Treatment options for heavy menstrual bleeding: Systematic review, pairwise and network meta-analysis
Lily Nicholson, David J. Fisher, Ewelina Rogozinska, Jayne F. Tierney, Claire L. Vale, Ekaterina Bordea, Ngawai Moss, Niccola Pascal-Hutchinson, Rachael Hunter, Khalid S. Khan, Davor Jurkovic, Bassel H. Al Wattar

Introduction:

Heavy menstrual bleeding (HMB) affects 1 in 3 women of reproductive age. There are many treatment options available for HMB, but evidence of treatment efficacy and safety is limited.

Objectives:

To provide up-to-date, comprehensive evidence on medical and surgical treatment options for women with heavy menstrual bleeding through systematic review, meta-analysis and network meta-analysis.

Methods:

• Systematic searches were conducted up to August 2024.
• Random-effects pairwise and network meta-analyses

Inclusion Criteria

• Randomised Controlled Trials (RCTs)
• Women with HMB
• Comparing any medical or surgical treatment compared to placebo or other active treatments

Primary Outcomes:

• Menstrual blood loss (MBL)
• Quality of Life (QoL)
• Adverse events (AEs)

Secondary Outcomes:

• Amenorrhea, Haemoglobin, Dysmenorrhea, Satisfaction, Treatment failure

Baseline data (presented as a table only)

Results 1: Medical treatments for HMB due to uterine fibroids
3 main treatment groups:

1. GnRH analogues (e.g. elagolix, linzagolix)
2. GnRH analogues + hormone replacement therapy
3. SPRMs (e.g. UPA, vilaprisan)

Menstrual Blood Loss: (results presented as figures and tables only)

Quality of Life: SPRMs, GnRH analogues and GnRH analogues with hormone replacement therapy all improve quality of life compared to placebo.

Safety: GnRH analogues alone significantly increase the risk of AEs compared to placebo (RR 1.28; 95%CI 1.20-1.36). No strong evidence that SPRMs or GnRH analogues + hormone replacement increase risk of AEs compared with placebo

Results 2: Medical treatments for HMB due to unknown causes
Variety of treatments:

1. Hormonal therapies (e.g. combined hormonal contraceptives (CHCs), progesterone-only pills (POPs), LNG-IUS)
2. Non-hormonal therapies (e.g. tranexamic acid, NSAIDs)

Menstrual blood loss: (results presented as figures and tables only)

Quality of Life: LNG-IUS and SPRMs seem to improve quality of life compared to placebo and compared to combined hormonal contraceptives.

Safety: No strong evidence that risk of AEs differs between combined hormonal contraceptives, tranexamic acid or placebo. There is no strong evidence that the risk of AEs differs between LNG-IUS, tranexamic acid and progesterone-only pills.

Results 3: Surgeries or procedures for HMB due to unknown causes

3 main treatment groups:

1. Endometrial ablation techniques (1st Generation or 2nd Generation)
2. Hysterectomy
3. LNG-IUS (commonly used as a comparator for surgical treatments)

Menstrual blood loss: (results presented as figures and tables only)

Quality of Life: LNG-IUS seems to improve quality of life compared to endometrial ablation techniques, although across all eligible trials, the reported quality of life data is very sparse.

Safety: Both 1st Generation and 2nd Generation endometrial ablation reduce the risk of AEs compared to LNG-IUS, but data is sparse. The risk of AEs seems lower with 2nd Generation compared to 1st Generation endometrial ablation (RR 0.55; 95% CI 0.34-0.89).

Conclusion:

• Compared to placebo, all the medical treatments assessed appear to reduce menstrual blood loss both in HMB due to fibroids and unknown causes
• Endometrial ablation techniques reduce menstrual blood loss to a greater degree than LNG-IUS
• Despite identifying many eligible trials, uncertainty remains. This is due to:
  • Sparse data for treatment comparisons
  • Many different treatment comparisons
  • Inconsistent measurement and reporting of outcomes

Next steps:

1. Complete analyses of secondary outcomes and sensitivity analyses to include data across all timepoints and treatment dosages
2. Explore methods to include more available HMB trial data in meta-analyses
3. Seek to improve consistency of outcome measurement and reporting in future trials

Acknowledgements: We are grateful to the NIHR Health Technology Assessment Programme (NIHR153187) for supporting this research. We are grateful to the investigators who have supplied additional unpublished data for the meta-analysis and to all the women who participated in the included trials.