title: The steroid metabolome in lamotrigine-treated women with epilepsy.
abstract: 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.
  
  
  OBJECTIVE
  To evaluate steroid alterations in women with epilepsy (WWE) on lamotrigine monotherapy.
  
  
  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.
authors.affiliation: Institute of Endocrinology, Národní třída 8, Praha 1, CZ 116 94, Czech Republic. mhill@endo.cz
authors.forename: Martin
authors.initials: M
authors.lastname: Hill
authors.forename: Jana
authors.initials: J
authors.lastname: Vrbíková
authors.forename: Jana
authors.initials: J
authors.lastname: Zárubová
authors.forename: Radmila
authors.initials: R
authors.lastname: Kancheva
authors.forename: Marta
authors.initials: M
authors.lastname: Velíková
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Kancheva
authors.forename: Jana
authors.initials: J
authors.lastname: Kubátová
authors.forename: Michaela
authors.initials: M
authors.lastname: Dušková
authors.forename: Petr
authors.initials: P
authors.lastname: Marusič
authors.forename: Antonín
authors.initials: A
authors.lastname: Pařízek
authors.forename: Luboslav
authors.initials: L
authors.lastname: Stárka
mesh_terms: D006907:17-alpha-Hydroxypregnenolone / Q000097:blood*; D000328:Adult; D000731:Androstanes / Q000097:blood* / Q000378:metabolism*; D000732:Androstanols / Q000097:blood; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy* / Q000378:metabolism*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D055442:Metabolome; D013254:Steroid 17-alpha-Hydroxylase / Q000097:blood; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000731:Androstanes; D000732:Androstanols; D000927:Anticonvulsants; D014227:Triazines; D006907:17-alpha-Hydroxypregnenolone; D013254:Steroid 17-alpha-Hydroxylase; D000077213:Lamotrigine