The steroid metabolome in lamotrigine-treated women with epilepsy

BackgroundEpilepsy 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.AimTo evaluate steroid alterations in women with epilepsy (WWE) on lamotrigine monotherapy.Subjects and methodsEleven 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).ResultsWWE 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 × 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 5α/β-reduced androstanes in WWE that were significantly higher than the controls were etiocholanolone (status p < 0.001), 5α-androstane-3α,17β-diol (status p < 0.001), and the 5α/β-reduced androstane polar conjugates (status p < 0.001).ConclusionsWWE showed a trend toward higher circulating 3α-hydroxy-5α/β-reduced androstanes, increased activity of 17α-hydroxylase/17,20 lyase in the Δ5-steroid metabolic pathway, and increased levels of the steroid polar conjugates.

Figure optionsDownload as PowerPoint slideHighlights
► Evaluation of circulating steroids in fertile lamotrigine-treated women with epilepsy.
► Patients exhibit higher levels of 3α-hydroxy-5α/β-reduced androstanes.
► Patients have increased activity of 17α-hydroxylase/17,20 lyase in Δ5-steroids.
► Patients show increased levels of steroid polar conjugates.