The steroid metabolome in lamotrigine-treated women with epilepsy

Background: Epilepsy in women may be associated with reproductive disorders and alterations in serum steroid levels. Some steroids can be induced by epilepsy and/or treatment with antiepileptic drugs; however, there are still limited data available concerning this effect on the levels of other neuroactive steroid metabolites such as 3a-hydroxy-5a/b-reduced androstanes. Aim: To evaluate steroid alterations in women with epilepsy (WINE) on lamotrigine monotherapy. Subjects and methods: Eleven WWE and 11 age-matched healthy women underwent blood sampling in both phases of their menstrual cycles (MCs). The steroid metabolome, which included 30 unconjugated steroids, 17 steroid polar conjugates, gonadotropins, and sex hormone-binding globulin (SHBG), was measured using gas chromatography-mass spectrometry (GC-MS) and radioimmunoassay (RIA). Results: WWE had lower cortisol levels (status p < 0.001), but elevated levels of unconjugated 17-hydroxypregnenolone (status p < 0.001). Progesterone was higher in the follicular menstrual phase (FP) in WWE than in the controls (status x menstrual phase p < 0.05, Bonferroni multiple comparisons p < 0.05), whereas 17-hydroxyprogesterone was higher in WWE in both menstrual phases (status p < 0.001). The steroid conjugates were mostly elevated in WWE. The levels of 54p-reduced androstanes in WWE that were significantly higher than the controls were etiocholanolone (status p <0.001), 5 alpha-androstane-3 alpha,17 beta-diol (status p < 0.001), and the 5 alpha/beta-reduced androstane polar conjugates (status p < 0.001). Conclusions: WWE showed a trend toward higher circulating 3 alpha-hydroxy-5 alpha/beta-reduced androstanes, increased activity of 17 alpha-hydroxylase/17,20 lyase in the Delta(5)-steroid metabolic pathway, and increased levels of the steroid polar conjugates. (C) 2011 Elsevier Inc. All rights reserved.