The Assessment of the Minimal Effective and Tolerated Dose of Tranexamic Acid in Women With Menorrhagia Who Have Bleeding Disorders

Menorrhagia, or heavy menstrual bleeding, represents an important health issue for premenopausal women and is a common cause for primary care consultations. Approximately 10-15% of women have heavy periods. This may be associated with iron deficiency anemia, fatigue, and time lost from school, work and regular activities. Up to 50% of women with menorrhagia who have an underlying bleeding disorder have functional limitations and reduction of quality of life during their menstrual period.

The literature reports that 10-30% of women with menorrhagia have an underlying bleeding disorder. The American Society of Hematology highlighted this as a major public health issue in 2006, and there have been ongoing efforts to address this problem. The prevalence of a bleeding disorder in the normal population is 1 in 100; von Willebrand Disease (VWD) being the most common. Studies have shown between 57% and 93% of women with bleeding disorders have menorrhagia. Therefore, women, who present with menorrhagia, should be considered for investigation of a bleeding disorder.

Obtaining an accurate history of menorrhagia from women is often difficult for several reasons. Women may be reluctant to initiate discussion about their heavy periods. Also, women with underlying hereditary bleeding disorders may have heavy periods but since they are the same as other affected women in their families they consider their menses "normal." Not infrequently,a mild bleeding disorder may go undiagnosed until adulthood.

Menorrhagia is objectively defined as menstrual blood loss of > 80mls. It is well known that assessment of menstrual blood loss by history alone is unreliable and inaccurate. The alkaline hematin method provides an objective and accurate technique for the measurement of menstrual blood loss and is considered the gold standard. However this method is time-consuming, not readily available for clinical use and impractical, as it requires women to collect all of their sanitary products for an entire menstrual cycle. The pictorial blood assessment chart (PBAC) is a simple, non-laboratory method that provides a semi-quantitative assessment of menstrual flow. Using this method, the patient records the number and degree of saturation of pads and/or tampons used for up to 8 days of their menstrual cycle on a pictorial chart and a corresponding score is calculated. In their original report, Higham et al defined menorrhagia as a PBAC score of > 100 with a sensitivity of 86% and a specificity of 81 %. Janssen et al later reported that a cut-off score of 185 provides high positive and negative predictive values for 'true' menorrhagia as opposed to the score of > 100 that was not validated by Reid et al, in a more recent publication. In both the Higham and the Janssen studies the confidence intervals of the estimates of sensitivity were not reported, therefore it is difficult to select either one as being definitively better to use as a cut-off score. In our study we have decided to use a cut-off PBAC score of 100 as a more conservative approach that will allow the inclusion of more patients with heavy menstrual flow.

There are a number of treatment options for women with menorrhagia including hormone therapy (combined oral estrogen/progesterone, progesterone alone), tranexamic acid (and other antifibrinolytic agents), danazol, non steroidal anti-inflammatory drugs (NSAIDs), progesterone releasing intrauterine devices, and, finally, the surgical options of endometrial ablation and hysterectomy. An additional therapy, for women with certain bleeding disorders (VWD, platelet dysfunction and Hemophilia A carriers) is desmopressin (DDAVP) (intranasal or subcutaneous). Tranexamic acid is a first line therapy for women with menorrhagia who do not require contraception and who prefer non-hormonal therapy. It is considered standard therapy around the world and in most countries (e.g. Canada), it is available by prescription only, but interestingly in Sweden it is obtained 'over-the-counter.'