Advertisement

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

Published:September 26, 2011DOI:https://doi.org/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.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Obstetrics & Gynecology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Tewari R.
        • Kay V.J.
        Compliance and user satisfaction with the intra-uterine contraceptive device in Family Planning Service: the results of a survey in Fife, Scotland, August 2004.
        Eur J Contracept Reprod Health Care. 2006; 11: 28-37
        • Hidalgo M.
        • Bahamondes L.
        • Perrotti M.
        • Diaz J.
        • Dantas-Monteiro C.
        • Petta C.
        Bleeding patterns and clinical performance of the levonorgestrel-releasing intrauterine system (Mirena) up to two years.
        Contraception. 2002; 65: 129-132
        • Andersson K.
        • Odlind V.
        • Rybo G.
        Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: a randomized comparative trial.
        Contraception. 1994; 49: 56-72
        • Faundes A.
        • Alvarez F.
        • Diaz J.
        A Latin American experience with levonorgestrel IUD.
        Ann Med. 1993; 25: 149-153
        • Andersson K.
        • Batar I.
        • Rybo G.
        Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T.
        Contraception. 1992; 46: 575-584
        • Abdel-Aleem H.
        • d'Arcangues C.
        • Vogelsong K.
        • Gulmezoglu A.M.
        Treatment of vaginal bleeding irregularities induced by progestin only contraceptives (review).
        Cochrane Database Syst Rev. 2007; (CD003449)
        • Kaewrudee S.
        • Taneepanichskul S.
        • Jaisamraun U.
        • Reinprayoon D.
        The effect of mefenamic acid on controlling irregular uterine bleeding secondary to Norplant use.
        Contraception. 1999; 60: 25-30
        • Tantiwattanakul P.
        • Taneepanichskul S.
        Effect of mefenamic acid on controlling irregular uterine bleeding in DMPA users.
        Contraception. 2004; 70: 277-279
        • Witjaksono J.
        • Lau T.M.
        • Affandi B.
        • Rogers P.A.
        Oestrogen treatment for increased bleeding in Norplant users: preliminary results.
        Hum Reprod. 1996; 11: 109-114
        • Diaz S.
        • Croxatto H.B.
        • Pavez M.
        • Belhadj H.
        • Stern J.
        • Sivin I.
        Clinical assessment of treatments for prolonged bleeding in users of Norplant implants.
        Contraception. 1990; 42: 97-109
        • Boonkasemsanti W.
        • Reinprayoon D.
        • Pruksananonda K.
        • et al.
        The effect of transdermal oestradiol on bleeding pattern, hormonal profiles and sex steroid receptor distribution in the endometrium of Norplant users.
        Hum Reprod. 1996; 11: 115-123
        • Said S.
        • Sadek W.
        • Rocca M.
        • et al.
        Clinical evaluation of the therapeutic effectiveness of ethinyl oestradiol and oestrone sulphate on prolonged bleeding in women using depot medroxyprogesterone acetate for contraception.
        Hum Reprod. 1996; 11: 1-13
        • Goldberg A.B.
        • Cardenas L.H.
        • Hubbard A.E.
        • Darney P.D.
        Post-abortion depot medroxyprogesterone acetate continuation rates: a randomized trial of cyclic estradiol.
        Contraception. 2002; 66: 215-220
        • Dempsey A.
        • Roca C.
        • Westhoff C.
        Vaginal estrogen supplementation during Depo-Provera initiation: a randomized controlled trial.
        Contraception. 2010; 82: 250-255
        • Secura G.M.
        • Allsworth J.E.
        • Madden T.
        • Mullersman J.L.
        • Peipert J.F.
        The Contraceptive CHOICE Project: reducing barriers to long-acting reversible contraception.
        Am J Obstet Gynecol. 2010; 203: 115.e1-115.e7
        • Mishell Jr, D.R.
        • Guillebaud J.
        • Westhoff C.
        • et al.
        Recommendations for standardization of data collection and analysis of bleeding in combined hormone contraceptive trials.
        Contraception. 2007; 75: 11-15
        • Long J.S.
        • Freese J.
        Regression models for categorical dependent variables using stata.
        second edition. Stata Press, College Station, TX2006
        • Suvisaari J.
        • Lahteenmaki P.
        Detailed analysis of menstrual bleeding patterns after postmenstrual and postabortal insertion of a copper IUD or a levonorgestrel-releasing intrauterine system.
        Contraception. 1996; 54: 201-208
        • Jones R.L.
        • Critchley H.O.
        Morphological and functional changes in human endometrium following intrauterine levonorgestrel delivery.
        Hum Reprod. 2000; 15: 162-172
        • Guttinger A.
        • Critchley H.O.
        Endometrial effects of intrauterine levonorgestrel.
        Contraception. 2007; 75: S93-S98
        • Fraser I.S.
        Bleeding arising from the use of exogenous steroids.
        Baillieres Best Pract Res Clin Obstet Gynaecol. 1999; 13: 203-222