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Acute Pain | Chronic Pain | General

Analgesics for primary dysmenorrhoea

Clinical bottom line:

Naproxen, ibuprofen and mefenamic acid are all effective in the treatment of primary dysmenorrhoea, with numbers-needed-to-treat of 2.4 (2.2 to 2.7), 2.6 (2.2 to 3.2) and 3.0 (2.4 to 4.0) respectively for at least 50% pain relief. Ibuprofen appears to have fewer adverse effects, and is therefore the drug of choice. Dosing regimens for these levels of efficacy are naproxen 550 or 275 mg, ibuprofen 400 mg and mefenamic acid 250 to 500 mg, all four times daily for three days.

Aspirin is less effective than these drugs, and paracetamol, based on a single trial, was not effective in primary dysmenorrhoea.


Dysmenorrhoea affects about 40% to 70% of women of reproductive age, and is a frequent cause of time lost from work or school as well as interfering with daily living. Treatment is usually with NSAIDs and minor analgesics, based on the findings that prostaglandins are implicated in the pathogenesis of dysmenorrhoea. NSAIDs are peripheral prostaglandin synthetase inhibitors, but paracetamol is not.

Systematic review

Zhang WY, Li Wan Po A. Efficacy of minor analgesics in primary dysmeonrrhoea: a systematic review. British Journal of Obstetrics and Gynaecology 1998; 105: 780-9.

Inclusion criteria were randomised, controlled trials of analgesics in dysmenorrhoea; pain outcome; at least single-blind. Searches were restricted to ibuprofen, aspirin, paracetamol (UK license for dysmenorrhoea) and naproxen, mefenamic acid (Ponstan) (comparitors). Primary dysmenorrhoea was defined as patient history of painful menstrual cycles not caused by organic disease or intrauterine device. Patients with secondary dysmenorrhoea were not included in the pooling of data.

Pain relief data were extracted to calculate the percentage of patients with at least 50% pain relief (or at least moderate pain relief) measured by area under curve. From this authors calculated a response rate ratio (with 95% confidence intervals) for each treatment comparison. Authors also calculated rate differences and number-needed-to-treat (with 95% confidence intervals).

Secondary outcomes were women requiring rescue analgesics, women experiencing restriction of daily living and women experiencing absence from work/school.

Findings

Most trials were double-blind and crossover, with dosing regimens of approximately three to five days per cycle.

Pain relief (active versus placebo)

Naproxen (550 mg or 275 mg four times daily), ibuprofen (400 mg four times daily), mefenamic acid (250-500 mg four times daily) and aspirin (650 mg four times daily) were all superior to placebo. Paracetamol (650 mg four times daily) was not.

Response rate ratios were 3.17 (2.72 to 3.70) for naproxen, 2.41 (1.58 to 3.68) for ibuprofen, 2.03 (1.65 to 2.48) for mefenamic acid and 1.60 ( 1.12 to 3.63) for aspirin. Numbers-needed-to-treat are shown below. They demonstrate that there is no real difference between naproxen, ibuprofen and mefenamic acid, with number-needed-to-treat ranging from 2.4 to 3.0. Aspirin had a high number-needed-to-treat of 9.2 indicating limited efficacy. One comparison of paracetamol showed no difference between paracetamol and placebo.

Figure: Randomised trials of pain relief for at least 50% pain relief for dysmenorrhoea

Table 1: Effectiveness of analgesics for pain relief of primary dysmenorrhoea

Analgesic
Number of Trials
Number of patients
Percent improved with analgesic
Percent improved with placebo
Relative benefit (95% CI)
NNT (95% CI)
Naproxen
13
1706
59
17
3.4 (2.9 to 4.0)
2.4 (2.2 to 2.7)
Ibuprofen
9
599
70
31
2.2 (1.9 to 2.7)
2.6 (2.2 to 3.2)
Mefenamic acid
3
518
64
31
2.1 (1.7 to 2.6)
3.0 (2.4 to 4.0)
Aspirin
5
416
29
18
1.6 (1.1 to 2.2)
9.2 (5.3 to 35)

Restriction of daily living

Women taking ibuprofen or naproxen were less likely to have restrictions of daily living (Table 2). The numbers-needed-to-treat were 2.4 (1.9 to 3.2) for ibuprofen and 3.8 (3.2 to 4.6) for naproxen. Aspirin did not have this beneficial effect, with a number-needed-to-treat of 8.0 (3.8 to >100), and no data were available for mefenamic acid.

Absence from work or school

Naproxen reduced greatly (by about 70%) the amount of time away from work or school (Table 2). The number-needed-to-treat was 3.9 (3.3 to 4.6). This benefit was also found in one trial of ibuprofen, but not in one trial of aspirin. No data were available for mefenamic acid.

Table 2: Effectiveness of analgesics for restriction of daily life and absence from work or school caused by primary dysmenorrhoea

Analgesic
Number of Trials
Number of patients
Percent affected with analgesic
Percent affected with placebo
Relative benefit (95% CI)
NNT (95% CI)
Restriction of daily living            
Naproxen
7
1341
60
86
0.69 (0.64 to 0.74)
3.8 (3.2 to 4.6)
Ibuprofen
3
234
12
55
0.22 (0.14 to 0.38)
2.4 (1.9 to 3.2)
Aspirin
3
203
50
62
0.80 (0.62 to 1.03)
8.0 (3.8 to >100)
Absence from work or school            
Naproxen
7
1345
8
34
0.24 (0.18 to 0.32)
3.9 (3.3 to 4.6)

Adverse effects

Adverse effects were mainly nausea, dizziness and headache. There was a suggestion that naproxen caused more adverse effects (mainly nausea), but the power of trials to detect this was low, and confidence intervals were wide.

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