Mirena is best non-surgical option for Menorrhagia
I wrote about Mirena to treat endometrial cancer and endometrial hyperplasia with atypia (a precursor lesion of endometrial cancer) only recently. This time, we talk about the results of a clinical trial on menorrhagia published in NEJM (1) three weeks ago. There are not too many clinical trials in gynaecology and not many of them are published so prominently. Just that makes it interstign enought to write about it. As we are all well aware, most of our clinical management is based on own experience and what our colleagues, bosses and friends do, rather than on good-quality research evidence. Here is an exemption:
571 women between 25 and 50 years of age with menorrhagia were enrolled. Women who had the following conditions were NOT eligible: women with uterine fibroids; women with intermenstrual or postcoital bleeding; intention to become pregnant in the next 5 years; women taking HRT or Tamoxifen.
Women were randomised to receive Mirena or one of the “usual” medical treatments; mefenamic acid, tranexamic acid, norethindrone, any oral contraceptive pill, or MPA injection. Three quarters of women in this group received received mefenamic acid or tranexamic acid (MA/TA). “Usual” medical treatment was chosen by the clinician and could also be changed over.
Outcomes were measured with the Menorrhagia Multi-Attribute Scale (MMAS) that measures the impact of menorrhagia on daily life, rather than just the estimated period blood loss.
A total of 571 women were enrolled from 63 centres in the U.K. Women’s mean age was 41 years and mean body mass index (BMI) was 29 kg/m2. The majority of women had menorrhagia for more than one year and also suffered from menstrual pain.
Menorrhagia improved with both treatment regimen but improvements were greater in women who received Mirena. The benefit of Mirena was greatest in women with a BMI of higher than 25. General Quality of Life was also better in the Mirena group but pleasure, discomfort and sexual activity were similar among the two treatment groups. Hysterectomy and endometrial ablation were the two most frequent surgical procedures in women with treatment failure. At two years, 64% of Mirena women still had a Mirena but only 38% of the women in the “usual” treatment group continued their treatment for 2 years. Lack of effectiveness was the most common reason for treatment discontinuation in both treatment arms.
In summary, Mirena IUD was more effective than “usual treatment” – however, when interpreting its findings, we should mention a few limitations of this study:
First, in Australia the majority of patients who receive systemic, conservative treatment for menorrhagia will not just have tranexamic acid (the majority of patients received only tranexamic acid in the control arm). In our country that treatment would be considered under-treatment. We use Tranexamic acid only as symptomatic treatment to minimise blood loss over a short time until definitive treatment becomes available. Hence, I am not surprised that the majority of patients in that treatment arm were unable to complete their treatment.
Second, the study aimed at primary care providers, whereas Mirena often requires the input of gynaecologists. Thus, the “usual” treatment was administered by GPs, whereas specialists in a large number of cases could have administered the Mirena. Specialists might have provided additional services that could have improved outcomes and those additional serrvices might not have been captured by the trial and we don’t know about.
Third, the rate of effective treatment in the Mirena arm was 64%, which is approximately the efficacy of Mirena that was published previously. Only women with newly diagnosed menorrhagia were enerolled (it would have been otherwise very difficult to understand how the UK ethics committees would have granted approval otherwise). We need to assume that women with recurrent and treatment resistant menorrhagia were excluded. Therefore, the results apply ony to women who consider "first line" treatment of menorrhagia.
I do like that the group of authors used a quality of life instrument than estimating the menstrual loss. Measuring the impact of menorrhagia allows quantifying the true burden of the disease. I personally have not used this questionnaire yet, but I am keen to try it; I’ll let you know.
In summary, Mirena is a very reasonable approach to treat women with newly diagnosed menorrhagia. The chance that Mirena works is approximately 60%. If Mirena fails, an endometrial ablation or a hysterectomy should be offered. Treatment with other “usual medication” (MPA, pill, tranexamic acid, etc.) is likely ineffective.
(1) Gupta J, Kai J, Middleton L, Pattison H, Gray R, Daniels J; ECLIPSE Trial Collaborative Group. Levonorgestrel intrauterine system versus medical therapy for menorrhagia. N Engl J Med. 2013 Jan 10;368(2):128-37. doi:10.1056/NEJMoa1204724. PubMed PMID: 23301731.