Abstracts

Several antiepileptic drugs have been found to induce changes in endocrine function in women with epilepsy. Valproate induces hyperandrogenism and polycystic ovaries while enzyme-inducing drugs lower biologically active sex steroid hormone values. Levetiracetam (LEV) is one of the newer antiepileptic drugs with no endocrine side effects reported so far in humans. Recently, however, we showed that long-term LEV treatment in rats affects ovarian morphology, with an increase in ovarian weights, a lower number of cysts, and a higher number of corpora lutea and secondary follicles. In the present study we wanted to investigate the endocrine changes in the same set of animals to compare morphology data with endocrine findings. Fifty female Wistar rats were fed per-orally through a gastric tube with levetiracetam 50 mg/kg (n=15), 150 mg/kg (n=15) or control (n=20) solution twice daily for 90-95 days. They were killed in diestrous/early proestrous phase. Serum levels of testosterone, 17[beta]-estradiol, progesterone, FSH, LH and se-LEV concentration were analysed. Mean LEV concentration measured 3-4 h after last dose was 122 umol/l in the low-dose, and 277 umol/l in the high dose group. FSH was reduced in both low and high dose treated animals (3.4 ng/ml, 3.3 ng/ml), compared to the controls (5.5 ng/ml, p[lt]0.05). LH was not affected by the treatment. Serum testosterone was significantly increased in both low and high dose treated animals (0.48 nmol/l, 0.52 nmol/l), compared to the control group (0.16 nmol/l, p[lt]0.05). Serum estradiol was significantly reduced in the treated animals (55.8 pmol/l, 145.3 pmol/l) compared to the controls (257.5 pmol/l, p[lt]0.05). Serum progesterone concentration was only significantly changed in the low dose group (56.8 nmol/l), compared to controls (34.7 nmol/l, p[lt]0.05). The results indicate an effect of levetiracetam on female sex steroid hormones. The changes in reproductive hormones may be due to a peripheral effect on the ovary with reduced transformation from testosterone to estradiol, or a central effect on the hypothalamus/pituitary level. Taken together with the morphology data an increased frequency of ovulatory cycles may occur. Human studies are needed to assess possible clinical relevance of the present findings.