Dysmenorrhoea

Abstract

Introduction

Dysmenorrhoea may begin soon after the menarche, after which it often improves with age; or it may originate later in life, after the onset of an underlying causative condition. Dysmenorrhoea is common, and in up to 20% of women it may be severe enough to interfere with daily activities.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical question: What are the effects of pharmacological treatments for primary dysmenorrhoea? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2013 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found eight studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review, we present information relating to the effectiveness and safety of the following interventions: contraceptives (combined oral), non-steroidal anti-inflammatory drugs (NSAIDs), progestogens (intrauterine), and simple analgesics (aspirin, paracetamol) .

Key Points

Dysmenorrhoea may begin soon after the menarche, where it often improves with age; or it may originate later in life, after the onset of an underlying causative condition.

Dysmenorrhoea is very common, and in up to 20% of women it may be severe enough to interfere with daily activities.

This review has searched for evidence on pharmacological interventions for primary dysmenorrhoea.

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce moderate to severe pain in women with primary dysmenorrhoea compared with placebo, but we don't know whether any one NSAID is superior to the others.

For simple analgesics, aspirin may reduce pain in women with primary dysmenorrhoea in the short term compared with placebo, although few studies have been of good quality.

• We don’t know whether paracetamol is more effective than placebo at reducing pain in women with primary dysmenorrhoea as we found insufficient evidence.

Combined oral contraceptives may be more effective at reducing pain in women with primary dysmenorrhoea compared with placebo; however, few trials have been of good quality.

We found insufficient evidence on whether intrauterine progestogens reduce dysmenorrhoea.

About this condition

Definition

Dysmenorrhoea is painful menstrual cramps of uterine origin. It is commonly divided into primary dysmenorrhoea (pain without organic pathology) and secondary dysmenorrhoea (pelvic pain associated with an identifiable pathological condition, such as endometriosis [see review on Endometriosis]). The initial onset of primary dysmenorrhoea is usually shortly after menarche (6–12 months), when ovulatory cycles are established. Pain duration is commonly 8 to 72 hours and is usually associated with the onset of menstrual flow. Secondary dysmenorrhoea can also occur at any time after menarche, but may arise as a new symptom in a woman's 40s or 50s, after the onset of an underlying causative condition. In this review we only consider trials in women with primary dysmenorrhoea. However, the results may also be generalisable to women with secondary dysmenorrhoea. Studies in women with endometriosis, adenomyosis, pelvic congestion, and fibroids may also examine dysmenorrhoea/pain as an outcome. For more information on these conditions and studies, see reviews on Endometriosis, Menorrhagia, Pelvic inflammatory disease, and Fibroids.

Incidence/ Prevalence

Variations in the definition of dysmenorrhoea make it difficult to determine prevalence precisely. Studies tend to report on prevalence in adolescent girls, and the type of dysmenorrhoea is not always specified. Adolescent girls tend to have a higher prevalence of primary dysmenorrhoea than older women (see Prognosis). Secondary dysmenorrhoea rates may be lower in adolescents, as onset of causative conditions may not yet have occurred. Therefore, the results from prevalence studies of adolescents may not always be extrapolated to older women, or be accurate estimates of the prevalence of secondary dysmenorrhoea. However, various types of studies have found a consistently high prevalence in women of different ages and nationalities. One systematic review (search date 1996) of the prevalence of chronic pelvic pain, summarising both community and hospital surveys from developed countries, estimated prevalence to be 45% to 95%. A second systematic review of studies in developing countries (search date 2002) found that 25% to 50% of adult women and about 75% of adolescents experienced pain with menstruation, with 5% to 20% reporting severe dysmenorrhoea or pain that prevents them from participating in their usual activities. A third systematic review and meta-analysis of prevalence rates among high-quality studies with samples representative of the general worldwide population (search date 2004) found that prevalence of dysmenorrhoea was 59% (95% CI 49% to 71%). Prevalence rates reported in the UK were between 45% and 97% for any dysmenorrhoea in community-based studies and between 41% and 62% in hospital-based studies. A further review of longitudinal, case-control, or cross-sectional studies with large community-based samples included 15 primary studies, published between 2002 and 2011. It found the prevalence of dysmenorrhoea to vary between 16% and 91% in women of reproductive age, with severe pain in 2% to 29% of women studied.

Aetiology/ Risk factors

A systematic review (search date 2004) of cohort and case-control studies concluded that age under 30 years, low BMI, smoking, earlier menarche (<12 years), longer cycles, heavy menstrual flow, nulliparity, premenstrual syndrome, sterilisation, clinically suspected pelvic inflammatory disease, sexual abuse, and psychological symptoms were associated with increased risk of dysmenorrhoea. Presence of an intrauterine contraceptive device may also be associated with dysmenorrhoea. A further review reported that age, parity, and use of oral contraceptives were inversely associated with dysmenorrhoea, and high stress increased the risk of dysmenorrhoea. The effect sizes were generally modest to moderate, with odds ratios varying between 1 and 4. There was inconclusive evidence for modifiable factors such as cigarette smoking, diet, obesity, depression, and abuse. Family history of dysmenorrhoea strongly increased its risk, with odds ratios between 3.8 and 20.7.

Prognosis

Primary dysmenorrhoea is a chronic recurring condition that affects most young women. Studies of the natural history of this condition are sparse. One longitudinal study in Scandinavia found that primary dysmenorrhoea often improves in the third decade of a woman's reproductive life, and is also reduced after childbirth. We found no studies that reliably examined the relationship between the prognosis of secondary dysmenorrhoea and the severity of the underlying pathology, such as endometriosis.

Aims of intervention

To relieve pain from dysmenorrhoea, with minimal adverse effects.

Outcomes

Pain: pain relief, measured either by a visual analogue scale, other pain scales (such as the TOTPAR [TOPAR] score, TOTPAR-8 [TOPAR-8], or SPID-8), or as a dichotomous outcome (pain relief achieved yes/no); overall improvement in dysmenorrhoea measured by change in dysmenorrhoeic symptoms either self-reported or observed, proportion of women requiring analgesics in addition to their assigned treatment. Quality of life: quality of life scales or other similar measures such as the Menstrual Distress or Menstrual Symptom Questionnaires. Daily activities and work: proportion of women reporting activity restriction or absences from work or school and hours or days of absence as a more selective measure. Adverse effects: incidence and type of adverse effects.

Methods

Clinical Evidence search and appraisal December 2013. The following databases were used to identify studies for this systematic review: Medline 1966 to December 2013, Embase 1980 to December 2013, and The Cochrane Database of Systematic Reviews 2013, issue 11 (1966 to date of issue). Additional searches were carried out in the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) database. We also searched for retractions of studies included in the review. Titles and abstracts identified by the initial search, run by an information specialist, were first assessed against predefined criteria by an evidence scanner. Full texts for potentially relevant studies were then assessed against predefined criteria by an evidence analyst. Studies selected for inclusion were discussed with an expert contributor. All data relevant to the review were then extracted by an evidence analyst. Study design criteria for inclusion in this review were: published RCTs and systematic reviews of RCTs in the English language, at least single-blinded, and containing 20 or more individuals (10 in each arm) of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We aimed to include studies in women with primary dysmenorrhoea or where a subgroup analysis was carried out in women with primary dysmenorrhoea. However, where studies included a mixture of primary and secondary dysmenorrhoea, we included studies in which at least 66% of women had primary dysmenorrhoea. We included RCTs and systematic reviews of RCTs where harms of an included intervention were assessed, applying the same study design criteria for inclusion as we did for benefits. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the MHRA, which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Dysmenorrhoea.

Important outcomes	Daily activities and work, Pain
Studies (Participants)	Outcome	Comparison	Type of evidence	Quality	Consistency	Directness	Effect size	GRADE	Comment
What are the effects of pharmacological treatments for primary dysmenorrhoea?
at least 34 (at least 1319)	Pain	NSAIDs versus placebo	4	–2	–1	0	+1	Low	Quality points deducted for incomplete reporting of results and weak methods; consistency point deducted for statistical heterogeneity; effect size point added for OR >2 and <0.5
at least 5 (at least 306)	Daily activities and work	NSAIDs versus placebo	4	–2	0	–1	+1	Low	Quality points deducted for incomplete reporting of results and weak methods; effect size point added for OR <0.5; directness point deducted for inclusion of data on aspirin
unclear (unclear)	Pain	Different NSAIDs versus each other	4	–3	0	0	0	Very low	Quality points deducted for incomplete reporting of results, comparing single agent versus rest of group, and weak methods
at least 3 (unclear)	Daily activities and work	Different NSAIDs versus each other	4	–3	0	0	0	Very low	Quality points deducted for incomplete reporting of results, comparing single agent versus rest of group, and weak methods
6 (unclear)	Pain	Aspirin versus placebo	4	–2	0	–1	0	Very low	Quality points deducted for weak methods and incomplete reporting of results; directness point deducted for different conclusions depending on the analysis performed
at least 3 (at least 203)	Daily activities and work	Aspirin versus placebo	4	–2	0	0	0	Low	Quality points deducted for weak methods and incomplete reporting of results
1 (30)	Pain	Paracetamol versus placebo	4	–3	0	0	0	Very low	Quality points deducted for sparse data, incomplete reporting, and reporting of results post-crossover
1 (30)	Pain	Paracetamol versus aspirin	4	–3	0	0	0	Very low	Quality points deducted for sparse data, incomplete reporting, and reporting of results post-crossover
3 (less than 175)	Pain	Aspirin versus NSAIDs	4	–3	0	–1	0	Very low	Quality points deducted for sparse data, incomplete reporting of results, and weak methods; directness point deducted for outcome data per cycle
1 (fewer than 96)	Daily activities and work	Aspirin versus NSAIDs	4	–3	0	0	0	Very low	Quality points deducted for sparse data, incomplete reporting of results, and weak methods
3 (fewer than 196)	Pain	Paracetamol versus NSAIDs	4	–3	0	0	0	Very low	Quality points deducted for sparse data, incomplete reporting of results, and weak methods
7 (604)	Pain	Combined oral contraceptives versus placebo/no treatment	4	–1	–1	0	0	Low	Quality point deducted for weak methods; consistency point deducted for statistical heterogeneity
1 (107)	Daily activities and work	Combined oral contraceptives versus placebo/no treatment	4	–1	0	–2	0	Very low	Quality point deducted for sparse data; directness points deducted for use of composite measure (including function and pain), no ITT analysis, and small number of comparators

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Low-quality evidence

Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

SPID-8

An outcome measure commonly used in pharmaceutical trials of treatments for pain. The difference in pain intensity from baseline up to 8 hours after dosing is measured. The SPID-8 is the sum of the pain intensity differences of all participants up to 8 hours after dosing. Pain intensity can be measured on any categorical scale, but typically a low score will mean less pain and a high score more pain.

TOTPAR (TOPAR) score

An outcome measure commonly used in pharmaceutical trials of treatment for pain. The pain relief scores for all participants at various time points after dosing are totalled and a mean calculated. Pain relief can be measured on any categorical scale, but typically a low score will mean less pain relief and a high score more pain relief.

TOTPAR-8 (TOPAR-8) score

The same as TOTPAR (see above), but measured up to 8 hours after dosing.

Very low-quality evidence

Any estimate of effect is very uncertain.

Visual Analogue Scale (VAS)

A commonly used scale in pain assessment. It is a 10-cm horizontal or vertical line with word anchors at each end, such as 'no pain' and 'pain as bad as it could be'. The person is asked to make a mark on the line to represent pain intensity. This mark is converted to distance in either centimetres or millimetres from the 'no pain' anchor to give a pain score that can range from 0–10 cm or 0–100 mm.

Endometriosis

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