The steroid metabolome in lamotrigine-treated women with epilepsy
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21787799
DOI
10.1016/j.steroids.2011.07.002
PII: S0039-128X(11)00226-1
Knihovny.cz E-resources
- MeSH
- 17-alpha-Hydroxypregnenolone blood MeSH
- Androstanols blood MeSH
- Androstanes blood metabolism MeSH
- Anticonvulsants adverse effects therapeutic use MeSH
- Adult MeSH
- Epilepsy drug therapy metabolism MeSH
- Lamotrigine MeSH
- Humans MeSH
- Metabolome MeSH
- Steroid 17-alpha-Hydroxylase blood MeSH
- Triazines adverse effects therapeutic use MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 17-alpha-Hydroxypregnenolone MeSH
- Androstanols MeSH
- Androstanes MeSH
- Anticonvulsants MeSH
- Lamotrigine MeSH
- Steroid 17-alpha-Hydroxylase MeSH
- Triazines MeSH
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 (WWE) 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×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). CONCLUSIONS: WWE showed a trend toward higher circulating 3α-hydroxy-5α/β-reduced androstanes, increased activity of 17α-hydroxylase/17,20 lyase in the Δ(5)-steroid metabolic pathway, and increased levels of the steroid polar conjugates.
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