NSAIDs May Be More Effective Than Paracetamol for Menstrual Pain

Laurie Barclay, MD

January 20, 2010

January 20, 2010 — Nonsteroidal anti-inflammatory drugs (NSAIDs) may be more effective than paracetamol for menstrual pain, according to the results of a systematic review reported online January 20 in the Cochrane Database of Systematic Reviews.

"Dysmenorrhoea is a common gynaecological problem consisting of painful cramps accompanying menstruation, which in the absence of any underlying abnormality is known as primary dysmenorrhoea," write Dr. Jane Marjoribanks, Cochrane Menstrual Disorders and Subfertility Group in Auckland, New Zealand, and colleagues. "Research has shown that women with dysmenorrhoea have high levels of prostaglandins, hormones known to cause cramping abdominal pain. ...NSAIDs are drugs which act by blocking prostaglandin production."

The goal of this review was to compare the effectiveness and safety of NSAIDs used in the treatment of primary dysmenorrhea vs placebo, paracetamol, and each other. The reviewers searched the Cochrane Menstrual Disorders and Subfertility Group trials register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Web of Science to May 2009. They also searched the National Research Register, the Clinical Trials Register, abstracts of major scientific meetings, and bibliographies of identified articles.

Inclusion criteria were all randomized controlled comparisons of NSAIDs vs placebo, other NSAIDs, or paracetamol for treatment of primary dysmenorrhea. Two reviewers independently evaluated trials for methodologic quality, extracted data, and calculated odds ratios (ORs) for dichotomous outcomes and mean differences for continuous outcomes. The reviewers then combined the data using inverse variance methods.

Based on 73 randomized controlled trials meeting selection criteria, NSAIDs were significantly more effective for pain relief than placebo among women with primary dysmenorrhea (OR, 4.50; 95% confidence interval [CI], 3.85 - 5.27), but there was marked heterogeneity for this finding (I2 statistic = 53%). Excluding 2 outlying studies with no or negligible placebo effect decreased heterogeneity (OR, 4.14; 95% CI, 3.52 - 4.86; I2 = 40%). Compared with paracetamol, NSAIDs were also significantly more effective for pain relief (OR, 1.90; 95% CI, 1.05 - 3.44), but NSAIDs were associated with significantly more overall adverse effects than placebo (OR, 1.37; 95% CI, 1.12 - 1.66).

"Women using these drugs need to be aware of the side effects," Dr. Marjoribanks said in a news release. "It would be interesting to see whether these could be reduced, without loss of effectiveness, by combining lower doses with other drugs such as paracetamol, or with other therapies such as transcutaneous electrical nerve stimulation."

Comparison of various NSAIDs vs other NSAIDs showed limited evidence that any individual NSAID was superior for either pain relief or safety.

Limitations of this review include limited power to detect differences among NSAIDs because most individual comparisons were based on very few trials with small sample size.

"NSAIDs are an effective treatment for dysmenorrhoea, though women using them need to be aware of the significant risk of adverse effects," the review authors conclude. "There is insufficient evidence to determine which (if any) individual NSAID is the safest and most effective for the treatment of dysmenorrhoea."

The University of Auckland School of Medicine and Princess of Wales Memorial Trust Fund administered by the Mercia Barnes Fund, New Zealand, supported this study. The study authors have disclosed no relevant financial relationships.

Cochrane Database Syst Rev. Published online January 20, 2010.

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