The use of levonorgestrel-releasing intrauterine system for treatment of menorrhagia in women with inherited bleeding disorders


Mr D. L. Economides, Royal Free Hospital, Pond Street, London NW3 2PG, UK.


Background  The levonorgestrel-releasing intrauterine system (LNG-IUS) is used commonly by gynaecologists as a contraceptive and to treat menorrhagia. However, its efficacy has not been examined in women with inherited bleeding disorders.

Design  A prospective pilot study.

Setting  A teaching hospital in north London with a designated haemophilia centre.

Population  Female patients with a known inherited bleeding disorder.

Methods  Sixteen women with subjective and objective menorrhagia caused by inherited bleeding disorders (13 von Willebrand's Disease, two factor XI deficiency and one Hermansky–Pudlak syndrome), who had previously undergone unsuccessful medical treatment were followed up for nine months after LNG-IUS insertion. Bleeding was measured by pictorial chart and haemoglobin concentration.

Main outcome measure 

Results  All women reported that their periods were improved, pictorial chart scores were lower and 56% became amenorrhoeic. None reported side effects.

Conclusion  The LNG-IUS is well tolerated and effective and improves quality of life.


Among women who have an inherited coagulopathy, bleeding complications are frequently seen, with menorrhagia being particularly prevalent.1 The most common inherited bleeding disorder is type 1 von Willebrand's disease, with reduced levels of von Willebrand's factor being present in about 1% of the general population.2 In the United Kingdom and Ireland, up to 13% of women seen in a general gynaecology clinic with menorrhagia and no pelvic pathology have been reported with an underlying bleeding disorder.3,4 In these women, menorrhagia is a severe problem. In a gynaecological review of such patients in our unit between the ages of 15 and 50 years, 10/116 (8.6%) women had had a hysterectomy for menorrhagia (with the mean age at hysterectomy of 38 years). Half of these had suffered bleeding morbidity such as a vault haematoma or secondary haemorrhage. Furthermore, quality of life scores were significantly lower during menstruation than in a control group with normal coagulation.5 Medical management options include the combined oral contraceptive pill, tranexamic acid or desmopressin (DDAVP).6–9 While all of these treatments have shown some efficacy in a proportion of these women, success depends on patient compliance and there may be systemic side effects. More invasive surgical options for those resistant to medical management include endometrial resection or hysterectomy; while some may respond to endometrial resection, a significant proportion will need further definitive surgery with its associated morbidity and mortality.

The levonorgestrel-releasing intrauterine system (LNG-IUS) has been shown to reduce menstrual blood loss by 74% and 97% at 3 and 12 months in women with menorrhagia and normal coagulation with minimal systemic side effects.10 Discontinuation rates were 20% in randomised controlled trials and 17% in case series reviewed. As yet there is no evidence about use in women with inherited bleeding disorders and no one has established whether efficacy, discontinuation rates and side effects are the same in patients whose menorrhagia is primarily due to abnormal coagulation. Our aim was to evaluate the use of the LNG-IUS in these women and determine its place in the management of menorrhagia caused by inherited bleeding disorders.


Women between the ages of 15 and 50 years suffering from von Willebrand's disease were identified from the database in the Haemophilia Centre. Additionally, our hospital has a large Ashkenazi Jewish population and hence a significant number of women with factor XI deficiency who are also registered. All these women (130 with von Willebrand's disease and 69 with factor XI deficiency) were contacted by post and offered an appointment in the Haemophilia Centre. Additionally, women with other inherited bleeding disorders who presented with menorrhagia were given the chance to participate. In total, 64 women attended for review. The inclusion criteria were subjective menorrhagia with no symptoms of pelvic pathology (such as intermenstrual or postcoital bleeding) and previous failed medical treatment (e.g. combined oral contraceptive pill, DDAVP (nasal spray), tranexamic acid). Exclusion criteria were planning a pregnancy within the next year or significant pelvic pathology on transvaginal ultrasound such as uterine fibroids.

Sixteen women fulfilled these criteria and they all consented to be included in the study. The study was approved by the Ethics Committee of the Royal Free Hospital NHS Trust and patients gave informed consent. Details of menstruation were taken, including the number of days per month that bleeding significantly affected quality of life. A full blood count was performed and the most recent relevant clotting factor level was recorded. Endocervical swabs were taken to exclude chlamydial infection. Over the next two cycles, a Pictorial Bleeding Assessment Chart as described by Higham et al.11 (cutoff for menorrhagia is a score of 100) was prospectively completed and the mean of the two scores was taken as their pretreatment score.

The LNG-IUS was inserted between day four and day seven of their cycle by one researcher (CK) using local anaesthesia where necessary in the form of topical lignocaine gel. In two cases, insertion was not possible (one was nulliparous and one multiparous but with no vaginal deliveries) and was performed the next month under general anaesthetic. Haemostatic cover was used in the form of intravenous DDAVP for those with von Willebrand's Disease and tranexamic acid for the patients with factor XI deficiency. Patients were observed for bleeding for one hour following the procedure prior to discharge and were then given charts for completion to monitor any subsequent bleeding. No additional treatment for bleeding or anaemia was given during the following months.

Patients were clinically reviewed after three and at least nine months for both objective symptoms and subjective improvement (periods at nine months were evaluated as being much worse, slightly worse, same, slightly better or much better). The length of any irregular bleeding was assessed as was the effect of this bleeding on quality of life (the choice given was of life being not affected, slightly affected or severely affected). A full blood count was taken at nine months along with Pictorial Bleeding Assessment Chart scores to measure any objective improvement. Results were collated using Microsoft Excel and analysed using SAS.


Of the 16 patients, seven were nulliparous and nine were parous, of whom one had had no vaginal deliveries. The age ranged from 26.5 to 39.6 (median 30.8) years. Thirteen had type 1 von Willebrand's Disease (with von Willebrand factor antigen between 31 and 48 IU/dL [normal range >50 IU/dL]) of which one was also a carrier of haemophilia A (factor VIII levels 55 IU/dL), two had factor XI deficiency (factor XI levels 54 and 56, respectively [normal range >70 IU/dL]) and one had Hermansky–Pudlak syndrome (platelet storage disorder associated with albinism and nystagmus). Aside from their menorrhagia, 15 of these women had a history of another significant bleeding symptom such as bleeding after tooth extraction or surgery and 13 had two or more family members with a bleeding history.

Prior to insertion of the LNG-IUS, all women had subjective menorrhagia and as a group they also had high Pictorial Bleeding Assessment Chart scores (range 98–386; median 213). The haemoglobin concentration ranged from 8.0 to 13.2 g/dL (median 12.1) with two women having an iron deficiency anaemia with a haemoglobin concentration of less than 11 g/dL. Both of these women had failed to tolerate oral iron treatment. All patients had at least one day per month where their life was significantly affected by their periods with 6 of the 16 (37.5%) reporting that three or more days were affected.

The insertion of the Mirena was well tolerated in general. However, insertion was difficult in two women who required general anaesthesia the subsequent month. Of the remaining 14, 11 found the insertion slightly painful and 3 found it very painful, all of whom were nulliparous. None needed any further treatment for bleeding after the insertion.

As in women with normal coagulation, irregular spotting was seen in all of the women. The length of the spotting ranged from 30 to 90 days (median 42 days). Eleven of the women did not think that the irregular bleeding affected their life, while the remaining five were only slightly affected.

Nine women became amenorrhoeic and in the remaining seven the Pictorial Bleeding Assessment Chart score ranged from 24 to 75 (Fig. 1; median 47; P= 0.0001). All 16 women reported at three and nine months that their periods were much better. At nine months, the haemoglobin concentrations had significantly increased (Fig. 2; range 12.3–14; median 13.1 g/dL; P= 0.0001) and no women had a haemoglobin concentration of less than 11 g/dL. At nine months, no women had any days of the month when their periods significantly affected their life and none reported any side effects.

Figure 1.

Pictorial Bleeding Assessment Chart scores pre- and post-insertion of the LNG-IUS.

Figure 2.

Haemoglobin concentration before and after insertion of the LNG-IUS.


This is the first study using the LNG-IUS in women with inherited bleeding disorders and we have shown it to be an effective and well-tolerated treatment for menorrhagia refractory to first line medical treatments.

We have treated a group of women who have subjective and objective menorrhagia, which has been resistant to standard medical treatments such as combined oral contraceptive pill and tranexamic acid, and in whom traditionally surgical treatment would have been their only option. All the women prior to insertion of the LNG-IUS had at least one day a month where their life was severely affected by their bleeding and 37.5% had at least three affected days per month. Nine months after insertion of the LNG-IUS, all women reported that their periods were much better, all of them had a higher haemoglobin concentration and none of them had any days of the month when their bleeding severely affected their life.

Menorrhagia is a common complication of inherited bleeding disorders such as von Willebrand's disease. Indeed, acute adolescent menorrhagia has long been seen as a classic presenting symptom of these disorders. Several studies have shown a high prevalence of menorrhagia amongst these women. Kadir et al. reported menorrhagia occurring in 74% of women with von Willebrand's disease and 59% of those with factor XI deficiency (compared with 29% of controls).2 Menorrhagia causes significant physical morbidity and also has been shown to significantly reduce quality of life in these women, particularly when their menstruation involves flooding or the passage of clots.5 In a survey of 99 patients with type 1 von Willebrand's disease attending four haemophilia centres in the United States, 78% reported their periods to be heavy of whom 71% required medical attention and 15% required a hysterectomy.12 Women with factor XI deficiency, including those with partial deficiency, are more likely to have menorrhagia than their unaffected relatives.13

Several medical treatments have been used to treat menorrhagia in women with a coagulopathy. Tranexamic acid has been shown to reduce menstrual blood loss by reducing endometrial plasminogen activator activity and antigen.8 However, high and frequent doses are necessary which may reduce patient compliance, although there is a report of the successful use of single high dose tranexamic acid in three patients with type 2 von Willebrand's disease.14 Antifibrinolytics are safe and inexpensive and useful as a first line treatment. Combined oral contraceptives are thought to increase factor VIII and von Willebrand factor activity and are commonly used to treat these patients. However, no significant increase in von Willebrand factor or factor VIII was seen with the use of 30 μg oestradiol preparations.15 In addition, these preparations are not without side effects and contraindications. Intranasal DDAVP increases plasma levels of factor VIII and von Willebrand factor in patients with von Willebrand's Disease.16,17 In the only randomised controlled trial, it was shown to reduce Pictorial Bleeding Assessment Chart scores significantly but this reduction was not significantly different to that of placebo.18 Treatment with DDAVP has a small risk of water intoxication and hyponatraemia and is not useful in the less common types 2 and 3 von Willebrand's disease.

The LNG-IUS was originally developed for use as an effective and reversible contraceptive. However, there is increasing evidence for its effectiveness in treating menorrhagia and it is commonly used to manage women who previously would have resorted to surgical treatments. It acts by suppressing growth of endometrium and spiral arterioles as well as increasing capillary thrombosis. Unlike copper-containing coils, it has been shown to have no effect on endometrial factor VIII activity.19 It has the advantage of also being a very effective contraceptive, not requiring patient compliance, and of being better tolerated than systemic progestogens20 as shown in our study. One concern is that women with a coagulopathy would be at increased risk of bleeding at the time of insertion of the system, however, with adequate haemostatic cover we have shown this is prevented. Additionally, the length of irregular spotting after insertion was no more than that previously seen in women with normal coagulation.21

Screening studies among women seen in the general gynaecology clinic with menorrhagia associated with no pelvic pathology (or dysfunctional uterine bleeding) have found a prevalence of up to 13% of hitherto undiagnosed inherited bleeding disorders.3,4 Given that the potential treatments for these women could be the same regardless of their coagulation, it has been suggested that screening these women, rather than just going ahead and treating them is not worthwhile. However, screening is required before any invasive investigations, treatments or surgery are undertaken to allow for adequate haemostatic cover to prevent bleeding complications.

Thus, we have shown the LNG-IUS to be effective in women with an inherited coagulopathy who have refractory menorrhagia and have demonstrated a reduction in the physical and social morbidity associated with their menorrhagia. All of our patients had mild to moderate factor deficiencies and it would be interesting to see if this treatment is as effective in those with severe factor deficiencies. This treatment should be considered in such cases prior to surgical management.


The authors would like to thank Anja Grifioen for her help with the statistics, and both her and Charlotte Kingman have received support from the Katharine Dormandy Trust for Haemophilia and Allied Disorders (Charity No. 1089911).

Accepted 17 February 2004