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Review2010;12:149–15410.1576/toag.12.3.149.27596 http://onlinetog.orgThe Obstetrician & Gynaecologist

© 2010 Royal College of Obstetricians and Gynaecologists

Review DysmenorrhoeaAuthors Suzanne Wallace / Amy Keightley / Clive Gie

Key content:• Dysmenorrhoea is a common condition of women in their reproductive years.• Local factors and the centralised response to pain are thought to be involved

in the pathophysiology.• The majority of women will respond to medical treatments.• The role of surgical treatments is small.• More evidence is now available on the use of complementary therapies to treat

dysmenorrhoea.

Learning objectives:• To understand the theories regarding the aetiology of dysmenorrhoea.• To update knowledge of evidenced-based treatments for dysmenorrhoea.

Ethical issues:• Is there a role for surgical treatments to interrupt nerve pathways in the

treatment of dysmenorrhoea?• Would women who fail to respond to medical treatments for dysmenorrhoea be

best treated by chronic pain teams?

Keywords combined oral contraceptive pill / menstruation / nonsteroidal anti-inflammatory drugs / presacral neurectomy / prostaglandins /uterosacral nerve ablation

Please cite this article as: Wallace S, Keightley A, Gie C. Dysmenorrhoea. The Obstetrician & Gynaecologist 2010;12:149–154.

Author details

Suzanne Wallace MA MRCOG

Specialist Registrar

Nottingham University Hospitals NHS Trust,

Derby Road, Nottingham NG7 2UH, UK

Amy Keightley BM BS BMedSci

Specialty Trainee Year 2

Derby Hospitals NHS Foundation Trust,

Royal Derby Hospital, Uttoxeter Road,

Derby DE22 3NE, UK

Clive Gie FRCOG FCOG (SA) DCH (SA)

Consultant Gynaecologist

Department of Obstetrics and Gynaecology,

Sherwood Forest Hospitals NHS Foundation

Trust, Sutton-in-Ashfield, UK

Email: [email protected]

(corresponding author)

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Review 2010;12:149–154 The Obstetrician & Gynaecologist

© 2010 Royal College of Obstetricians and Gynaecologists150

IntroductionDysmenorrhoea is one of the most commongynaecological conditions that affect the quality of life of many women in their reproductive years. This article explores current ideas on themanagement of dysmenorrhoea and considerscauses, appropriate investigations and treatments.In particular, it looks at the trend away fromtherapies solely targeted at the pelvis towards amore holistic approach to pain management.

DefinitionThe term dysmenorrhoea is derived from theGreek words dys, meaning difficult/painful/abnormal; meno, month; and rrhea, to flow.Dysmenorrhoea can occur a few days prior tomenstruation as well as during menstruation but normally subsides as menstruation finishes.Primary dysmenorrhoea occurs in the absence of any underlying uterine condition whereassecondary dysmenorrhoea occurs where pelvicpathology is present.

EpidemiologyPrevalence rates of dysmenorrhoea are thought to be high, although estimates vary widely in theliterature. A systematic review1 of dysmenorrhoeain the UK population more than 10 years agofound prevalence rates of 41–97%, with 11–14% of cases described as severe. However, the studiesidentified by that review were generally small andstudy populations differed widely in age andbaseline characteristics.

A Swedish cross-sectional study2 of nearly 600 women aged 19 years reporteddysmenorrhoea in 72%, of whom 15% haddysmenorrhoea that was not responsive toanalgesics and which limited their activities.This study further identified that more than50% of these women had been absent fromwork or school on at least one occasion due todysmenorrhoea and that 7.9% were absent everymenstruation for at least half a day. At 5-yearfollow-up, rates of dysmenorrhoea had fallen to67% with 10% having dysmenorrhoea that wasnot responsive to analgesics and which limitedtheir activities.3 This was a significant fall butstill shows that many women continue to sufferwith dysmenorrhoea beyond their teenageyears.

Risk factors for dysmenorrhoea include earlymenarche, nulliparity and family history.2,3

Women with a longer duration of menstruationand heavier menstrual flow were significantlymore likely to have dysmenorrhoea but therewas no association with cycle length. Themajority of studies have shown cigarettesmoking to be positively correlated withdysmenorrhoea.3,4

Pathophysiology of primarydysmenorrhoeaThis appears to be multifactorial. Towards the endof the menstrual cycle, progesterone withdrawalupregulates various inflammatory cytokines,prostaglandins, vascular endothelial growth factorand several matrix metalloproteinases (MMPs).These MMPs act to degrade, leading to loss ofintegrity of blood vessels, destruction ofendometrial interstitial matrix and the resultantbleeding characteristic of menstruation. Theoriesof the aetiology of dysmenorrhoea look at howthese normal pathways have the potential to causepain. There are several theories and it is likely thatan individual may have varying contributionsfrom a combination of these mechanisms. Thesecan be split into three main categories: uterinecontraction and vasoconstriction; modulationand stimulation of pain fibres; and behaviouraland psychological factors.

Uterine contraction and vasoconstrictionThe uterine contraction and vasoconstrictiontheory currently has the strongest scientific basis.Disintegrating endometrial cells releaseprostaglandin F2�, a myometrial stimulant andvasoconstrictor. This mediates prolonged uterinecontractions and reduced blood flow, which ispostulated to cause pain.5 Women experiencingprimary dysmenorrhoea have an abnormal patternof contraction with a higher basal resting tone.Peak uterine work correlates with the greatestamount of pain.6 Elevated prostaglandin levels arefound in the endometrial fluid of women withdysmenorrhoea and correlate with the degree ofpain.7 Other factors implicated in the aetiology ofdysmenorrhoea include leukotrienes, vasopressinand a reduction in prostacyclin levels. Leukotrienesincrease myometrial stimulation andvasoconstriction; women who fail to respond toprostaglandin inhibitors have been shown tohave elevated levels of leukotrienes.8 Vasopressinappears either to have a direct influence onmyometrial blood flow and myometrialhypersensitivity, or to exert actions viaprostaglandin release.9 Prostacyclin is a potentvasodilator and myometrial relaxant in vivo, thusreduced levels may lead to hypoxia, ischaemia andpain.10

Modulation and stimulation of pain fibresThe stimulation of pain fibres in the uteruscauses activation of the afferent pain pathwaystransmitted up to the central nervous system.In addition, there is some evidence of a directeffect on the pain fibres themselves in cases ofdysmenorrhoea. This theory is based on thepotential effect of ischaemia on pain fibres.Vasoconstriction leads to ischaemia and it isthought that type C pain neurons are stimulatedby the anaerobic metabolites generated by an

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ischaemic endometrium.11 It has also beensuggested that leukotrienes can increase thesensitivity of pain fibres.12

The multimodal response to painThe impact of psychological and behaviouralmodification on dysmenorrhoea is yet to be fullyunderstood.

Pain is defined by the International Associationfor the Study of Pain as ‘an unpleasant sensory andemotional experience associated with actual orpotential tissue damage.’13 Understanding theimpact of pain must, therefore, acknowledge boththe stimulation of sensory receptors by a harmfulstimulus and other factors acting centrally andcontributing to pain perception.

There is a general consensus that primarydysmenorrhoea often coexists with other painconditions, such as dyspareunia, irritable bowelsyndrome and fibromyalgia. Research is beingundertaken to investigate the degree of thisoverlap. It may be partly due to the difficulty inobjective assessment of the symptoms and thechallenge in diagnosing some of the chronic painconditions, as many of these conditions arediagnoses of exclusion.14

Primary dysmenorrhoea, as with chronic pelvicpain, seems to be more prevalent in those with ahistory of sexual abuse.15,16 However, comparedwith other pelvic pain syndromes, there is limitedresearch into the impact of psychosocial factors ondysmenorrhoea.

Pathophysiology of secondarydysmenorrhoeaThere are a number of clinical conditions withunderlying pelvic pathology which can lead tosecondary dysmenorrhoea (see Box 1). Many of theways in which each specific pathology causes painoverlap with the mechanisms found in primarydysmenorrhoea. This may explain why theyrespond, in part, to treatment strategies used in primary dysmenorrhoea.

The most common cause of secondarydysmenorrhoea is endometriosis. Many trialshave failed to show a correlation between diseaseseverity and the severity of pain; the exactmechanism as to how ectopic endometrial tissuecauses pain has not been established. However,some studies have suggested increased levels ofprostaglandin (including prostaglandin F2�) in women with endometriosis.17

Another common cause of secondarydysmenorrhoea is chronic pelvic inflammatorydisease. Pain may be caused by the release ofinflammatory mediators, prostaglandins, scar

tissue formation and abnormal uterinecontraction.

Adenomyosis is thought to cause secondarydysmenorrhoea by causing tonic uterinecontractions through endometrial glanddestruction. Intrauterine polyps, submucosalfibroids and intrauterine contraceptive devicescan also cause dysmenorrhoea by abnormaluterine contraction in the attempt to expel them.

Less common causes of secondary dysmenorrhoeainclude Allen-Masters syndrome (scarringsecondary to laceration of the broad ligaments,usually during childbirth), congenital uterineabnormalities, cervical stenosis, Ashermansyndrome, uterine retroversion and pelviccongestion syndrome. Theories of pain causationin all of these conditions relate to the productionof abnormal uterine contractions.

Ovarian cysts and tumours are associated withdysmenorrhoea but the mechanism by which thisoccurs is not clear.

Clinical presentationPrimary dysmenorrhoea typically presents 6–12 months after menarche. Pain is usuallycramping in nature and occurs in the lowerabdomen or pelvis but may radiate to the back ordown the thighs. It may commence before the onsetof bleeding and usually lasts 8–72 hours. Associatedsymptoms include nausea and vomiting, fatigueand headache.

By contrast, secondary dysmenorrhoea usuallyoccurs a number of years after the menarche andpain may occur throughout the luteal phase of themenstrual cycle as well as during menstruation.Deep dyspareunia may also be present.

Symptoms of bowel disturbance should besought to identify cases of irritable bowelsyndrome and enquiry should be made as to the coexistence of other pain conditions.Examination findings are usually normal incases of primary dysmenorrhoea, whereas insecondary dysmenorrhoea examination findingsmay be abnormal, reflecting the underlyingdisease.

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Box 1

Causes of secondary

dysmenorrhoea

Common Less common

• Endometriosis • Allen-Masters syndrome

• Chronic pelvic • Congenital uterine

inflammatory disease abnormalities

• Adenomyosis • Cervical stenosis

• Intrauterine polyps • Asherman syndrome

• Submucosal fibroids • Uterine retroversion

• Intrauterine contraceptive • Pelvic congestion

devices syndrome

• Ovarian cysts


InvestigationsWhere the history and examination findings aresuggestive of primary dysmenorrhoea, furtherinvestigations are rarely warranted. However,if there are atypical symptoms, abnormalexamination findings, or if a trial of therapy insuspected primary dysmenorrhoea is unsuccessful,then pelvic ultrasound and laparoscopy should beconsidered. The role of laparoscopy is still debated;one study reported that 35% of laparoscopies forpelvic pain or suspected secondarydysmenorrhoea were negative.18

TreatmentTreatments for primary dysmenorrhoea (see Box 2)are predominantly based on the three main theoriesof aetiology. In secondary dysmenorrhoea, anytreatment strategy should be based on treatment of the underlying disease, although some of thetreatment strategies employed for primarydysmenorrhoea may also have some benefit even with organic pathology.

A preferred approach is to individualise therapybased on a woman’s concomitant symptoms (for example, menorrhagia), age and need forcontraception.

Targeting uterine contraction andvasoconstrictionThe mainstays of treatment for dysmenorrhoeahave been nonsteroidal anti-inflammatory drugs(NSAIDs) and the combined oral contraceptivepill. Nonsteroidal anti-inflammatory drugs act by blocking prostaglandin production and so potentially may target the high levels of prostaglandins found in women withdysmenorrhoea. A Cochrane review19 found thatNSAIDs were significantly more effective for painrelief than placebo (OR 7.91; 95% CI 5.65–11.09)but with a significant risk of adverse effects, inparticular gastric reflux. There is no evidence tosuggest a greater benefit of any specific NSAID.

The oral contraceptive pill has long been held tobe a successful treatment for dysmenorrhoea,based on epidemiological studies showing lowerrates of dysmenorrhoea in women on thecombined oral contraceptive pill.2,3 The presumedmode of action is a combination of ovulationinhibition and reduced prostaglandin productionby endometrial glands. However, a recentCochrane review20 concluded that there is limitedevidence for improvement in symptoms ofdysmenorrhoea with the oral contraceptive pillmainly because of a lack of well-conductedstudies. Nevertheless, there was some evidencethat low and medium-dose estrogen pills may bemore effective than placebo. There were norandomised controlled trials comparing the oralcontraceptive pill with NSAIDs. The oralcontraceptive pill has the added benefit ofcontraception if required, although the adverseeffects, from weight gain through to venousthromboembolism and cardiovascular effects, arewell described.

The levonorgestrel-releasing intrauterine systemis increasingly being used for both contraceptionand as a treatment for menstrual disorders. Itachieves a contraceptive effect through a variety of mechanisms but effects on menstruation arethought to be due to resultant atrophy ofendometrial glands. Whilst there are no good-quality studies looking specifically at the effect of the intrauterine system on dysmenorrhoea,reductions in dysmenorrhoea have been reportedas secondary outcomes in other trials.21 It has alsobeen shown to be effective in the treatment ofsecondary dysmenorrhoea associated withendometriosis and adenomyosis.21,22 Theintrauterine system can be used in women inwhom estrogen is contraindicated and is welltolerated.21

Other medical treatments that have been suggestedto reduce uterine contractility through their effectson relaxing the myometrium include calciumchannel blockers and glyceryl trinitrate, but theseare still under evaluation.8

Although many women do respond to medicaltherapy there is an overall failure rate of 20–25%.23

Targeting pain pathwaysThe persistence of dysmenorrhoea despitemedical management has led to increased interestin surgical interruption of visceral pain pathwaysin women for whom medical therapy has failed.Two main surgical techniques have been described:uterosacral nerve ablation and presacralneurectomy. In the former, the uterosacralligaments are transected, causing interruption tothe visceral afferent nerves from the pelvis; in thelatter the presacral plexus of visceral nerves isremoved. Both procedures can be carried out

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Box 2

Treatments for primary

dysmenorrhoea

Medical

Nonsteroidal anti-inflammatory drugs

Combined oral contraceptive pill

Levonorgestrel-releasing intrauterine system

Surgical

Uterosacral nerve ablation (can be carried out

laparoscopically)

Presacral neurectomy (can be carried out laparoscopically)

Complementary therapies

High frequency transcutaneous electrical nerve stimulation

(TENS)

Dietary therapy; for example, vitamin B1 and magnesium

Acupuncture

Chinese herbal medicine

Behavioural therapies, including relaxation training, biofeedback

techniques and pain management sessions


laparoscopically. Presacral neurectomy inparticular requires a high level of laparoscopicskill. A Cochrane review23 found only limitedevidence to support this approach, concluding thatuterosacral nerve ablation was not associated withany improvement of pain in the short term,although there was some evidence of improvementin pain in the long term (more than 12 monthspost-procedure). The results were slightlyimproved with presacral neurectomy but this wasat the expense of more frequent adverse effects,including constipation, urinary urgency andpainless labour.

A recent large UK randomised controlled trial oflaparoscopic uterosacral nerve ablation (LUNA)in women with chronic pelvic pain includingdysmenorrhoea showed no significant differencein pain scores when denervation was carried out.Follow-up reached 5 years in 72% ofparticipants.24 Given these findings, it appears thatthere is no longer a role for LUNA in themanagement of dysmenorrhoea.

The multimodal approach to pain managementInterest in managing dysmenorrhoea is nowturning towards a more holistic approach, in linewith other chronic pain conditions. Highfrequency transcutaneous electrical nervestimulation (TENS) has been used in other painconditions and has been shown to be effective intreating dysmenorrhoea in a small number oftrials, with 42–60% of women having at leastmoderate relief.25 There is also some evidence thatdietary therapy may be of benefit, in particularvitamin B1 (taken at a dose of 100 mg daily) andmagnesium.26 There is some evidence for the useof acupuncture and Chinese herbal medicine buttrials are often small.25,27 A recent Cochranereview28 looked at behavioural therapies, includingrelaxation training, biofeedback techniques andpain management sessions, with some evidence ofefficacy, although, again, trials were small and ofvariable methodological quality. However, not allcomplementary therapies evaluated have showneffectiveness; for example, meta-analysis hasshown no evidence for the role of spinalmanipulation in treating dysmenorrhoea.29

Other therapiesHistorically, surgical treatments fordysmenorrhoea have included cervical dilatationand ventrosuspension; however, their role inmanagement has been discredited and they arenow rarely used.30 Hysterectomy continues to beused occasionally as a treatment for refractorydysmenorrhoea. The evidence base for this islimited, although in our experience hysterectomymay be warranted in women with severesymptoms where other therapies have failed, whohave coexisting symptoms such as menorrhagia,

who have completed their family, and who are fullycounselled about the short and long-term risks ofthe procedure.

ConclusionDysmenorrhoea is a common condition affectingyoung women. As with other pain conditions, theaetiology appears to be multifactorial and involvesinflammatory mediators, pain pathways and acentralised response. Many women will obtainrelief from a combined individualised approach totreatment, reflecting the likely multiple underlyingmechanisms.

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