Polycystic ovaries, obesity and insulin resistance in women with epilepsy: A comparative study of carbamazepine and valproic acid in 105 women

In order to investigate the possible role of valproic acid therapy in the development of obesity, hyperinsulinism and polycystic ovaries (PCOs), we have studied metabolic parameters and ovarian morphology in epileptic women. A total of 105 women, who were treated for at least 2 years with valproate (n = 52) or carbamazepine monotherapy (n = 53), were included in the examination. Menstrual disturbances were reported by 29 (28 %) of the women, 12 (11 %) of the VPA treated women, and 17 (16 %) in the CBZ group. On ultrasound scan polycystic ovaries were found in 28 patients (27 %) of the whole study population, of whom 13 (12 %) received VPA and 15 (14 %) CBZ. The mean body mass index (BMI) was significantly higher in the VPA group (24.4 kg/m(2) +/- 4.1) than in CBZ treated patients (22.9 kg/m(2) +/- 2.4;p < 0.022), and serum triglycerides tended to be increased, while total cholesterol values (178.9 +/- 30.5) and LDL-cholesterol values (92.6 +/- 27.4) were significantly lower in the valproate group, than in the carbamazepine group (207.1 +/- 43.0 vs 115.1 +/- 42.0; p < 0.001). Postprandial insulin, C-peptide and proinsulin levels were significantly higher in VPA treated patients compared with those treated with CBZ, while no differences could be found in the fasting state. In conclusion we could thus demonstrate that the frequency of PCOs in 27 % of epileptic women seems to be similar to that in the general population with a frequency of 20-30 %. The development of PCOs did not reveal a difference with the administration of VPA or CBZ. With respect to the metabolic side-effects of VPA therapy our data indicate that VPA increases glucose stimulated pancreatic insulin secretion, which might be followed by an increase in body weight.