Tranexamic Acid Reduces Menstrual Blood Loss
Abstract & Commentary
By Jeffrey T. Jensen, MD, MPH, Editor, Leon Speroff, Professor and Vice Chair for Research, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, is Editor for OB/GYN Clinical Alert.
Synopsis: Oral tranexamic acid is well-tolerated and significantly reduces menstrual blood loss and improves health-related quality of life in women with heavy menstrual bleeding.
Source: Lukes AS, et al. Tranexamic acid treatment for heavy menstrual bleeding: A randomized controlled trial. Obstet Gynecol 2010;116:865-875.
The authors randomized women with objectively validated heavy menstrual bleeding (mean menstrual blood loss [MBL] of 80 mL or more per cycle, confirmed using the alkaline hematin methodology during two pretreatment cycles) to treatment with oral tranexamic acid 3.9 g/d or placebo for up to 5 days per cycle for 6 menstrual cycles. The primary outcome was a 3-component efficacy endpoint that specified that treatment with tranexamic acid needed to result in a reduction in MBL that was: 1) significantly greater than placebo, 2) greater than 50 mL, and 3) greater than an amount established to be meaningful to women. Health-related quality of life was measured using the Menorrhagia Impact Questionnaire (MIQ), a validated patient reported outcome instrument.
Compared to those women that received placebo (n = 72), subjects randomized to tranexamic acid (n = 115) experienced a significantly greater reduction in MBL (-69.6 mL [40.4%] vs -12.6 mL [8.2%]; P < 0.001), and all women treated with tranexamic acid met the 3-component efficacy endpoint with a reduction of at last 50 mL, which surpassed the threshold (-36 mL) considered meaningful to women. Furthermore, women treated with tranexamic acid experienced significant improvements in quality of life with fewer limitations in social, leisure, and physical activities, work inside and outside the home, and self-perceived menstrual blood loss not experienced by women that received placebo (P < 0.01). The treatment was well-tolerated and the incidence and severity of adverse events was similar to placebo.
Although I reviewed oral tranexamic acid as a treatment for heavy menstrual bleeding (HMB) in the Special Feature section of the September 2010 issue of OB/GYN Clinical Alert, I wanted to draw your attention back to this drug now that the pivotal U.S. trial has been published. A rigorous placebo-controlled double-blind study was performed, and the criterion for successful treatment was a three-component outcome. The first required that treatment with the drug should result in a significantly greater reduction in MBL than placebo. Since statistical significance is primarily a question of sample size, the other two criteria actually attempt to bridge the gap between statistical significance and clinical relevance. The study set a 50 mL reduction as the minimum threshold for a clinically important drop in MBL. In addition, successful treatment required that subjects experience a reduction in MBL blood loss that women considered meaningful. Another study was performed (but not published) to determine that the minimum reduction in blood loss that women considered meaningful was 36 mL; therefore, the requirement of a 50 mL minimum reduction effectively trumped this criterion. More simply put, this study demonstrated that tranexamic acid was effective in reducing MBL by 50 mL.
So how does this stack up with other therapies? First, a reduction in MBL occurred during the first treatment cycle, and there was no significant difference in the magnitude of the reduction from the first to the sixth treated cycle. Therefore, women taking tranexamic acid will have a pretty good idea of the ultimate benefit after the first treatment cycle. Reduction in MBL with tranexamic acid was about the same regardless of the presence of leiomyomas or heavier baseline MBL. This rapid and consistent effect will make counseling very easy. Women simply need to initiate therapy at the onset of bleeding, and take two 650 mg tablets three times each day as long as the bleeding remains heavy. Many of our patients use a similar approach with NSAIDs to manage menstrual symptoms. Compliance with therapy is better when you are actively treating a symptom like bleeding (or pain), as the severity of symptoms motivates behavior.
As I mentioned in the September Special Feature, the research definition of excessive MBL is > 80 mL as women become anemic with losses that exceed this level. Therefore, it is important to note that only 43% of subjects that received tranexamic acid (and 17% using placebo) had a reduction in MBL below this threshold. Although women will appreciate any reduction in blood loss, clinicians need to be aware of the limitations of this new treatment. Comparator studies have shown that the absolute reduction of MBL with tranexamic acid is slightly greater than that achieved with NSAIDs, but less than that achieved with hormonal treatments.1
Although there were no serious adverse events with treatment, the product carries labeling that it should not be used in women at risk for thrombosis. Women with idiopathic HMB without this contraindication who would prefer not to use a hormonal therapy or NSAID will benefit from tranexamic acid. Those women with modestly heavy bleeding who prefer to take treatment as needed rather than every day will find tranexamic acid particularly appealing. Women seeking pregnancy will appreciate the fact that tranexamic acid is category B.
Beyond this, I think that women and clinicians that wish to achieve a greater reduction in MBL will likely be disappointed with tranexamic acid. Fortunately, we have other good medical options including the LNG IUS.2 The September issue of the Green journal published results of the US HMB study with the LNG IUS (please note that I am a coauthor on that publication and am a consultant for Bayer Healthcare). The LNG-IUS reduced measured MBL by an average of -128.8 mL (compared to only -17.8 mL for the active comparator, oral medroxyprogesterone acetate). The reduction of bleeding with the IUS was more than 70%. The proportion of women with successful treatment (MBL < 80 mL and a 50% reduction) was significantly higher for the levonorgestrel-releasing intrauterine system (84.8%) compared to MPA (22.2%; P < 0.001). The new oral contraceptive with estradiol valerate and dienogest also looks interesting. This is a hot topic and we will see more in the coming months.
- Milsom I, et al. A comparison of flurbiprofen, tranexamic acid, and a levonorgestrel-releasing intrauterine contraceptive device in the treatment of idiopathic menorrhagia. Am J Obstet Gynecol 1991;164:879-883.
- Kaunitz AM, et al. Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding: A randomized controlled trial. Obstet Gynecol 2010;116:625-632.