title: Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations.
abstract: OBJECTIVE
  To study the interaction between lamotrigine (LTG) and hormonal contraception.
  
  
  METHODS
  LTG serum concentrations of female patients using either no hormonal contraception (n=18), an ethinyl estradiol (EE)-containing (n=11), or a progestogen (PG)-only-containing compound (n=16) were analyzed. Patients were recruited prospectively, and blood samples were drawn during drug fasting and at steady-state conditions. Comedication with enzyme inducers, valproate, topiramate, or sertraline was not allowed. Some patients changed groups and thus served as their own controls. Samples were analyzed by a gas chromatography/ mass spectroscopy method. The Mann-Whitney U test was used for statistical comparison of the groups.
  
  
  RESULTS
  The LTG serum concentration-to-dose ratio (CDR), expressed as (mg/L)/(mg/d) was significantly lower in women using EE than in the control group (mean+/-SD, 0.010+/-0.004 vs. 0.017+/-0.006; p=0.003). The CDR in women using PG was 0.02+/-0.007, which was not statistically different from controls. No difference was found in CDR between women using either oral, topical, or parenteral PG. Five women switched from the control to the EE group and experienced a considerable reduction in CDR. An increase of the CDR toward control level was seen in the two women who changed from EE to PG.
  
  
  CONCLUSIONS
  It is the EE component of oral contraceptives that interacts with LTG. The PG-only compounds did not alter LTG serum concentrations in this study. These findings should be considered when counselling women with epilepsy in the childbearing ages.
authors.affiliation: Department of Clinical Pharmacology, St. Olavs Hospital, and Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. arne.reimers@legemidler.no
authors.forename: Arne
authors.initials: A
authors.lastname: Reimers
authors.forename: Grethe
authors.initials: G
authors.lastname: Helde
authors.forename: Eylert
authors.initials: E
authors.lastname: Brodtkorb
mesh_terms: D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D011372:Progestins / Q000009:adverse effects / Q000493:pharmacokinetics*; D014227:Triazines / Q000097:blood* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D003278:Contraceptives, Oral, Hormonal; D011372:Progestins; D014227:Triazines; D004997:Ethinyl Estradiol; D000077213:Lamotrigine