Study participants were women ages 18 to 49 years who had heavy menstrual bleeding, a normal pelvic exam, and a normal transvaginal ultrasound; current use of a nonhormonal birth control method was also required. Women with fibroids were not excluded unless surgery was planned. Exclusion criteria included significant coagulation issues, endocrinopathy, ocular disease, pregnancy or lactation, endometrial abnormalities, cervical cancer, anovulatory dysfunctional uterine bleeding, metrorrhagia, menometrorrhagia, and polymenorrhea.
Participants were randomized to receive either tranexamic acid 1.3 g by mouth 3 times a day for 5 days per menstrual cycle, beginning with the onset of heavy bleeding, or a matched placebo. The use of anticoagulants or NSAIDs during the menstrual period was not permitted.
Heavy bleeding was defined as ≥60 mL of blood loss in one measured cycle and an average ≥80 mL of blood loss over 2 measured cycles.
Mean reduction in blood loss per cycle over 6 cycles was 70 mL (a 40.4% reduction) in the active treatment group vs 13 mL (an 8.2% reduction) in the placebo group (P<.001). The proportion of women with a ≥50% reduction from baseline in blood loss was greater in the tranexamic acid group compared with the placebo group (35% vs 7%; P<.001), yielding a number needed to treat of 4. The mean reduction in perceived blood loss was also greater in the treatment group, but the difference was not statistically significant.
The researchers used a validated menstrual quality-of-life scale that measured social and physical quality of life using a 5-point Likert scale. Women treated with tranexamic acid had a mean reduction of 0.89 points from baseline on the social and leisure activity question, compared with a mean reduction of 0.38 points for those in the placebo group. On the physical activity question, those in the tranexamic acid group had a mean reduction of 0.90 points from baseline, vs a mean decline of 0.35 points in the placebo group.
These findings indicate that the women who received tranexamic acid experienced significantly fewer limitations in social and physical activities. Responses to a question about limitations in work activities showed that the treatment group had significant improvements there, as well. The ER form of tranexamic acid used in the study was well tolerated, with no significant differences in adverse effects between the intervention and control groups.
WHAT’S NEW: Women with heavy menstrual bleeding have a new option
The ER formulation of tranexamic acid used in the study does not appear to have the GI side effects associated with the immediate-release formula.
Tranexamic acid is taken only during the menstrual cycle and does not interfere with ovulation. Thus, it can be used by women who desire fertility but are troubled by heavy bleeding.
CAVEATS: Questions about related conditions, use with hormones remain
The study included women with regular heavy menstrual periods (menorrhagia) and therefore may not be applicable to those with irregular heavy periods or anovulatory, dysfunctional uterine bleeding. In clinical practice, these conditions may overlap, but the safety and efficacy of tranexamic acid in such cases is unclear.
Another caveat, at least theoretically, is that research to date has neither identified nor excluded the possibility that tranexamic acid with concomitant use of hormonal agents might increase the risk of thrombotic events.13 This risk is low based on evidence to date, but the theoretical uncertainty leads us to be cautious about the combination of tranexamic acid and hormonal therapy for long-term use.
Xanodyne Pharmaceuticals (which manufactured Lysteda) and Ferring Pharmaceuticals (its current owner) were major sponsors of this study. While we cannot recognize any source of bias as a result of sponsorship, the independence of the investigators in publishing the findings was not clearly stated, so it is possible that future independent studies would contradict these findings.
CHALLENGES TO IMPLEMENTATION: The treatment is costly
Lysteda is expensive, costing about $170 for 30 tablets of 650 mg each.14 Cost aside, ER tranexamic acid appears to be safe, with no major barriers to its use.
Acknowledgement
The PURLs Surveillance System is supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.