Naproxen or estradiol for bleeding and spotting with the levonorgestrel intrauterine system: a randomized controlled trial

Am J Obstet Gynecol. 2012 Feb;206(2):129.e1-8. doi: 10.1016/j.ajog.2011.09.021. Epub 2011 Sep 24.


Objective: The purpose of this study was to evaluate whether oral naproxen or transdermal estradiol decreases bleeding and spotting in women who are initiating the levonorgestrel-releasing intrauterine system.

Study design: We conducted a randomized controlled trial of naproxen, estradiol, or placebo that was administered over the first 12 weeks of levonorgestrel-releasing intrauterine system use. Participants completed a written bleeding diary. We imputed missing values and performed an intention-to-treat analysis.

Results: There were 129 women who were assigned randomly to naproxen (n = 42 women), estradiol (n = 44 women), or placebo (n = 43 women). The naproxen group was more likely to be in the lowest quartile of bleeding and spotting days compared with placebo (42.9% vs 16.3%; P = .03). In the multivariable analysis, the naproxen group had a 10% reduction in bleeding and spotting days (adjusted relative risk, 0.90; 95% confidence interval, 0.84-0.97) compared with placebo. More frequent bleeding and spotting was observed in the estradiol group (adjusted relative risk, 1.25; 95% confidence interval, 1.17-1.34).

Conclusion: The administration of naproxen resulted in a reduction in bleeding and spotting days compared with placebo.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Estradiol / therapeutic use*
  • Estrogens / therapeutic use*
  • Female
  • Humans
  • Intrauterine Devices, Medicated / adverse effects*
  • Levonorgestrel / administration & dosage*
  • Levonorgestrel / therapeutic use
  • Metrorrhagia / drug therapy*
  • Metrorrhagia / etiology
  • Naproxen / therapeutic use*
  • Treatment Outcome


  • Anti-Inflammatory Agents, Non-Steroidal
  • Estrogens
  • Estradiol
  • Naproxen
  • Levonorgestrel