Are non-steroidal anti-inflammatory drugs safe and effective for treating heavy menstrual bleeding?

Review question

Cochrane authors investigated whether non-steroidal anti-inflammatory drugs (NSAIDs) helped reduce heavy menstrual bleeding (HMB) in women before they reach the menopause.

Background

NSAIDs reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding. It was suggested that they might help with heavy bleeding and may have a beneficial effect on painful menstrual periods.

Study characteristics

Authors search medical databases and identified 19 randomised controlled trials (RCTs; clinical studies where people are randomly put into one of two or more treatment groups) with 759 women that could be included in the review, but data from only nine trials were suitable for analyses.

Key results

Women sought help for HMB when it affected their quality of life. Levels of prostaglandin (a naturally occurring hormone) are higher in women with HMB and are reduced by NSAIDs. The review of trials found that NSAIDs were modestly effective in reducing HMB, but other medicines, such as danazol, tranexamic acid and levonorgestrel-releasing intrauterine system (LNG IUS), are more effective. These results were based on a small number of low- to moderate-quality trials.

Quality of the evidence

The evidence quality ranged from low to moderate, the main limitations being poor reporting of study methods and imprecision resulting from small study numbers.

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.

Read the full 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 strategy: 

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.

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