A pilot study of levonorgestrel concentrations and bleeding patterns in women with epilepsy using a levonorgestrel IUD and treated with antiepileptic drugs

Contraception. 2019 Apr;99(4):251-255. doi: 10.1016/j.contraception.2018.11.018. Epub 2018 Dec 4.


Objectives: We explored levonorgestrel (LNG) concentrations, bleeding patterns and endometrial thickness in women with epilepsy (WWE) initiating an LNG-intrauterine device (IUD) co-administered with antiepileptic drugs (AEDs).

Study design: This pilot study included 20 WWE ages 18 to 45 years with well-controlled seizures and stable AED regimens initiating a 52-mg LNG-IUD (20 mcg/d initial release). We collected blood and measured endometrial thickness before IUD placement and 21 days, 3 months and 6 months thereafter. Participants recorded bleeding/spotting daily. We measured total LNG (radioimmunoassay), serum hormone binding globulin (SHBG, immunoassay) and calculated the free LNG index. We compared total LNG, free LNG index, SHBG and endometrial thickness over time using a linear mixed-effects model.

Results: Total LNG, free LNG index and SBHG levels remained stable from day 21 throughout. Endometrial thickness decreased from a median of 5.9 mm [interquartile range (IQR) 4.6-7.5] at day 21 to 3.3mm (2.8-4.9) by month 6 (p=0.02). Bleeding and spotting days decreased from a median of 16 (IQR 13-23) in month 1 to 6.5 (IQR 4-8.5) in month 6 regardless of AED regimen.

Conclusion: Like women without epilepsy, WWE initiating the LNG-IUD experience stable total LNG concentrations and decreasing endometrial thickness and bleeding over the first 6 months of use.

Implications: Like women without epilepsy, WWE using antiepileptic drugs can expect a stable LNG concentration and decreasing bleeding during the first 6 months of LNG-IUD use. Our data can be useful for guidance of WWE considering use the LNG-IUD.

Trial registration: ClinicalTrials.gov NCT02362373.

Keywords: Antiepileptic drugs; Bleeding patterns; Contraception; Epilepsy; Levonorgestrel; Levonorgestrel-releasing intrauterine device.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticonvulsants / therapeutic use*
  • Contraceptive Agents, Hormonal / administration & dosage
  • Contraceptive Agents, Hormonal / blood*
  • Endometrium / drug effects*
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Intrauterine Devices, Medicated
  • Levonorgestrel / administration & dosage
  • Levonorgestrel / blood*
  • Pilot Projects
  • Young Adult


  • Anticonvulsants
  • Contraceptive Agents, Hormonal
  • Levonorgestrel

Associated data

  • ClinicalTrials.gov/NCT02362373