PHT did not have any effect on neither basal nor LH stimulated testosterone secretion.
Basal estradiol secretion was significantly reduced at all concentrations only by VPA (57.6, 36.0, 24.4 and 21.1 ng estradiol/ml after exposure to 0, 100, 250 and 350 ug/ml VPA). LEV decreased basal estradiol secretion only at 50 and 80 ug/ml. VPA in all doses used decreased FSH-stimulated estradiol secretion while LEV had no effect on FSH-stimulated estradiol secretion. PHT had no effect on basal, but increased FSH-stimulated estradiol secretion at the highest drug concentration. LEV at therapeutic drug concentrations increased basal testosterone secretion while higher concentrations also reduced estradiol secretion. Similar changes were observed with VPA. However, in contrast to VPA, LEV did not affect gonadotropin-stimulated steroid secretion. Human studies are, however, needed to assess possible clinical relevance of the present findings.