Key results
Evidence suggests that the levonorgestrel-releasing intrauterine system (LNG-IUS) is the best first-line option for reducing menstrual bleeding, while antifibrinolytics are probably the second best, and long-cycle progestogens are the third best. Because of some limitations in the evidence, we are not sure what the true effect of these first-line treatments is for the perception of improvement and satisfaction.
For second-line treatments, evidence suggests any type of hysterectomy is the best treatment for reducing bleeding, even though this is a major surgery, and resectoscopic endometrial ablation (REA) and non-resectoscopic endometrial ablation (NREA) are second and third best. We are uncertain of the true effect of the second-line treatments on amenorrhoea (absence of menstrual blood loss). Evidence suggests that minimally invasive hysterectomy results in a large increase in satisfaction, and NREA increases satisfaction, but we are uncertain of the true effect of the remaining interventions.
What is heavy menstrual bleeding?
Heavy menstrual bleeding is defined as excessive menstrual blood loss that interferes with the quality of life of people who menstruate. It is very common and can affect 20% to 50% of people who menstruate during their reproductive years. There are different treatments available, each with their own pros and cons. The best treatment depends on the person's age, whether they have or want to have children, their personal preferences, and their medical history, among other things.
What did we want to find out?
We wanted to get an overview of all the published evidence on different treatments for heavy menstrual bleeding. We were most interested in finding out if the treatments were effective for reducing menstrual bleeding and for improving women's satisfaction. We also wanted to know how the treatment affected quality of life, what side effects it caused, and whether women required further treatment.
What did we do?
This study is an overview of reviews, which means we looked for published studies that synthesised the results of other studies on different treatments for heavy menstrual bleeding. Then we tried to give a broad overview of all that evidence. We analysed the certainty of the evidence based on factors like study size and methodological rigour. We categorised the treatments based on patient characteristics, including the desire (intention) for future pregnancy, failure of previous treatment or having been referred for surgery. First-line treatment included medical interventions and second-line treatment included the LNG-IUS plus surgical interventions; thus, the LNG-IUS was included in both first- and second-line treatments. We used network meta-analysis, a statistical method that compares all the interventions at the same time, to find out which treatments produced the best results for patients.
What did we find?
We found nine reviews with 104 studies, involving a total of 11,881 participants. Altogether, the data we analysed came from 85 trials and 9950 participants. The medical interventions included were: non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics (tranexamic acid), combined oral contraceptives (COC), combined vaginal ring (CVR), long-cycle and luteal oral progestogens, the LNG-IUS, ethamsylate and danazol (included only to provide indirect evidence). These were compared to placebo (sham treatment). The surgical interventions included were: open (abdominal), minimally invasive (vaginal or laparoscopic) and unspecified (or surgeon's choice of) route of hysterectomy, REA, NREA and unspecified endometrial ablation (EA).
What are the limitations of the evidence?
Our confidence in some evidence is moderate, but for most of it, our confidence is low to very low. The main reasons were because the studies were often not blinded, which means the participants knew which treatment they were receiving, and that could have changed their perception; the direct and indirect evidence was not similar enough to compare in the network; and the range of the results was too wide.
How up to date is this evidence?
The last search for reviews was in July 2021.
Evidence suggests LNG-IUS is the best first-line treatment for reducing menstrual blood loss (MBL); antifibrinolytics are probably the second best, and long-cycle progestogens are likely the third best. We cannot make conclusions about the effect of first-line treatments on perception of improvement and satisfaction, as evidence was rated as very low certainty. For second-line treatments, evidence suggests hysterectomy is the best treatment for reducing bleeding, followed by REA and NREA. We are uncertain of the effect on amenorrhoea, as evidence was rated as very low certainty. Minimally invasive hysterectomy may result in a large increase in satisfaction, and NREA also increases satisfaction, but we are uncertain of the true effect of the remaining second-line interventions, as evidence was rated as very low certainty.
Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a very common condition in women of reproductive age, affecting 2 to 5 of every 10 women. Diverse treatments, either medical (hormonal or non-hormonal) or surgical, are currently available for HMB, with different effectiveness, acceptability, costs and side effects. The best treatment will depend on the woman's age, her intention to become pregnant, the presence of other symptoms, and her personal views and preferences.
To identify, systematically assess and summarise all evidence from studies included in Cochrane Reviews on treatment for heavy menstrual bleeding (HMB), using reviews with comparable participants and outcomes; and to present a ranking of the first- and second-line treatments for HMB.
We searched for published Cochrane Reviews of HMB interventions in the Cochrane Database of Systematic Reviews. The primary outcomes were menstrual bleeding and satisfaction. Secondary outcomes included quality of life, adverse events and the requirement of further treatment. Two review authors independently selected the systematic reviews, extracted data and assessed quality, resolving disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool and evaluated the certainty of the evidence for each outcome using GRADE methods. We grouped the interventions into first- and second-line treatments, considering participant characteristics (desire for future pregnancy, failure of previous treatment, candidacy for surgery). First-line treatments included medical interventions, and second-line treatments included both the levonorgestrel-releasing intrauterine system (LNG-IUS) and surgical treatments; thus the LNG-IUS is included in both groups. We developed different networks for first- and second-line treatments. We performed network meta-analyses of all outcomes, except for quality of life, where we performed pairwise meta-analyses. We reported the mean rank, the network estimates for mean difference (MD) or odds ratio (OR), with 95% confidence intervals (CIs), and the certainty of evidence (moderate, low or very low certainty).
We also analysed different endometrial ablation and resection techniques separately from the main network: transcervical endometrial resection (TCRE) with or without rollerball, other resectoscopic endometrial ablation (REA), microwave non-resectoscopic endometrial ablation (NREA), hydrothermal ablation NREA, bipolar NREA, balloon NREA and other NREA.
We included nine systematic reviews published in the Cochrane Library up to July 2021. We updated the reviews that were over two years old. In July 2020, we started the overview with no new reviews about the topic. The included medical interventions were: non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics (tranexamic acid), combined oral contraceptives (COC), combined vaginal ring (CVR), long-cycle and luteal oral progestogens, LNG-IUS, ethamsylate and danazol (included to provide indirect evidence), which were compared to placebo. Surgical interventions were: open (abdominal), minimally invasive (vaginal or laparoscopic) and unspecified (or surgeon's choice of route of) hysterectomy, REA, NREA, unspecified endometrial ablation (EA) and LNG-IUS. We grouped the interventions as follows.
First-line treatments
Evidence from 26 studies with 1770 participants suggests that LNG-IUS results in a large reduction of menstrual blood loss (MBL; mean rank 2.4, MD −105.71 mL/cycle, 95% CI −201.10 to −10.33; low certainty evidence); antifibrinolytics probably reduce MBL (mean rank 3.7, MD −80.32 mL/cycle, 95% CI −127.67 to −32.98; moderate certainty evidence); long-cycle progestogen reduces MBL (mean rank 4.1, MD −76.93 mL/cycle, 95% CI −153.82 to −0.05; low certainty evidence), and NSAIDs slightly reduce MBL (mean rank 6.4, MD −40.67 mL/cycle, −84.61 to 3.27; low certainty evidence; reference comparator mean rank 8.9). We are uncertain of the true effect of the remaining interventions and the sensitivity analysis for reduction of MBL, as the evidence was rated as very low certainty.
We are uncertain of the true effect of any intervention (very low certainty evidence) on the perception of improvement and satisfaction.
Second-line treatments
Bleeding reduction is related to the type of hysterectomy (total or supracervical/subtotal), not the route, so we combined all routes of hysterectomy for bleeding outcomes. We assessed the reduction of MBL without imputed data (11 trials, 1790 participants) and with imputed data (15 trials, 2241 participants). Evidence without imputed data suggests that hysterectomy (mean rank 1.2, OR 25.71, 95% CI 1.50 to 439.96; low certainty evidence) and REA (mean rank 2.8, OR 2.70, 95% CI 1.29 to 5.66; low certainty evidence) result in a large reduction of MBL, and NREA probably results in a large reduction of MBL (mean rank 2.0, OR 3.32, 95% CI 1.53 to 7.23; moderate certainty evidence). Evidence with imputed data suggests hysterectomy results in a large reduction of MBL (mean rank 1.0, OR 14.31, 95% CI 2.99 to 68.56; low certainty evidence), and NREA probably results in a large reduction of MBL (mean rank 2.2, OR 2.87, 95% CI 1.29 to 6.05; moderate certainty evidence). We are uncertain of the true effect for REA (very low certainty evidence). We are uncertain of the effect on amenorrhoea (very low certainty evidence).
Evidence from 27 trials with 4284 participants suggests that minimally invasive hysterectomy results in a large increase in satisfaction (mean rank 1.3, OR 7.96, 95% CI 3.33 to 19.03; low certainty evidence), and NREA also increases satisfaction (mean rank 3.6, OR 1.59, 95% CI 1.09 to 2.33; low certainty evidence), but we are uncertain of the true effect of the remaining interventions (very low certainty evidence).