Ethinyl estradiol, not progestogens, reduces lamotrigine serum concentrations

Epilepsia. 2005 Sep;46(9):1414-7. doi: 10.1111/j.1528-1167.2005.10105.x.


Purpose: 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.

MeSH terms

  • Anticonvulsants / blood*
  • Anticonvulsants / pharmacokinetics
  • Anticonvulsants / therapeutic use
  • Contraceptives, Oral, Hormonal / adverse effects
  • Contraceptives, Oral, Hormonal / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Ethinyl Estradiol / adverse effects
  • Ethinyl Estradiol / pharmacokinetics*
  • Female
  • Humans
  • Lamotrigine
  • Progestins / adverse effects
  • Progestins / pharmacokinetics*
  • Triazines / blood*
  • Triazines / metabolism
  • Triazines / therapeutic use


  • Anticonvulsants
  • Contraceptives, Oral, Hormonal
  • Progestins
  • Triazines
  • Ethinyl Estradiol
  • Lamotrigine