By Rebecca H. Allen, MD, MPH, Assistant Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI. Dr. Allen reports no financial relationships relevant to this field of study.
Synopsis: In this randomized, controlled trial, tranexamic acid and mefanamic acid were no better than placebo in reducing the number of bleeding or spotting days in the first 3 months after LNG-IUS placement.
Source: Sordal T, et al. Management of initial bleeding or spotting after levonorgestrel-releasing intrauterine system placement: A randomized controlled trial. Obstet Gynecol 2013;121:934-941.
In this double-blind, randomized, placebo-controlled trial, the investigators evaluated two treatments for the “nuisance” bleeding that commonly occurs in the first few months after the levonorgestrel intrauterine system (LNGIUS) is placed. The first treatment, tranexamic acid, is an anti-fibrinolytic agent approved for the treatment of heavy menstrual bleeding. The second treatment, mefanamic acid, is a non-steroidal anti-inflammatory drug (NSAID) that is approved for the treatment of primary dysmenorrhea. Women aged 18-45 years with regular menstrual cycles using the LNG-IUS for contraception were included. All women received standardized counseling regarding expected bleeding patterns after LNG-IUS placement. The device was placed within 7 days of the onset of menses and women were randomized to tranexamic acid (500 mg three times daily), mefanamic acid (500 mg three times daily), or placebo (three times daily). The women took the study medications only during a spotting or bleeding episode and were followed for 90 days. Women recorded their bleeding pattern on diary cards: 1) spotting, less than associated with normal menstruation with no need for sanitary protection (except for pantyliners), and 2) bleeding, defined as need for sanitary protection.
A total of 187 women were randomized to one of the three treatments and compliance was high in all three arms (> 80%). The women were recruited from Norway, Ireland, and Denmark and were mainly white (> 96%) with an average body mass index (BMI) of 25 kg/m2. The median number of bleeding or spotting days during the 90-day treatment period was 25 for tranexamic acid, 29 for mefanamic acid, and 33 for placebo. This difference was not statistically significant. There was also no difference between the three groups in the number or length of bleeding or spotting episodes. Age, BMI, and smoking did not influence the results. Overall satisfaction with the LNG-IUS was high in all three groups with 85% or more women reporting being satisfied.
The majority of women who discontinue the LNG-IUS device do so in the first 6 months of use and irregular bleeding is the number one reason cited.1 On average, in the first 90 days after LNG-IUS insertion, women may experience 36 days of bleeding or spotting.2 However, this pattern improves over time and at the end of 1 year, approximately 20% of women will be amenorrheic.3 Therefore, women should be counseled on expected bleeding patterns with the LNG-IUS. However, if an effective treatment for “nuisance” or unscheduled bleeding and spotting existed, it may prevent discontinuation and increase satisfaction rates. The purpose of this trial was to evaluate two potential treatments for the “nuisance” bleeding that women may experience in the first few months of LNG-IUS use and compare those to standard counseling about expected bleeding patterns. The authors of this study chose to administer the treatment when the bleeding actually occurred rather than prophylactically. Unfortunately, they were unable to show that mefanamic acid or tranexamic acid decreased bleeding or spotting in the first 3 months of LNG-IUS use. However, the dose of tranexamic acid used was much lower than that typically prescribed for heavy menstrual bleeding (1300 mg three times daily for 5 days).
Most of the research performed on unscheduled bleeding with progestin-only contraceptives has been conducted with contraceptive implants or depot medroxyprogesterone acetate.4 Agents studied have included NSAIDs, tranexamic acid, mifepristone, estradiol, and doxycycline. Interventions for the LNG-IUS are less studied, perhaps because the evidence shows the bleeding pattern will improve so most providers and women are willing to wait. One previous study mentioned by the authors of this current paper examined naproxen and transdermal estradiol administration for unscheduled bleeding in the first 3 months after insertion.5 In this randomized, controlled trial, the naproxen was dosed at 500 mg twice daily for the first 5 days of each 4-week period after LNG-IUS insertion and transdermal estradiol was dosed at 0.1 mg continuously regardless of bleeding patterns. The investigators found that transdermal estradiol increased the number of bleeding and spotting days (median 44) while the naproxen arm experienced slightly less bleeding and spotting days (median 27.5) compared to placebo (median 32). None of these differences were statistically significant. However, when the data were analyzed by quartiles, women in the naproxen group were more likely to be in the lowest quartile of bleeding and spotting (2-21 days) than women in the placebo group (43% vs 16%). The authors concluded that use of naproxen prophylactically, as studied, contributed to a small decrease in the number of bleeding and spotting days (10%).
A new lower-dose LNG-IUS is now available that contains 13.5 mg of levonorgestrel and releases 14 mcg per day initially, compared to the 52 mg of levonorgestrel in the larger system that releases 20 mcg per day initially.2 Now that this lower-dose system is on the market, the issue of “nuisance” bleeding with the LNG-IUS may increase. A comparative study did show that, on average, women using the lower dose LNG-IUS seem to experience slightly more bleeding and spotting days over a 3-year period compared to the full dose LNG-IUS.2 It remains to be seen in clinical practice whether the bleeding profile of the lower-dose system leads to greater discontinuation rates or dissatisfaction compared to the higher-dose system. Our current practice should include thorough counseling about bleeding patterns post-insertion so that women know what to expect. I tell my patients to anticipate 3-6 months of irregular spotting or bleeding before the LNG-IUS exerts its full effect. As far as interventions to offer for unscheduled bleeding, it seems that a trial of NSAIDs would be reasonable. I think it is worth offering some intervention if it will encourage women to continue with the IUD given the benefits of long-acting reversible contraception. We can also look forward to the upcoming release of the Centers for Disease Control and Prevention’s Selected Practice Recommendations for Contraceptive Use that will provide some response as to how to treat irregular vaginal bleeding with progestin-only contraceptives.
1. Hidalgo M, et al. Contraception 2002;65:129-132.
2. Gemzell-Danielsson K, et al. Fertil Steril 2012;97:616-22.e1-3.
3. Jensen JT, et al. Contraception 2008;77:22-29.
4. Abdel-Aleem H, et al. Cochrane Database Syst Rev 2007:CD003449.
5. Madden T, et al. Am J Obstet Gynecol 2012;206:129.e1-8.