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

Abstract

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.

Conflict of interest statement

Disclosure: Dr. Madden is a speaker for Bayer Healthcare Pharmaceuticals. None of the other authors have a potential conflict of interest.

Copyright © 2012 Mosby, Inc. All rights reserved.

Figures

Figure 1

Consort Study Flowchart

Figure 2

Distribution of the Total Number of Bleeding and Spotting Days for the Entire Study Population (2A) Showing Right-Skewed Distribution and Distribution of Bleeding and Spotting by Study Arm Presented as Box Plots (2B).

Figure 3

Distribution of Bleeding and Spotting Days by Quartile for Each Group Over the 12-week Treatment Period* *25th percentile for bleeding and spotting ranged from 0–21 days over the 12 week treatment period. Quartiles for 50%, 75%, and 99% were in the ranges of 22–33, 34–54, and 55–84 days respectively.