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

• Published in: American journal of obstetrics and gynecology 2012-02, Vol.206 (2), p.129.e1-129.e8
• Main Authors: Madden, Tessa, MD, MPH, Proehl, Sarah, BS, Allsworth, Jenifer E., PhD, Secura, Gina M., PhD, MPH, Peipert, Jeffrey F., MD, PhD
• Format: Article
• Language: English
• Subjects: Adult; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; contraception; Estradiol - therapeutic use; Estrogens - therapeutic use; Female; Gynecology. Andrology. Obstetrics; Humans; Intrauterine Devices, Medicated - adverse effects; irregular bleeding; Levonorgestrel - administration & dosage; Levonorgestrel - therapeutic use; levonorgestrel intrauterine system; Medical sciences; Metrorrhagia - drug therapy; Metrorrhagia - etiology; Naproxen - therapeutic use; Obstetrics and Gynecology; Pharmacology. Drug treatments; progestin-only contraception; Treatment Outcome
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2011.09.021

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.