Efficacy and safety of Mirena in treating idiopathic menorrhagia

Efficacy of Mirena

Mirena has been shown to be highly effective in reducing menstrual blood loss (MBL) as well as other symptoms associated with idiopathic menorrhagia. The National Institute for Health and Clinical Excellence (NICE) in the UK has made a recommendation that Mirena should be considered as a first-line treatment when no structural or histological abnormalities are suspected¹.

In a comparative study by Milsom et al.² that investigated the effects of Mirena, tranexamic acid and flurbiprofen on menorrhagia, Mirena proved significantly superior to both forms of oral treatment in reducing blood loss and was the only treatment that achieved normalization of menstrual blood loss (<80 mL) (Figure 8). In addition, the duration of bleeding was not altered by either tranexamic acid or flurbiprofen and the frequency of side-effects with these forms of treatment was greater than with Mirena.

Figure 8: Reduction in menstrual blood loss as a percentage of mean or two control cycles for Mirena, tranexamic acid (TA) and flurbiprofen (FLURB)².

Another comparative study by Irvine et al.³ showed that Mirena reduced menstrual blood loss by 94% after a treatment period of 3 menstrual cycles (Table 4), compared with 87% with oral norethisterone (5 mg three times daily from day 5 to 26 of the menstrual cycle). After this period of treatment, 76% of women in the Mirena group wished to continue with treatment, compared with only 22% in the oral norethisterone group, indicating better tolerability of Mirena.

Reid and Virtanen-Kari⁴ showed that the median reduction in blood loss after 6 cycles in women using Mirena was significantly greater in women using Mirena than in women treated with mefenamic acid (96% and 17% respectively).

Mirena represents a well-tolerated, effective and less invasive alternative to endometrial ablation^5,6,7,8,9, endometrial resection^10,11 or hysterectomy^12,13,14. Furthermore, it allows women to preserve their fertility and may therefore become the first-line treatment in women with menorrhagia^10,15. Mirena has similar efficacy to endometrial ablation in the treatment of menorrhagia⁹. In a randomized, comparative study, the reduction in the pictorial blood loss assessment chart (PBAC) score achieved with Mirena was greater than that with endometrial ablation after 1 year of treatment (Figure 9). The rate of women requiring an alternative treatment method was similar in the two groups⁹. Similar findings were also observed in a randomized study by Barrington et al.⁸.

Figure 9: Reduction in menstrual blood loss (assessed by pictorial bleeding assessment chart [PBAC] score) with thermal balloon ablation and Mirena vs. thermal balloon ablation (p=0.002⁹).
Another randomized study that compared the effects of Mirena and transcervical endometrial resection (TRCE) on menstrual bleeding, patient satisfaction and quality of life showed that the reduction in menstrual bleeding at 1 year after treatment was greater with TRCE¹⁶. However, the improvement in health-related quality of life was equal in both patient groups¹⁶.

In a 5-year randomized comparison of Mirena (n=119) and hysterectomy (n=117), quality-of-life scores, general and psychological health parameters and hemoglobin and ferritin levels improved to a similar extent in both treatment groups¹². Women assigned to the two treatments were equally satisfied with their treatment at 5 years after randomization, with satisfaction rates of over 90% in each group¹².

Non-comparative studies of women with menorrhagia report a reduction in menstrual blood loss of 79 - 98% among users of Mirena (see Table 4²²). These studies have used quantitative measurement of menstrual blood loss. Andersson and Rybo¹⁴ demonstrated an 86% reduction in menstrual blood loss at 3 months after placement and a 97% reduction at 1 year after placement (Figure 10; see also Table 6).

Scholten¹⁷ studied women with menorrhagia during 7-12 months’ treatment with Mirena. Menstrual blood loss was reduced by 86% (see Table 4²²). At the end-point of both studies, recipients of Mirena showed a significant increase in hemoglobin and, with one exception, in the serum ferritin concentration, indicating a recovery of body iron stores (Figure 11). Tang and Lo¹⁸ confirmed the efficacy of Mirena in the treatment of menorrhagia without organic cause. Menstrual blood loss was reduced by 54%, 87% and 95% after 1, 3 and 6 months of treatment, respectively, compared with pre-treatment cycles (see Table 4). Hemoglobin levels also increased during the study. After 6 months, the total number of bleeding days had been reduced by a median of 6 days, and menstrual cycle length increased by a median of 12 days in 9 months. In addition, Xiao et al.¹⁹ showed that Mirena significantly reduced menstrual blood loss and increased hemoglobin and ferritin levels over the 3 years’ follow-up, suggesting that Mirena effectively manages the symptoms of idiopathic menorrhagia over long-term treatment (see Table 4²²).

Figure 10: Reduction in menstrual blood loss (MBL) in women with menorrhagia after 3, 6 and 12 months of Mirena use. P<0.001 vs. baseline¹⁴

Figure 11: Mean concentrations (+SD) of a) haemoglobin and b) serum ferritin with menorrhagia before Mirena placement 3, 6 and 12 months of use (ferritin). **p<0.01, ***p<0.001¹⁴

Safety

There have been many studies assessing the safety of Mirena across a range of parameters. See Mirena in contraception section for information on the safety of Mirena.