Review question
We reviewed the evidence about the effect and safety of non-surgical treatments versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders. This is an update of a previously published Cochrane Review.
Background
Heavy menstrual bleeding is one of the most common symptoms in women with bleeding disorders. A sizeable population of women with heavy menstrual bleeding are affected by either inherited or acquired bleeding disorders and at the time of presentation these women are considerably younger than the women who suffer from this due to other reasons. Since heavy menstrual bleeding starts at the very onset of menarche and continues throughout reproductive life, the quality of life of these women is severely affected and they are at an increased risk of developing iron-deficiency anaemia.
Search date
The evidence is current to: 25 August 2016.
Study characteristics
The review included three studies on non-surgical treatments in 175 women with a bleeding disorder who were experiencing heavy menstrual bleeding. Two studies compared desmopressin to placebo and one study compared desmopressin to tranexamic acid. The women included in the studies were selected for one treatment or the other randomly. The studies lasted from two to four months.
Key results
Two studies of the three studies (with a total of 59 women) found no clear evidence of a difference in desmopressin (1-deamino-8-D-arginine vasopressin) in reducing menstrual blood loss when compared to placebo. One of these studies continued with an open non-randomised comparison of a combination of desmopressin with tranexamic acid versus placebo and found a significant reduction in menstrual blood loss. However, the non-randomised design of this comparison is an additional potential source of bias.
The third study (116 women), which had more participants than the other two studies combined, found a greater reduction in menstrual blood loss with tranexamic acid use than with desmopressin. We were unable to present any data on quality of life from this study, since no differences in between the two intervention groups were reported. There was no clear evidence of difference in the risk of side effects with desmopressin as compared to tranexamic acid. None of the studies dealt with cost effectiveness.
Quality of the evidence
We were not able to adequately assess the studies in relation to how the women were allocated to the treatment groups and we judged the overall quality of the evidence as poor.
Evidence from randomised controlled studies on the effect of desmopressin when compared to placebo in reducing menstrual blood loss is very limited and inconclusive. Two studies, each with a very limited number of participants, have shown uncertain effects in menstrual blood loss and adverse effects. A non-randomised comparison in one of the studies points to the value of combining desmopressin and tranexamic acid, which needs to be tested in a formal randomised controlled study comparison.
When tranexamic acid was compared to desmopressin, a single study showed a reduction in menstrual blood loss with tranexamic acid use compared to desmopressin.
There is a need to evaluate non-surgical methods for treating of menorrhagia in women with bleeding disorders through randomised controlled studies. Such methods would be more acceptable than surgery for women wishing to retain their fertility. Given that women may need to use these treatments throughout their entire reproductive life, long-term side-effects should be evaluated.
Heavy menstrual bleeding without an organic lesion is mainly due to an imbalance of the various hormones which have a regulatory effect on the menstrual cycle. Another cause of heavy menstrual bleeding with no pelvic pathology, is the presence of an acquired or inherited bleeding disorder. The haemostatic system has a central role in controlling the amount and the duration of menstrual bleeding, thus abnormally prolonged or profuse bleeding does occur in most women affected by bleeding disorders. Whereas irregular, pre-menarchal or post-menopausal uterine bleeding is unusual in inherited or acquired haemorrhagic disorders, severe acute bleeding and heavy menstrual bleeding at menarche and chronic heavy menstrual bleeding during the entire reproductive life are common. This is an update of a previously published Cochrane Review.
To determine the efficacy and safety of non-surgical interventions versus each other, placebo or no treatment for reducing menstrual blood loss in women with bleeding disorders.
We searched the Cochrane Cystic Fibrosis Haemoglobinopathies Trials Register (25 August 2016), Embase (May 2013), LILACS (February 2013) and the WHO International Clinical Trial registry (February 2013).
Randomised controlled studies of non-surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women of reproductive age suffering from a congenital or acquired bleeding disorder.
Two authors independently assessed studies for inclusion, extracted data and assessed the risk of bias.
Three cross-over studies, with 175 women were included in the review. All three studies had an unclear risk of bias with regards to trial design and overall, the quality of evidence generated was judged to be poor.
Two of the studies (n = 59) compared desmopressin (1-deamino-8-D-arginine vasopressin) with placebo. Menstrual blood loss was the primary outcome for both of these studies. Neither study found clear evidence of a difference between groups. The first of these reported a mean difference in menstrual blood loss in the desmopressin versus placebo group of 21.20 mL (95% confidence interval -19.00 to 61.50)
The second study reported that even though there was an improvement of pictorial bleeding assessment chart scores with desmopressin and placebo when compared to pretreatment assessment, there was no clear evidence of difference in these scores when the two were compared to each other (results presented graphically, P = 0.51). The data from these studies could not be combined.
The third study (n = 116) compared desmopressin with tranexamic acid (n = 116). This study found a decrease in pictorial bleeding assessment chart scores after both treatments as compared to baseline. The decrease in these scores was greater for tranexamic acid than for desmopressin, with a mean difference of 41.6 mL (95% confidence interval 19.6 to 63) (P < 0.0002).
In relation to adverse events, across two studies, there was no clear evidence of a difference when placebo was compared to desmopressin, risk ratio 1.17 (95% confidence interval 0.41 to 3.34) . The same was also true when desmopressin was compared to tranexamic acid, risk ratio 1.17 (95% confidence interval 0.41 to 3.34).
Only the study that compared desmopressin to tranexamic acid assessed quality of life. However, we are unable to present any data from this study, since no differences in this outcome between the two intervention groups were reported.