Dysmenorrhoea
Dysmenorrhoea - Summary
Dysmenorrhoea is painful cramping, usually in the lower abdomen, occurring shortly before or during menstruation, or both. It may occur in the absence of any identifiable underlying pelvic pathology (primary dysmenorrhoea) or it may be associated with underlying pelvic pathology such as endometriosis, fibroids, endometrial polyps, or pelvic inflammatory disease (secondary dysmenorrhoea).
Primary dysmenorrhoea usually starts 6–12 months after the menarche, once cycles are regular. Pain often starts shortly before the onset of menstruation, and lasts for up to 72 hours, improving as the menses progresses. Other gynaecological symptoms are not usually present although non-gynaecological symptoms may be (such as nausea, vomiting, and migraine). Pelvic examination is normal.
Secondary dysmenorrhoea often starts after several years of painless periods. Pain may persist after menstruation finishes; or may be present throughout the menstrual cycle, but exacerbated by menstruation. Other gynaecological symptoms are often present. Pelvic examination may be abnormal; however, the absence of abnormal findings does not exclude secondary dysmenorrhoea.
Dysmenorrhoea is the most common gynaecological symptom reported by women, affecting between 50% and 90% of menstruating women.
Red flag symptoms (which may indicate a serious underlying pathology) include:
Abnormal cervix on examination.
Persistent intermenstrual bleeding.
A palpable abdominal or pelvic mass on examination that is not obviously uterine fibroids nor of gastrointestinal or urological origin.
For primary dysmenorrhoea:
A nonsteroidal anti-inflammatory drug (such as ibuprofen, naproxen, or mefenamic acid) or paracetamol (with or without codeine) will usually provide pain relief in primary dysmenorrhoea.
Hormonal contraception is an alternative first-line treatment and has the additional advantage of providing contraception.
Local application of heat (e.g. a hot water bottle or heat patch) and transcutaneous electrical nerve stimulation (TENS) may also help to reduce pain.
Herbal and dietary supplements, acupuncture, exercise, spinal manipulation, and behavioural interventions are not recommended for the treatment of primary dysmenorrhoea.
Women with secondary dysmenorrhoea will need to be referred to a gynaecologist for further investigation.
A nonsteroidal anti-inflammatory drug (such as ibuprofen, naproxen, or mefenamic acid) or paracetamol (with or without codeine) will help relieve pain.
Have I got the right topic?
This CKS topic covers the management of dysmenorrhoea in primary care.
This CKS topic does not cover the management of chronic or non-cyclical pelvic pain, or premenstrual syndrome. It also does not cover in detail the management of secondary causes of dysmenorrhoea.
There are separate CKS topics on Endometriosis and Pelvic inflammatory disease.
The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary health care.
How up-to-date is this topic?
How up-to-date is this topic?
Changes
February 2013 — minor update. The 2013 QIPP options for local implementation have been added to this topic [NICE, 2013].
October 2012 — minor update. The 2012 QIPP options for local implementation have been added to this topic [NPC, 2012].
May 2011 — minor update. The 2010/2011 QIPP options for local implementation have been added to this topic [NPC, 2011]. Issued in June 2011.
October 2010 — minor update. From mid-October 2010, Nexplanon® will replace Impanon®. Nexplanon® is bioequivalent to Implanon®. The main differences are that Nexplanon® is radio-opaque, and the insertion technique is different [FSRH, 2010]. Issued in October 2010.
September 2010 — minor update. A prescription for Rigevidon®, another new ethinylestradiol plus levonorgestrel combined oral contraceptive pill, has been added. Issued in September 2010.
June 2010 — minor update. A prescription for Levest®, a new ethinylestradiol plus levonorgestrel combined oral contraceptive pill, has been added. Issued in June 2010.
March 2010 — minor update. Results of the updated Cochrane systematic review on nonsteroidal anti-inflammatory drugs for dysmenorrhoea have been updated in the Supporting evidence section. Issued in March 2010.
June 2009 — minor update. Correction to prescription title. Issued in June 2009.
December 2008 to March 2009 — converted from CKS guidance to CKS topic structure. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.
Progestogen-only contraceptives are now recommended as an alternative to combined oral contraceptives.
Previous changes
February 2009 — minor update. The upper age limit on the combined oral contraceptive pill prescriptions has been reduced to 50 years. Issued in March 2009.
October 2006 — minor update. Analgesia prescriptions updated because new doses of ibuprofen for children are recommend by the British National Formulary. Issued in October 2006.
October–December 2005 — reviewed. Validated in March 2006 and issued in May 2006.
This guidance has been reviewed and updated following a full literature review.There have been no major changes to the recommendations. A more detailed evidence section to support the recommendations has been included.
August 2002 — reviewed. Validated in December 2002 and issued in February 2003.
November 1999 — written. Validated in March 2000 and issued in May 2000.
Update
New evidence
Evidence-based guidelines
No new evidence-based guidelines since 1 November 2008.
HTAs (Health Technology Assessments)
No new HTAs since 1 November 2008.
Economic appraisals
No new economic appraisals relevant to England since 1 November 2008.
Systematic reviews and meta-analyses
Systematic reviews published since the last revision of this topic:
Brown, J., and Brown, S. (2010) Exercise for dysmenorrhoea (Cochrane Review). The Cochrane Library. Issue 2. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Cho, S.H., and Hwang, E.W. (2010) Acupressure for primary dysmenorrhoea: a systematic review. Complementary Therapies in Medicine 18(1), 49-56. [Abstract]
Cho, S.H., and Hwang, E.W. (2010) Acupuncture for primary dysmenorrhoea: a systematic review. BJOG 117(5), 509-521. [Abstract]
Chung, Y.C., Chen, H.H., and Yeh, M.L. (2010) Acupoint stimulation intervention for people with primary dysmenorrhea: systematic review and meta-analysis of randomized trials. Complementary Therapies in Medicine 20(5), 353-363. [Abstract]
Fedorowicz, Z., Nasser, M., Jagannath, V.A., et al. (2012) Beta2-adrenoceptor agonists for dysmenorrhoea (Cochrane Review). The Cochrane Library. Issue 5. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Marjoribanks, J., Proctor, M., Farquhar, C., and Derks, R.S. (2010) Nonsteroidal anti-inflammatory drugs for dysmenorrhoea (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Smith, C.A., Zhu, X., He, L., and Song, J. (2011) Acupuncture for primary dysmenorrhoea (Cochrane Review). The Cochrane Library. Issue 1. John Wiley & Sons, Ltd. www.thecochranelibrary.com [Free Full-text]
Primary evidence
Randomized controlled trials published since the last revision of this topic:
Ozgoli, G., Goli, M., Moattar, F. (2009) Comparison of effects of ginger, mefenamic acid, and ibuprofen on pain in women with primary dysmenorrhea. Journal of Alternative and and Complementary Medicine 15(2), 129-132. [Abstract]
An epidemiological study has been published since the last revision of this topic:
Lindh, I., Ellstrom, A.A. and Milsom, I. (2012) The effect of combined oral contraceptives and age on dysmenorrhoea: an epidemiological study. Human Reproduction 27(3), 676-682. [Abstract]
New policies
No new national policies or guidelines since 1 November 2008.
New safety alerts
No new safety alerts since 1 November 2008.
Changes in product availability
No changes in product availability since 1 November 2008.
Goals and outcome measures
Goals
Distinguish between primary and secondary dysmenorrhoea
Minimize the adverse impact of primary dysmenorrhoea on the woman's life
Refer appropriately to secondary care or other specialist service
Treat primary dysmenorrhoea appropriately in primary care
Provide advice to patients regarding non-drug treatment for primary dysmenorrhoea
QIPP — Options for local implementation
QIPP — Options for local implementation
Non-steroidal anti-inflammatory drugs (NSAIDs)
Review the appropriateness of NSAID prescribing widely and on a routine basis, especially in people who are at higher risk of both gastrointestinal (GI) and cardiovascular (CV) morbidity and mortality (e.g. older patients).
If initiating an NSAID is obligatory, use ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).
Review patients currently prescribed NSAIDs. If continued use is necessary, consider changing to ibuprofen (1200 mg per day or less) or naproxen (1000 mg per day or less).
Review and, where appropriate, revise prescribing of etoricoxib to ensure it is in line with MHRA advice and the NICE clinical guideline on osteoarthritis [CSM, 2005; NICE, 2008].
Co-prescribe a proton pump inhibitor (PPI) with NSAIDs for people with osteoarthritis, rheumatoid arthritis, or low back pain (for people over 45 years) in accordance with NICE guidance [NICE, 2008; NICE, 2009a; NICE, 2009b].
Take account of drug interactions when co-prescribing NSAIDs with other medicines (see Summaries of Product Characteristics). For example, co-prescribing NSAIDs with ACE inhibitors or angiotensin receptor blockers (ARBs) may pose particular risks to renal function; this combination should be especially carefully considered and regularly monitored if continued.
Background information
Definition
What is it?
Dysmenorrhoea is painful cramping, usually in the lower abdomen, occurring shortly before or during menstruation, or both.
Primary dysmenorrhoea occurs in the absence of any identifiable underlying pelvic pathology.
Secondary dysmenorrhoea is associated with underlying pelvic pathology (such as endometriosis, fibroids, or endometrial polyps).
[Society of Obstetricians and Gynaecologists of Canada, 2005; Proctor and Farquhar, 2006]
Prevalence
How common is it?
Dysmenorrhoea is the most common gynaecological symptom reported by women.
It affects between 50% and 90% of menstruating women. The wide variation in reported prevalence rates is probably due to differences in definition.
In a longitudinal survey of 404 nurses with primary dysmenorrhoea, mild symptoms were present in 53%, moderate symptoms in 20%, and severe symptoms in 2% [Weissman et al, 2004].
Despite the high prevalence of dysmenorrhoea and the impact it has on quality of life and general well-being, few women seek medical treatment for dysmenorrhoea.
[Society of Obstetricians and Gynaecologists of Canada, 2005; Proctor and Farquhar, 2006]
Impact
What is the impact on daily life?
Dysmenorrhoea can lead to absence from school or work; 13–51% of women report ever having been absent and 5–14% report being frequently absent because of dysmenorrhoea.
[Society of Obstetricians and Gynaecologists of Canada, 2005; Proctor and Farquhar, 2006]
Management
Management
Scenario: Dysmenorrhoea
Scenario: Dysmenorrhoea
Assessment
How should I assess a woman with painful periods?
Ask about:
Onset — was the initial onset of symptoms related to the menarche, or was it after several years of painless periods?
The timing of pain in relation to the menstrual cycle.
Non-gynaecological symptoms that may be associated with primary dysmenorrhoea (for example, nausea, vomiting, migraine, bloating, and emotional symptoms).
Other gynaecological symptoms (for example, dyspareunia, vaginal discharge, menorrhagia, intermenstrual bleeding, and postcoital bleeding) that may suggest underlying pathology.
Other non-gynaecological symptoms (for example, rectal pain and bleeding) that may suggest underlying pathology.
Establish the impact of dysmenorrhoea on the woman's life (for example, time off work, interference with daily activities).
Determine which treatments have already been tried, and their effectiveness.
Perform an abdominal examination in all women.
Perform a pelvic examination, unless the woman is an adolescent with a typical history of mild-to-moderate dysmenorrhoea who has never been sexually active.
Consider taking swabs if the woman is at risk of a sexually transmitted infection. See the CKS topic on Vaginal discharge.
Determine whether dysmenorrhoea is likely to be of primary or secondary origin:
Primary dysmenorrhoea:
Usually starts 6–12 months after the menarche, once cycles are regular.
Pain often starts shortly before the onset of menstruation, and lasts for up to 72 hours, improving as the menses progresses.
Other gynaecological symptoms are not usually present.
Non-gynaecological symptoms may be present.
Pelvic examination is normal.
Menstrual pain appears after several years of painless periods.
Pain may persist after menstruation finishes; or may be present throughout the menstrual cycle, but exacerbated by menstruation.
Other gynaecological symptoms are often present.
Rectal pain or bleeding may indicate recto-vaginal endometriosis.
Pelvic examination may be abnormal; however, the absence of abnormal findings does not exclude secondary dysmenorrhoea.
Refer urgently for further assessment if red flags are present including:
Abnormal cervix on examination.
Persistent intermenstrual bleeding.
A palpable abdominal or pelvic mass on examination that is not obviously uterine fibroids nor of gastrointestinal or urological origin.
Common causes of secondary dysmenorrhoea
Common causes of secondary dysmenorrhoea
Common causes of secondary dysmenorrhoea include:
Endometriosis — cyclical or chronic pelvic pain, that frequently occurs prior to menstruation and may be accompanied by heavy menstrual bleeding and deep dyspareunia.
Adenomyosis — painful menstruation, that may be accompanied by heavy menstrual bleeding.
Fibroids (myomas) — lower abdominal pain, frequently accompanied by menorrhagia; a pelvic mass may be identified on examination.
Endometrial polyps — more common in women older than 50 years of age. Abnormal vaginal bleeding may occur.
Pelvic inflammatory disease — lower abdominal pain and tenderness that may be accompanied by dyspareunia, abnormal vaginal bleeding, and abnormal vaginal discharge. In acute infection, fever may be present.
Intrauterine device (IUD) — a history of IUD insertion, usually 3–6 months previously. Pain may be accompanied by longer and heavier periods, often with bleeding or spotting in between periods.
[BASHH, 2005; Society of Obstetricians and Gynaecologists of Canada, 2005; Proctor and Farquhar, 2006]
Basis for recommendation
Basis for recommendation
Referral criteria for red flags are based on the National Institute for Health and Clinical Excellence guidelines, Referral for suspected cancer [NICE, 2005].
Features that can help distinguish between primary and secondary dysmenorrhoea have been summarized from a consensus guideline on primary dysmenorrhoea [Society of Obstetricians and Gynaecologists of Canada, 2005], and from several reviews of dysmenorrhoea [Rees, 2003; Proctor and Farquhar, 2006].
The recommendation to ask about rectal pain and bleeding is based on the opinion of an expert reviewer, and supported by a published review on endometriosis [Brosens, 1997].
The recommendation to perform a pelvic examination is based on a consensus guideline on primary dysmenorrhoea [Society of Obstetricians and Gynaecologists of Canada, 2005].
Primary dysmenorrhoea
How do I manage primary dysmenorrhoea?
Offer a nonsteroidal anti-inflammatory drug (NSAID) first line unless NSAIDs are contraindicated.
Ibuprofen, naproxen, and mefenamic acid are the NSAIDs of choice.
See the CKS topic on NSAIDs - prescribing issues for further information.
Offer paracetamol first line if NSAIDs are contraindicated or not tolerated, or in addition to an NSAID if the response is insufficient.
Codeine may be added to paracetamol or an NSAID if the response is insufficient.
If the woman does not wish to conceive, consider hormonal contraception as alternative first-line treatment.
Monophasic combined oral contraceptive (COC) preparations containing 30–35 micrograms of ethinylestradiol, and norethisterone, norgestimate, or levonorgestrel, are usually first choice.
Oral (Cerazette®), parenteral (Depo-Provera®, Nexplanon® [formerly Implanon®]), and intrauterine progestogen-only (Mirena®) contraceptives may also be considered, after a full discussion of the advantages and disadvantages.
See the CKS topics on Contraception - combined hormonal methods, Contraception - IUS/IUD and Contraception - progestogen-only methods for detailed information on prescribing hormonal contraceptives.
Combination of an NSAID (or paracetamol, with or without codeine) and hormonal contraception is an option for women who do not respond to a single treatment.
Refer the woman if her symptoms are severe and not responding to initial treatment, or if there is doubt about the diagnosis.
Non-drug measures that may help to reduce pain include:
Local application of heat (e.g. a hot water bottle or heat patch).
Transcutaneous electrical nerve stimulation (TENS).
There is insufficient evidence available to recommend herbal and dietary supplements, acupuncture, exercise, spinal manipulation, or behavioural interventions for the treatment of primary dysmenorrhoea.
Basis for recommendation
Basis for recommendation
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.
Secondary dysmenorrhoea
How do I manage secondary dysmenorrhoea?
Refer women with suspected secondary dysmenorrhoea to a gynaecologist for further investigation.
Whilst awaiting referral, offer a nonsteroidal anti-inflammatory drug (such as ibuprofen, naproxen, or mefenamic acid) or paracetamol (with or without codeine) for pain relief.
Basis for recommendation
Basis for recommendation
Recommendations regarding when to refer women with dysmenorrhoea are based on a consensus guideline on primary dysmenorrhoea [Society of Obstetricians and Gynaecologists of Canada, 2005] and expert opinion from the literature [Proctor and Farquhar, 2006].
Evidence
Evidence
Supporting evidence
NSAIDs
Evidence on NSAIDs
Evidence from two systematic reviews supports the use of standard nonsteroidal anti-inflammatory drugs (NSAIDs) for the management of primary dysmenorrhoea. There is insufficient evidence to indicate whether any one NSAID is more effective than another for the treatment of dysmenorrhoea. Low quality evidence suggests that the efficacy of cyclo-oxygenase-2 (COX-2) inhibitors is superior to placebo, and similar to that of NSAIDs. The COX-2 inhibitors rofecoxib and valdecoxib have since been withdrawn from the UK market because of cardiovascular concerns and potentially life-threatening skin reactions.
Standard nonsteroidal anti-inflammatory drugs (NSAIDs)
CKS found one Cochrane review of standard NSAIDs for primary dysmenorrhoea (search date: to May 2009) [Marjoribanks et al, 2010].
Data from 32 randomized controlled trials (RCTs) comparing NSAIDs with placebo were pooled. Pooled analysis found that NSAIDs were significantly better than placebo at producing moderate or excellent pain relief (odds ratio [OR] 4.50, 95% CI 3.85 to 5.27). However, there was substantial heterogeneity for this finding.
Two studies compared ibuprofen with paracetamol and one compared naproxen with paracetamol. Pooled data from these three studies found more women using NSAIDs reported good, excellent, or complete pain relief compared with women using paracetamol (OR 1.89, 95% CI 1.05 to 3.43).
There were 15 RCTs comparing one NSAID with another NSAID. Most of the comparisons were based on small trials, which were unsuitable for meta-analysis. However, the authors concluded that there was little evidence of the superiority of any individual NSAID with regard to either efficacy or safety.
CKS found an earlier systematic review of minor analgesics for primary dysmenorrhoea (including aspirin, naproxen, ibuprofen, and mefenamic acid; search date: to March 1997) [Zhang and Li Wan Po, 1998].
The systematic review identified 23 RCTs comparing naproxen with placebo, 17 RCTs comparing ibuprofen with placebo, and five RCTs comparing mefenamic acid with placebo.
The pooled response rate ratios for pain relief were:
In favour of naproxen, 3.17 (95% CI 2.72 to 3.65).
In favour of ibuprofen, 2.41 (95% CI 1.58 to 3.68).
In favour of mefenamic acid, 2.03 (95% CI 1.65 to 2.48).
Three women would have to be treated with naproxen (NNT 3) for one woman to experience pain relief, and two women would have to be treated with ibuprofen (NNT 2) or mefenamic acid (NNT 2) for one women to experience pain relief.
The systematic review identified eight RCTs (n = 486) comparing aspirin (usual dose 650 mg, four times a day) with placebo. Pooled data from the eight RCTs showed that:
Compared with placebo, aspirin significantly increased the proportion of women who experienced at least moderate pain relief (RR 1.60, 95% CI 1.12 to 2.29). Ten women would need to be treated with aspirin for one woman to experience at least moderate pain relief (NNT 10, 95% CI 5 to 50).
There was a high drop-out rate in the studies of aspirin (27% overall), which questions the reliability of the results.
There was no evidence of a significant difference in the incidence of adverse effects between the two groups (7–17% with aspirin compared with 3–17% with placebo; RR 1.3, 95% CI 0.79 to 2.17).
The systematic review included 12 RCTs comparing one NSAID with another NSAID. Most of the comparisons involved small single trials, and it is difficult to draw conclusions regarding comparative efficacy.
Pooled data from three RCTs did not show a significant difference in pain relief between naproxen and ibuprofen (RR 1.08, 95% CI 0.79 to 1.48).
Cyclo-oxygenase-2 (COX-2) inhibitors
CKS found one meta-analysis of single-dose rofecoxib for primary dysmenorrhoea [Edwards et al, 2004].
The meta-analysis used data from three industry-sponsored crossover RCTs comparing rofecoxib 25 mg or 50 mg with placebo or an active comparator; the comparator was ibuprofen 400 mg in one study and in naproxen 550 mg in two studies. Active or placebo drugs were randomly assigned over three consecutive menstrual cycles. Data from 231 women were included in the analysis.
Pain intensity was measured using a 4-point pain intensity scale (0, none; 1, mild; 2, moderate; 3, severe) and pain relief was measured using a 5-point pain relief scale (0, none; 1, a little; 2, some; 3, a lot; 4, complete). The time at which a woman requested a second dose of trial medication (or rescue analgesic), if required, was also recorded.
All active treatments were significantly more effective than placebo at 6, 8, and 12 hours. For all the active treatments the proportion of women with at least 50% pain relief was about 60% at all time points, and with placebo it was about 30% at all time points.
There were no significant differences in efficacy between the active treatments. After 12 hours the proportion of women who required additional medication was 28% of those receiving rofecoxib 25 mg, 27% receiving rofecoxib 50 mg, 29% receiving naproxen 550 mg, 41% receiving ibuprofen 400 mg, and 50% receiving placebo. Confidence intervals were not presented.
Few adverse effects were reported, and none were considered to be serious in any of the trials.
CKS found a technology appraisal (search date: to April 2005) of COX-2 inhibitors for the treatment of dysmenorrhoea [Alberta Heritage Foundation for Medical Research, 2005].
The technology appraisal identified three published studies that reported results from four RCTs. In one RCT 337 women were randomly assigned to receive meloxicam 7.5 mg, meloxicam 15 mg, or mefenamic acid 500 mg, and were followed up for three cycles. The other two studies were crossover studies in which a total of 256 women received both trial and comparator treatments in three consecutive cycles. The trial drugs were etoricoxib 120 mg, lumiracoxib 400 mg, and rofecoxib 50 mg; comparators were placebo or naproxen. All studies were industry-sponsored.
There were no significant differences in efficacy between the COX-2 inhibitors and standard NSAIDs in terms of pain relief. Both COX-2 inhibitors and standard NSAIDs were significantly more effective than placebo.
The authors reported good tolerance to COX-2 selective inhibitors with few, but no serious, adverse events. The most frequent adverse events noted were dyspepsia, diarrhoea, gastritis, and vomiting in the RCT that compared mefenamic acid (common adverse effects [AEs] in 20%) with meloxicam 7.5 mg (common AEs in 6%) and meloxicam 15 mg (common AEs in 7%); and headache and nausea in the RCT that compared treatment with naproxen (common AEs in 25%), placebo (common AEs in 15%), and etoricoxib (common AEs in 12%).
Three additional RCTs (in two publications) have subsequently been published investigating valdecoxib and lumiracoxib for the treatment of primary dysmenorrhoea [Daniels et al, 2005; Daniels et al, 2008].
These three double-blind crossover studies in a total of 397 women with primary dysmenorrhoea of moderate-to-severe intensity compared valdecoxib (20 mg or 40 mg twice a day) or lumiracoxib (200 mg once, or 200 mg when required) with placebo and naproxen.
The results confirmed that all active treatments were superior to placebo, and that there was no evidence of a significant difference in pain relief provided by the COX-2 inhibitor (valdecoxib or lumiracoxib) and naproxen.
All treatments were reported to be well tolerated.
Paracetamol
Evidence on paracetamol
The evidence on paracetamol is poor. One small 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. Despite the limited evidence, paracetamol is widely used by women who cannot take nonsteroidal anti-inflammatory drugs (NSAIDs).
CKS found one systematic review (search date: to March 1997) of minor analgesics, including paracetamol, for primary dysmenorrhoea [Zhang and Li Wan Po, 1998].
The systematic review identified one crossover randomized controlled trial (RCT) comparing paracetamol 500 mg four times a day with placebo and aspirin 500 mg four times a day in 35 women with dysmenorrhoea.
There was no evidence of a significant difference in pain relief between paracetamol and placebo: relative risk (RR) 1.0 (95% CI 0.28 to 3.63).
There was no evidence of a significant difference in pain relief between paracetamol and aspirin: median pain relief 1.6 (95% CI 0.4 to 3.3) with paracetamol compared with 1.2 (95% CI 0 to 2.7) with aspirin.
In addition, a Cochrane review included two further studies comparing paracetamol with an NSAID [Marjoribanks et al, 2003]; this evidence is reviewed in the section on NSAIDs.
Hormonal contraceptives
Evidence on hormonal contraceptives
Combined oral contraceptives
Evidence on combined oral contraceptives
A Cochrane review of combined oral contraceptives (COCs) for the treatment of primary dysmenorrhoea found insufficient evidence to prove that COCs are effective at relieving pain. However, 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 (RCT) 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.
CKS found one Cochrane review (search date: to December 1999) [Wong et al, 2001].
Nine RCTs were identified, but four were excluded (two trials for lack of randomization, and two trials because they included COCs that are now discontinued due to a very high oestrogen content). One further trial was excluded from the meta-analysis because of poor reporting of data.
Pooling the results of the four RCTs (n = 320) using a fixed-effects model found that medium-dose oestrogen COCs were more effective than placebo at relieving pain: odds ratio (OR) 2.01 (95% CI 1.22 to 3.33).
However, there was significant heterogeneity between the studies and when the data were analysed using a random effects model, no significant effect was found and the confidence interval was wide: OR 1.68 (95% CI 0.29 to 9.81).
Additional concerns are that 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.
Two RCTs of COCs as treatment for primary dysmenorrhoea have subsequently been published [Hendrix and Alexander, 2002; Davis et al, 2005].
A double-blind, placebo-controlled RCT (n = 77) investigated the effectiveness of a low-dose COC in the treatment of women with primary dysmenorrhoea for four consecutive 28-day cycles [Hendrix and Alexander, 2002]. However, the COC used was not typical of most COCs, providing a shortened pill-free interval (a 1-month pack consisted of 21 tablets of ethinylestradiol 20 micrograms and desogestrel 150 micrograms, two placebo tablets, and five tablets of ethinylestradiol 10 micrograms).
There was no significant difference in overall pain score between the COC group and the placebo group (mean change –0.5 compared with –0.2, p = 0.074).
Women taking COCs had less menstrual cramping than those taking placebo (mean change from baseline –1.4 compared with –0.3, p < 0.001).
A double-blind, placebo-controlled RCT (n = 76) investigated the effectiveness of a low-dose COC (containing oestrogen 20 micrograms) in adolescents with primary dysmenorrhoea [Davis et al, 2005]. Treatment was continued over 3 months. Pain was assessed using the Moos Menstrual Distress Questionnaire, which has been validated for use in adolescents. By the third menstrual cycle:
Pain score was significantly less in the COC group compared with the placebo group (3.1 versus 5.8; p = 0.004).
Further evidence supporting the use of COCs comes from an observational study of women with dysmenorrhoea (n = 346) that reported a decrease in pain-intensity score (from 6.8 to 1.8, p < 0.001) after use of a low-dose COC containing oestrogen 20 micrograms [Callejo et al, 2003].
Progestogen-only contraceptives
Evidence on progestogen-only contraceptives
Evidence from observational studies suggests that the progestogen-only pill, Cerazette®, and the levonorgestrel-releasing intrauterine system, Mirena®, may be effective at relieving pain associated with menstruation. Evidence from a review of open-label, non-comparative and comparative studies suggests that the etonogestrel subdermal implant, Implanon® (now replaced by Nexplanon®) may reduce both the incidence and severity of dysmenorrhoea.
Oral progestogen-only contraceptives (POPs)
CKS found one observational study of POPs for the treatment of dysmenorrhoea [Ahrendt et al, 2007].
In this study, 406 women with dysmenorrhoea who also required contraception took desogestrel 75 micrograms daily (Cerazette®) continuously for a period of three 28-day cycles.
By the end of the study (mean 3.5 cycles), the proportion of women with moderate or severe dysmenorrhoea decreased from 84.2% to 7.0%; dysmenorrhoea was absent (51%) or mild (39%) in most women. Overall, dysmenorrhoea was reported to have resolved or improved in 93% of women, and to have worsened in only one woman (0.2%).
No notable changes in mean body weight or blood pressure were reported during the study.
A total of 33 adverse events were reported by 28 (7%) women; 24 of these events were considered to be related to the Cerazette® (none serious). The most common adverse events were bleeding irregularities (menorrhagia [n = 8], non-cyclical bleeding [n = 6], amenorrhoea [n = 1], and oligomenorrhoea [n = 1]), or skin-related problems (acne [n = 5] and hypertrichosis [n = 1]).
Levonorgestrel-releasing intrauterine system
An observational study (n = 165) found that fewer women experienced menstrual pain after the use of the levonorgestrel-releasing intrauterine system (Mirena®) — 60% before use compared with 29% after 36 months of use (p = 0.025) [Baldaszti et al, 2003].
A Cochrane review (search date: January 2006) studied the post-operative use of the levonorgestrel-releasing intrauterine system (LNG-IUS) to see if it relieved pain due to endometriosis or reduced the recurrence rate compared with treatment with surgery alone, placebo, or systemic hormones [Abou-Setta et al, 2006].
One small open-label, parallel-group, prospective randomized controlled trial (RCT) was found comparing LNG-IUS with a gonadotrophin-releasing hormone agonist. This included 40 women aged 41 years of age and older who had had disabling pain for at least 6 months and who were undergoing laparoscopy.
There was a significant reduction in the recurrence of painful periods in the LNG-IUS group compared with the control group (OR 0.14, 95% CI 0.02 to 0.75).
Another systematic review (search date: to February 2005) found limited evidence to suggest that LNG-IUS may be beneficial in women with endometriosis [Varma et al, 2006]. The studies included women with early and late stage endometriosis, rectovaginal endometriosis, history of endometriosis, chronic pelvic pain, and women who had just had surgical treatment.
The review included two RCTs and three prospective observational studies; however, all studies had limited sample sizes (ranged from 11 to 39) and there was considerable heterogeneity between studies, which limits the strength and validity of the findings.
The results suggested that the LNG-IUS reduces pain associated with endometriosis, with symptom control lasting up to 3 years.
Etonogestrel subdermal implant (Implanon®/Nexplanon®)
In a review of 11 clinical trials (n = 923) looking at the effects of the etonogestrel subdermal implant, Implanon®, 22% of women became amenorrhoeic [Mansour et al, 2008]. At baseline, nearly half of the women reported having dysmenorrhoea, which was mild in 34% of women and severe in 15%. At the end of treatment (between 1 and 5 years) 77% of women with dysmenorrhoea reported that their symptoms had resolved and 6% reported a decrease in severity of symptoms. Dysmenorrhoea developed or became worse in 5.5% of women.
Note that Nexplanon® is bioequivalent to Implanon®. The main differences are that Nexplanon® is radio-opaque, and the insertion technique is different [FSRH, 2010].
Locally applied heat
Evidence on locally applied heat
Evidence from two randomized control trials (RCTs) suggests that locally applied heat is an effective treatment for dysmenorrhoea.
CKS found two RCTs that compared the local application of heat with standard analgesia (paracetamol or ibuprofen) for the treatment of dysmenorrhoea [Akin et al, 2001; Akin et al, 2004].
The first RCT (n = 84) compared the application of heat to the lower abdomen with oral ibuprofen and placebo [Akin et al, 2001]. Pain relief was measured by changes from baseline (reductions) in pain relief score (a six-point scale: no relief, 0; a little relief, 1; less than half relief, 2; more than half relief, 3; a lot of relief, 4; and complete relief, 5). Data were analysed per-protocol, with only 81 women completing the study, two of whom were excluded from analysis.
Women were randomized to one of four treatments: an unheated patch plus placebo tablets (n = 20), a heated patch plus placebo (n = 20), an unheated patch plus ibuprofen (n = 21), and a heated patch plus ibuprofen (n = 20).
During the 2 days of the study, the heated patch plus placebo group (mean pain relief score [PRS] 3.27, p < 0.001), the unheated patch plus ibuprofen group (mean PRS 3.07, p = 0.001), and the heated patch plus ibuprofen group (mean PRS 3.55, p < 0.001) had significantly greater pain relief than the unheated patch plus placebo group (mean PRS 1.95).
No difference in pain relief was found between women treated with a heated patch plus ibuprofen compared with those treated with an unheated patch and ibuprofen. However, the time to noticeable pain relief was shorter with the heated patch plus ibuprofen compared with the unheated patch plus ibuprofen (median time to pain relief 1.5 hours compared with 2.8 hours, p = 0.01).
A second RCT (n = 367) reported that an abdominal heat wrap (providing continuous, low level heat) was significantly more effective at relieving pain (p = 0.015) than paracetamol (1 g over 1 day) [Akin et al, 2004].
Transcutaneous electrical nerve stimulation
Evidence on transcutaneous electrical nerve stimulation (TENS)
Evidence from a Cochrane review including eight randomized controlled trials (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 nonsteroidal anti-inflammatory drugs (NSAIDs).
CKS found one Cochrane review (search date: to August 2001) investigating the effects of TENS in the treatment of primary dysmenorrhoea [Proctor et al, 2002].
Four RCTs compared high-frequency TENS with placebo TENS for the relief of pain. Overall results showed that high frequency TENS was more effective than placebo:
Two trials (n = 53) reporting dichotomous data found that high-frequency TENS was more beneficial than placebo TENS (odds ratio [OR] 7.2, 95% CI 3.1 to 16.5).
A third trial (n = 9) using a 100-point visual analogue scale reported in favour of high frequency TENS (difference in scores 45 points, 95% CI 22.5 to 67.5).
The fourth trial (n = 12) could not be included in the meta-analysis as the authors reported only descriptive data. There was no difference in pain between high-frequency TENS and placebo TENS.
Four RCTs compared low-frequency TENS with placebo TENS and two studies compared low-frequency TENS with a placebo tablet for the relief of pain. Overall results suggested no significant difference between low-frequency TENS and placebo:
Two trials (n = 29) reported pain relief as a dichotomous variable and found no difference between low-frequency TENS and placebo TENS (OR 1.3, 95% CI 0.4 to 4.1).
One trial (n = 9) measured pain relief on a visual analogue scale and found no difference between low-frequency TENS and placebo TENS (weighted mean difference [WMD] 24.1, 95% CI –2.9 to +51.1).
One trial (n = 21) found no difference between low-frequency TENS and placebo tablet (OR 2.9, 95% CI 0.4 to 24.4).
The remaining two trials reported descriptive data; one trial (n = 24) found that low-frequency TENS was more effective than placebo TENS (p < 0.05), and the other trial (n = 20) found that low-frequency TENS was more effective at reducing pain than placebo tablet (p < 0.05).
Three RCTs compared high-frequency TENS with low frequency TENS:
One trial (n = 21) reported pain relief as dichotomous data and found that high-frequency TENS was more effective than low-frequency TENS (OR 3.9, 95% CI 1.1 to 13.0).
One trial (n = 9) reported pain relief on a visual analogue scale and found no evidence of a difference between high-frequency TENS and low-frequency TENS (WMD 20.9, 95% CI –4.4 to +46.1), but reported a trend towards high-frequency TENS achieving more pain relief.
The third trial (n = 24) reported descriptive data using a visual analogue scale and found a trend towards low-frequency TENS being more effective at reducing pain.
Two RCTs compared TENS with NSAIDs.
One trial (n = 32) found that ibuprofen (400 mg four times daily) was significantly better at reducing pain than high-frequency TENS (OR 0.3, 95% CI 0.1 to 0.8).
A second trial (n = 12), not included in the meta-analysis as the authors reported descriptive data, found no difference between naproxen (500 mg once daily) and high-frequency TENS.
In an RCT published since the Cochrane review, high-frequency TENS was compared with interferential current (IFC, a non-pharmacological, noninvasive method of pain-relief known to reduce pain and oedema in musculoskeletal problems) [Tugay et al, 2007]. A total of 34 women were randomized to receive either TENS or IFC for 20 minutes when they were experiencing dysmenorrhoea.
Intensity of menstrual pain (measured on a visual analogue scale) decreased by approximately 50% in each group (p < 0.05). There was no evidence of a difference between the two groups.
One further crossover study investigated the use of a new portable high-frequency TENS device (OVA®) [Schiotz et al, 2007]. The study duration was four consecutive menstrual cycles, with the women (n = 21) using the TENS device during every other cycle, with the remaining cycles acting as controls. The study was not blinded and the order of assigning women to TENS or control was not randomized. Pain was measured on a 10-point visual analogue scale (0, no pain; 10, worst possible pain); the mean score for pre-study dysmenorrhoea was 6.9.
A significant reduction in pain score was reported during the months when the women used the TENS device (p = 0.0009). However, the clinical significance of the reduction is questionable (control cycle mean pain score 6.7 [range 2.5 to 10], TENS cycle mean pain score 5.2 [range 0 to 8.6]).
Herbal and dietary supplements
Evidence on herbal and dietary supplements
The evidence on herbal and dietary supplements is limited by poor quality studies and small sample sizes. There is limited evidence from one randomized controlled trial (RCT) 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. Studies of fish oils and the Japanese herbal remedy toki-shakuyaku-san are too small to draw meaningful conclusions.
A Cochrane review (search date: to October 2000) examined the efficacy and safety of herbal and dietary therapies when compared with each other, placebo, no treatment, or other conventional treatments (such as nonsteroidal anti-inflammatory drugs) in the treatment of primary or secondary dysmenorrhoea [Proctor and Murphy, 2001]. The studies identified were generally small and of poor quality.
Vitamin B1 (thiamine): one crossover trial (n = 556) in India compared vitamin B1 100 mg daily for 3 months with placebo for 2 months in young women with moderate-to-very-severe pain. The proportion of women who gained pain relief with vitamin B1 was significantly greater than with placebo (142/277 [51%] compared with 0/279 [0%]; odds ratio [OR] 14.7, 95% CI 10.1 to 21.6). As the diet of the population studied may be different to that of women in the UK it is difficult to extrapolate the results of this trial to the UK.
Magnesium was compared with placebo in three RCTs (n = 96). Data from these studies were not pooled because of heterogeneity in study outcomes. Overall, magnesium was more effective than placebo for pain relief, and the need for additional pain relief was less. However, the disparity in dosing regimens and a high drop out rate makes it difficult to draw conclusions from the results.
Vitamin B6 (pyridoxine) alone (200 mg/day; n = 10) was compared with magnesium alone (500 mg/day; n = 13), placebo (n = 11), and a combination of magnesium and vitamin B6 (n = 12) in one small study. Vitamin B6 alone was more effective at relieving pain and reducing the use of additional medication than either placebo or a combination of magnesium and vitamin B6. No differences were noted between vitamin B6 alone and magnesium alone.
Daily vitamin E combined with ibuprofen taken during menses was compared with ibuprofen alone taken during the menses in 50 women. After 1 month of treatment there was no evidence of a significant difference between the two groups in the proportion of women experiencing pain relief (23/26 [88%] compared with 17/24 [71%]; OR 2.9, 95% CI 0.8 to 11.6).
Fish oil (omega-3 fatty acids) was compared with placebo in 42 women in a crossover trial. The use of additional pain relief appeared to be significantly lower in the treatment group (weighted mean difference –5.4 tablets, 95% CI –6.6 to –4.2, p < 0.001). However these figures refer to the average of the two groups after the allocated treatments were crossed over, and follow up was only for 2 months. There were significantly more adverse effects (e.g. nausea, exacerbation of acne) in the fish oil group (OR 8.65, 95% CI 1.1 to 66.3).
Herbal remedies: one RCT (n = 40) found limited evidence that toki-shakuyaku-san reduced pain after 2 months of treatment (and this difference was maintained after a further 2 months on no treatment) and reduced the need for additional medication. However, there is no information about adverse effects. There were no RCTs identified regarding other herbal remedies.
In addition to the Cochrane review, CKS found four further RCTs.
Fish oils:
Significant improvement in abdominal pain was reported (n = 70) with Neptune Krill Oil® after 45 and 90 days compared with baseline, and control (omega-3 fish oil) [Sampalis et al, 2003]. Neptune Krill Oil® is a natural health product extracted from Antarctic krill and is rich in phospholipids and triglycerides carrying long-chain omega-3 polyunsaturated fatty acids, and antioxidants (vitamins A and E).
One RCT (n = 78) randomized participants into four groups: fish oil with vitamin B12, fish oil, seal oil, and placebo [Deutch et al, 2000]. Pain only decreased significantly in the fish oil with vitamin B12 arm although all active treatment groups experienced a significant change in other menstrual symptoms.
Vitamin E:
One RCT (n = 278) found that although both the placebo and the vitamin E (400 units) group showed significant reductions in pain score and pain duration, this was greater for the vitamin E group [Ziaei et al, 2005]. The participants were also allowed to take ibuprofen (200 mg 8-hourly) in addition to the allocated treatment.
Fennel:
One RCT (n = 120) compared the effectiveness of fennel extract and mefenamic acid in high school girls (mean age: 13 years) with primary dysmenorrhoea [Modaress and Asadipour, 2006]. After 2 months there was no significant difference between the two groups in the proportion of girls experiencing total pain relief (80% compared with 73%).
Chinese herbal medicine
A Cochrane review (search date: to January 2007) included 39 RCTs comparing Chinese herbal medicine with placebo, no treatment, conventional treatment, heat therapy, or acupuncture. A number of these were of small sample size and poor methodological quality [Zhu et al, 2008].
The review found that Chinese herbal medicine resulted in significant improvements in pain relief compared with conventional treatment (nonsteroidal anti-inflammatory drugs or oral contraceptives), acupuncture, or heat therapy. Results for Chinese herbal medicines compared with placebo are unclear as data could not be combined.
The authors concluded that the results are limited by the poor methodological quality of the included trials.
Other treatments
Evidence on 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.
Acupuncture
A Cochrane review (search date: to August 2001) included one randomized controlled trial (RCT) comparing acupuncture with sham acupuncture [Proctor et al, 2002]. Although pain relief was significantly greater in the acupuncture group, the authors concluded that there was insufficient evidence to determine the effectiveness of acupuncture in reducing dysmenorrhoea.
A more recent systematic review (search date: to 2008) included 32 trials (30 of which were randomized) evaluating the effects of acupuncture-related therapies for treating primary dysmenorrhea [Yang et al, 2008].
Most of the trials were of low methodologic quality.
Meta-analysis was not possible because of the heterogeneity of the trials.
Analysis indicated that there were conflicting results regarding whether acupuncture-related therapies were more effective than controls.
The authors concluded that, because of low methodologic quality and small sample size, there is no convincing evidence for acupuncture in the treatment of primary dysmenorrhoea.
Spinal manipulation
A Cochrane review (search date: to April 2006) included five RCTs examining the efficacy and safety of spinal manipulation for primary and secondary dysmenorrhoea [Proctor et al, 2006].
Results from four of the trials using high velocity, low amplitude (HVLA) manipulation suggest that HVLA is no more effective than sham manipulation for the treatment of dysmenorrhoea. There was no difference in adverse effects between the two groups.
In one trial the Toftness technique was shown to be more effective than sham treatment, however methodological limitations of this trial, including small sample size, prevent any meaningful conclusions being drawn.
The authors concluded that there is no evidence to suggest that spinal manipulation is effective in the treatment of primary or secondary dysmenorrhoea.
Behavioural Therapy
A Cochrane review (search date: to April 2005) included five RCTs comparing behavioural interventions with placebo or other interventions in women with dysmenorrhoea [Proctor et al, 2007]. Behavioural interventions included relaxation training, imagery, coping skills, biofeedback, and pain management training.
Although results from the five RCTs provides some evidence to suggest that behavioural therapies may be effective, the heterogeneity of the interventions and the poor quality of the studies makes it difficult to make any recommendations.
Exercise
A review of four RCTs and two observational studies, found that exercise was associated with a reduction in dysmenorrhea [Golomb et al, 1998]. A more recent study found that women who exercise more than three times per week reported fewer physical symptoms during menstruation than women who had a more sedentary lifestyle [Choi and Salmon, 1995].
Numerous methodological flaws in these studies make it difficult to draw definitive conclusions regarding the role of exercise as a treatment option for dysmenorrhoea.
Search strategy
Scope of search
A literature search was conducted for guidelines, systematic reviews and randomized controlled trials on the primary care management of dysmenorrhoea.
Search dates
January 2005 – November 2008
Key search terms
Various combinations of searches were carried out. The terms listed below are the core search terms that were used for Medline and these were adapted for other databases. Further details are available on request.
exp dysmenorrhea/, dysmenorrhea$.tw, dysmenorrhoea$.tw
Table 1. Key to search terms.| Search commands | Explanation |
|---|---|
| / | indicates a MeSH subject heading with all subheadings selected |
| .tw | indicates a search for a term in the title or abstract |
| exp | indicates that the MeSH subject heading was exploded to include the narrower, more specific terms beneath it in the MeSH tree |
| $ | indicates that the search term was truncated (e.g. wart$ searches for wart and warts) |
Sources of guidelines
National Institute for Health and Clinical Excellence (NICE)
Scottish Intercollegiate Guidelines Network (SIGN)
National Guidelines Clearinghouse
British Columbia Medical Association
Institute for Clinical Systems Improvement
Guidelines International Network
National Library of Guidelines
National Health and Medical Research Council (Australia)
University of Michigan Medical School
Michigan Quality Improvement Consortium
National Resource for Infection Control
NHS Scotland National Patient Pathways
Agency for Healthcare Research and Quality
UK Ambulance Service Clinical Practice Guidelines
RefHELP NHS Lothian Referral Guidelines
Medline (with guideline filter)
Sources of systematic reviews and meta-analyses
Systematic reviews
Protocols
Database of Abstracts of Reviews of Effects
Medline (with systematic review filter)
EMBASE (with systematic review filter)
Sources of health technology assessments and economic appraisals
NIHR Health Technology Assessment programme
NHS Economic Evaluations
Health Technology Assessments
Canadian Agency for Drugs and Technologies in Health
International Network of Agencies for Health Technology Assessment
Sources of randomized controlled trials
Central Register of Controlled Trials
Medline (with randomized controlled trial filter)
EMBASE (with randomized controlled trial filter)
Sources of evidence based reviews and evidence summaries
DynaMed
Central Services Agency COMPASS Therapeutic Notes
Sources of national policy
Health Management Information Consortium (HMIC)
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