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.

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.

• Authors: Martin Hill, Jana Vrbíková, Jana Zárubová, Radmila Kancheva, Marta Velíková, Lyudmila Kancheva, Jana Kubátová, Michaela Dušková, Petr Marusič, Antonín Pařízek, Luboslav Stárka
• Journal: Steroids (Steroids) Vol. 76 Issue 12 Pg. 1351-7 (Nov 2011) ISSN: 1878-5867 [Electronic] United States
• PMID: 21787799 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Androstanes
• Androstanols
• Anticonvulsants
• Triazines
• 17-alpha-Hydroxypregnenolone
• Steroid 17-alpha-Hydroxylase
• Lamotrigine

Topics

• 17-alpha-Hydroxypregnenolone (blood)
• Adult
• Androstanes (blood, metabolism)
• Androstanols (blood)
• Anticonvulsants (adverse effects, therapeutic use)
• Epilepsy (drug therapy, metabolism)
• Female
• Humans
• Lamotrigine
• Metabolome
• Steroid 17-alpha-Hydroxylase (blood)
• Triazines (adverse effects, therapeutic use)