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. 2019 Sep 19;9(9):CD000400.
doi: 10.1002/14651858.CD000400.pub4.

Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding

Magdalena Bofill Rodriguez  1 , Anne Lethaby, Cindy Farquhar
Affiliations

Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding

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

Abstract

Background: Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.

Objectives: To determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB.

Search methods: We searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles.

Selection criteria: The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB.

Data collection and analysis: We identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis.

Main results: As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision.

Authors' conclusions: NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.

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Conflict of interest statement

MB: none.

AL: none.

CF: none.

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 NSAIDs versus placebo, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).
1.2
1.2. Analysis
Comparison 1 NSAIDs versus placebo, Outcome 2 Proportion with no subjective improvement in MBL.
1.3
1.3. Analysis
Comparison 1 NSAIDs versus placebo, Outcome 3 Adverse events.
2.1
2.1. Analysis
Comparison 2 NSAIDs versus tranexamic acid, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).
2.2
2.2. Analysis
Comparison 2 NSAIDs versus tranexamic acid, Outcome 2 Proportion with no subjective improvement in MBL.
2.3
2.3. Analysis
Comparison 2 NSAIDs versus tranexamic acid, Outcome 3 Number of days' bleeding.
2.4
2.4. Analysis
Comparison 2 NSAIDs versus tranexamic acid, Outcome 4 Proportion with no improvement in quality of life or dysmenorrhoea (or both).
2.5
2.5. Analysis
Comparison 2 NSAIDs versus tranexamic acid, Outcome 5 Proportion who found treatment unacceptable.
3.1
3.1. Analysis
Comparison 3 NSAIDs versus ethamsylate, Outcome 1 Menstrual blood loss after treatment (mL/cycle).
3.2
3.2. Analysis
Comparison 3 NSAIDs versus ethamsylate, Outcome 2 Menstrual blood loss 1–6 months after treatment (mL/cycle).
3.3
3.3. Analysis
Comparison 3 NSAIDs versus ethamsylate, Outcome 3 Proportion with no subjective improvement in MBL.
3.4
3.4. Analysis
Comparison 3 NSAIDs versus ethamsylate, Outcome 4 Proportion with no improvement in quality of life or dysmenorrhoea (or both).
3.5
3.5. Analysis
Comparison 3 NSAIDs versus ethamsylate, Outcome 5 Number of days' bleeding.
3.6
3.6. Analysis
Comparison 3 NSAIDs versus ethamsylate, Outcome 6 Proportion who found treatment unacceptable.
4.1
4.1. Analysis
Comparison 4 NSAIDs versus danazol, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).
4.2
4.2. Analysis
Comparison 4 NSAIDs versus danazol, Outcome 2 Proportion with no improvement in quality of life or dysmenorrhoea (or both).
4.3
4.3. Analysis
Comparison 4 NSAIDs versus danazol, Outcome 3 Number of days' bleeding.
4.4
4.4. Analysis
Comparison 4 NSAIDs versus danazol, Outcome 4 Proportion who found treatment unacceptable.
4.5
4.5. Analysis
Comparison 4 NSAIDs versus danazol, Outcome 5 Adverse events.
5.1
5.1. Analysis
Comparison 5 NSAIDs versus oral progestogens, Outcome 1 Menstrual blood loss (MBL) (mL/cycle).
5.2
5.2. Analysis
Comparison 5 NSAIDs versus oral progestogens, Outcome 2 Number of days' bleeding.
5.3
5.3. Analysis
Comparison 5 NSAIDs versus oral progestogens, Outcome 3 Proportion with non‐adherence.
5.4
5.4. Analysis
Comparison 5 NSAIDs versus oral progestogens, Outcome 4 Total adverse events.
5.5
5.5. Analysis
Comparison 5 NSAIDs versus oral progestogens, Outcome 5 Adverse events – headache.
5.6
5.6. Analysis
Comparison 5 NSAIDs versus oral progestogens, Outcome 6 Adverse events – abdominal pain.
5.7
5.7. Analysis
Comparison 5 NSAIDs versus oral progestogens, Outcome 7 Adverse events – nausea.
6.1
6.1. Analysis
Comparison 6 NSAIDs versus progesterone‐releasing intrauterine system (IUS), Outcome 1 Menstrual blood loss (MBL) (mL/cycle).
6.3
6.3. Analysis
Comparison 6 NSAIDs versus progesterone‐releasing intrauterine system (IUS), Outcome 3 Number of days' bleeding.
6.4
6.4. Analysis
Comparison 6 NSAIDs versus progesterone‐releasing intrauterine system (IUS), Outcome 4 Adverse events.
7.1
7.1. Analysis
Comparison 7 NSAIDs versus oral contraceptive pill (OCP), Outcome 1 Menstrual blood loss (mL/cycle).
8.1
8.1. Analysis
Comparison 8 Mefenamic acid versus naproxen, Outcome 1 Menstrual blood loss (mL/cycle).
8.2
8.2. Analysis
Comparison 8 Mefenamic acid versus naproxen, Outcome 2 Number of days' bleeding.
8.3
8.3. Analysis
Comparison 8 Mefenamic acid versus naproxen, Outcome 3 Total adverse events.
8.4
8.4. Analysis
Comparison 8 Mefenamic acid versus naproxen, Outcome 4 Gastrointestinal adverse events.
8.5
8.5. Analysis
Comparison 8 Mefenamic acid versus naproxen, Outcome 5 Central nervous system adverse events.
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Update of

References

References to studies included in this review

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Famuyide 2017 {published data only}
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References to other published versions of this review

Lethaby 1997
    1. Lethaby A, Augood C, Duckitt K, Farquhar C. Nonsteroidal anti‐inflammatory drugs vs either placebo or any other medical treatment for menorrhagia. Cochrane Database of Systematic Reviews 1997, Issue 3. [DOI: 10.1002/14651858.CD000400] - DOI
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