Nonsteroidal anti-inflammatory drugs (NSAIDs)

• Evidence from two systematic reviews supports the use of NSAIDs for the management of primary dysmenorrhoea.
• There is insufficient evidence to indicate whether one NSAID is more effective than another for the treatment of dysmenorrhoea.
• Ibuprofen is considered to have a lower risk of gastrointestinal adverse effects than other NSAIDs. It is licensed for use in the management of dysmenorrhoea in girls and women of all ages [BNF 56, 2008].
• Naproxen is associated with an intermediate risk of gastrointestinal adverse effects. Mefenamic acid, having a short half-life, is likely to be associated with a low-to-intermediate risk. Naproxen is licensed for use in dysmenorrhoea from 16 years of age onwards, and mefenamic acid is licensed for use in acute pain including dysmenorrhoea, from 12 years of age onwards [García Rodríguez and Hernández-Díaz, 2001; BNF 56, 2008].
• Although there is some evidence to support the use of aspirin for dysmenorrhoea, aspirin is not recommended because it has a higher risk of gastrointestinal adverse effects. Aspirin should not be given to children less than 16 years of age because it is associated with Reye's syndrome [CSM, 2002].
• Cyclo-oxygenase-2 (COX-2) inhibitors are not recommended as first-line treatment for dysmenorrhoea, but they may be appropriate for some women (see the CKS topic on NSAIDs - prescribing issues).
• There is some evidence to suggest that the efficacy of COX-2 inhibitors is superior to placebo, and similar to that of NSAIDs.

Paracetamol

• Paracetamol is a widely used alternative to NSAIDs for musculoskeletal pain.
• The evidence on paracetamol for the management of dysmenorrhoea is poor. One small crossover study showed it to be no more effective than placebo at providing pain relief. However, the study was probably underpowered to detect such differences. The same study failed to show a significant difference between aspirin and paracetamol.

Codeine

• CKS found no evidence on the use of codeine in the treatment of dysmenorrhoea, however, the addition of codeine to paracetamol or an NSAID seems reasonable in women who do not experience adequate pain relief from paracetamol or an NSAID alone.

Combined oral contraceptives

• Despite only limited trial evidence on combined oral contraceptives (COCs) for the treatment of primary dysmenorrhoea, they are widely recommended by experts [Society of Obstetricians and Gynaecologists of Canada, 2005; Proctor and Farquhar, 2006]. The added contraceptive advantage may make them a first-line option for some women.
• A Cochrane review of COCs for the treatment of primary dysmenorrhoea found insufficient evidence to conclude that COCs are effective at relieving pain. The quality of the trials was poor, they are over 25 years old, and they used COCs with higher doses of oestrogen than in currently prescribed products.
• A more recent randomized controlled trial (n = 76) using a COC containing a low dose of oestrogen (20 micrograms) suggested that low-dose COCs may be effective at reducing pain associated with dysmenorrhoea. This is supported by evidence from an observational study.
• COCs containing 20 micrograms of ethinylestradiol are less preferred because they are more likely to cause unscheduled bleeding.

Progestogen-only contraceptives

• Some experts recommend that parenteral progestogens (for example depot medroxyprogesterone acetate) may be considered in the treatment of dysmenorrhea [Society of Obstetricians and Gynaecologists of Canada, 2005; Proctor and Farquhar, 2006].
• Depot medroxyprogesterone acetate works primarily by suppressing ovulation. It can also induce endometrial atrophy. One of its benefits is amenorrhea with a resultant reduction in the incidence of dysmenorrhea.
• The Committee on Safety of Medicines has advised that [BNF 56, 2008]:
• In adolescents, medroxyprogesterone acetate (Depo-Provera^®) should only be used when other methods of contraception are inappropriate.
• In all women, the benefits of using medroxyprogesterone acetate for longer than 2 years should be evaluated against the risks.
• In women with risk factors for osteoporosis a method of contraception other than medroxyprogesterone acetate should be considered.
• Evidence from a review of open-label, non-comparative and comparative studies suggests that the etonogestrel subdermal implant, Implanon^®, may reduce both the incidence and severity of dysmenorrhoea.
• Implanon^® has now been replaced by Nexplanon^®. Note that Nexplanon^® is bioequivalent to Implanon^®. The main differences are that Nexplanon^® is radio-opaque, and the insertion technique is different [FSRH, 2010].
• Evidence from observational studies suggests that the progestogen-only pill, Cerazette^®, and the levonorgestrel-releasing intrauterine system (LNG-IUS), Mirena^®, may be effective at relieving pain associated with menstruation.
• The progestogen only pill (POP) may decrease menstrual flow, and up to 10% of POP users develop amenorrhea. Cerazette^® suppresses ovulation and thus has a higher rate of amenorrhoea than other POPs.
• Although it does not suppress ovulation, the LNG-IUS has a local effect on the endometrium, which becomes atrophic and inactive. The effect of this is to reduce blood loss by 74–97%, with 16–35% of users developing amenorrhoea after 1 year of use.
• There is limited evidence that the LNG-IUS may relieve dysmenorrhoea associated with endometriosis [Abou-Setta et al, 2006; Varma et al, 2006].
• Expert reviewers agree that the LNG-IUS is an option for women with dysmenorrhoea who require contraception. It is also an option for those who do not require contraception, particularly older women who have had children and women with heavy menstrual bleeding.

Locally-applied heat

• Evidence from two randomized controlled trials (RCTs) suggests that locally-applied heat is an effective treatment for dysmenorrhoea.

Transcutaneous electrical stimulation (TENS)

• Evidence from a Cochrane review including eight RCTs suggests that high-frequency TENS (pulses delivered between 50 Hz and 120 Hz) reduces pain compared with placebo. The evidence suggests that low-frequency TENS (pulses delivered between 1 Hz and 4 Hz) is less effective than high-frequency TENS and may be no more effective than placebo.
• There is insufficient evidence to draw any conclusions regarding the relative efficacy of TENS and NSAIDs.
• TENS machines cannot be prescribed on the NHS, but can be purchased over-the-counter (costing from around £25).

Herbal and dietary supplements

• The evidence on herbal and dietary supplements is limited by poor quality studies and small sample sizes. When advising women about herbal and dietary supplements for dysmenorrhoea, the uncertainty about long-term efficacy, safety, and interactions should always be considered.
• There is limited evidence from one RCT undertaken in India that vitamin B₁ may be more effective than placebo in relieving dysmenorrhoea, although the applicability of these results to the UK population is unclear.
• There is some evidence that both magnesium and vitamin B₆ may provide pain relief; however a disparity of dosing and high drop out rates make it difficult to draw firm conclusions.
• There is also some evidence that vitamin E may be effective in relieving dysmenorrhoea; however none of the studies reported adverse effects, which have been noted in other studies of vitamin E.
• Studies of fish oils and the Japanese herbal remedy toki-shakuyaku-san, are too small to draw meaningful conclusions.

Other treatments

• Evidence on other treatments for dysmenorrhoea is too limited by the poor methodological quality of the available studies to make any recommendations for practice.

Referral

• The recommendations for referral are based on expert opinion from the literature [Proctor and Farquhar, 2006] and from expert reviewers.