Abstract: We included 80 randomised controlled trials (5820 women). They compared 20 different NSAIDs (18 non-selective and two COX-2-specific) versus placebo, paracetamol or each other. NSAIDs versus placebo Among women with primary dysmenorrhoea, NSAIDs were more effective for pain relief than placebo (OR 4.37, 95% CI 3.76 to 5.09; 35 RCTs, I2 = 53%, low quality evidence). This suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so. However, NSAIDs were associated with more adverse effects (overall adverse effects: OR 1.29, 95% CI 1.11 to 1.51, 25 RCTs, I2 = 0%, low quality evidence; gastrointestinal adverse effects: OR 1.58, 95% CI 1.12 to 2.23, 14 RCTs, I2 = 30%; neurological adverse effects: OR 2.74, 95% CI 1.66 to 4.53, seven RCTs, I2 = 0%, low quality evidence). The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so. NSAIDs versus other NSAIDs When NSAIDs were compared with each other there was little evidence of the superiority of any individual NSAID for either pain relief or safety. However, the available evidence had little power to detect such differences, as most individual comparisons were based on very few small trials. Non-selective NSAIDs versus COX-2-specific selectors Only two of the included studies utilised COX-2-specific inhibitors (etoricoxib and celecoxib). There was no evidence that COX-2-specific inhibitors were more effective or tolerable for the treatment of dysmenorrhoea than traditional NSAIDs; however data were very scanty. NSAIDs versus paracetamol NSAIDs appeared to be more effective for pain relief than paracetamol (OR 1.89, 95% CI 1.05 to 3.43, three RCTs, I2 = 0%, low quality evidence). There was no evidence of a difference with regard to adverse effects, though data were very scanty. Most of the studies were commercially funded (59%); a further 31% failed to state their source of funding. NSAIDs appear to be a very effective treatment for dysmenorrhoea, though women using them need to be aware of the substantial risk of adverse effects. There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods.

Plain-language summary: We found 80 randomised controlled trials (RCTs), which included a total of 5820 women and compared 20 different types of NSAIDs with placebo (an inactive pill), paracetamol or each other. Most of the studies were commercially funded (59%), and a further 31% did not state their source of funding. The review found that NSAIDs appear to be very effective in relieving period pain. The evidence suggests that if 18% of women taking placebo achieve moderate or excellent pain relief, between 45% and 53% taking NSAIDs will do so. NSAIDs appear to work better than paracetamol, but it is unclear whether any one NSAID is safer or more effective than others. NSAIDs commonly cause adverse effects (side effects), including indigestion, headaches and drowsiness. The evidence suggests that if 10% of women taking placebo experience side effects, between 11% and 14% of women taking NSAIDs will do so. Based on two studies that made head-to-head comparisons, there was no evidence that newer types of NSAID (known as COX-2-specific inhibitors) are more effective for the treatment of dysmenorrhoea than traditional NSAIDs (known as non-selective inhibitors), nor that there is a difference between them with regard to adverse effects. We rated the quality of the evidence as low for most comparisons, mainly due to poor reporting of study methods.