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. 2022 May 31;5(5):CD013180.
doi: 10.1002/14651858.CD013180.pub2.

Interventions for heavy menstrual bleeding; overview of Cochrane reviews and network meta-analysis

Magdalena Bofill Rodriguez  1 , Sofia Dias  2 , Vanessa Jordan  3 , Anne Lethaby  4 , Sarah F Lensen  5 , Michelle R Wise  1 , Jack Wilkinson  6 , Julie Brown  7 , Cindy Farquhar  3
Affiliations

Interventions for heavy menstrual bleeding; overview of Cochrane reviews and network meta-analysis

Magdalena Bofill Rodriguez et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: 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.

Methods: 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.

Main results: 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).

Authors' conclusions: 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.

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Conflict of interest statement

Magdalena Bofill Rodriguez, Julie Brown, Michelle Wise, Cindy Farquhar, Vanessa Jordan and Anne Lethaby have been involved as authors or co‐authors of Cochrane Reviews that may be included in this overview of reviews. Magdalena Bofill, Michelle Wise and Vanessa Jordan became involved updating the already selected reviews.

Julie Brown has been employed as a medical writer; we are satisfied that her employer had no financial interest in any intervention of interest to this overview.

Sofia Dias, Sarah Lensen and Jack Wilkinson have no conflict of interest.

Cindy Farquhar, Vanessa Jordan and Anne Lethaby are editors of Cochrane Gynecology and Fertility. They took no part in the editorial process.

Figures

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Review flow diagram
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Risk of bias of individual trials contributing with direct evidence for the network meta‐analysis.
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The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.
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Network diagram for mean menstrual blood loss with first‐line treatments (combined at the end of treatments and change from baseline) (26 studies, 10 treatments). The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.
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Forest plot for menstrual blood loss (mean blood loss at the end of treatment and change from baseline) for first‐line treatments. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Cumulative rankogram comparing each treatment for menstrual blood loss (mean blood loss at the end of treatment and change from baseline) for first‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a Cumulative Ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments. Danazol (†): despite being effective in reducing menstrual bleeding, its adverse events advise against its use for heavy menstrual bleeding. Please refer to the last paragraph of the medical interventions in Description of the interventions.
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Risk of bias of trials contributing with data for menstrual blood loss (mean blood loss at the end of treatment and mean change from baseline) for first‐line treatments.
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Network for menstrual blood loss mean blood loss at follow‐up (23 studies, 10 treatments, sensitivity analysis) for first‐line treatments.The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.
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Forest Plot for mean blood loss (sensitivity analysis) for first‐line treatments. All the evidence has very low certainty.
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Cumulative rankogram comparing each treatment for mean blood loss at the end of treatment (sensitivity analysis) for first‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA, the higher its rank among all available treatments. Danazol (†): despite being effective in reducing menstrual bleeding, its adverse events advise against its use for heavy menstrual bleeding. Please refer to the last paragraph of the medical interventions in Description of the interventions.
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Risk of bias of trials contributing with data for mean blood loss at the end of treatment, sensitivity analysis, for first‐line treatment.
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Network for women with perception of improvement for first‐line treatments (16 studies, 10 treatments). The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.
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Forest plot for perception of bleeding improvement forfirst‐line treatments. All evidence has very low certainty.
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Cumulative rankogram comparing each treatment for perception of improvement forfirst‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments. Danazol (†): despite being effective in reducing menstrual bleeding, its adverse events advise against its use for heavy menstrual bleeding. Please refer to the last paragraph of the medical interventions in Description of the interventions.
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Risk of bias of trials contributing with data to proportion of women with perception of improvement for first‐line treatment.
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Network for satisfaction for first‐line treatments (2 studies, 4 treatments).The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.
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Forest plot for satisfaction with first‐line treatments All evidence has very low certainty.
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Cumulative rankogram comparing each treatment for satisfaction forfirst‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Risk of bias of studies included on the network for satisfaction for first‐line treatments.
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Network diagram for any adverse events withfirst‐line treatments (combined at the end of treatments and change from baseline) (26 studies 26, 10 treatments). The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.
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First‐line treatments. Forest plot any adverse event. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Cumulative rankogram comparing each treatment for any adverse events withfirst‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments. Danazol (†): despite being effective in reducing menstrual bleeding, its adverse events advise against its use for heavy menstrual bleeding. Please refer to the last paragraph of the medical interventions in Description of the interventions.
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Risk of bias of studies included on the network for any adverse event for first‐line treatments.
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The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.
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Network for bleeding (PBAC) improvement (no imputed data) for second‐line treatments (11 studies, 4 treatments). The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Forest plot bleeding (PBAC) reduction forsecond‐line treatments. With and without imputed data. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Cumulative rankogram comparing each treatment for bleeding (PBAC) improvement for second‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Risk of bias of studies included on the network for for bleeding (PBAC) improvement for second‐line treatments.
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Network for bleeding (PBAC) improvement for second‐line treatmentswith imputed data (15 studies, five treatments). The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Cumulative rankogram comparing each treatment for bleeding (PBAC) improvement with imputed data for second‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Risk of bias of studies included on the network for for bleeding (PBAC) improvement for second‐line treatmentswith imputed data.
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Network for amenorrhoea at one year for second‐line treatments (18 studies, 4 treatments). The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison.Multiarm trials contribute to more than one comparison.
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Forest plot amenorrhoea for second‐line treatments. All evidence has very low certainty. All evidence has very low certainty.
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Cumulative rankogram comparing each treatment for amenorrhoea at one year follow‐up for second‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Risk of bias of studies contributing with direct evidence for the network for amenorrhoea for second‐line treatments.
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Network for satisfaction for second‐line treatments (27 studies, seven treatments). The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Forest plot for satisfaction. Second‐line treatments. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Cumulative rankogram comparing each treatment for satisfaction at one year follow‐up for second‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Risk of bias of studies included on the network for satisfaction for second‐line treatments.
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Network for any adverse event for second‐line treatments. The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Forest plot for any adverse events for second‐line treatments
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Cumulative rankogram comparing each treatment for any adverse events for second‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Risk of bias of studies contributing with direct evidence for any adverse events for second‐line treatments.
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Network for requirement of further surgery (22 studies, seven treatments) for second‐line treatments. The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Forest plot for the requirement of further surgery for the treatment of heavy menstrual bleeding. Second‐line treatments. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Cumulative rankogram comparing each treatment for requirement of further surgery for HMBat one year follow‐up for second‐line treatments. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface under the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Risk of bias of studies included on the network for requirement of further surgery for second‐line treatments.
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Subgroup analysis EA. Network, bleeding (PBAC) improvement at one year follow‐up. The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Subgroup analysis EA. Forest plot bleeding (PBAC) improvement. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Subgroup analysis EA. Cumulative rankogram comparing each treatment for menstrual bleeding (PBAC) reduction. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Subgroup analysis EA. Risk of bias of trials contributing with direct evidence for bleeding (PBAC) improvement.
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Subgroup analysis EA. Network: women with amenorrhoea at one year follow‐up. The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Subgroup EA. Forest plot for amenorrhoea. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Subgroup analysis EA. Cumulative rankogram comparing each treatment amenorrhoea at one year follow‐up. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Subgroup analysis EA. Risk of bias amenorrhoea at one year follow‐up.
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Subgroup analysis EA. Network: satisfaction at one year follow‐up.The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Subgroup analysis EA. Forest plot satisfaction. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Subgroup analysis EA. Cumulative rankogram comparing each treatment for satisfaction. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Subgroupanalysis EA. Risk of bias of trials contributing with direct evidence for Satisfaction.
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Subgroup analysis EA. Subnetwork connected. Perforation. The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Subgroup analysis EA. Forest plot for perforation. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Subgroup analysis EA.Cumulative rankogram comparing each treatment for perforation. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.. Higher rank reflects a lower chance of perforation.
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Subgroup analysis EA. Risk of bias of trials contributing with direct evidence to perforation.
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Subgroup analysis EA. Network: requirement of further surgery (ablation or hysterectomy) for HMB.The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Subgroup analysis EA. Forest plot for requirement of any further surgery for HMB treatment. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Subgroup analysis EA. Cumulative rankogram comparing each treatment for requirement of further surgery for HMB treatment. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Subgroup analysis EA. Risk of bias of trials contributing with direct evidence to any further surgery for HMB treatment.
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Subgroup analysis EA. Network: requirement of further hysterectomy for HMB. The nodes represent an intervention, and their size is proportional to the number of trials comparing this intervention to any other intervention in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. Multiarm trials contribute to more than one comparison.
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Subgroup EA. Forest plot requirement of further hysterectomy for HMB. Colours of the lines are according to the certainty of the evidence: dark green, high certainty evidence (HCE); light green, moderate certainty evidence (MCE); yellow, low certainty evidence (LCE); and red, very low certainty evidence (VLCE).
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Subgroup analysis EA. Cumulative rankogram comparing each treatment for requirement of further hysterectomy for HMB. Ranking indicates the cumulative probability of being the best treatment, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis, the cumulative probability of each ranking. The surface underneath the curve is a cumulative ranking line (SUCRA); the larger the SUCRA the higher its rank among all available treatments.
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Subgroup analysis EA. Risk of bias of trials contributing with direct evidence to further hysterectomy for HMB.
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Formula 1 second‐line treatments imputation.
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Formula 2 second‐line treatments imputation
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Formula 3 second‐line treatments imputation.
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Update of

  • doi: 10.1002/14651858.CD013180

References

References to included reviews

Beaumont 2007
    1. Beaumont H, Augood C, Duckitt K, Lethaby A. Danazol for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No: CD001017. [DOI: 10.1002/14651858.CD001017.pub2] - DOI - PMC - PubMed
Bofill Rodriguez 2019a
    1. Bofill Rodriguez M, Lethaby A, Grigore M, Brown J, Hickey M, Farquhar C. Endometrial resection and ablation techniques for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No: CD001501. [DOI: 10.1002/14651858.CD001501.pub5] - DOI - PMC - PubMed
Bofill Rodriguez 2019b
    1. Bofill Rodriguez M, Lethaby A, Low C, Cameron I. Cyclical progestogens for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2019, Issue 8. Art. No: CD001016. [DOI: 10.1002/14651858.CD001016.pub3] - DOI - PMC - PubMed
Bofill Rodriguez 2019c
    1. Bofill Rodriguez M, Lethaby A, Farquhar C. Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No: CD000400. [DOI: 10.1002/14651858.CD000400.pub4] - DOI - PMC - PubMed
Bofill Rodriguez 2020
    1. Bofill Rdriguez M, Lethaby A, Jordan V. Progestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2020, Issue 4. Art. No: CD002126. [DOI: 10.1002/14651858.CD002126.pub3] - DOI - PMC - PubMed
Bofill Rodriguez 2021
    1. Bofill Rodriguez M, Lethaby A, Fergusson R. Endometrial resection and ablation versus hysterectomy for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2021, Issue 2. Art. No: CD000329. [DOI: 10.1002/14651858.CD000329.pub4] - DOI - PMC - PubMed
Bryant‐Smith 2018
    1. Bryant‐Smith AC, Lethaby A, Farquhar C, Hickey M. Antifibrinolytics for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2018, Issue 4. Art. No: CD000249. [DOI: 10.1002/14651858.CD000249.pub2] - DOI - PMC - PubMed
Lethaby 2019
    1. Lethaby A, Wise MR, Weterings MAJ, Bofill Rodriguez M, Brown J. Combined hormonal contraceptives for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2019, Issue 2. Art. No: CD000154. [DOI: 10.1002/14651858.CD000154.pub3] - DOI - PMC - PubMed
Marjoribanks 2016
    1. Marjoribanks J, Lethaby A, Farquhar C. Surgery versus medical therapy for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2016, Issue 1. Art. No: CD003855. [DOI: 10.1002/14651858.CD003855.pub3] - DOI - PubMed

References to excluded reviews

Grimes 2006
    1. Grimes DA, Hubacher D, Lopez LM, Schulz KF. Non‐steroidal anti-inflammatory drugs for heavy bleeding or pain associated with intrauterine‐device use. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No: CD006034. [DOI: 10.1002/14651858.CD006034.pub2] - DOI - PMC - PubMed
Gupta 2014
    1. Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database of Systematic Reviews 2014, Issue 12. Art. No: CD005073. [DOI: 10.1002/14651858.CD005073.pub4] - DOI - PMC - PubMed
Hickey 2012
    1. Hickey M, Higham JM, Fraser I. Progestogens with or without oestrogen for irregular uterine bleeding associated with anovulation. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No: CD001895. [DOI: 10.1002/14651858.CD001895.pub3] - DOI - PMC - PubMed
Liu 2013
    1. Liu JP, Yang H, Xia Y, Cardini F. Herbal preparations for uterine fibroids. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No: CD005292. [DOI: 10.1002/14651858.CD005292.pub3] - DOI - PMC - PubMed
Murji 2017
    1. Murji A, Whitaker L, Chow TL, Sobel ML. Selective progesterone receptor modulators (SPRMs) for uterine fibroids. Cochrane Database of Systematic Reviews 2017, Issue 4. Art. No: CD010770. [DOI: 10.1002/14651858.CD010770.pub2] - DOI - PMC - PubMed
Ping Liu 2013
    1. Liu JP, Yang H, Xia Y, Cardini F. Herbal preparations for uterine fibroids. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No: CD005292. [DOI: 10.1002/14651858.CD005292.pub3] - DOI - PMC - PubMed
Ray 2016
    1. Ray S, Ray A. Non‐surgical interventions for treating heavy menstrual bleeding (menorrhagia) in women with bleeding disorders. Cochrane Database of Systematic Reviews 2016, Issue 11. Art. No: CD010338. [DOI: 10.1002/14651858.CD010338.pub3] - DOI - PMC - PubMed
Sangkomkamhang 2013
    1. Sangkomkamhang U, Lumbiganon P, Laopaiboon M, Mol BWJ. Progestogens or progestogen‐releasing intrauterine systems for uterine fibroids. Cochrane Database of Systematic Reviews 2013, Issue 2. Art. No: CD008994. [DOI: 10.1002/14651858.CD008994.pub2] - DOI - PubMed
Song 2013
    1. Song H, Lu D, Navaratnam K, Shi G. Aromatase inhibitors for uterine fibroids. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No: CD009505. [DOI: 10.1002/14651858.CD009505.pub2] - DOI - PMC - PubMed
Tan 2013
    1. Tan YH, Lethaby A. Pre‐operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No: CD010241. [DOI: 10.1002/14651858.CD010241.pub2] - DOI - PMC - PubMed
Tristan 2012
    1. Tristan M, Orozco LJ, Steed A, Ramírez-Morera A, Stone P. Mifepristone for uterine fibroids. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No: CD007687. [DOI: 10.1002/14651858.CD007687.pub2] - DOI - PMC - PubMed

Additional references

(D) Abbott 2003
    1. Abbott J, Hawe J, Hunter D, Garry R. A double-blind randomized trial comparing the Cavaterm and the Novasure endometrial ablation systems for the treatment of dysfunctional uterine bleeding. Fertility and Sterility 2003;80(1):203-8. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Agarwal 2016
    1. Agarwal N, Gupta M, Kriplani A, Bhatla N, Singh N. Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: a pilot study. Journal of Obstetrics & Gynecology 2016;36:71-5. [Included in Lethaby 2019] - PubMed
(D) Ashraf 2017
    1. Ashraf MN, Habib-Ur-Rehman A, Shehzad Z, AlSharari SD, Murtaza G. Clinical efficacy of levonorgestrel and norethisterone for the treatment of chronic abnormal uterine bleeding. Journal of Pakistan Medical Association 2017;67(9):1331-8. [Included in Bofill Rodriguez 2019b and Bofill Rodriguez 2019d] [PMID: 28924270] - PubMed
(D) Athanatos 2015
    1. Athanatos D, Pados G, Venetis C, Stamatopoulos P, Rousso D, Tsolakidis D, et al. Novasure impedance control system versus microwave endometrial ablation for the treatment of dysfunctional uterine bleeding: a double-blind, randomized controlled trial. Clinical and Experimental Obstetrics & Gynecology 2015;42(3):347-51. [Included in Bofill Rodriguez 2019a] [PMID: 26152008] - PubMed
(D) Barrington 2002
    1. Barrington JW, Arunkalaivanan AS, Abdel-Fattah M. Comparison between the levonorgestrel intrauterine system (LNG-IUS) and thermal balloon ablation in the treatment of menorrhagia. European Journal of Obstetrics and Gynaecology and Reproductive Biology 2003;108:72-4. [Included in Marjoribanks 2016 and Bofill Rodriguez 2019d] - PubMed
(D) Bhattacharya 1997
    1. Bhattacharya S, Cameron IM, Parkin DE, Abramovich DR, Mollison J, Pinion SB, et al. A pragmatic randomised comparison of transcervical resection of the endometrium with endometrial laser ablation for the treatment of menorrhagia. British Journal of Obstetrics and Gynaecology 1997;104:601-7. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Bonduelle 1991
    1. Bonduelle M, Walker JJ, Calder AA. A comparative study of danazol and norethisterone in dysfunctional uterine bleeding presenting as menorrhagia. Postgraduate Medical Journal 1991;67:833-6. [Included in Bofill Rodriguez 2019b and Beaumont 2007] - PMC - PubMed
(D) Bongers 2004
    1. Bongers MY, Bourdrez P, Mol BWJ, Heintz APM, Brolmann HAM. Randomised controlled trial of bipolar radio-frequency endometrial ablation and balloon endometrial ablation. British Journal of Obstetrics and Gynaecology 2004;111:1095-102. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Bonnar 1996
    1. Bonnar J, Sheppard B. Treatment of menorrhagia during menstruation: randomized controlled trial of ethamsylate, mefenamic acid and tranexamic acid. BMJ 1996;313(7057):579-82. [Included in Bryant-Smith 2018 and Bofill Rodriguez 2019c] - PMC - PubMed
(D) Brun 2006
    1. Brun J-L, Raynal J, Burlet G, Galand B, Quereux C, Bernard P. Cavaterm thermal balloon endometrial ablation versus hysteroscopic endometrial resection to treat menorrhagia: the French, multicenter, randomized study. Journal of Minimally Invasive Gynecology 2006;13:424-30. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Buyru 1995
    1. Buyru F, Yalcin O, Kovanci E, Turfanda A. Danazol therapy in dysfunctional uterine bleeding. Istanbul Tip Fakultesi Mecmuasi 1995;58(3):37-40. [Included in Bofill Rodriguez 2019b and Beaumont 2007]
(D) Callender 1970
    1. Callender ST, Warner GT, Cope E. Treatment of menorrhagia with tranexamic acid. A double blind trial. British Medical Journal 1970;4(5729):214-6. [Included in Bryant-Smith 2018] - PMC - PubMed
(D) Cameron 1990
    1. Cameron IT, Haining R, Lumsden MA, Thomas VR, Smith SK. The effects of mefenamic acid and norethisterone on measured menstrual blood loss. Obstetrics and Gynecology 1990;76:85-8. [Included in Bofill Rodriguez 2019b and Bofill Rodriguez 2019c] - PubMed
(D) Chamberlain
    1. Chamberlain G, Freeman R, Price F, Kennedy A, Green D, Eve L. Raw data from RCT (as supplied prior to 28 April 2022). Lorex Synthélabo Laboratory, UK. [Included in Bofill Rodriguez 2019c]
(D) Clark 2011
    1. Clark TJ, Samuel N, Malick S, Middleton LJ, Daniels J, Gupta JK. Bipolar radiofrequency compared with thermal balloon endometrial ablation in the office. Obstetrics and Gynecology 2011;117:109-18. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Cooper 1999
    1. Cooper KG, Bain C, Parkin DE. Comparison of microwave endometrial ablation and transcervical resection of the endometrium for treatment of heavy menstrual loss: a randomised trial. Lancet 1999;354:1859-63. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Cooper 2002
    1. Cooper J, Gimpelson R, Laberge P, Galen D, Garza-Leal JG, Scott J, et al. A randomized, multicenter trial of safety and efficacy of the NovaSure system in the treatment of menorrhagia. Journal of the American Association of Gynecologic Laparoscopists 2002;9(4):418-28. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Cooper 2004
    1. Cooper JM, Anderson TL, Fortin CA, Jack SA, Plentl MB. Microwave endometrial ablation vs rollerball electroablation for menorrhagia: a multicenter randomized trial. Journal of the American Association of Gynecologic Laparoscopists 2004;11(3):394-403. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Cooper 2019
    1. Cooper K, Breeman S, Scott N, Scotland G, Clark J, et al, on behalf of the HEALTH Study Group. Laparoscopic supracervical hysterectomy versus endometrial ablation for women with heavy menstrual bleeding (HEALTH). Lancet 2019;394(10207):1425-36. [DOI: ] [Included in Ferguson 2020] - PMC - PubMed
(D) Corson 2000
    1. Corson SL, Brill AI, Brooks PG, Cooper JM, Indman PD, Liu JH, et al. One-year results of the Vesta system for endometrial ablation. Journal of the American Association of Gynecologic Laparoscopists 2000;7(4):489-97. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Corson 2001
    1. Corson SL. A multicenter evaluation of endometrial ablation by hydrothermablator and rollerball for treatment of menorrhagia. Journal of the American Association of Gynecologic Laparoscopists 2001;8(3):359-67. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Crosignani 1997
    1. Crosignani PG, Vercellini P, Apolone G, De Giorgi O, Cortesi I, Meschia M. Endometrial resection versus vaginal hysterectomy for menorrhagia: long-term clinical and quality-of-life outcomes. American Journal of Obstetrics and Gynecology 1997;177(1):95-101. [Included in Ferguson 2020] - PubMed
(D) Crosignani 1997a
    1. Crosignani PG, Vercellini P, Mosconi P, Oldani S, Cortesi I, Giorgi O. Levonorgestrel-releasing intrauterine device versus hysteroscopic endometrial resection in the treatment of dysfunctional uterine bleeding. Obstetrics and Gynecology 1997;90:257-63. [CRSREF 286340] [Included in Marjoribanks 2016 and Included in Bofill Rodriguez 2019d] - PubMed
(D) Dahiya 2016
    1. Dahiya P, Dalal M, Yadav A, Dahiya K, Jain S, Silan V. Efficacy of combined hormonal vaginal ring in comparison to combined hormonal pills in heavy menstrual bleeding. European Journal of Obstetrics & Gynecology and Reproductive Biology 2016;203:147-51. [DOI: 10.1016/j.ejogrb.2016.05.009] [Included in Lethaby 2019] - DOI - PubMed
(D) De Souza 2010
    1. De Souza SS, Camargos AF, Rezende CP, Pereira FA, Araujo CA, Silva Filho AL. A randomized prospective trial comparing the levonorgestrel-releasing intrauterine system with thermal balloon ablation for the treatment of heavy menstrual bleeding [Contraception]. 2010 81;3:226-31. [CRSREF 286343] [Included in Marjoribanks 2016 and Bofill Rodriguez 2019d] - PubMed
(D) Dickersin 2007
    1. Dickersin K, Munro MG, Clark M, Langenberg P, Scherer R, Frick K, et al. Hysterectomy compared with endometrial ablation for dysfunctional uterine bleeding. Obstetrics and Gynecology 2007;110(6):1279-89. [Included in Ferguson 2020] - PubMed
(D) Dockeray 1989
    1. Dockeray CJ, Sheppard BL, Bonnar J. Comparison between mefenamic acid and danazol in the treatment of established menorrhagia. British Journal of Obstetrics and Gynaecology 1989;96:840-4. [Included in Beaumont 2007] - PubMed
(D) Duleba 2003
    1. Duleba AJ, Heppard MC, Soderstrom RM, Townsend DE. A randomized study comparing endometrial cryoablation and rollerball electroablation for treatment of dysfunctional uterine bleeding. Journal of the American Association of Gynecologic Laparoscopists 2003;10(1):17-26. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Dunphy 1998
    1. Dunphy BC, Goerzen J, Greene CA, De La Ronde S, Seidel J, Ingelson B. A double blind randomised study comparing danazol and medroxyprogesterone acetate in the management of menorrhagia. Journal of Obstetrics and Gynaecology 1998;18(6):553-5. [Included in Beaumont 2007] - PubMed
(D) Dwyer 1993
    1. Dwyer N, Hutton J, Stirrat GM. Randomised controlled trial comparing endometrial resection with abdominal hysterectomy for the surgical treatment of menorrhagia. British Journal of Obstetrics and Gynaecology 1993;100(3):237-43. [Included in Ferguson 2020] - PubMed
(D) Edlund 1995
    1. Edlund M, Andersson K, Rybo G, Lindoff CC, Astedt B, Schoult BV. Reduction of menstrual blood loss in women suffering from idiopathic menorrhagia with a novel antifibrinolytic drug (Kabi2161). British Journal of Obstetrics and Gynaecology 1995;102(11):913-7. [Included in Bryant-Smith 2018] - PubMed
(D) Endrikat 2009
    1. Endrikat J, Shapiro H, Lukkari-Lax E, Kunz M, Schmidt W, Fortier M. A Canadian, multicentre study comparing efficacy of a levonorgestrel-releasing intrauterine system to an oral contraceptive in women with idiopathic menorrhagia. Journal of Obstetrics and Gynaecology Canada 2009;31(4):340-7. [Included in Lethaby 2019 and Bofill Rodriguez 2019d] - PubMed
(D) Ergun 2012
    1. Ergun B, Kuru O, Sen S, Kilic Y, Bastu E. Roller-ball endometrial ablation versus levonorgestrel releasing intrauterine system in the management of abnormal uterine bleeding. Gineco.eu 2012;8(4):199-201. [CRSREF 286346] [Included in Marjoribanks 2016 and Bofill Rodriguez 2019d]
(D) Fraser 1981
    1. Fraser IS, Pearse C, Shearman RP, Elliott PM, McIlveen J, Markham R. Efficacy of mefenamic acid in patients with a complaint of menorrhagia. Obstetrics & Gynaecology 1981;58(5):543-51. [Included in Bofill Rodriguez 2019c] - PubMed
(D) Fraser 1991
    1. Fraser IS, McCarron G. Randomized trial of 2 hormonal and 2 prostaglandin-inhibiting agents in women with a complaint of menorrhagia. Australian & New Zealand Journal of Obstetrics & Gynaecology 1991;31:66-70. [Included in Lethaby 2019, Bofill Rodriguez 2019c and Beaumont 2007] - PubMed
(D) Fraser 2011
    1. Fraser IS, Romer T, Parke S, Zeun S, Mellinger U, Machlitt A, Jet al. Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized double-blind Phase III trial. Human Reproduction 2011;26(10):2698-708. [DOI: 10.1093/humrep/der224] [Included in Lethaby 2019] - DOI - PubMed
(D) Freeman 2011
    1. Freeman EW, Lukes A, VanDrie D, Mabey RG, Gersten J, Adomako TL. A dose-response study of a novel, oral tranexamic formulation for heavy menstrual bleeding. American Journal of Obstetrics and Gynecology 2011;205(4):319.e1-319.e7. [Included in Bryant-Smith 2018] - PubMed
(D) Gannon 1991
    1. Gannon MJ, Holt EM, Fairbank J, Fitzgerald M, Milne MA, Crystal AM, et al. A randomised trial comparing endometrial resection and abdominal hysterectomy for the treatment of menorrhagia. BMJ (Clinical Research Ed.) 1991;303(6814):1362-4. [Included in Ferguson 2020] - PMC - PubMed
(D) Ghazizadeh 2014
    1. Ghazizadeh S, Panahi Z, Ghanbari Z, Menshadi AT, Farahmandian T, Javadian P. Comparative efficacy of NovaSure, the levonorgestrel-releasing intrauterine system, and hysteroscopic endometrial resection in the treatment of menorrhagia: a randomized clinical trial. Journal of Gynecologic Surgery 2014;30(4):215-8. [Data reported in a way that do not allowed comparisons] [Included in Marjoribanks 2016, Bofill Rodriguez 2019a and Bofill Rodriguez 2019d]
(D) Goshtasebi 2013
    1. Goshtasebi A, Moukhah S, Gandevani SB. Treatment of heavy menstrual bleeding of endometrial origin: randomized controlled trial of medroxyprogesterone acetate and tranexamic acid. Archives of Gynecology and Obstetrics 2013;288(5):1055-60. [Included in Bryant-Smith 2018 and Bofill Rodriguez 2019b] - PubMed
(D) Grover 1990
    1. Grover V, Usha R, Gupta U, Kalra S. Management of cyclical menorrhagia with prostaglandin synthetase inhibitor. Asia-Oceania Journal of Obstetrics & Gynaecology 1990;16:255-9. [Included in Bofill Rodriguez 2019c] - PubMed
(D) Hashim 2012
    1. Hashim HA, Alsherbini W, Bazeed M. Contraceptive vaginal ring treatment of heavy menstrual bleeding: a randomized controlled trial with norethisterone. Contraception 2012;85:246-52. [Included in Lethaby 2019 and Bofill Rodriguez 2019b] - PubMed
(D) Hawe 2003
    1. Hawe J, Abbott J, Hunter D, Phillips G, Garry R. A randomised controlled trial comparing the Cavaterm endometrial ablation system with the Nd:YAG laser for the treatment of dysfunctional uterine bleeding. British Journal of Obstetrics and Gynaecology 2003;110:350-7. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Herman 2013
    1. Beelen P, Van Den Brink MJ, Geomini P, Dekker J, Herman M, Duijnhoven R, Mol B, Berger M, Bongers M. RCT comparing the LNG-IUS versus endometrial ablation in women with heavy menstrual bleeding (MIRA). International Journal of Gynecology and Obstetrics 2018;143(3):318-319. [10.1002/ijgo.12582] [Included in Bofill Rodriguez 2019d]
(D) Higham 1993
    1. Higham JM, Shaw RW. A comparative study of danazol, a regimen of decreasing doses of danazol, and norethindrone in the treatment of objectively proven unexplained menorrhagia. American Journal of Obstetrics and Gynecology 1993;169:1134-9. [Included in Bofill Rodriguez 2019b and Beaumont 2007] - PubMed
(D) Hurskainen 2004
    1. Hurskainen R, Teperi J, Rissanen P, Aalto AM, Grenman S, Kivela A, et al. Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for the treatment of menorrhagia. JAMA 2004;291(12):1456-63. [Included in Marjoribanks 2016 and Bofill Rodriguez 2019d] - PubMed
(D) Irvine 1988
    1. Irvine GA, Campbell-Brown MB, Lumsden MA, Heikkila A, Walker JJ, Cameron IT. Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia. British Journal of Obstetrics and Gynaecology 1988;105(6):592-8. [Included in Bofill Rodriguez 2019b] - PubMed
(D) Istre 1998
    1. Rauramo I, Elo I, Istre O. Long-term treatment of menorrhagia with levonorgestrel intrauterine system versus endometrial resection. Obstetrics and Gynecology 2004;104(6):1314-21. [Included in Marjoribanks 2016] - PubMed
(D) Jain 2016
    1. Jain P, Rajaram S, Gupta B, Goel N, Srivastava H. Randomized controlled trial of thermal balloon ablation versus vaginal hysterectomy for leiomyoma-induced heavy menstrual bleeding. International Journal of Gynaecology and Obstetrics 2016;135(2):140-4. [Included in Ferguson 2020] [https://doi.org/10.1016/j.ijgo.2016.04.020] - PubMed
(D) Jaisamrarn 2006
    1. Jaisamrarn U, Sitavarin S, Suwikrom S, Kamolpornwijit W. Randomized trial of medical therapies for menorrhagia: clinical efficacy and effect on quality of life. In: XVIII FIGO World Congress of Gynecology and Obstetrics; 2006 Nov 5-10; Kuala Lumpur (Malaysia). Vol. 3. 2006:83. [Included in Bryant-Smith 2018 and Bofill Rodriguez 2019c]
(D) Jensen 2011
    1. Jensen JT, Parke S, Mellinger U, Machlitt A, Fraser IS. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest. Obstetrics & Gynecology 2011;117:777-87. [DOI: 10.1097/AOG.Ob013e3182118ac3] [Included in Lethaby 2019] - DOI - PubMed
(D) Kaunitz 2010
    1. Kaunitz AM, Bissonnette F, Monteiro I, Lukkari-Lax E, Muysers C, Jensen JT. Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding. Obstetrics and Gynecology 2010;116:3625-32. [CRSREF: 328939] [Included in Bofill Rodriguez 2019b and Bofill Rodriguez 2019d] - PubMed
(D) Kiseli 2016
    1. Kiseli M, Kayikcioglu F, Evliyaoglu O, Haberal A. Comparison of therapeutic efficacies of norethisterone, tranexamic acid and levonogestrel-releasing intrauterine system for the treatment of heavy menstrual bleeding: a randomized controlled study. Gynecologic and Obstetric Investigation 2016;81(5):447-53. [Included in Bryant-Smith 2018, Bofill Rodriguez 2019b and Bofill Rodriguez 2019d] - PubMed
(D) Kittelsen 1998
    1. Kittelsen N, Istre O. A randomized study comparing levonorgestrel intrauterine system (LNG IUS) and transcervical resection of the endometrium (TCRE) in the treatment of menorrhagia: preliminary results. Gynecological Endocrinology 1998;7:61-5. [Included in Bofill Rodriguez 2019d]
(D) Kriplani 2006
    1. Kriplani A, Kulshrestha V, Agarwal N, Diwakar S. Role of tranexamic acid in management of dysfunctional uterine bleeding in comparison with medroxyprogesterone acetate. Journal of Obstetrics and Gynaecology 2006;26(7):673-8. [Included in Bryant-Smith 2018 and Bofill Rodriguez 2019b] - PubMed
(D) Laberge 2017
    1. Laberge P, Garza-Leal J, Fortin C, Grainger D, Johns DA, Adkins RT, et al. A randomized controlled multicenter US Food and Drug Administration trial of the safety and efficacy of the Minerva Endometrial Ablation System: one-year follow-up results. Journal of Minimally Invasive Gynecology 2017;24(1):124-32. [DOI: 10.1016/j.jmig.2016.09.009] [Included in Bofill Rodriguez 2019a] - DOI - PubMed
(D) Lukes 2010
    1. Lukes AS, Moore KA, Muse KN, Gersten JK, Hecht BR, Edlund M, et al. Tranexamic acid treatment for heavy menstrual bleeding. Obstetrics and Gynecology 2010;116(4):865-75. [Included in Bryant-Smith 2018] - PubMed
(D) Malak 2006
    1. Malak KA, Shawki O. Management of menorrhagia with the levonorgestrel intrauterine system versus endometrial resection. Gynecological Surgery 2006;3:275-80. [Included in Marjoribanks 2016 and Bofill Rodriguez 2019d]
(D) McClure 1992
    1. McClure N, Marners M, Healy DL, Hill DJ, Lawrence AS, Wingfield M, et al. A quantitative assessment of endometrial electrocautery in the management of menorrhagia and a comparative report of argon laser endometrial ablation. Gynaecological Endoscopy 1992;1:199-202. [Included in Bofill Rodriguez 2019a]
(D) Meyer 1998
    1. Meyer WR, Walsh BW, Grainger DA, Peacock LM, Loffer FD, Steege JF. Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter comparison. Obstetrics and Gynecology 1998;92:98-103. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Muggeridge 1983
    1. Muggeridge J, Elder MG. Mefenamic acid in the treatment of menorrhagia. Research and Clinical Forums 1983;5:83-8. [Included in Bofill Rodriguez 2019c]
(D) O'Connor 1997
    1. O'Connor H, Broadbent JA, Magos AL, McPherson K. Medical Research Council randomised trial of endometrial resection versus hysterectomy in management of menorrhagia. Lancet 1997;349(9056):897-901. [Included in Ferguson 2020] - PubMed
(D) Ozdegirmenci 2011
    1. Ozdegirmenci O, Kayikcioglu F, Akgul MA, Kaplan M, Karcaaltincaba M, Haberal A, et al. Comparison of levonorgestrel intrauterine system versus hysterectomy on efficacy and quality of life in patients with adenomyosis. Fertility and Sterility 2011;95(2):497-502. [Included in Bofill Rodriguez 2019d] - PubMed
(D) Pellicano 2002
    1. Pellicano M, Guida M, Acunzo G, Cirillo D, Bifulco G, Nappi C. Hysteroscopic transcervical endometrial resection versus thermal destruction for menorrhagia: a prospective randomized trial on satisfaction rate. American Journal of Obstetrics and Gynecology 2002;187:545-50. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Penninx 2010
    1. Penninx JPM, Mol BW, Engels R, Rumste MME, Kleijn C, Koks CAM, et al. Bipolar radiofrequency endometrial ablation compared with hydrothermablation for dysfunctional uterine bleeding. Obstetrics and Gynecology 2010;116:819-26. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Penninx 2016
    1. Penninx J, Herman M, Kruitwagen R, Ter Haar A, Mol B, Bongers M. Bipolar versus balloon endometrial ablation in the office: a randomized controlled trial. European Journal of Obstetrics & Gynecology and Reproductive Biology 2016;196:52-6. [DOI: 10.1016/j.ejogrb.2015.10.010] [Included in Bofill Rodriguez 2019a] - DOI - PubMed
(D) Perino 2004
    1. Perino A, Castelli A, Cucinella G, Biondo A, Pane A, Venezia R. A randomized comparison of endometrial laser intrauterine thermotherapy and hysteroscopic endometrial resection. Fertility and Sterility 2004;82:731-4. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Pinion 1994
    1. Pinion SB, Parkin DE, Abramovich DR, Naji A, Alexander DA, Russell IT, et al. Randomised trial of hysterectomy, endometrial laser ablation, and transcervical endometrial resection for dysfunctional uterine bleeding. British Medical Journal (Clinical Research Ed.) 1994;309(6960):979-83. [Included in Ferguson 2020] - PMC - PubMed
(D) Preston 1995
    1. Preston JT, Cameron IT, Adams EJ, Smith SK. Comparative study of tranexamic acid and norethisterone in the treatment of ovulatory menorrhagia. British Journal of Obstetrics and Gynaecology 1995;102(5):401-6. [Included in Bryant-Smith 2018 and Bofill Rodriguez 2019b] - PubMed
(D) Romer 1998
    1. Romer T. The treatment of recurrent menorrhagias - Cavaterm-balloon-coagulation versus Rollerball-endometrial ablation - a prospective randomized comparative study [Die therapie rezidivierender Menorrhagien - Cavaterm-Ballon-Koagulatioon versus Roller-Ball-Endometriumkoagulation - eine prospektive randomisierte Vergleichsstudie]. Zentralblatt fur Gynakologie 1998;120(10):511-4. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Sambrook 2009
    1. Sambrook AM, Cooper KG, Campbell MK, Cook JA. Clinical outcomes from a randomised comparison of microwave endometrial ablation with thermal balloon endometrial ablation for the treatment of heavy menstrual bleeding. British Journal of Obstetrics and Gynaecology 2009;116:1038-45. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Sayed 2011
    1. Sayed GH, Zakherah MS, El-Nashar SA, Shaaban MM. A randomised clinical trial of a levonorgestrel-releasing intrauterine system and a low-dose combined oral contraceptive for fibroid-related menorrhagia. International Journal of Gynecology and Obstetrics 2011;112:126-30. [Included in Bofill Rodriguez 2019d] - PubMed
(D) Sesti 2011
    1. Sesti F, Ruggeri V, Pietropolli A, Piancatelli R, Piccione E. Thermal balloon ablation versus laparoscopic supracervical hysterectomy for the surgical treatment of heavy menstrual bleeding: a randomized study. Journal of Obstetrics and Gynaecology Research 2011;37(11):1650-7. [Included in Ferguson 2020] - PubMed
(D) Sesti 2012
    1. Sesti F, Piancatelli R, Pietropolli A, Ruggeri V, Piccione E. Levonorgestrel-releasing intrauterine system versus laparoscopic supracervical hysterectomy for the treatment of heavy menstrual bleeding: a randomized study. Journal of Women's Health 2012;21(8):851-7. [Included in Marjoribanks 2016 and Included in Bofill Rodriguez 2019d] - PubMed
(D) Shabaan 2011
    1. Shabaan MM, Zakherah MS, El-Nashar SA, Sayed GH. Levonorgestrel-releasing intrauterine system compared to low dose combined oral contraceptive pills for idiopathic menorrhagia: a randomized clinical trial. Contraception 2011;83:48-54. [DOI: 10.1016/j.contraception.2010.06.011] [Included in Lethaby 2019 and Included in Bofill Rodriguez 2019d] - DOI - PubMed
(D) Shaw 2007
    1. Shaw R, Symonds IM, Tamizian O, Chaplain J, Mukhopadhyay S. Randomised comparison of thermal balloon ablation and levonorgestrel intrauterine system in patients with idiopathic menorrhagia. Australian and New Zealand Journal of Obstetric and Gynaecology 2007;47:335-40. [Included in Marjoribanks 2016 and Bofill Rodriguez 2019d] - PubMed
(D) Soysal 2002
    1. Soysal M, Soysal S, Ozer S. A randomized controlled trial of levonorgestrel releasing IUD and thermal balloon ablation in the treatment of menorrhagia. Zentralblatt fur Gynakologie 2002;124(4):213-9. [Included in Marjoribanks 2016 Bofill Rodriguez 2019d] - PubMed
(D) Talis 2006
    1. Busfield RA, Farquhar CM, Sowter MC, Lethaby A, Sprecher M, Yu Y, et al. A randomised trial comparing the levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding. BJOG: an International Journal of Obstetrics and Gynaecology 2006;113:257-63. [Included in Marjoribanks 2016 and Bofill Rodriguez 2019d] - PubMed
(D) Tam 2006
    1. Tam WH, Yuen PM, Ng DPS, Lung PL, Lok IH, Rogers MS. Health status function after treatment with thermal balloon endometrial ablation and levonorgestrel intrauterine system for idiopathic menorrhagia: a randomised study. Gynecologic and Obstetric Investigation 2006;62:84-8. [Included in Marjoribanks 2016 Bofill Rodriguez 2019d] - PubMed
(D) Tsang 1987
    1. Tsang BK, Domingo MT, Spence JE, Garner PR, Dudley DK, Oxorn H. Endometrial prostaglandins and menorrhagia: influence of a prostaglandin synthetase inhibitor in vivo. Canadian Journal of Physiology and Pharmacology 1987;65:2081-4. [Included in Bofill Rodriguez 2019c] - PubMed
(D) van Eijkeren 1992
    1. Eijkeren MA, Christiaens GC, Geuze HJ, Haspels AA, Sixma JJ. Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia. American Journal of Obstetrics and Gynecology 1992;166:1419-28. [Included in Bofill Rodriguez 2019c] - PubMed
(D) van Zon‐Rabelink 2003
    1. Zon-Rabelink IAA, Vleugels MPH, Merkus HMWM, Graaf R. Endometrial ablation by rollerball electrocoagulation compared to uterine balloon thermal ablation. Technical and safety aspects. European Journal of Obstetrics, Gynecology, and Reproductive Biology 2003;110:220-3. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Vercellini 1999
    1. Vercellini P, Oldani S, Yaylayan L, Zaina B, De Giorgi O, Crosignani PG. Randomised comparison of vaporising electrode and cutting loop for endometrial ablation. Obstetrics and Gynecology 1999;94:521-7. [Included in Bofill Rodriguez 2019a] - PubMed
(D) Ylikorkala 1986
    1. Ylikorkala O, Pekonen F. Naproxen reduces idiopathic but not fibromyoma-induced menorrhagia. Obstetrics & Gynaecology 1986;68:10-2. [Included in Bofill Rodriguez 2019c] - PubMed
(D) Zhang 2008
    1. Zhang Y, He F, Sun Z, LI S, Bi S, Huang X, et al. A multicenter, prospective, randomized, open comparator study on the treatment of ovulatory menorrhagia with tranexamic acid and norethisterone in China. Chinese Journal of Obstetrics and Gynaecology 2008;43(4):247-50. [Included in Bryant-Smith 2018 and Bofill Rodriguez 2019b] - PubMed
(D) Zupi 2003
    1. Zupi E, Zullo F, Marconi D, Sbracia M, Pellicano M, Solima E, et al. Hysteroscopic endometrial resection versus laparoscopic supracervical hysterectomy for menorrhagia: a prospective randomised trial. American Journal of Obstetrics and Gynecology 2003;188(1):7-12. [Included in Ferguson 2020] - PubMed
(N) Andersch 1988
    1. Andersch B, Milsom I, Rybo G. An objective evaluation of flurbiprofen and tranexamic acid in the treatment of idiopathic menorrhagia. Acta Obstetricia et Gynecologica Scandinavica 1988;67:645-8. [Data reported in a way that do not allow comparisons] [Included in Bofill Rodriguez 2019c] - PubMed
(N) Boujida 2002
    1. Boujida VH, Philipsen T, Pelle J, Joergensen JC. Five-year follow-up of endometrial ablation: endometrial coagulation versus endometrial resection. Obstetrics and Gynecology 2002;99:988-92. [Included in Bofill Rodriguez 2019a] - PubMed
(N) Cameron 1987
    1. Cameron IT, Leask R, Kelly RW, Baird DT. The effects of danazol, mefenamic acid, norethisterone and a progesterone-impregnated coil on endometrial prostaglandin concentrations in women with menorrhagia. Prostaglandins 1987;34:99-110. [Included in Bofill Rodriguez 2019b, Bofill Rodriguez 2019c and Beaumont 2007] - PubMed
(N) Chimbira 1980
    1. Chimbira T, Andreson A, Naish C, Cope E, Turnbull A. Reduction of menstrual blood loss by danazol in unexplained menorrhagia: lack of effect of placebo. British Journal of Obstetrics and Gynaecology 1980;87(12):1152-8. [Excluded as is a comparison between different dosages of danazol] [Included in Beaumont 2007] [PMID: ] - PubMed
(N) Cooper 1997
    1. Cooper KG, Parkin DE, Garratt AM, Grant AM. A randomised comparison of medical and hysteroscopic management in women consulting a gynaecologist for treatment of heavy menstrual loss. British Journal of Obstetrics and Gynaecology 1997;104:1360-6. [CRSREF 2868337] [Included in Marjoribanks 2016] [No randomization on the medical treatment arm] - PubMed
(N) Fathima 2012
    1. Fathima A, Sultana A. Clinical efficacy of a Unani formulation ‘Safoof Habis’ in menorrhagia: a randomized controlled trial. European Journal of Integrative Medicine 2012;4(3):e315-22. [Excluded as comparison is not medical treatment] [Included in Bryant-Smith 2018]
(N) Goshtasebi 2015
    1. Goshtasebi A, Mazari Z, Behboudi Gandevani S, Naseri M. Anti-hemorrhagic activity of Punica granatum L. flower (Persian Golnar) against heavy menstrual bleeding of endometrial origin: a double-blind, radomized controlled trial. Medical Journal of the Islamic Republic of Iran 2015;29:199. [Comparison was not a medical treatment] [Included in Bryant-Smith 2018] - PMC - PubMed
(N) Gupta 2013
    1. Gupta J, Kai J, Middleton L, Pattison H, Gray R, Daniels J. Levonorgestrel intrauterine system versus medical therapy for menorrhagia. New England Journal of Medicine 2013;368:128-37. [Included in Bofill Rodriguez 2019d] [one arm was not randomized] - PubMed
(N) Hall 1987
    1. Hall P, MacLachlan N, Thorn N, Nudd MW, Taylor CG, Garrioch DB. Control of menorrhagia by the cyclo-oxygenase inhibitors naproxen sodium and mefenamic acid. British Journal of Obstetrics and Gynaecology 1987;94:554-8. [Included in Bofill Rodriguez 2019c] - PubMed
(N) Khajehei 2013
    1. Khajehei N, Abdali K, Tabatabaee. The effect of mefenamic acid and naproxen on heavy menstrual bleeding: A placebo-controlled study. South African Journal of Obstetricsand gynaecology 2013;19(2):31-34. [DOI: 10.7196/SAJOG.587] - DOI
(N) Kilic 2009
    1. Kilic S, Yuksel B, Doganay M, Bardakci H, Akinsu F, Uzunlar O, et al. The effect of levonorgestrel-releasing intrauterine device on menorrhagia in women taking anticoagulant medication after cardiac valve replacement. Contraception 2009;80(2):152-7. [Included in Bofill Rodriguez 2019d] - PubMed
(N) Kupperman 2004
    1. Kupperman M, Varner RE, Summitt RL, Learman LA, Ireland C, Vittinghoff E, et al. Effect of hysterectomy vs medical treatment on health-related quality of life and sexual functioning. JAMA 2004;291(12):1447-55. [Included in Marjoribanks 2016] [No randomization on the medical treatment arm] - PubMed
(N) Lamb 1987
    1. Lamb MP. Danazol in menorrhagia: a double blind placebo controlled trial. Journal of Obstetrics and Gynaecology 1987;7:212-16. [Compares Danazol and placebo] [Included in Beaumont 2007]
(N) Makarainen 1986
    1. Makarainen L, Ylikorkala O. Primary and myoma-associated menorrhagia: role of prostaglandin and effects of ibuprofen. British Journal of Obstetrics and Gynaecology 1986;93:974-8. [Included in Bofill Rodriguez 2019c] - PubMed
(N) Najam 2010
    1. Najam R, Agarwald D, Tyagi R, Singh S. Comparison of tranexamic acid with a combination of tranexamic acid and mefenamic acid in reducing menstrual blood loss in ovulatory dysfunctional uterine bleeding. Journal of Clinical and Diagnostic Research 2010;4:3020-5. [Included in Bofill Rodriguez 2019c] [No data available for the comparisons]
(N) Onoglu 2007
    1. Onoglu A, Taskin O, Inal M, Sadik S, Simsek M, Akar M, et al. Comparison of the long-term histopathologic and morphologic changes after endometrial rollerball ablation and resection: a prospective randomized trial. Journal of Minimally Invasive Gynecology 2007;14:39-42. [(E) The only review outcome reported was surgical time] [Included in Bofill Rodriguez 2019a] - PubMed
(N) Reid 2005
    1. Reid PC, Virtanen-Kari S. Randomised comparative trial of the levonorgestrel intrauterine system and mefenamic acid for the treatment of idiopathic menorrhagia: a multiple analysis using total menstrual fluid loss, menstrual blood loss and pictorial blood loss assessment charts. British Journal of Obstetrics and Gynaecology 2005;112:1121-5. [Data reported in ranges] [Included in Bofill Rodriguez 2019c and Bofill Rodriguez 2019d] - PubMed
(N) Shravage 2011
    1. Shravage J, Mekhala D, Bellad MB, Ganachari MS, Dhumale HA. Ormeloxifene versus medroxyprogesterone acetate (MPA) in the treatment of dysfunctional uterine bleeding. A double blind randomized controlled trial. Journal of South Asian Federation of Obstetrics and Gynaecology 2011;3(1):21-4. [10.5005/jp-journals-10006-1116] [Data was reported in a format that do not allow comparisons] [Included in Bofill Rodriguez 2019b]
(N) Thabet 2010
    1. Thabet SMA. New attempt using ablative curettage technique for managing benign premenopausal uterine bleeding. Obstetrics and Gynaecology Research 2010;36(4):803-9. [Included in Bofill Rodriguez 2019a] [No data for comaprisons (overcouretage)] - PubMed
Alvarado 2001
    1. Alvarado RG, Liu JY, Zwolak RM. Danazol and limb-threatening arterial thrombosis: two case reports. Journal of Vascular Surgery 2001;34(6):1123-6. [DOI: 10.1067/mva.2001.118078] - DOI - PubMed
Alvaro 1996
    1. Alvaro D, Piat C, Francia C, Franchitto A, Furfaro S, Valente C et al. Ultrastructural features of danazol-induced cholestasis: a case study. Ultrastructural Pathology 1996;20(5):491-5. [DOI: 10.3109/01913129609016353] - DOI - PubMed
Audia 2016
    1. Audia S, Godeau B, Bonnotte B. Is there still a place for "old therapies" in the management of immune thrombocytopenia? La Revue de Medecine Interne 2016;37(1):43-9. [DOI: 10.1016/j.revmed.2015.08.007] - DOI - PubMed
Bacchi 2012
    1. Bacchi S, Palumbo P, Sponta A, Coppolino M. Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2012;11(1):52-64. [DOI: 10.2174/187152312803476255] - DOI - PubMed
Blacker 1902
    1. Blacker JF. Vaporization of the uterus. British Journal of Obstetrics and Gynaecologu: An International Journal of Obstetrics & Gynaecology 1902;1(5):488-511.
Bofill Rodriguez 2020a
    1. Bofill Rodriguez M, Lethaby A, Farquhar C, Duffy JM. Interventions commonly available during pandemics for heavy menstrual bleeding: an overview of Cochrane Reviews.. Cochrane Database of Systematic Reviews 2020, Issue 7. Art. No: CD013651. [DOI: 10.1002/14651858.CD013651.pub2] - DOI - PMC - PubMed
Bongers 2004
    1. Bongers MY, Mol BW, Brölmann HA. Current treatment of dysfunctional uterine bleeding. Maturitas 2004;47(3):159-74. [DOI: 10.1016/j.maturitas.2003.08.002. PMID: 15036486] - PubMed
Bradley 2016
    1. Bradley L, Guyen N. The medical management of abnormal uterine bleeding in reproductive-aged women. American Journal of Obstetrics and Gynecology 2015;214(1):31-44. [DOI: 10.1016/j.ajog.2015.07.044] - DOI - PubMed
Brignardello‐Petersen2017
    1. Brignardello-Petersen R, Bonner A, Alexander PE, Siemieniuk RA, Furukawa TA, Rochwerg B, et al. GRADE Working Group. Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis.. Journal of Clinical Epidemiology 2018;93:36-44. [DOI: 10.1016/j.jclinepi.2017.10.005] [Erratum in: J Clin Epidemiol. 2018 Jun;98:162. PMID: 29051107.] - DOI - PubMed
Brignardello‐Petersen 2019
    1. Brignardello-Petersen R, Mustafa RA, Siemieniuk RAC, Murad MH, Agoritsas T, Izcovich A et al, GRADE Working Group. GRADE approach to rate the certainty from a network meta-analysis: addressing incoherence. Journal of Clinical Epidemiology 2019;108:77-85. [DOI: 10.1016/j.jclinepi.2018.11.025] - DOI - PubMed
Brignardello‐Petersen 2020
    1. Brignardello-Petersen R, Izcovich, A, Rochwerg B, Florez I, Hazlewood G, et al. GRADE approach to drawing conclusions from a network meta-analysis using a partially contextualised framework. BMJ 2020;371:m3907. [DOI: 10.1136/bmj.m3907] - DOI - PubMed
Brunskill 1992
    1. Brunskill P. The effects of fetal exposure to danazol. British Journal of Obstetetrics and Gynaecology 1992;99(3):212-5. [PMID: ] - PubMed
Caldwell 2014
    1. Caldwell DM. An overview of conducting systematic reviews with network meta-analysis. Systematic Reviews Journal 2014;3:109. [DOI: 10.1186/2046-4053-3-109] - DOI - PMC - PubMed
Clarke‐Pearson 2013
    1. Clarke-Pearson D, Geller E. Complications of hysterectomy. Obstetrics & Gynecology 2013;121(3):654-73. [DOI: 10.1097/AOG.0b013e3182841594] - DOI - PubMed
Cole 1971
    1. Cole S, Billewicz W, Thomson A. Sources of variation in menstrual blood loss. Journal of Obstetrics and Gynaecology of the British Commonwealth 1971;78:933-9. [PMID: ] - PubMed
COMET 2018
    1. Cooper N, Khan K, Rivas C. Defining core outcomes for clinical trials of heavy menstrual bleeding. A Core Outcome sets for Gynaecological conditions (COGS) project. www.comet-initiative.org/studies/details/789 (accessed prior to 28 April 2022).
Coulter 1995
    1. Coulter A, Kelland J, Peto V, Rees M. Treating menorrhagia in primary care. An overview of drug trials and a survey of prescribing practice. International Journal of Technology Assessment in Health Care 1995;11(3):456-71. [PMID: ] - PubMed
Daniels 2012
    1. Daniels J, Middleton L, Champaneria R, Khan K, Cooper K, Bhattacharya S, et al. Second generation endometrial ablation techniques for heavy menstrual bleeding: network meta-analysis. BMJ 2012;344:e2564. [DOI: ] - PMC - PubMed
De Bastos 2014
    1. De Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, et al. Combined oral contraceptives: venous thrombosis. Cochrane Database of Systematic Reviews 2014, Issue 3. Art. No: CD010813. [DOI: 10.1002/14651858.CD010813.pub2] - DOI - PMC - PubMed
Dias 2010
    1. Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Statistics in Medicine 2010;28(7-8):932-44. [DOI: 10.1002/sim.3767] - DOI - PubMed
Dias 2018
    1. Dias S, Ades AE, Welton NJ, Jansen JP, Sutton AJ. Network Meta-analysis for Decision Making. Wiley, 2018. [DOI: 10.1002/9781118951651] [Online ISBN:9781118951651] - DOI
Dias 2019
    1. Dias S, Caldwell D. Network meta-analysis explained. Archives of Disease in Childhood. Fetal and Neonatal Edition 2019;104(1):F8-F12. [DOI: 10.1136/archdischild-2018-315224] - DOI - PMC - PubMed
Di Carlo, 2015
    1. Di Carlo C, Guida M, De Rosa N, Sansone A, Gargano V, Cagnacci A, et al. Bleeding profile in users of an etonogestrel sub-dermal implant: effects of anthropometric variables. An observational uncontrolled preliminary study in Italian population. Gynaecological Endocrinology 2015;31(6):491-4. [DOI: 10.3109/09513590.2015.1018163] - DOI - PubMed
Edlund 2011
    1. Edlund M. Nonhormonal treatments for heavy menstrual bleeding. Journal of Women's Health 2011;20(11):1645-53. [DOI: 10.1089/jwh.2010.2696] - DOI - PubMed
Famuyide 2018
    1. Famuyide A. Endometrial Ablation. Journal of Minimally Invasive Gynecoly 2018;25(2):299-307. [DOI: 10.1016/j.jmig.2017.08.656] - DOI - PubMed
Fraser 2009
    1. Fraser I, Langham S, Uhl-Hochgraeber K. Health-related quality of life and economic burden of abnormal uterine bleeding. Expert Review of Obstetrics & Gynecology 2009;4(2):179-89. [DOI: 10.1586/17474108.4.2.179] - DOI
Friberg 2006
    1. Friberg B, Orno A, Lindgren A, Lethagen S. Bleeding disorders among young women: a population-based prevalence study. Acta Obstetetrica et Gynecologica Scandinavica 2006;85(2):200-6. [DOI: ] - PubMed
Fritz 2012
    1. Fritz M, Speroff L. Clinical Gynecologic Endocrinology and Infertility. Wolters Kluwer Health/Lippincott Williams & Wilkins, 2012. [https://slycksyxr01.storage.googleapis.com/MDc4MTc3OTY4NQ==01.pdf]
Garay 2006
    1. Garay RP, Chiavaroli C, Hannaert P. Therapeutic efficacy and mechanism of action of ethamsylate, a long-standing hemostatic agent. American Journal of Therapeutics 2006;13(3):236-47. [DOI: 10.1097/01.mjt.0000158336.62740.54.] - DOI - PubMed
Gleeson 1994
    1. Gleeson N. Cyclic changes in endometrial tissue plasminogen activator and plasminogen activator inhibitor type 1 in women with normal menstruation and essential menorrhagia. American Journal of Obstetrics and Gynecology 1994;171(1):178-83. [PMID: ] - PubMed
GRADEpro GDT 2015 [Computer program]
    1. GRADEpro GDT. Hamilton (ON): McMaster University (developed by Evidence Prime), accessed prior to 28 April 2022. Available at gradepro.org.
Hallberg 1966
    1. Hallberg L, Hogdahl A, Nilsson LM, Rybo G. Menstrual blood loss - a population study. Variation at different ages and attempts to define normality. Acta Obstetetrica et Gynecologica Scandinava 1966;45(3):320-51. [DOI: 10.3109/00016346609158455] - DOI - PubMed
Harlow 2004
    1. Harlow S, Campbell OM. Epidemiology of menstrual disorders in developing countries: a systematic review. British Journal of Obstetricas and Gynecology 2004;111(1):6-16. [PMID: ] - PubMed
Harrison 1976
    1. Harrison RF Campbell S. A double-blind trial of ethamsylate in the treatment of primary and intrauterine-device menorrhagia. Lancet 1976;308(7980):283-5. [DOI: ] - PubMed
Haththotuwa 2011
    1. Haththotuwa R, Goonewardene M, Desai S, Senanayake L, Tank J, Fraser I. Management of abnormal uterine bleeding in low- and high-resource settings: consideration of cultural issues. Seminars in Reproductive Medicine 2011;29(5):446-58. [DOI: 10.1055/s-0031-1287668] - DOI - PubMed
Herman 2013
    1. Herman MC, den Brink MJ, Geomini PM, Meurs HS, Huirne JA, Eising HP, et al. Levonorgestrel releasing intrauterine system (Mirena) versus endometrial ablation (Novasure) in women with heavy menstrual bleeding: a multicentre randomised controlled trial. BioMed Central Womens Health 2013;13:32. [DOI: 10.1186/1472-6874-13-32] - DOI - PMC - PubMed
Higgins 2011
    1. Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Higgins 2021
    1. Higgins J, Thomas J, Chandler J, Cumpston M, Li T, Page MJ. Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from training.cochrane.org/handbook. [www.training.cochrane.org/handbook]
Hurskainen 2007
    1. Hurskainen R, Grenman S, Komi I, Kujansuu E, Luoto R, Orrainen M, et al. Diagnosis and treatment of menorrhagia. Acta Obstetetrica et Gynecologica Scandinava 2007;86(6):749-57. [DOI: 10.1080/00016340701415400] - DOI - PubMed
Jacobsten 2014
    1. Jacobstein R, Polis CB. Progestin-only contraception: injectables and implants. Best Practice & Research: Clinical Obstetrics & Gynaecology 2014;28(6):795-806. [DOI: 10.1016/j.bpobgyn.2014.05.003] - DOI - PubMed
Jick 1995
    1. Jick SS, Myers MW. A study of danazol's safety. Pharmacotherapy 1995;15(6):740-1. [PMID: ] - PubMed
Karlsson 2014
    1. Karlsson T, Marions L, Edlund M. Heavy menstrual bleeding significantly affects quality of life. Acta Obstetrica et Gynecologica Scandinava 2014;93(1):52-7. [DOI: 10.1111/aogs.12292] - DOI - PubMed
Kumar 2016
    1. Kumar V, Chodankar R, Gupta J. Endometrial ablation for heavy menstrual bleeding. Women's Health 2016;12:45-52. [DOI: 10.2217/whe.15.86] - DOI - PMC - PubMed
Laberge 2015
    1. Laberge P, Leyland N, Murji A, Fortin C, Martyn P, Vilos G, et al. Endometrial ablation in the management of abnormal uterine bleeding. Journal of Obstetrics and Gynaecology Canada 2015;37(4):362-79. [DOI: 10.1016/s1701-2163(15)30288-7] - DOI - PubMed
Lecker I 2016
    1. Lecker I, Wang D, Whissell P, Avramescu S, Mazer D, Orser B. Tranexamic acid–associated seizures: causes and treatment. Annals of Neurology 2016;79:18-26. [PMID: ] - PMC - PubMed
Liu 2007
    1. Liu Z, Doan Q, Blumenthal P, Dubois R. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value in Health 2007;10(3):183-94. [DOI: 10.1111/j.1524-4733.2007.00168.x] - DOI - PubMed
Micks 2013
    1. Micks EA, Jensen JT. Treatment of heavy menstrual bleeding with the estradiol valerate and dienogest oral contraceptive pill. Advances in Therapy 2013;30(1):1-13. [DOI: 10.1007/s12325-012-0071-3] - DOI - PubMed
Miller 2015
    1. Miller J, Lenhart G, Bonafede M, Basinski C, Lukes A, Troeger K. Cost effectiveness of endometrial ablation with the NovaSure (R) system versus other global ablation modalities and hysterectomy for treatment of abnormal uterine bleeding: US commercial and Medicaid payer perspectives. International Journal of Women's Health 2015;7:59-73. [DOI: 10.2147/ijwh.s75030] - DOI - PMC - PubMed
Morrison 2008
    1. Morrison J, Patel S, Watson W, Zaidi Q, Mangione A, Goss T. Assessment of the prevalence and impact of anemia on women hospitalized for gynecologic conditions associated with heavy uterine bleeding. Journal of Reproductive Medicine 2008;53(5):323-30. [PMID: ] - PubMed
Munro 2012
    1. Munro M, Critchley H, Fraser I. The FIGO systems for nomenclature and classification of causes of abnormal uterine bleeding in the reproductive years: who needs them? American Journal of Obstetetrics and Gynecology 2012;207(4):259-65. [DOI: 10.1016/j.ajog.2012.01.046] - DOI - PubMed
Munro 2018
    1. Munro M. Endometrial ablation. Best Practice & Research Clinical Obstetrics & Gynaecology 2018;46:120-39. [DOI: ] - PubMed
NICE 2007
    1. National Institute for Health and Clinical Excellence. Heavy Menstrual Bleeding. Clinical Guideline No. 44. National Collaborating Centre for Women's and Children’s Health Commissioned by the National Institute for Health and Clinical Excellence 2007. [https://www.nice.org.uk/guidance/cg44]
NICE 2018a
    1. National Institute for Health and Clinical Excellence. Heavy Menstrual Bleeding. Clinical Guideline No. 88. National Collaborating Centre for Women's and Children’s Health Commissioned by the National Institute for Health and Clinical Excellence 2018. [https://www.nice.org.uk/guidance/ng88/evidence]
NICE 2018b
    1. RCOG, National Guideline Alliance, hosted by the Royal College of Obstetrician and Gynaecologists. Evidence reviews for management of heavy menstrual bleeding. National Institute for Health and Clinical Excellence 2018. [file:///P:/FMHSfiles/network%20meta-analisis/NICE%20NMA%20HMB.pdf] - PubMed
Pincus 1899a
    1. Pincus L. Response to the article of Mr Duhrssen about "autmocausis" [Erwiderung auf den Aufsatz des Herrn Duhrssen uber “Atmocausis”]. Centralblatt für Gynäkologie 1899;13:352.
Pincus 1899b
    1. Pincus L. Some remarks on the article on Zestocausis the Treub's Clinic [Einege Bemerkungen zu dem Aufsatz Zestocausis aus der Treub'schen Klinic]. Centralblatt für Gynäkologie 1899;4:113.
Puhan 2014
    1. Puhan M, Schünemann H, Hasan Murad, M, Li T, Brigardello-Petersen R et al, GRADE working group. A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis. BMJ 2014;349:g5630. [DOI: ] - PubMed
RCOG 2012
    1. Royal College of Obstetricians and Gynaecologists. National Heavy Menstrual Bleeding Audit. London: RCOG; 2012. Second Annual Report. [https://www.rcog.org.uk/en/news/rcog-release-four-year-national-audit-sh...]
Rees 1987
    1. Rees M, DiMarzo V, Tippins J, Morris H, Turnbull A. Leukotriene release by endometrium and myometrium throughout the menstrual cycle in dysmenorrhoea and menorrhagia. Journal of Endocrinology 1987;113(2):291-5. [PMID: ] - PubMed
Review Manager 2020 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2020. [https://training.cochrane.org/online-learning/core-software-cochrane-rev...]
Salanti 2014
    1. Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JP. Evaluating the quality of evidence from a network meta-analysis. PLOS ONE 2014;9(7):e99682. [DOI: 10.1371/journal.pone.0099682] - DOI - PMC - PubMed
Santesso 2020
    1. Santesso N, Glenton C, Dahm P, Garner P, Akl E, Alper B, et al. GRADE guidelines 26: informative statements to communicate the findings of systematic reviews of interventions. Journal of Clinical Epidemiology 2020;119:126-35. [DOI: Journal of Clinical Epidemiology] - PubMed
Shaw 1972
    1. Shaw S, Aaronson D, Moyer D. Quantitation of menstrual blood loss- further evaluation of the alkaline hematin method. Contraception 1972;5(6):497-513. [DOI: 10.1016/0010-7824(72)90015-7] - DOI - PubMed
Shea 2007
    1. Shea B, Grimshaw J, Wells G, Boers M, Andersson N, Hamel C, et al. Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. Bio Med Central Medical Research Methodology 2007;7:10. [DOI: 10.1186/1471-2288-7-10] - DOI - PMC - PubMed
Shea 2017
    1. Shea BJ, Reeves BC, Wells G, Thuku M, Hamel C, Moran J, et al. AMSTAR 2: a critical appraisal tool for systematic reviews that include randomised or non-randomised studies of healthcare interventions, or both. BMJ 2017;257:j4008. [DOI: ] - PMC - PubMed
Smith 1981
    1. Smith SK, Abel MH, Kelly RW, Baird DT. Prostaglandin synthesis in the endometrium of women with ovular dysfunctional uterine bleeding. British Journal Obstetrics & Gynaecology 1981;88(4):434-42. [PMID: ] - PubMed
Speroff 2010
    1. Speroff L, Darney P. Clinical Guide for Contraception. Philadelphia: Lippincott Williams & Wilkins (LWW), 2010. [ISBN: 978-1-60-831610-6]
Tanaka 2013
    1. Tanaka E, Momoeda M, Osuga Y, Rossi B, Nomoto K, Hayakawa M, et al. Burden of menstrual symptoms in Japanese women: results from a survey-based study. Journal of Medical Economics 2013;16(11):1255-66. [DOI: 10.3111/13696998.2013.830974] - DOI - PubMed
Uhm 2014
    1. Uhm S, Perriera L. Hormonal contraception as treatment for heavy menstrual bleeding: a systematic review. Clinical Obstetrics and Gynecology 2014;57(4):694-717. [DOI: 10.1097/grf.0000000000000061] - DOI - PubMed
Van der Heijden 2017
    1. Van der Heijden P, Geomini P, Herman M, Veersema S, Bongers M. Timing of insertion of levonorgestrel-releasing intrauterine system: a randomised controlled trial. British Journal of Obstetrics and Gynecology 2016;124(2):299-305. [DOI: 10.1111/1471-0528.14445] - DOI - PubMed
Van Valkenhoef 2016
    1. Van Valkenhoef G, Dias S, Ades AE, Welton N. Automated generation of node-splitting models for assessment of inconsistency in network meta-analysis. Research Synthesis Methods 2016;7(1):80-93. [DOI: 10.1002/jrsm.1167] - DOI - PMC - PubMed
White 2015
    1. White IR. Network meta analysis. Stata Journal 2015;15:951-85. [https://www.stata-journal.com/article.html?article=st0410]
Yepes‐Nunez 2019
    1. Yepes-Nunez J, Lic SA, Guyatta G, Jacka SM, Brozek JL, Beyenea J, et al. Development of the summary of findings table for network meta-analysis. Journal of Clinical Epidemiology 2019;115:1-13. [DOI: ] - PubMed

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