Non-surgical interventions for the management of chronic pelvic pain

  • Review
  • Intervention

Authors


Abstract

Background

Chronic pelvic pain is a common and debilitating condition; its aetiology is multifactorial, involving social, psychological and biological factors. The management of chronic pelvic pain is challenging, as despite interventions involving surgery, many women remain in pain without a firm gynaecological diagnosis.

Objectives

To assess the effectiveness and safety of non-surgical interventions for women with chronic pelvic pain.

Search methods

We searched the Menstrual Disorders and Subfertility Group Specialised Register. We also searched (from inception to 5 February 2014) AMED, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS. We handsearched sources such as citation lists, trial registers and conference proceedings.

Selection criteria

Randomised controlled trials (RCTs) on non-surgical management of chronic pelvic pain were eligible for inclusion. We included studies of women with a diagnosis of pelvic congestion syndrome or adhesions but excluded those with pain known to be caused by endometriosis, primary dysmenorrhoea (period pain), active chronic pelvic inflammatory disease or irritable bowel syndrome. We considered studies of any non-surgical intervention, including lifestyle, physical, medical and psychological treatments.

Data collection and analysis

Study selection, quality assessment and data extraction were performed independently by two review authors. Meta-analysis was performed using the Peto odds ratio (Peto OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). The primary outcome measure was pain relief, and secondary outcome measures were psychological outcomes, quality of life, requirement for analgesia and adverse effects. The quality of the evidence was assessed by using GRADE methods.

Main results

Twenty-one RCTs were identified that involved non-surgical management of chronic pelvic pain: 13 trials were included in the review, and eight were excluded. The studies included a total of 750 women—406 women in the intervention groups and 344 in the control groups. Included studies had high attrition rates, and investigators often did not blind adequately or did not clearly describe randomisation procedures.

Medical treatment versus placebo

Progestogen (medroxyprogesterone acetate (MPA)) was more effective than placebo at the end of treatment in terms of the number of women achieving a greater than 50% reduction in visual analogue scale (VAS) pain score immediately after treatment (Peto OR 3.00, 95% CI 1.70 to 5.31, two studies, n = 204, I2 = 22%, moderate-quality evidence). Evidence of benefit was maintained up to nine months after treatment (Peto OR 2.09, 95% CI 1.18 to 3.71, two studies, n = 204, I2 = 0%, moderate-quality evidence). Women treated with progestogen reported more adverse effects (e.g. weight gain, bloatedness) than those given placebo (high-quality evidence). The estimated effect of lofexidine on pain outcomes when compared with placebo was compatible with benefit and harm (Peto OR 0.42, 95% CI 0.11 to 1.61, one study, 39 women, low-quality evidence). Women in the lofexidine group reported more adverse effects (including drowsiness and dry mouth) than women given placebo (moderate-quality evidence).

Head-to-head comparisons of medical treatments

Head-to-head comparisons showed that women taking goserelin had greater improvement in pelvic pain score (MD 3, 95% CI 2.08 to 3.92, one study, n = 47, moderate-quality evidence) at one year than those taking progestogen. Women taking gabapentin had a lower VAS pain score than those taking amytriptyline (MD -1.50, 95% CI -2.06 to -0.94, n = 40, low-quality evidence). Study authors reported that no statistically significant difference was observed in the rate of adverse effects among women taking gabapentin compared with women given amytriptyline. The study comparing goserelin versus progestogen did not report on adverse effects.

Psychological treatment

Women who underwent reassurance ultrasound scans and received counselling were more likely to report improved pain than those treated with a standard 'wait and see' policy (Peto OR 6.77, 95% CI 2.83 to 16.19, n = 90, low-quality evidence). Significantly more women who had writing therapy as a disclosure reported improvement in pain than those in the non-disclosure group (Peto OR 4.47, 95% CI 1.41 to 14.13, n = 48, very low-quality evidence). No difference between groups in pain outcomes was noted when other psychological therapies were compared with standard care or placebo (quality of evidence ranged from very low to low). Studies did not report on adverse effects.

Complementary therapy

Distension of painful pelvic structures was more effective for pain when compared with counselling (MD 35.8, 95% CI 23.08 to 48.52 on a zero to 100 scale, one study, n = 48, moderate-quality evidence). No difference in pain levels was observed when magnetic therapy was compared with use of a control magnet (very low-quality evidence). Studies did not report on adverse effects.

The results of studies examining psychological and complementary therapies could not be combined to yield meaningful results.

Authors' conclusions

Evidence of moderate quality supports progestogen as an option for chronic pelvic pain, with efficacy reported during treatment. In practice, this option may be most acceptable among women unconcerned about progestogenic adverse effects (e.g. weight gain, bloatedness—the most common adverse effects). Although some evidence suggests possible benefit of goserelin when compared with progestogen, gabapentin as compared with amytriptyline, ultrasound versus 'wait and see' and writing therapy versus non-disclosure, the quality of evidence is generally low, and evidence is drawn from single studies.

Given the prevalence and healthcare costs associated with chronic pelvic pain in women, RCTs of other medical, lifestyle and psychological interventions are urgently required.

Résumé scientifique

Interventions non-chirurgicales pour la prise en charge des douleurs pelviennes chroniques

Contexte

La douleur pelvienne chronique est un problème courant et invalidant; son étiologie est multifactorielle, comprenant des facteurs sociaux, psychologiques et biologiques. La prise en charge de la douleur pelvienne chronique est difficile, car malgré les interventions comprenant la chirurgie, de nombreuses femmes continuent de ressentir de la douleur sans diagnostic gynécologique définitif.

Objectifs

Évaluer l'efficacité et l'innocuité des interventions non-chirurgicales chez les femmes souffrant de douleur pelvienne chronique.

Stratégie de recherche documentaire

Nous avons effectué des recherches dans le registre spécialisé du groupe sur les troubles menstruels et l'hypofertilité. Nous avons également effectué des recherches dans AMED, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL et LILACS (depuis leur création jusqu'au 5 février 2014). Nous avons manuellement effectué une recherche des sources, telles que les listes de références bibliographiques, les registres d'essais et les actes de conférence.

Critères de sélection

Les essais contrôlés randomisés (ECR) sur la prise en charge non-chirurgicale des douleurs pelviennes chroniques étaient éligibles pour l'inclusion. Nous avons inclus les études portant sur des femmes présentant un diagnostic de syndrome de congestion pelvienne ou d'adhérence, mais exclus celles dont la douleur était due à l'endométriose, à la dysménorrhée primaire (douleur menstruelle), à une maladie pelvienne inflammatoire chronique active ou au syndrome du côlon irritable. Nous avons pris en compte les études de n'importe quelle intervention non-chirurgicale, y compris les traitements physiques, médicaux, psychologiques et portant sur le mode de vie.

Recueil et analyse des données

La sélection des études, l'évaluation de la qualité et l'extraction des données ont été réalisées indépendamment par deux auteurs de la revue. Une méta-analyse a été effectuée en utilisant le rapport des cotes de Peto (RC de Peto) pour les résultats dichotomiques et la différence moyenne (DM) pour les résultats continus, avec des intervalles de confiance (IC) à 95 %. Le critère de jugement principal était le soulagement de la douleur et les critères de jugement secondaires étaient les résultats psychologiques, la qualité de vie, le besoin d'analgésie et les effets indésirables. La qualité des preuves a été évaluée au moyen de l'échelle GRADE.

Résultats principaux

Vingt-et-un ECR ont été identifiés qui portaient sur la prise en charge non-chirurgicale des douleurs pelviennes chroniques : 13 essais ont été inclus dans la revue et huit ont été exclus. Les études incluaient un total de 750 femmes - 406 femmes dans les groupes d'intervention et 344 dans les groupes témoins. Les études incluses présentaient des taux d'attrition élevés, et souvent, les investigateurs utilisaient la mise en aveugle de manière inadéquate ou ne décrivaient pas clairement les procédures de randomisation.

Un traitement médical par rapport à un placebo

Le progestatif (acétate de médroxyprogestérone) était plus efficace que le placebo à la fin du traitement en termes de nombre de femmes atteignant une réduction du score de la douleur de plus de 50 % sur l'échelle visuelle analogique (EVA), immédiatement après le traitement (rapport des cotes de Peto de 3,00, IC à 95 % 1,70 à 5,31, deux études, n = 204, I 2 = 22%, preuves de qualité modérée). L'effet bénéfique persistait jusqu'à neuf mois après le traitement (rapport des cotes de Peto de 2,09, IC à 95 % 1,18 à 3,71, deux études, n = 204, I 2 = 0%, preuves de qualité modérée). Les femmes traitées avec un progestatif rapportaient plus d'effets indésirables (par exemple une prise de poids, des ballonnements) que les patients sous placebo (preuves de qualité élevée). L'effet estimé de la lofexidine pour les résultats de la douleur par rapport au placebo étaient compatibles avec les effets bénéfiques et nocifs (rapport des cotes de Peto de 0,42, IC à 95 % 0,11 à 1,61, une étude, 39 femmes, preuves de faible qualité). De femmes dans le groupe de la lofexidine rapportaient davantage d'effets indésirables (y compris une somnolence et une sensation de bouche sèche) que les femmes ayant reçu un placebo (preuves de qualité modérée).

Comparaisons en face à face des traitements médicaux

Les comparaisons en face à face ont montré que les femmes prenant de la goséréline avaient une plus grande amélioration du score de la douleur pelvienne (DM 3, IC à 95 % 2,08 à 3,92, une étude, n = 47, preuves de qualité modérée) à un an, comparées à celles prenant un progestatif. Les femmes prenant de la gabapentine présentaient un score d'EVA sur la douleur inférieur à celles prenant de l'amytriptyline (DM -1,50, IC à 95 % -2,06 à -0,94, n = 40, preuves de faible qualité). Les auteurs des études n'ont rapporté aucune différence statistiquement significative dans les taux d'effets indésirables chez les femmes prenant de la gabapentine par rapport aux femmes ayant reçu de l'amytriptyline. L'étude comparant la goséréline par rapport aux progestatifs n'a pas rendu compte des effets indésirables.

Traitement psychologique

Les femmes ayant passé une échographie de rassurance et ayant reçu des conseils étaient plus susceptibles de rapporter une amélioration de la douleur que celles traitées avec une politique « attentiste » standard (rapport des cotes de Peto de 6,77, IC à 95 % 2,83 à 16,19, n = 90, preuves de faible qualité). Beaucoup plus de femmes ayant reçu une thérapie de révélation par l'écriture rapportaient une amélioration de la douleur par rapport à celles du groupe de non- révélation (rapport des cotes de Peto de 4,47, IC à 95 % 1,41 à 14,13, n = 48, preuves de très faible qualité). Aucune différence entre les groupes pour les résultats de la douleur n'était observée lorsque d'autres thérapies psychologiques étaient comparées à des soins standards ou à un placebo (preuves de très faible à faible qualité). Les études n'avaient pas rendu compte des effets indésirables.

Thérapie complémentaire

La distension des structures pelviennes douloureuses était plus efficace au niveau de la douleur par rapport à des conseils (DM 35,8, IC à 95 % 23,08 à 48,52 sur une échelle de zéro à 100, une étude, n = 48, preuves de qualité modérée). Aucune différence dans les niveaux de douleur n'était observée lorsque la thérapie magnétique était observée par rapport à l'utilisation d'un contrôle par magnétoscopie (preuves de très faible qualité). Les études n'avaient pas rendu compte des effets indésirables.

Les résultats des études, examinant les thérapies psychologiques et complémentaires, n'ont pas pu être combinés pour produire des résultats significatifs.

Conclusions des auteurs

Des preuves de qualité modérée favorisent le progestatif comme une option pour les douleurs pelviennes chroniques, avec une efficacité rapportée au cours du traitement. Dans la pratique, cette option pourrait être plus acceptable chez les femmes indifférentes aux effets indésirables des progestogéniques (par exemple la prise de poids, les ballonnements - les effets indésirables les plus courants. Bien que certaines preuves suggèrent un effet bénéfique possible de la goséréline par rapport à un progestatif, de la gabapentine par rapport à l'amytriptyline, de l'échographie par rapport à la politique « attentiste » et de la thérapie par l'écriture par rapport à la non-révélation, la qualité des preuves est généralement faible et les preuves proviennent d'études uniques.

Compte tenu de la prévalence et des coûts médicaux associés aux douleurs pelviennes chroniques chez les femmes, des ECR portant sur d'autres interventions médicales, psychologiques et sur le mode de vie sont urgemment nécessaires.

摘要

慢性骨盆腔疼痛管理的非外科性介入

背景

慢性骨盆腔疼痛 (chronic pelvic pain) 是一種常見但會令人衰弱的疾病,由多重因素造成,包括社會、心理和生理因素。慢性骨盆腔疼痛的管理極富挑戰性,因為很多無明確婦科診斷的女性患者,儘管接受包含外科手術的介入,仍然無法緩解疼痛。

目的

針對慢性骨盆腔疼痛女性患者,評估非外科性介入的療效和安全性。

搜尋策略

我們搜尋月經疾病及不孕症群組專業註冊 (Menstrual Disorders and Subfertility Group Specialised Register),也搜尋 (從頭開始搜尋至2014年2月5日為止) AMED、CENTRAL、MEDLINE、EMBASE、 PsycINFO、CINAHL和LILACS。我們以人工搜尋引用清單、試驗註冊和研討會記錄等來源。

選擇標準

我們納入針對慢性骨盆腔疼痛非外科性管理的隨機對照試驗(randomized controlled trial, RCT)。我們所納入的試驗,收錄診斷罹患骨盆腔充血症候群 (pelvic congestion syndrome) 或粘黏的女性患者,但排除已知由子宮內膜異位症 (endometriosis)、原發性經痛 (經期疼痛)、活動性慢性骨盆腔炎症或腸躁症,而引起骨盆腔疼痛的患者。我們考慮任何非外科性介入的試驗,包括生活型態、物理治療、內科治療和心理治療。

資料收集與分析

由2位文獻回顧作者獨立進行試驗篩選、品質評估和資料萃取的工作。在進行綜合分析時,以Peto勝算比 (Peto odds ratio, Peto OR) 計算二元性結果,以平均差 (mean difference, MD) 和95%信賴區間(confidence interval, CI),計算連續變項的結果。主要結果測量為疼痛緩解,次要結果測量為心理結果、生活品質、止痛劑的使用狀況,以及不良作用。本次文獻回顧採用GRADE方法評估證據品質。

主要結果

我們找到21篇與慢性骨盆腔疼痛非外科性管理有關的RCT,將其中13篇試驗納入文獻回顧,排除其餘8篇試驗。這些試驗共計收錄750名女性,其中介入組含406名女性,對照組含344名女性。所納入的試驗具有高損耗率 (attrition rate),試驗主持人通常並未進行適當的盲性處理,或未清楚描述隨機分配的程序。

內科治療相對於安慰劑

於治療結束時,孕激素(progestogen)(medroxyprogesterone acetate, MPA) 的療效優於安慰劑,孕激素組在治療後視覺類比量表 (VAS) 的疼痛分數降幅立即超過50%的人數,多於安慰劑組 (Peto OR為3.00,95% CI為1.70至5.31,2篇試驗,n = 204,I2 = 22%,證據品質中等)。證據顥示,治療後效益可持續達9個月(Peto OR為 2.09, 95% CI為 1.18 至 3.71, 2篇試驗, n = 204, I2 = 0%,中等證據品質)。相對於安慰劑組患者,接受孕激素治療的女性通報較多不良作用 (例如體重增加、腫脹)(證據品質高)。依據估計,lofexidine對疼痛結果的療效和傷害性影響,與安慰劑相似 (Peto OR為 0.42,95% CI為0.11至1.61,1篇試驗,39名女性,證據品質低)。相對於安慰劑組,lofexidine組的女性通報較多不良作用 (包括嗜睡和口乾)(證據品質中等)。

不同內科治療的直接比較

直接比較的結果顯示,接受1年治療後,goserelin治療組的骨盆腔疼痛分數改善幅度,高於接受孕激素治療組 (MD為3, 95% CI為2.08至3.92,1篇試驗,n = 47,證據品質中等)。服用gabapentin女性的VAS疼痛分數,低於使用amytriptyline的女性 (MD為-1.50,95% CI為-2.06至-0.94,n = 40,證據品質低)。試驗作者指出,gabapentin治療組與amytriptyline治療組的不良作用發生率,並無顯著差異。比較goserelin和孕激素的試驗,並未提及不良作用。

心理治療

相較於接受標準「繼續觀察」(wait and see) 策略的女性,再次接受超音波掃描確認,以及接受諮商的女性,疼痛的改善情況較佳 (Peto OR為6.77,95% CI為2.83至16.19,n = 90,證據品質低)。相較於未公開組,以書面公開接受治療組中,顯然有較多女性通報疼痛狀況改善 (Peto OR為 4.47,95% CI為1.41至14.13,n = 48,證據品質極低)。若以其他心理治療與標準照護或安慰劑相較,則疼痛結果並未出現組間差異 (證據品質範圍介於極低和低之間)。這些試驗並未提及不良作用。

輔助療法

擴張疼痛的骨盆構造以改善疼痛的效果優於諮商 (MD為35.8,95% CI為23.08至48.52,量表分數介於0至100分之間,1篇試驗,n = 48,證據品質中等)。磁療法(magnetic therapy) 組與對照磁石組的疼痛程度,並無組間差異 (證據品質極低)。這些試驗並未提及不良作用。

無法綜合分析心理治療和輔助療法的試驗結果,並得到有意義的結果。

作者結論

證據品質中等的試驗顯示, 以孕激素治療慢性骨盆腔疼痛,在治療期間就可以發揮療效。在實務上,對不在意孕激素副作用 (例如最常見的體重增加、腫脹等不良作用) 的女性而言,孕激素是接受度最高的治療選擇。儘管部分證據顯示goserelin的療效可能優於孕激素,但比較gabapentin與amytriptyline、超音波與「繼續觀察」治療、公開與不公開治療的試驗,證據品質通常偏低,而且來自單一試驗。

基於女性慢性骨盆腔疼痛的盛行率及所產生的健康照護成本,我們迫切需要進行其他內科、生活品質和心理介入的RCT。

譯註


翻譯者:臺北醫學大學實證醫學研究中心
本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

アブストラクト

慢性骨盤痛管理に対する非外科的介入

背景

慢性骨盤痛はよくみられる消耗性の疾患である。その病因は、社会的、心理的および生物学的要因を含む多因性のものである。手術を含む介入にも関わらず、多くの女性は婦人科の確定診断が得られないまま痛みが続くため、慢性骨盤痛の管理は困難である。

目的

慢性骨盤痛の女性に対する非外科的介入の有効性と安全性を評価すること。

検索戦略

Menstrual DisordersおよびSubfertility Group Specialised Registerを検索した。(最初から2014年2月5日まで)AMED、CENTRAL、MEDLINE、EMBASE、PsycINFO、CINAHL および LILACSについても検索した。引用リスト、試験登録一覧表や会議の議事録のような情報源をハンドサーチした。

選択基準

慢性腰痛の非外科的管理に関するランダム化比較試験(RCT)を適格基準とした。骨盤内うっ血症候群もしくは癒着と診断された女性に関する研究を含めたが、子宮内膜症、本態性月経困難症(生理痛)、慢性活動性骨盤炎症性疾患もしくは過敏性腸症候群を除外した。生活習慣、身体的、内科的および心理的治療を含めたあらゆる非外科的介入の研究を検討した。

データ収集と分析

研究の選択、品質評価およびデータ抽出は2名のレビュー著者により独立して行われた。2値アウトカムにはPetoオッズ比(Peto OR)、連続アウトカムには平均差(MD)、および、95%信頼区間(CI)を用いて、メタアナリシスを実施した。主要アウトカム指標は疼痛軽減で、副次アウトカム指標は心理的アウトカム、QOL、鎮痛剤の要求および有害作用であった。エビデンスの質はGRADE法を用いて評価した。

主な結果

慢性骨盤痛の非外科的管理を含む21件のRCTが同定されたが、13件の試験はレビューに加えられ、8件は除外された。この研究には介入群406例の女性および対照群344例の女性の総計750例の女性が含まれた。含まれた研究は高い症例減少率で、試験責任者は十分に盲検化していないことが多かったり、もしくは明確なランダム化手順を説明していなかった。

治療群とプラセボ群の比較

プロゲストゲン(酢酸メドロキシプロゲステロン(MPA))は、治療終了時点において、治療直後の視覚的アナログスケール(VAS)の疼痛スコアの減少が50%を超えた女性の人数に関して、プラセボに比較して有効であった。 (Peto OR 3.00、95% CI 1.70〜5.31、2試験、n = 204、 I 2= 22%、エビデンスの質は中程度)有益性に関するエビデンスは治療後最大9カ月まで維持された。(Peto OR 2.09、95% CI 1.18 〜3.71、2試験、n = 204、 I2= 0%、エビデンスの質は中程度)プロゲストゲンで治療された女性はプラセボを与えられた女性に比べて有害作用(体重増加、腹部膨満感など)がより多く報告された。(エビデンスの質は高い) ロフェキシジンの疼痛アウトカムに対する効果の推定値は、プラセボと比較した場合の有益性および有害性とつじつまが合うものであった。(Peto OR 0.42、95% CI 0.11〜1.61、1試験、39例の女性、エビデンスの質は低い)ロフェキシジン群の女性はプラセボを投与された群に比較して有害作用(眠気および口内乾燥を含む)が多く報告された。(エビデンスの質は中等度)

内科的治療法の直接比較

直接比較は、1年目の時点での骨盤痛スコア(MD 3、95% CI 2.08〜3.92、1試験、n = 47、エビデンスの質は中程度)において、ゴセレリンを服用した女性は、プロゲストゲンを服用した女性よりも大きな改善を示した。ガバペンチンを服用した女性はアミトリプチリンを服用した群より低いVAS疼痛スコアであった。(MD -1.50、95% CI -2.06 〜 -0.94、n = 40、エビデンスの質は低い)研究著者らは、アミトリプチリンを服用した女性に比較して、ガバペンチンを服用した女性では有害作用の割合において、統計的に有意な差が観察されなかったと報告した。ゴセレリンをプロゲストゲンと比較した研究では有害作用は報告されなかった

心理療法

再確認のための超音波スキャンを受け、カウンセリングを受けた女性は、標準的な「様子を見る」方針で治療された群に比較して疼痛が改善したと報告する傾向が強かった。(Peto OR 6.77、95% CI 2.83〜16.19、n = 90、エビデンスの質は低い)自己開示の方法としてライティングセラピーを受けた有意により多くの女性が、非自己開示群より 疼痛の改善が報告された。(Peto OR 4.47、95% CI 1.41〜14.13、n = 48、エビデンスの質は非常に低い)他の心理療法は標準的療法もしくはプラセボと比較した場合、疼痛のアウトカムにおいて群間の差は示されなかった。(エビデンスの質は、非常に低い〜低い)研究では有害作用について報告されなかった。

代替療法

痛みのある骨盤を拡張させることはカウンセリングを受けた群と比較して疼痛に対してより有効であった。(MD 35.8、0から100までのスケールで95% CI 23.08〜48.52 、1試験、n = 48、エビデンスの質は中程度)磁気療法は、対照の磁気の使用と比較した場合疼痛のレベルに差は観察されなかった。研究では有害作用について報告されなかった。

心理学的療法および代替療法を検討した研究の結果を統合し意味のある結果を得ることができなかった。

著者の結論

中等度の質のエビデンスから、治療中に報告された有効性により、プロゲストゲンが 慢性骨盤痛に対する選択肢であることが裏づけられる。日常診療では、この選択肢はプロゲストゲンの有害作用(例えば、体重増加、腹部膨満感−最も見られる有害作用)について懸念のない女性の間で最も受け入れられるであろう。プロゲストゲンとゴセレリン、アミトリプチリンとガバペンチン、超音波検査と「様子を見る」方針、およびライティングセラピーと自己開示の方法を用いない場合の比較では、一部のエビデンスは有益性の可能性を示唆したが、エビデンスの質は概して低く、エビデンスは単一の研究から得られたものであった。

慢性骨盤痛のある女性の有病割合と医療費を考えると、他の内科的、生活習慣および心理学的介入のRCTは至急に必要とされる。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.7.27]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Plain language summary

Non-surgical interventions for the management of chronic pelvic pain

Review question

Cochrane authors considered the evidence for effectiveness and safety of non-surgical treatrments for managing chronic pelvic pain in women.

Background

Chronic pelvic pain in women is a common problem. Specific causes are often difficult to identify, even after investigation with ultrasound and inspection of the pelvis with key hole surgery. Treatment is frequently limited to relief of symptoms obtained with a concoction of medicines. Cochrane review authors examined the evidence about non-surgical interventions for the management of chronic pelvic pain.

Study characteristics

Twenty-one randomised controlled studies were identified, of which 13 were included. Eight studies were excluded. The studies included a total of 750 women—406 women in the intervention groups and 344 women in the control groups. The interventions assessed included medical treatment and psychological, cognitive, behavioural, complementary and physical therapies. The evidence is current to February 2014.

Key results

The review concludes that evidence shows improvement of pain in women given a high dose of progestogen (50 mg medroxyprogesterone acetate) immediately post-treatment and for up to nine months after treatment. However, progestogen was associated with adverse effects such as weight gain and bloating. Women who underwent reassurance ultrasound scans and who received counselling were more likely to report improved pain than those whose treatment involved a 'wait and see' policy. Some evidence of benefit was seen with writing disclosure therapy and with distension of painful pelvic structures. No good evidence of benefit was noted with other interventions when compared with standard care or placebo.

The quality of the evidence was low or moderate for most comparisons, and in most cases evidence was derived from single small studies. Moreover, we were unable to draw meaningful conclusions on quality of life and physical and functional outcomes because of the large variation in outcome measures used by the included studies. Many interventions identified in this review involved only single studies with small sample sizes. Additional studies will be required in the future to replicate results obtained with the use of specific medical interventions.

Résumé simplifié

Interventions non-chirurgicales pour la prise en charge des douleurs pelviennes chroniques

Question de la revue

Les auteurs de la revue Cochrane ont examiné les preuves concernant l'efficacité et l'innocuité des traitements pour la prise en charge non-chirurgicale des douleurs pelviennes chroniques chez les femmes.

Contexte

La douleur pelvienne chronique est un problème courant chez les femmes. Les causes spécifiques sont souvent difficiles à identifier, même après un examen par échographie et une inspection du bassin par endoscopie. Le traitement est souvent limité au soulagement des symptômes obtenu grâce à une concoction de médicaments. Les auteurs de la revue Cochrane ont examiné les preuves des interventions non chirurgicales pour la prise en charge des douleurs pelviennes chroniques.

Les caractéristiques de l'étude

Vingt-et-une études contrôlées randomisées ont été identifiées, dont 13 ont été inclues. Huit études ont été exclues. Les études incluaient un total de 750 femmes - 406 femmes dans les groupes d'intervention et 344 femmes dans les groupes témoins. Les interventions évaluées incluaient un traitement médical et des thérapies psychologiques, cognitives, comportementales, complémentaires et physiques. Les preuves sont à jour en février 2014.

Résultats principaux

Cette revue conclut que les preuves montrent une amélioration de la douleur chez les femmes recevant une dose élevée de progestatif (50 mg d'acétate de médroxyprogestérone) immédiatement après le traitement et jusqu'à neuf mois après le traitement. Cependant, le progestatif était associé à des effets indésirables, tels que la prise de poids et des ballonnements. Les femmes ayant passé une échographie de rassurance et ayant reçu des conseils étaient plus susceptibles de rapporter une amélioration de la douleur que celles dont le traitement impliquait une politique attentiste. Certains bénéfices étaient observés avec la thérapie de révélation par écrit et avec la distension de structures pelviennes douloureuses. Aucune preuve solide de bénéfice n'a été notée dans d'autres interventions lorsque comparée aux soins standard ou à un placebo.

La qualité des preuves était faible ou modérée pour la plupart des comparaisons et, dans la plupart des cas, les preuves provenaient d'études uniques de petite taille. De plus, nous ne sommes pas en mesure d'apporter de conclusions significatives sur la qualité de vie et sur les résultats physiques et fonctionnels en raison de la grande variabilité des mesures de résultats utilisées dans les études incluses. De nombreuses interventions identifiées dans cette revue portaient seulement sur des études uniques avec des petits effectifs. Des études supplémentaires seront à l'avenir nécessaires afin de répliquer les résultats obtenus avec l'utilisation d'interventions médicales spécifiques.

Notes de traduction

Traduit par: French Cochrane Centre 22nd June, 2014
Traduction financée par: Financeurs pour le Canada : Instituts de Recherche en Santé du Canada, Ministère de la Santé et des Services Sociaux du Québec, Fonds de recherche du Québec-Santé et Institut National d'Excellence en Santé et en Services Sociaux; pour la France : Ministère en charge de la Santé

淺顯易懂的口語結論

慢性骨盆腔疼痛管理的非外科性介入

問題回顧

考科藍作者針對慢性骨盆腔疼痛的女性患者,考慮非外科治療的相關療效及安全性證據。

背景

慢性骨盆腔疼痛是女性常見的問題,通常很難確認特定病因,即使利用超音波檢查,或以微創手術探查骨盆腔,仍然不容易確定病因。治療通常局限於混合各種藥物以緩解症狀。考科藍文獻回顧作者檢驗關於慢性骨盆腔疼痛非外科性介入管理的證據。

試驗特色

我們找到21篇隨機對照試驗,納入其中13篇試驗,排除其餘8篇試驗。這些試驗共計收錄750名女性,其中介入組含406名女性,對照組含344名女性。接受評估的介入包括內科治療,以及心理、認知、行為、輔助和物理治療。截至2014年2月為止,這些證據依然流通。

重要結果

本篇文獻回顧的結論指出,證據顯示使用高劑量孕激素 (50 mg medroxyprogesterone acetate)的女性,在接受治療後疼痛立即改善,且療效可持續至治療後9個月。不過孕激素會引起某些副作用,例如體重增加和腫脹。相較於接受「繼續觀察」策略治療的女性,再度接受超音波掃描確認的女性,以及接受諮商的女性,疼痛狀況比較可能改善。部分證據顯示,以書面公開治療和擴張疼痛的骨盆構造也具有療效。相較於標準療法或安慰劑,其他介入並無完善的療效證據。

大部分比較試驗的證據品質偏低或中等,而且在大多數的證據都衍生自1篇小型試驗。此外,我們無法針對生活品質和生理及功能性結果,提出有意義的結論,因為所納入的試驗對結果的測量,歧異甚大。本篇文獻回顧所納入的許多介入,只有1篇研究試驗,而且所收錄的樣本數很小。未來需要進行其他試驗,複製使用特定醫學介入所得到的結果。

譯註


翻譯者:臺北醫學大學實證醫學研究中心
本翻譯計畫由衛生福利部補助經費,臺北醫學大學實證醫學研究中心、台灣實證醫學學會及東亞考科藍聯盟(EACA)統籌執行。

平易な要約

慢性骨盤痛管理への非外科的介入

レビューの論点

コクランの著者らは、女性の慢性骨盤痛の管理において非外科的治療の有効性と安全性についてのエビデンスを検討した。

背景

慢性骨盤痛は女性に多く見られる症状である。超音波を用いた研究および骨盤のキーホール手術による検査をしても、多くの場合個々の原因を確認することは困難である。治療はしばしば薬剤の調合により得られた症状の軽減に限定される。コクランレビュー著者らは慢性骨盤痛の管理に対する非外科的介入に関するエビデンスを検討した。

研究の特性

21のランダム化比較試験(RCT)が同定され、そのうちの13試験を含めた。8つの研究が除外された。研究には406例の女性の介入群と344例の対照群との合計750例の女性が含まれた。介入群には内科的治療および心理的、認知的、行動的、代替療法および理学療法を含んで評価した。本エビデンスは2014年2月現在のものである。

主な結果

今回のレビューにより、高用量のプロゲストゲン(50mgの酢酸メドロキシプロゲストロン)を投与された女性では、治療直後および治療後9カ月までの間で疼痛の改善を示したことがエビデンスによって示されていると結論付けられた。しかしながら、プロゲストゲンは体重増加や腹部膨満感のような有害作用に関連していた。再確認のための超音波スキャンを受け、カウンセリングを受けた女性は、「様子を見る」方針を必要とした治療群よりも痛みが改善したと報告する傾向が強かった。ライティングセラピーによる自己開示および痛みのある骨盤の拡張は、有益性のエビデンスが一部認められた標準的なケアもしくはプラセボと比較した場合他の介入によって有益性についての好ましいエビデンスは示唆されなかった。

エビデンスの質は大部分の比較に対して低いか中等度であり、大部分の症例においてエビデンスは小規模な単一試験由来のものであった。さらに、含まれた研究によって使用されたアウトカム指標における大きなばらつきのために、QOLおよび身体的および機能的アウトカムについての意味のある結果を得られなかった。このレビューの中で同定された多くの介入には小さいサンプル・サイズの単一試験しか含まれていなかった。追加的研究は将来、個々の医学的介入の利用によって得られた結果を再現することが求められると思われる。

訳注

《実施組織》厚生労働省「「統合医療」に係る情報発信等推進事業」(eJIM:http://www.ejim.ncgg.go.jp/)[2016.7.27]
《注意》この日本語訳は、臨床医、疫学研究者などによる翻訳のチェックを受けて公開していますが、訳語の間違いなどお気づきの点がございましたら、eJIM事務局までご連絡ください。なお、2013年6月からコクラン・ライブラリーのNew review, Updated reviewとも日単位で更新されています。eJIMでは最新版の日本語訳を掲載するよう努めておりますが、タイム・ラグが生じている場合もあります。ご利用に際しては、最新版(英語版)の内容をご確認ください。

Summary of findings(Explanation)

Summary of findings for the main comparison. Medical treatment compared with placebo for the management of chronic pelvic pain
  1. 140% dropout rate in one of the two studies.

    2> 10% dropout rate.

    3Wide confidence intervals compatible with no effect or with higher rates of improvement in placebo group.

Medical treatment compared with placebo for the management of chronic pelvic pain

Population: women with chronic pelvic pain

Setting: any
Intervention: medical treatment
Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Placebo Medical treatment
Improvement in pain score at end of treatment: progesterone versus placebo24/85541 per 1000
(401 to 676)
Peto OR 3.00 (1.70 to 5.31)204
(two studies)
⊕⊕⊕⊝
moderate1,2
Improvement defined as ≥ 50% reduction in VAS pain score
Improvement in pain score (up to nine months after treatment): progesterone versus placebo27/85493 per 1000
(355 to 633)
Peto OR 2.09 (1.18 to 3.71)204
(two studies)
⊕⊕⊕⊝
moderate1
Improvement defined as ≥ 50% reduction in VAS pain score
Weight gain: progesterone versus placebo14/40808 per 1000
(638 to 909)
Peto OR 7.82 (3.28 to 18.65)85
(one study)
⊕⊕⊕⊕
high
 
Bloatedness: progesterone versus placebo14/40633 per 1000
(425 to 801)
Peto OR 3.20 (1.37 to 7.47)85
(one study)
⊕⊕⊕⊕
high
 
Improvement in pain score: lofexidine versus placeboeight/20219 per 1000
(68 to 518)
Peto OR 0.42 (0.11 to 1.61)39
(one study)
⊕⊕⊝⊝
low1,2,3
Improvement defined as ≥ 50% reduction in VAS pain score
Drowsiness/lethargy: lofexidine versus placeboeight/20717 per 1000
(421 to 898)
Peto OR 3.80 (1.09 to 13.26)39
(one study)
⊕⊕⊕⊝
moderate2
 
Dry mouth: lofexidine versus placebothree/20603 per 1000
(301 to 842)
Peto OR 8.60 (2.44 to 30.31)39
(one study)
⊕⊕⊕⊝
moderate2
 
*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; OR: Odds ratio.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: 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.
Very low quality: We are very uncertain about the estimate.

Summary of findings 2 Medical treatment of chronic pelvic pain: head-to-head comparisons

Summary of findings 2. Medical treatment of chronic pelvic pain: head-to-head comparisons
  1. 1Participants not blinded.

    2> 10% attrition.

Medical treatment of chronic pelvic pain: head-to-head comparisons
Patient or population: management of chronic pelvic pain
Settings: any
Intervention: medical treatment: head-to-head comparison
Outcomes Medical treatment: head-to-head comparisonNo. of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Improvement in pelvic pain at one year: goserelin versus progestogenImprovement in mean pelvic pain score in the goserelin group was three points greater than in the progestogen group (95% CI 2.08 higher to 3.92 higher)47
(one study)
⊕⊕⊕⊝
moderate1
Improvement in pelvic pain score measured on a scale of one to 100
Pain at 24 months: gabapentin versus amytriptylineMean pain score in the gabapentin group was 1.5 points lower than in the amytriptyline group (95% CI 2.06 lower to 0.94 lower)40
(one study)
⊕⊕⊝⊝
low1,2
Pain score measured on a VAS scale of zero to 10
CI: Confidence interval.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: 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.
Very low quality: We are very uncertain about the estimate.

Summary of findings 3 Psychological therapy compared with control interventions for the management of chronic pelvic pain

Summary of findings 3. Psychological therapy compared with control interventions for the management of chronic pelvic pain
  1. 110% attrition.

    2Sequence generation method not described.

    3No attrition figures stated, but at one year, only 13 women in each group had completed the questionnaires.

    4Unblinded.

    5Wide confidence intervals compatible with no effect or with benefit from intervention.

    6Participants not blinded.

    720% loss to follow-up.

    8Allocation concealment methods not described.

    9Unclear whether participants blinded.

    10Wide confidence intervals compatible with no effect or with increased pain from intervention.

    1118% attrition.

Psychological therapy compared with control interventions for the management of chronic pelvic pain

Population: women with chronic pelvic pain

Setting: any
Intervention: psychological therapy
Comparison: control intervention

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Control Psychological therapy
Improvement in pain scores—Ultrasound scan and counselling session versus 'wait and see'113 per 1000465 per 1000
(266 to 675)
Peto OR 6.77 (2.83 to 16.19 )90
(one study)
⊕⊕⊕⊝
low1,2,6
Improvement defined as a change of five or more points on McGill Pain Questionnaire
Improvement in pain scores—Somatocognitive therapy (Mensendieck) versus standard gynaecological clinical care250 per 1000530 per 1000
(244 to 797)
Peto OR 3.38 (0.97 to 11.80 )40
(one study)
⊕⊝⊝⊝
very low3,4,5
Improvement defined as ≥ 50% reduction in VAS pain score
Improvement in pain scores—Integrated approach (somatic, psychological, dietary, environmental and physiotherapeutic factors) versus standard care510 per 1000613 per 1000
(425 to 773)
Peto OR 1.52 (0.71 to 3.27 )106
(one study)
⊕⊕⊝⊝
low2,5,6
Improvement defined as ≥ 50% reduction in VAS pain score
Improvement in pain scores—Writing therapy (disclosure of pain) versus non-disclosure200 per 1000528 per 1000
(261 to 779)
Peto OR 4.47 (1.41 to 14.13 )48
(one study)
⊕⊕⊝⊝
very low2,7,8,9
Improvement considered an improvement of at least one point on a zero to five pain scale
Improvement in pain scores—Psychotherapy versus placebo, measured at end of treatment320 per 1000271 per 1000
(101 to 549)
Peto OR 0.79 (0.24 to 2.59 )51
(one study)
⊕⊕⊕⊝
low10,11
Improvement defined as ≥ 50% reduction in VAS pain score
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: 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.
Very low quality: We are very uncertain about the estimate.

Summary of findings 4 Complementary therapy compared with control interventions for the management of chronic pelvic pain

Summary of findings 4. Complementary therapy compared with control interventions for the management of chronic pelvic pain
  1. 1Unclear whether blinded, 12% attrition.

    241% dropout rate at two to four weeks.

    3Wide confidence interval compatible with no effect or benefit from magnetic therapy.

Complementary therapy compared with control interventions for the management of chronic pelvic pain
Population: women with chronic pelvic pain
Settings: any
Intervention: complementary therapy
Comparison: control intervention
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No. of participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
Control Complementary therapy
Reduction in pain score: distension of painful pelvic structures versus counselling23Mean reduction in pain score in the intervention group was 35.8 higher (23.08 higher to 48.52 higher)-48
(one study)
⊕⊕⊕⊝
moderate1
Reduction in pain score, measured on a self assessed one to 100 VAS scale
Pain score after treatment: magnetic therapy versus control magnet11Mean pelvic pain score in the intervention group was 0.5 lower (1.92 lower to 0.92 higher)-19
(one study)
⊕⊝⊝⊝
very low2,3
Post-treatment pelvic pain score on a zero to five-point scale, where 0 = no pain and 5 = excruciating pain
*The basis for the assumed risk is the median control group risk across studies. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval.
GRADE Working Group grades of evidence.
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: 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.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

The management of women with chronic pelvic pain (CPP) has for many years posed a challenge for healthcare professionals. Among women in the reproductive age group, the estimated prevalence of CPP varies widely, depending on study definitions, from 2.1% to 24% of the female population worldwide (Latthe 2006), with a notably high prevalence in the USA and the UK (14.7% and 24%, respectively) (Daniels 2010; Mathias 1996; Zondervan 1999). The reported incidence of CPP in primary care of 38 per 1000 women is comparable with the incidence of back pain (41 per 1000) and asthma (37 per 1000) (Zondervan 1999). Up to 20% of visits to gynaecologists, 40% of laparoscopies and 15% of hysterectomies in gynaecology are attributed to CPP (Gelbaya 2001; Howard 1993). At laparoscopy, a significant proportion of women with CPP (up to 55%) have no obvious pathological cause for their pain (Daniels 2009; Howard 1993). As the pathophysiology of CPP is not well understood, its treatment is often unsatisfactory and limited to symptom relief. Treatment options, ranging from conservative management to opioid analgesia and surgical intervention, vary accordingly, as do treatment outcomes (Cheong 2006). In a large proportion of women, treatment does not necessarily result in relief of pain. Thus, living with CPP carries a significant mental, social and physical burden for the sufferer, and its chronic nature puts a heavy burden on healthcare systems worldwide (Daniels 2010; Latthe 2006).

Description of the intervention

Diagnosis and treatment of CPP is complex and may be complicated by psychosocial circumstances. Non-surgical management often includes an entire concoction of treatments, such as analgesics, adjunctive agents such as anticonvulsants and antidepressants, hormonal drugs (medroxyprogesterone acetate, goserelin), α2-adrenoceptor agonists (lofexidine hydrochloride), venoconstrictor drugs (ergotamine) and venomimetics (daflon). The non-surgical approach also encompasses psychological drug interventions, which have been suggested to be beneficial in the treatment of CPP (Williams 2012). Other alternatives to medical management of CPP include psychological therapy, cognitive therapy, physiotherapy and various forms of complementary therapies (Cheong 2006). Multidisciplinary management, which is a common approach to many chronic conditions such as asthma and diabetes, still is not commonly available in gynaecology because of cost factors and the limited availability of interested specialists (Cheong 2007).

How the intervention might work

The aetiology of chronic pelvic pain is complex. Pelvic congestion, adhesions, musculoskeletal nerve-related disorders and psychosomatic factors have been suggested as causes of CPP. Interventions targeting these factors have been used in the management of CPP.

It is suggested that pelvic pain in women can be of visceral and/or neuropathic origin. If treatment using anti-nociceptive medication (e.g. Tramadol) for visceral pain fails, second-line treatment generally consists of anti-convulsants targeting neuropathic pain (Sator-Katzenschlager 2005). Women with CPP, similar to those with other chronic pain syndromes, often have co-existing conditions such as depression. Although anti-depressants may indirectly improve the pain experience by enhancing mood, they may also have a direct analgesic effect, as both depressive symptoms and pain are modulated by the neurotransmitters serotonin and norepinephrine (Brown 2008).

A possible vascular basis for CPP has prompted the evaluation of vasoactive agents for treatment, by analogy with cerebral migraine (Stones 2001). It has been suggested that pelvic congestion syndrome, which is responsible for CPP in a large proportion of women with no detectable organic pathology, is the result of ovarian dysfunction, and that inducing a hypo-oestrogenic state or antagonising the effects of oestrogens by using progesterone results in resolution of symptoms, hence the trials of medroxyprogesterone acetate versus placebo (Farquhar 1989).

Evidence suggests that up to 85% of women with CPP have dysfunction of the musculoskeletal system, including postural changes, as well as changes in the pelvic muscles, such as spasm of the levator ani (Baker 1993; Prendergast 2003). Such chronic pain caused by spasm of the pelvic floor muscles has been treated by various modalities such as local anaesthetic blockade (Langford 2007). Another technique that is being studied increasingly is the injection of type A botulinum toxin into affected muscles of the pelvic floor. This agent is thought to act selectively on the endings of cholinergic peripheral nerves, thus inhibiting the presynaptic release of acetylcholine and reducing excessive muscle tone (Gupta 2006; Thompson 2005). Other possibilities that have been explored in the treatment of high-tone dysfunction of the pelvic floor in women with CPP include transvaginal manual therapy and transvaginal electrostimulation of pelvic floor musculature. Electrical stimulation is thought to promote analgesia through the counterirritative effect that results in activation of the pain suppression system, thus offering pain relief at low cost and with few side effects (Duleba 1996).

Diagnosis and treatment of CPP is complex and may be complicated by psychosocial circumstances. Apart from medical and surgical approaches, it has been suggested that psychological treatments are helpful in reducing the frequency and severity of symptoms in all sorts of chronic pain, including unexplained pelvic pain (Williams 2012).

Why it is important to do this review

This review is important because it will inform women with chronic pelvic pain and healthcare professionals about available evidence on management of this disease.

Objectives

To assess the effectiveness and safety of non-surgical interventions for women with chronic pelvic pain. 

Methods

Criteria for considering studies for this review

Types of studies

We included published and unpublished randomised controlled trials (RCTs). We excluded trials that were not properly randomised. We included cross-over studies if first-phase data were valid.

Types of participants

Women with CPP, defined as intermittent or constant pain of at least three to six months' duration localised in the abdomen or pelvis, not limited to the period of menstruation or intercourse and not associated with pregnancy. We excluded studies examining specific cohorts of women known to have solely endometriosis, primary dysmenorrhoea and/or pain due to active chronic pelvic inflammatory disease.

Types of interventions

We considered comparisons made within the following intervention groups.

  • Medical interventions versus placebo/no treatment or other types of interventions.

    • Medical interventions included interventions such as non-steroidal anti-inflammatory drugs (NSAIDs), oral contraceptive pills (OCPs), oral and non-oral progestogen, danazol, gonadotropin-releasing hormone (GnRH) analogues (alone or with ‘add-back’ oestrogen), progestogen-releasing intrauterine devices (IUCDs), drugs affecting blood vessels, anticholinergic drugs, antidepressants, anticonvulsants, analgesics, combined analgesic and caffeine preparations and local anaesthetic infiltration alone or in combination with corticosteroids.

  • Psychological/behavioural/cognitive treatments versus no treatment/placebo/other non-surgical treatments or other types of interventions.

    • Interventions in this category included investigations for reassurance, written or oral emotional disclosures, psychotherapy, counselling, cognitive and biofeedback therapy and lifestyle interventions.

  • Physical and complementary treatments versus no treatment/sham or placebo or other types of interventions.

    • Interventions such as magnetic field therapy, therapies encompassed in traditional Chinese medicine (TCM) (acupuncture, herbal therapy, moxibustion), transcutaneous nerve stimulation and transcranial current stimulation and physical and massage therapy were considered.

Types of outcome measures

Primary outcomes
  • Effectiveness of treatment: pain measured by validated pain scales, for example, visual analogue pain scale (VAS) scores, the McGill Pain Questionnaire (MPQ), a pain improvement rating scale, general pain experience and a gynaecological pain questionnaire.

Secondary outcomes
  • Psychological outcomes indicated by scores such as depression scores (Hamilton Depression Rating Scale (HAM-D) score, Hospital Anxiety Depression Scale) and mood scores.

  • Quality of life: indicated by, for example, the Medical Outcomes Study Short Form 36 (SF-36), the Social Adjustment Survey (SAS-WR), the Sickness Impact Profile (SIP), a general health questionnaire (GHQ), the revised Sabbatsberg Sexual Rating Scale (rSSRS) and EuroQOL-5D (EQ-5D).

  • Requirement for analgesia.

  • Adverse outcomes (e.g. treatment intolerance, side effects of intervention).

Search methods for identification of studies

We searched all published and unpublished RCTs to 5 February 2014 with no language restriction and in consultation with the Menstrual Disorders and Subfertility Group (MDSG)Trials Search Co-ordinator.

Electronic searches

We searched the following electronic databases, trial registers and websites.

  • The Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of Controlled Trials.

  • The Cochrane Central Register of Controlled Trials (CENTRAL).

  • MEDLINE.

  • EMBASE.

  • PsycINFO.

  • CINAHL.

Other electronic sources of trials included the following.

  • Trial registers for ongoing and registered trials (http://www.controlled-trials.com, http://clinicaltrials.gov/ct2/home, http://www.who.int/trialsearch/Default.aspx).

  • Citation indexes (http://scientific.thomson.com/products/sci/).

  • Conference abstracts in the Web of Knowledge (http://wokinfo.com/).

  • LILACS database, for trials from the Portuguese- and Spanish-speaking world (http://bases.bireme.br/cgibin/wxislind.exe/iah/online/?IsisScript=iah/iah.xis&base=LILACS&lang=i&form=F).

  • PubMed (http://www.ncbi.nlm.nih.gov/pubmed/).

  • OpenSIGLE database (http://opensigle.inist.fr/ and Google for grey literature).

See Appendix 1, Appendix 2, Appendix 3, Appendix 4, Appendix 5 and Appendix 6.

Searching other resources

  • We searched the citation lists of relevant publications, review articles and included studies.

  • We handsearched relevant journals, abstracts and conference proceedings and several key grey literature sources.

  • We personally contacted study authors to request further information, if needed.

  • We approached drug/device manufacturers and experts in the field to ask for references.

Data collection and analysis

Selection of studies

After an initial screen of titles and abstracts retrieved by the search conducted by the MDSG Trials Search Co-ordinator, the full texts of all potentially eligible studies were retrieved. Two review authors (GS and YCC) reviewed the titles and abstracts independently, examining these articles for compliance with the inclusion criteria and selecting studies eligible for inclusion in the review. We corresponded with study investigators as required. Disagreements as to study eligibility were resolved by discussion or by a third review author (AW). The selection process has been documented with a PRISMA flow chart Figure 1. See also Figure 2 and Figure 3.

Figure 1.

Study flow diagram.

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Data extraction and management

GS and YCC independently extracted the information for each included trial, using a data extraction form designed and pilot tested by the review authors. Any disagreements were resolved by discussion or by a third review author (AW). When studies had multiple publications, the main trial report was used as the reference, and additional details were derived from secondary papers. We corresponded with study investigators to request further data on methods and/or results, as required.

Assessment of risk of bias in included studies

Two review authors (GS and YCC) independently assessed the risk of bias of included studies. The included studies were assessed using the Cochrane risk of bias assessment tool (Version 5.1) to assess the following domains: selection bias (random sequence generation and allocation concealment); performance bias (blinding of participants and personnel); detection bias (blinding of outcome assessors); attrition bias (incomplete outcome data); reporting bias (selective reporting); and other bias. We resolved disagreements by discussion.

Measures of treatment effect

For dichotomous data, we used the numbers of events in the control and intervention groups of each study to calculate Peto odds ratios (ORs). For continuous data, we calculated the mean difference (MD) between treatment groups. We presented 95% confidence intervals (CIs) for all treatment outcomes.

Unit of analysis issues

No unit of analysis issues were noted, as women were the unit of randomisation.

Dealing with missing data

Data were analysed on an intention-to-treat basis as far as possible, and attempts were made to obtain missing data from the original trialists. When these could not be obtained, only the available data were analysed. If studies reported sufficient detail for calculation of MDs but no information on associated standard deviation (SD), we planned to assume that the outcome had an SD equal to the highest SD from other studies within the same analysis.

Assessment of heterogeneity

We considered whether the clinical and methodological characteristics of the included studies were sufficiently similar for meta-analysis to provide a clinically meaningful summary. Heterogeneity assessment was performed by measuring I2. An I2 measurement greater than 50% was taken to indicate substantial heterogeneity (Higgins 2011).

Assessment of reporting biases

In view of the difficulty in detecting and correcting for publication bias and other reporting biases, we minimised their potential impact by ensuring a comprehensive search for eligible studies and duplication of data. When appropriate, we planned to use a funnel plot to assess the possibility of small-study effects. We planned to construct a funnel plot to assess potential publication bias if sufficient studies reported the same comparison.

Data synthesis

When continuous measurements were used to assess the effects of interventions, we calculated the mean difference or, alternatively, the standardised mean difference if different scales were used. We combined the data of studies that were sufficiently similar using a fixed-effect model for the following comparisons. For binary (or dichotomous) outcomes, we expressed results for each study as Peto ORs with 95% CIs. We applied a fixed-effect model to assess outcomes if heterogeneity was minor; otherwise we planned to use a random-effects Mantel-Haenszel model. We performed statistical analysis using Review Manager software (RevMan 2012). When data were skewed or SDs were not calculable, the data were entered in "Other data" tables.

  • Medical interventions

    • Medical interventions versus placebo/no treatment or other interventions, specifically:

      • Progestogen versus placebo;

      • Sertaline versus placebo; or

      • Lofexidine versus placebo.

    • Medical interventions: head-to-head comparisons.

      • Goserelin versus progestogen.

      • Gabapentin versus amytriptyline.

  • Psychological treatments versus placebo/no treatment, or other interventions, specifically:

    • Psychotherapy versus no treatment;

    • Ultrasound versus traditional treatment;

    • Somatocognitive therapy versus no treatment;

    • Somatic, psychological or dietary therapy or physiotherapy versus no treatment; or

    • Written disclosure versus no treatment.

  • Complementary treatments versus no treatment/sham or placebo or other interventions.

    • Magnetic field therapy versus placebo magnet.

    • Physical therapy versus standard treatment (counselling).

Subgroup analysis and investigation of heterogeneity

If substantial heterogeneity was noted, the review authors planned to reassess the data and perform a random-effects meta-analysis. We also planned to consider doing meta-regression analysis or subgroup analysis for the following variables.

  • Intervention type.

    • Physical therapy.

    • Hormonal therapy.

    • Non-hormonal therapy.

    • Multi-disciplinary treatment.

  • Duration of intervention: one session versus repeated sessions.

  • Duration of follow-up: immediately after treatment versus post-treatment, for example, two weeks, four weeks, three months, six months, 12 months.

Sensitivity analysis

If sufficient studies were making the same comparison, the review authors planned to conduct sensitivity analyses for the primary outcome while considering the following issues: risk of bias, assessment of inclusion or exclusion of a study, nature of the data analysed and methods of analysis used.

Overall quality of the body of evidence: summary of findings table

We prepared a summary of findings table using Guideline Development Tool software. This table evaluates the overall quality of the body of evidence for outcomes of pain and adverse effects, using GRADE criteria (study limitations (i.e. risk of bias), consistency of effect, imprecision, indirectness and publication bias). Judgements about evidence quality (high, moderate or low) have been incorporated into the reporting of results for each outcome.

Results

Description of studies

Results of the search

The search revealed 21 studies that were potentially eligible and were retrieved in full text. A total of 13 studies met our inclusion criteria. Eight studies were excluded. See the study tables Characteristics of included studies and Characteristics of excluded studies.

Included studies

Study design and setting

A total of 13 RCTs were included in the review. Besides Walton 1992, which was a multicentre study, all other studies were single-centre studies. Four were conducted in the UK, three in the USA, one in Sweden, one in the Netherlands, one in Turkey, one in Austria (Sator-Katzenschlager 2005), one in Australia (Abbott 2006) and one in Norway (Haugstad 2008).

Participants

The studies included 406 women in the intervention group and 344 women in the control group.

Study populations had a similar age distribution, with mean ages of 27 to 35 years. All studies had comparable control and treatment groups with respect to parity except for Stones 2001, in which the intervention group had higher parity. All study populations had similar chronicity of pain, except in Soysal 2001, in which chronicity was not stated. All participants were women with chronic pelvic pain.

Interventions

  • Medical interventions versus placebo/no treatment or other medical interventions (seven studies).

    • Two of seven studies compared medroxyprogesterone against placebo (Farquhar 1989; Walton 1992).

    • One of seven studies compared medroxyprogesterone versus goserelin (Soysal 2001).

    • One of seven studies compared sertraline versus placebo (Engel 1998).

    • One of seven studies compared lofexidine versus placebo (Stones 2001).

    • One of seven studies compared gabapentin versus amytriptyline versus both (Sator-Katzenschlager 2005).

    • One of seven studies compared injection of botulinum toxin A versus placebo (Abbott 2006).

  • Complementary treatments versus no treatment/sham or placebo or other medical interventions (two studies).

    • One of two studies compared static magnetic fields versus placebo magnets (Brown 2002).

    • One of two studies compared physical treatment (distension of painful pelvic structures) versus control (usual care with counselling) (Heyman 2006).

  • Psychological/behavioural/cognitive treatments versus no treatment/placebo/other interventions (five studies).

    • One of five studies compared writing therapy (disclosure about their pain) versus control (non-disclosure) (Norman 2004).

    • One of five studies compared ultrasound scan and counselling session versus 'wait and see' (Ghaly 1994).

    • One of five studies examined an integrated approach (somatic, psychological, dietary, environmental and physiotherapeutic factors) versus standard care (Peters 1991).

    • One of five studies compared somatocognitive therapy (Mensendieck) versus standard care (Haugstad 2008).

    • One of five studies compared psychotherapy versus placebo (Farquhar 1989).

Outcomes

  • Primary outcomes.

  • Secondary outcomes.

The above outcomes were reported over the following follow-up duration.

Excluded studies

Eight studies were excluded from the review for the following reasons.

  • Two of eight studies were randomised cross-over trials with no washout period (Fenton 2008;Simsek 2007).

  • One of eight studies was an open-label uncontrolled trial (Brown 2008).

  • One of eight studies was excluded as it was an abstract with insufficient available information (Pearce 1986).

  • One of eight studies was excluded as this pilot study showed very inconsistent findings, leading the authors to not undertake analysis of outcomes (Hawk 2002).

  • One of eight studies had participants entered and evaluated at different time points in control and active groups, making comparison between groups difficult (Elcombe 1997).

  • One of eight studies was excluded as it included a surgical treatment (Onwude 2004).

  • One of eight studies was excluded as it was not an RCT (Reginald 1987).

Risk of bias in included studies

Allocation

Five studies were at low risk of selection bias related to sequence generation, as they used computer randomisation or a random numbers table (Abbott 2006; Farquhar 1989; Norman 2004; Soysal 2001; Stones 2001). The other eight studies did not describe the method used and were at unclear risk of this bias (Brown 2002; Engel 1998; Ghaly 1994; Haugstad 2008; Heyman 2006; Peters 1991; Sator-Katzenschlager 2005; Walton 1992).

Seven studies were at low risk of selection bias related to allocation concealment (Abbott 2006; Farquhar 1989; Haugstad 2008; Norman 2004; Peters 1991; Soysal 2001; Stones 2001). The other six studies were at unclear risk of this bias (Brown 2002; Engel 1998; Ghaly 1994; Heyman 2006; Sator-Katzenschlager 2005; Walton 1992).

Blinding

We considered blinding to influence the findings of the outcome.

Six studies were at low risk for blinding of participants and personnel (Abbott 2006; Brown 2002; Engel 1998; Farquhar 1989; Haugstad 2008; Stones 2001). Seven studies were at low risk for blinding of outcome assessors (Abbott 2006; Brown 2002; Engel 1998; Ghaly 1994; Norman 2004; Peters 1991; Soysal 2001). Blinding was not stated in one study (Walton 1992). Blinding of participants was not fully possible in four studies (Heyman 2006; Norman 2004; Peters 1991; Sator-Katzenschlager 2005).

Incomplete outcome data

Four studies analysed most (> 90%) of the randomly assigned women, and we judged them as low risk (Abbott 2006; Engel 1998; Peters 1991; Soysal 2001). One had 10% loss to follow-up and was deemed to be at unclear risk (Ghaly 1994).

Eight studies were considered at high risk of attrition bias (Brown 2002; Farquhar 1989; Haugstad 2008; Heyman 2006; Norman 2004; Sator-Katzenschlager 2005; Stones 2001; Walton 1992).

Selective reporting

Protocols were available for all studies.

Other potential sources of bias

None were identified.

Effects of interventions

See: Summary of findings for the main comparison Medical treatment compared with placebo for the management of chronic pelvic pain; Summary of findings 2 Medical treatment of chronic pelvic pain: head-to-head comparisons; Summary of findings 3 Psychological therapy compared with control interventions for the management of chronic pelvic pain; Summary of findings 4 Complementary therapy compared with control interventions for the management of chronic pelvic pain

1) Medical interventions versus placebo/no treatment

1.1 Progesterone versus placebo/no treatment
Primary outcome: pain
Medroxyprogesterone acetate versus placebo

Progestogen (MPA) was effective at the end of treatment, as denoted by the rate of women achieving a > 50% reduction in VAS pain score (Peto OR 3.00, 95% CI 1.70 to 5.31, two studies, n = 204, I2 = 22%). Evidence of benefit was maintained up to nine months after treatment (Peto OR 2.09, 95% CI 1.18 to 3.71, two studies, n = 204, I2 = 0%) (Analysis 1.1).

Secondary outcomes

No studies reported psychological outcomes, quality of life or requirement for analgesia.

Adverse outcomes

Farquhar 1989 reported a higher risk of weight gain and bloating in the MPA group than in the placebo group (weight gain 7.82, 95% CI 3.28 to 18.65, n = 85; bloatedness Peto OR 3.20, 95% CI 1.37 to 7.47, n = 85). No significant difference was noted between MPA and placebo groups in other reported medical events (e.g. leg colour change, benign breast lumps (Peto OR 1.74, 95% CI 0.52 to 5.82, n = 64)) (Walton 1992) (Analysis 1.1; Figure 4).

Figure 4.

Forest plot of comparison: 1 Medical treatment versus placebo, outcome: 1.1 Progesterone versus placebo.

1.2 Lofexidine hydrochloride versus placebo
Primary outcome: pain

No evidence showed a significant difference between lofexidine hydrochloride and placebo in the rate of women achieving a > 50% reduction in VAS pain score (Peto OR 0.42, 95% CI 0.11 to 1.61, one study, n = 39) (Analysis 1.2).

Secondary outcomes

No studies reported psychological outcomes, quality of life or requirement for analgesia.

Adverse outcomes

Women taking lofexidine reported significantly higher rates of dry mouth (Peto OR 8.6, 95% CI 2.44 to 30.31, one study, n = 39), drowsiness (Peto OR 3.8, 95% CI 1.09 to 13.26, one study, n = 39) and dizziness (Peto OR 4.77, 95% CI 1.29 to 15.46, one study, n = 39) than women who took placebo. No significant difference between groups was noted in the incidence of headache or migraine (Peto OR 0.33, 95% CI 0.09 to 1.16, one study, n = 39) (Analysis 1.2).

1.3 Sertraline versus placebo
Primary outcome: pain

No analysable data were available for this outcome, but one study reported no evidence of a significant difference between sertraline and placebo in pain scores on a zero to ten scale (MD -0.02, 95% CI -0.6 to -0.6, one study, n = 25) (Table 1).

Table 1. Change in pain, depression, somatisation and functional status
Engel 1998  
Composite pain intensitySF-36 functioning-emotional subscaleHealth perception
-0.02, 95% CI -0.6 to 0.6-30.4, 95% CI -50.3 to -10.63.0, 95% CI 0.3 to 5.7
Secondary outcomes
Psychological outcomes

No studies reported psychological outcomes.

Quality of life
Sertraline versus placebo
  • No analysable data were available for this outcome, but one study reported that the SF-36 subscale for health perception (range zero to ten) showed a small but statistically significant improvement in the sertraline arm (MD 3.0, 95% CI 0.3 to 5.7, one study, n = 25), and the functioning-emotional subscale (range not specified) showed a large, statistically significant decrement in the sertraline arm (MD -30.4, 95% CI -50.3 to -10.6, one study, n = 25) (Engel 1998) (Table 1).

Requirement for analgesia

No studies reported this outcome.

Adverse outcomes

No studies reported this outcome.

2) Medical treatment versus other medical treatment

2.1 Goserelin versus progestogen
Primary outcome: pain

Women taking goserelin showed greater improvement in pelvic pain score at one year (as measured on a scale of one to 100) than those taking progesterone (MD 3, 95% CI 2.08 to 3.92, one study, n = 47) (Analysis 2.1).

Secondary outcomes
Psychological outcomes

Mood and sexual function were improved to a greater extent one year after treatment among women taking goserelin than among those taking progestogen (Soysal 2001) (HADS total score, MD 1.3, 95% CI 0.42 to 2.18, n = 47; rSSRS score (revised Sabbatsberg Sexual Rating scale), MD 15.5, 95% CI 11.7 to 19.23, n = 47). HADS is a self assessment mood scale that is designed specifically for use in non-psychiatric hospital outpatients to assess anxiety and depression (Zigmond 1983). The score is out of a total of 42, and the higher the score, the greater the anxiety or depression. The rSSRS is a 12-item questionnaire of sexual functioning (Garrat 1995). A higher score (scale of zero to 100) represents greater sexual satisfaction (Analysis 2.1).

This study did not report on our other secondary outcomes (quality of life, requirement for analgesia or adverse outcomes).

2.2 Gabapentin versus amytriptyline
Primary outcome: pain

The VAS pain score (on a one to ten scale) favoured gabapentin compared with amytriptyline at 24 months' follow-up (MD -1.50, 95% CI -2.06 to -0.94, n = 40) (Sator-Katzenschlager 2005) (Analysis 2.2).

Secondary outcomes

This study did not report on our other secondary outcomes (psychological outcomes, quality of life or requirement for analgesia).

Adverse outcomes

Study authors reported no significant difference in the rate of side effects among women taking gabapentin compared with women who took amytriptyline (no extractable data).

3) Psychological treatment versus placebo/no treatment or other interventions

3.1 Improvement in pain scores
Primary outcome: pain
Ultrasound scan and counselling session versus 'wait and see'

At four to nine months' follow-up, women who had ultrasound reassurance and counselling were more likely to have improved pain than those given a 'wait and see' policy (Peto OR 6.77, 95% CI 2.83 to 16.19, n = 90) (Ghaly 1994) (Analysis 3.1; Figure 5). Assessment was based on a 40-point scale on the McGill Pain Questionnaire, with a change in score of five points deemed a meaningful improvement.

Figure 5.

Forest plot of comparison: 3 Psychological therapy versus control, outcome: 3.1 Improvement in pain scores.

Somatocognitive therapy (Mensendieck) versus standard gynaecological clinical care

Rates of improvement in pain (≥ 50% reduction in VAS score) did not significantly differ between women who underwent somatocognitive therapy and those who underwent standard gynaecological treatment (Peto OR 3.38, 95% CI 0.97 to 11.80, n = 40) (Haugstad 2008) (Analysis 3.1).

Integrated approach (somatic, psychological, dietary, environmental and physiotherapeutic factors) versus standard care

Rates of improvement in pain (≥ 50% reduction in VAS score) did not significantly differ between women who underwent the integrated approach and those who underwent standard care (Peto OR 1.52, 95% CI 0.71 to 3.27, n = 106) (Peters 1991) (Analysis 3.1).

Writing therapy (disclosure of pain) versus non-disclosure

Rates of improvement in pain (measured on a pain scale of zero to five, with improvement considered an improvement of at least one point) showed that a significantly higher number of 'disclosure patients' improved compared with 'non-disclosure patients' (Peto OR 4.47, 95% CI 1.41 to 14.13, n = 48) (Norman 2004) (Analysis 3.1).

Psychotherapy versus placebo

No significant difference was noted between the psychotherapy group and the placebo group in rates of pain improvement (≥ 50% reduction in VAS score) immediately after treatment (Peto OR 0.79, 95% CI 0.24 to 2.59, n = 51) or at nine months' follow-up (Peto OR 0.46, 95% 0.14 to 1.49, n = 51) (Farquhar 1989) (Analysis 3.1).

Secondary outcomes
3.2 Psychological outcomes
Physiotherapy and psychotherapy versus standard gynaecological advice

Depression scores (as measured on the depression scale of the GHQ-30) did not differ significantly between women who received psychological treatment (physiotherapy and psychotherapy) and those who received standard gynaecological advice (MD -0.30, 95% CI -0.80 to 0.20, n = 26) (Haugstad 2008) (Analysis 3.2).

Writing therapy (disclosure of pain) versus non-disclosure

Mood at the end of two months (as measured on the negative affect scale of the Positive Affect Negative Affect Scale (PANAS)) did not differ significantly between women who underwent writing therapy (disclosure of pain) and controls (non-disclosure) (MD -0.02, 95% CI -0.43 to 0.39, n = 48) (Norman 2004) (Analysis 3.2).

Studies of psychological treatment did not report other secondary outcomes (quality of life, requirement for analgesia or adverse effects).

4) Complementary treatments versus no treatment/sham or placebo or other interventions

Physical treatment versus standard treatment
Primary outcome: pain

Physical treatment (distension of painful pelvic structures) was found to be significantly better than standard treatment (counselling), as reflected by a greater reduction in self rating scores on a VAS one to 100 scale for pain intensity (MD 35.80, 95% CI 23.08 to 48.52) and for pain during intercourse (MD 19.13, 95% CI 3.61 to 34.65) (Heyman 2006) (Analysis 4.1).

Magnetic therapy versus placebo magnet
Primary outcome: pain

No evidence of benefit was found in women receiving active magnets who completed four weeks of double-blind treatment compared with those having placebo magnets in terms of the Pelvic Pain Index (MD 0.50, 95% CI -1.92 to 0.92, one study, n = 19), Clinical Global Impressions-Severity (MD -0.90, 95% CI -2.05 to 0.25, one study, n = 19) and McGill Pain Disability scores (MD -16.70, 95% CI -34.05 to 0.65, one study, n = 19) (Brown 2002) (Analysis 4.2).

Studies of physical treatment did not report secondary outcomes (quality of life, requirement for analgesia or adverse effects).

Other analyses

Too few studies reported the same comparison for planned subgroup and sensitivity analyses to be conducted, or for a funnel plot to be constructed.

Discussion

Summary of main results

Progestogen (MPA) was more effective than placebo at the end of treatment in terms of the number of women achieving a > 50% reduction in VAS pain score immediately after treatment (Peto OR 3.00, 95% CI 1.70 to 5.31, two studies, n = 204, I2 = 22%). Evidence of benefit was maintained up to nine months after treatment (Peto OR 2.09, 95% CI 1.18 to 3.71, two studies, n = 204, I2 = 0%). Women receiving medical treatment with progestogen reported more adverse effects (weight gain and bloating) than those given placebo.

Head-to-head comparisons showed that women taking goserelin had greater improvement in pelvic pain score (MD 3, 95% CI 2.08 to 3.92, one study, n = 47), mood (HADS total score, MD 1.3, 95% CI 0.42 to 2.18, n = 47) and sexual function at one year than those taking progestogen (rSSRS score (revised Sabbatsberg Sexual Rating Scale), MD 15.5, 95% CI 11.7 to 19.23, n = 47). Women taking gabapentin had a more favourable VAS pain score than those taking amytriptyline (MD -1.50, 95% CI -2.06 to -0.94, n = 40). Women who underwent reassurance ultrasound scans and counselling were more likely to have improved pain than those given a standard 'wait and see' policy (Peto OR 6.77, 95% CI 2.83 to 16.19, n = 90). Significantly more women who had writing therapy as a disclosure had improvement in pain compared with those in the non-disclosure group (MD -0.02, 95% CI -0.43 to 0.39, n = 48).

Because of the heterogeneity of the included studies, we were not able to combine the results of studies examining the effects of various forms of psychological and complementary treatment on pain and quality of life in women with CPP.

Overall completeness and applicability of evidence

Many of the interventions were single randomised controlled studies, and this limited the available evidence on which current clinical practice can be based. Progestogen appears to be an effective treatment for chronic pelvic pain, but its efficacy beyond 12 months and in older women has not been studied. High-dose progestogen treatments are often limited by side effects and are contraindicated in women attempting to conceive. The use of neuromodulators such as gabapentin has attracted much interest, and undoubtedly, results from the feasibility study of the efficacy of action of gabapentin (Horne 2012), which is currently under way, will help shed some light on the question of whether neuromodulators are effective in the management of CPP.

We were unable to combine different treatments that involve psychological interventions to provide meaningful analysis. Although in principle, each of the interventions could be tested more rigorously in RCTs, it makes more sense in clinical terms to apply effective methods of cognitive and behavioural pain management (Williams 2012) to pelvic pain because it shares so much of the impact and problems of chronic pain at other sites (Daniels 2010).

This review is not able to conclude on the effect of non-surgical interventions on quality of life because of diversity or absence of outcome measures in the studies reviewed. It would be helpful if trialists observed the recommendations of the IMMPACT initiative on outcome measurement in pain trials (Dworkin 2005; Dworkin 2010).

Quality of the evidence

Thirteen RCTs were included in this review. These studies included 406 women in the intervention groups and 344 women in the control groups. The conclusion of evidence of benefit drawn mainly from improvement in pain assessment scores (VAS specifically) cannot be directly translated to improvement in functional outcomes and quality of life, the latter being key contributors to the morbidity associated with chronic pelvic pain. RCTs included in this review also suffered from high attrition rates, which contributed to incomplete outcome data. A wide range of follow-up was provided (range four weeks to 12 months); studies with shorter follow-up data lend themselves to confounding effects of placebo, although studies with longer follow-up are associated with higher attrition rates.

The quality of the evidence, which was rated using GRADE methods, ranged from very low to high. The main reasons for downgrading evidence quality were high attrition rates, lack of blinding, failure to clearly describe randomisation procedures and lack of precision.

Potential biases in the review process

Both YCC and GS independently screened and identified relevant studies; furthermore, a final search was performed at the completion of the review to ensure that no new studies had been published during preparation of the manuscript. However, despite all efforts, studies in press may have been missed.

Agreements and disagreements with other studies or reviews

None known.

Authors' conclusions

Implications for practice

Evidence of moderate quality supports progestogen as an option for chronic pelvic pain, with efficacy during treatment. In practice, it may be most acceptable among women unconcerned about progestogenic side effects such as weight gain and bloating. No evidence indicates that lofexidine or sertraline was more effective than placebo, although data were very scanty.

Head-to-head comparisons revealed that women taking goserelin showed greater improvement in pelvic pain score, mood and sexual function at one year compared with those taking progestogen; women taking gabapentin had a more favourable VAS pain score than those taking amytriptyline, although these results were based on single studies and therefore have to be interpreted with caution.

Women who underwent reassurance ultrasound scans and counselling were more likely to have improved pain compared with those having a standard 'wait and see' policy. Significantly more women who had writing therapy as a disclosure had improvement in pain compared with those in the non-disclosure group. Again, as these findings are based on single studies, more studies will be required to confirm the results.

The quality of the evidence was low or moderate for most comparisons, and in most cases, evidence was derived from single small studies at a high or unclear risk of bias

Implications for research

This update of the review has shown that a wide range of interventions have been tried for the non-surgical management of chronic pelvic pain. But the fact that many of these therapies were single randomised controlled studies greatly limits the available evidence on which current clinical practice can be based. Hence, more studies are required to be replicated on these individual interventions to confirm the findings of existing studies.

Future trials should employ recommended objective and patient-reported measures that capture not just pain measures but outcome measures focused on the biopsychosocial aspects of women with CPP (Dworkin 2005; Dworkin 2010).

Future researchers in this area should consider taking advantage of advancements in technology to design studies that can capture more accurate activity and quality of life data than the limited snap-shot data that questionnaires can generate.

As chronic pelvic pain has a multifactorial aetiology, shifting the research paradigm from single-intervention RCTs to those for which the main objective is to develop and deliver effective integrated multidisciplinary care pathways will be critical to the successful management of this disorder.

Acknowledgements

Marian Showell (Trial Search Co-ordinator of the Cochrane Menstrual Disorders and Subfertility Group) for designing and running the search. Helen Nagels and Jane Marjoribanks for methodological and editorial help.

Data and analyses

Download statistical data

Comparison 1. Medical treatment versus placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Progesterone versus placebo2 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
1.1 Improvement in pain score at end of treatment2204Peto Odds Ratio (Peto, Fixed, 95% CI)3.00 [1.70, 5.31]
1.2 Improvement in pain score (up to nine months after treatment)2204Peto Odds Ratio (Peto, Fixed, 95% CI)2.09 [1.18, 3.71]
1.3 Weight gain185Peto Odds Ratio (Peto, Fixed, 95% CI)7.82 [3.28, 18.65]
1.4 Bloatedness185Peto Odds Ratio (Peto, Fixed, 95% CI)3.20 [1.37, 7.47]
1.5 Other medical events—leg colour change, breast lumps164Peto Odds Ratio (Peto, Fixed, 95% CI)1.74 [0.52, 5.82]
2 Lofexidine versus placebo1 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
2.1 Improvement in pain score139Peto Odds Ratio (Peto, Fixed, 95% CI)0.42 [0.11, 1.61]
2.2 Drowsiness/lethargy139Peto Odds Ratio (Peto, Fixed, 95% CI)3.80 [1.09, 13.26]
2.3 Dry mouth139Peto Odds Ratio (Peto, Fixed, 95% CI)8.60 [2.44, 30.31]
2.4 Dizziness139Peto Odds Ratio (Peto, Fixed, 95% CI)4.47 [1.29, 15.46]
2.5 Headache/migraine139Peto Odds Ratio (Peto, Fixed, 95% CI)0.33 [0.09, 1.16]
Analysis 1.1.

Comparison 1 Medical treatment versus placebo, Outcome 1 Progesterone versus placebo.

Analysis 1.2.

Comparison 1 Medical treatment versus placebo, Outcome 2 Lofexidine versus placebo.

Comparison 2. Medical treatment: head-to-head comparison
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Goserelin versus progestogen1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Improvement in pelvic pain score at one year1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 rSSRS score1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.3 HADS total score at one year1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Gabapentin versus amytriptyline1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 VAS pain score at 24 months1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 2.1.

Comparison 2 Medical treatment: head-to-head comparison, Outcome 1 Goserelin versus progestogen.

Analysis 2.2.

Comparison 2 Medical treatment: head-to-head comparison, Outcome 2 Gabapentin versus amytriptyline.

Comparison 3. Psychological therapy versus control
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Improvement in pain scores5 Peto Odds Ratio (Peto, Fixed, 95% CI)Subtotals only
1.1 Ultrasound scan and counselling session versus 'wait and see'190Peto Odds Ratio (Peto, Fixed, 95% CI)6.77 [2.83, 16.19]
1.2 Somatocognitive therapy (Mensendieck) versus standard gynaecological clinical care140Peto Odds Ratio (Peto, Fixed, 95% CI)3.38 [0.97, 11.80]
1.3 Integrated approach (somatic, psychological, dietary, environmental and physiotherapeutic factors) versus standard care1106Peto Odds Ratio (Peto, Fixed, 95% CI)1.52 [0.71, 3.27]
1.4 Writing therapy (disclosure of pain) versus non-disclosure148Peto Odds Ratio (Peto, Fixed, 95% CI)4.47 [1.41, 14.13]
1.5 Psychotherapy versus placebo: at end of treatment151Peto Odds Ratio (Peto, Fixed, 95% CI)0.79 [0.24, 2.59]
1.6 Psychotherapy versus placebo: nine months post-treatment151Peto Odds Ratio (Peto, Fixed, 95% CI)0.46 [0.14, 1.49]
2 Depression/negative mood scores2 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Physiotherapy and psychotherapy versus standard gynaecological advice1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.2 Writing therapy (disclosure of pain) versus non-disclosure1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 3.1.

Comparison 3 Psychological therapy versus control, Outcome 1 Improvement in pain scores.

Analysis 3.2.

Comparison 3 Psychological therapy versus control, Outcome 2 Depression/negative mood scores.

Comparison 4. Complementary therapy versus control
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Distension of painful pelvic structures versus counselling1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
1.1 Intensity of pelvic pain: change in pain score1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
1.2 Painful intercourse: change in pain score1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Magnetic therapy versus control magnet1 Mean Difference (IV, Fixed, 95% CI)Totals not selected
2.1 Pelvic Pain Index1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.2 Clinical Global Impression-Severity1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
2.3 Pain Disability Index1 Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]
Analysis 4.1.

Comparison 4 Complementary therapy versus control, Outcome 1 Distension of painful pelvic structures versus counselling.

Analysis 4.2.

Comparison 4 Complementary therapy versus control, Outcome 2 Magnetic therapy versus control magnet.

Appendices

Appendix 1. Ovid MEDLINE

1 exp Life Style/ (55316)
2 exp exercise/ or exp exercise therapy/ or exp relaxation techniques/ or exp walking/ or exp yoga/ (119058)
3 Life Style$.tw. (8185)
4 exercis$.tw. (172356)
5 (walk$ or jog or run or yoga).tw. (108651)
6 exp Diet/ (169662)
7 diet$.tw. (334694)
8 (treatment$ or therap$).tw. (3515613)
9 exp psychology/ or exp cognitive science/ or exp psychology, medical/ (55140)
10 psycholog$.tw. (141613)
11 (cognitive adj5 therap$).tw. (9657)
12 psychotherap$.tw. (28610)
13 meditation.tw. (1882)
14 (biofeedback or hypnosis or reassur$).tw. (17256)
15 ultraso$.tw. (213950)
16 exp analgesics/ or exp clonidine/ or exp analgesics, non-narcotic/ or exp anti-inflammatory agents, non-steroidal/ or exp diclofenac/ or exp ibuprofen/ or exp naproxen/ or exp cyclooxygenase inhibitors/ (398830)
17 non-steroidal anti-inflammator$.tw. (9925)
18 NSAIDS.tw. (11889)
19 exp Contraceptives, Oral/ (39927)
20 (oral contracept$ or OCP).tw. (22244)
21 exp Progestins/ (58187)
22 (progestin$ or progestogen$).tw. (13525)
23 (danazol or GnRH analogue$).tw. (3231)
24 exp Antidepressive Agents/ (112330)
25 Antidepress$.tw. (41592)
26 anticonvuls$.tw. (18010)
27 analges$.tw. (77720)
28 caffeine.tw. (20048)
29 local anaesth$.tw. (9304)
30 corticosteroid$.tw. (67567)
31 (counselling or counseling).tw. (50580)
32 iucd.tw. (414)
33 transcutaneous nerve stimulation.tw. (248)
34 exp complementary therapies/ or exp acupressure/ or exp acupuncture therapy/ or exp electroacupuncture/ or exp moxibustion/ or exp holistic health/ or exp medicine, traditional/ or exp mind-body therapies/ or exp "biofeedback (psychology)"/ or exp hypnosis/ or exp "imagery (psychotherapy)"/ or exp meditation/ or exp relaxation therapy/ or exp yoga/ or exp phytotherapy/ or exp reflexotherapy/ (157318)
35 exp anesthetics, local/ or exp lidocaine/ (84838)
36 local anesthetic$.tw. (12217)
37 referral$.tw. (56399)
38 magnetic field$.tw. (22048)
39 sertraline.tw. (2747)
40 medroxyprogesterone$.tw. (5030)
41 emotional disclosure.tw. (102)
42 reinforcement.tw. (20607)
43 goserelin.tw. (696)
44 dihydroergotamine.tw. (1274)
45 lofexidine.tw. (146)
46 (chinese medicine$ or chinese herb$).tw. (12418)
47 pain relief.tw. (18775)
48 gonadotropin-releasing hormone analogue$.tw. (367)
49 or/1-48 (5112093)
50 exp Pelvic Pain/ (5690)
51 (Pelv$ adj1 Pain$).tw. (5141)
52 (Pelv$ adj1 congest$).tw. (203)
53 abdomin$ pain$.tw. (31974)
54 or/50-53 (40525)
55 49 and 54 (22265)
56 randomized controlled trial.pt. (322734)
57 controlled clinical trial.pt. (83763)
58 randomized.ab. (238641)
59 placebo.tw. (137933)
60 clinical trials as topic.sh. (158570)
61 randomly.ab. (175416)
62 trial.ti. (102055)
63 (crossover or cross-over or cross over).tw. (52722)
64 or/56-63 (791047)
65 (animals not (humans and animals)).sh. (3594930)
66 64 not 65 (730147)
67 66 and 55 (2640)
68 (200909$ or 200910$ or 200911$ or 200912$).ed. (242918)
69 (2011$ or 2012$).ed. (1175160)
70 68 or 69 (1418078)
71 67 and 70 (293)

This search was updated on 15 May 2013, and again on 5 February 2014.

Appendix 2. PsycINFO

1 (Pelv$ adj1 Pain$).tw. (344)
2 (Pelv$ adj1 congest$).tw. (7)
3 1 or 2 (348)
4 random.tw. (34819)
5 control.tw. (271098)
6 double-blind.tw. (15805)
7 clinical trials/ (5895)
8 placebo/ (3166)
9 exp Treatment/ (511206)
10 or/4-9 (774043)
11 3 and 10 (158)
12 limit 11 to yr="2009 -Current" (37)

This search was updated on 15 May 2013, and again on 5 February 2014.

Appendix 3. EMBASE

1 Life Style$.tw. (10557)
2 exercis$.tw. (206770)
3 (walk$ or jog or run or yoga).tw. (129681)
4 exp Diet/ (162989)
5 diet$.tw. (385363)
6 psycholog$.tw. (200082)
7 (cognitive adj5 therap$).tw. (14563)
8 psychotherap$.tw. (40897)
9 meditation.tw. (2356)
10 (biofeedback or hypnosis or reassur$).tw. (21541)
11 ultraso$.tw. (269667)
12 non-steroidal anti-inflammator$.tw. (12612)
13 NSAIDS.tw. (16871)
14 (oral contracept$ or OCP).tw. (22315)
15 (progestin$ or progestogen$).tw. (14259)
16 (danazol or GnRH analogue$).tw. (4102)
17 Antidepress$.tw. (55468)
18 anticonvuls$.tw. (22015)
19 analges$.tw. (98950)
20 caffeine.tw. (23068)
21 local anaesth$.tw. (11695)
22 corticosteroid$.tw. (84150)
23 (counselling or counseling).tw. (62272)
24 iucd.tw. (464)
25 transcutaneous nerve stimulation.tw. (286)
26 local anesthetic$.tw. (14301)
27 referral$.tw. (71060)
28 magnetic field$.tw. (19054)
29 sertraline.tw. (3769)
30 medroxyprogesterone$.tw. (5409)
31 emotional disclosure.tw. (132)
32 reinforcement.tw. (21250)
33 goserelin.tw. (937)
34 dihydroergotamine.tw. (1486)
35 lofexidine.tw. (195)
36 (chinese medicine$ or chinese herb$).tw. (17182)
37 pain relief.tw. (25378)
38 gonadotropin-releasing hormone analogue$.tw. (435)
39 nerve block.tw. (4772)
40 exp nerve block/ (21291)
41 exp lifestyle/ (59627)
42 exp exercise/ (169176)
43 exp psychology/ (143266)
44 exp analgesic agent/ (555528)
45 exp nonsteroid antiinflammatory agent/ (370296)
46 exp oral contraceptive agent/ (48771)
47 exp antidepressant agent/ (270421)
48 exp gestagen/ (126786)
49 exp alternative medicine/ (29258)
50 exp local anesthetic agent/ (158486)
51 or/1-50 (2794136)
52 Pelv$ Pain$.tw. (6765)
53 Pelv$ congest$.tw. (252)
54 abdomin$ pain$.tw. (42822)
55 exp pelvis pain syndrome/ (8090)
56 CPP.tw. (6602)
57 or/52-56 (58811)
58 Clinical Trial/ (862803)
59 Randomized Controlled Trial/ (318508)
60 exp randomization/ (57568)
61 Single Blind Procedure/ (15595)
62 Double Blind Procedure/ (107813)
63 Crossover Procedure/ (33346)
64 Placebo/ (194847)
65 Randomi?ed controlled trial$.tw. (72598)
66 Rct.tw. (8838)
67 random allocation.tw. (1124)
68 randomly allocated.tw. (16791)
69 allocated randomly.tw. (1783)
70 (allocated adj2 random).tw. (703)
71 Single blind$.tw. (11911)
72 Double blind$.tw. (125667)
73 ((treble or triple) adj blind$).tw. (263)
74 placebo$.tw. (171422)
75 prospective study/ (199004)
76 or/58-75 (1231050)
77 case study/ (14928)
78 case report.tw. (221515)
79 abstract report/ or letter/ (824756)
80 or/77-79 (1056765)
81 76 not 80 (1196494)
82 51 and 57 and 81 (2878)
83 (2011$ or 2012$).em. (1317175)
84 82 and 83 (336)

This search was updated on 15 May 2013, and again on 5 February 2014.

Appendix 4. Cochrane Central Register of Controlled Trials

1 exp Life Style/ (1848)
2 exp exercise/ or exp exercise therapy/ or exp relaxation techniques/ or exp walking/ or exp yoga/ (13798)
3 Life Style$.tw. (230)
4 exercis$.tw. (25842)
5 (walk$ or jog or run or yoga).tw. (11305)
6 exp Diet/ (9692)
7 diet$.tw. (20782)
8 (treatment$ or therap$).tw. (287111)
9 exp psychology/ or exp cognitive science/ or exp psychology, medical/ (731)
10 psycholog$.tw. (8177)
11 (cognitive adj5 therap$).tw. (3502)
12 psychotherap$.tw. (2268)
13 meditation.tw. (367)
14 (biofeedback or hypnosis or reassur$).tw. (2025)
15 ultraso$.tw. (9144)
16 exp analgesics/ or exp clonidine/ or exp analgesics, non-narcotic/ or exp anti-inflammatory agents, non-steroidal/ or exp diclofenac/ or exp ibuprofen/ or exp naproxen/ or exp cyclooxygenase inhibitors/ (31219)
17 non-steroidal anti-inflammator$.tw. (1089)
18 NSAIDS.tw. (1154)
19 exp Contraceptives, Oral/ (2830)
20 (oral contracept$ or OCP).tw. (1584)
21 exp Progestins/ (1708)
22 (progestin$ or progestogen$).tw. (1379)
23 (danazol or GnRH analogue$).tw. (451)
24 exp Antidepressive Agents/ (8730)
25 Antidepress$.tw. (5618)
26 anticonvuls$.tw. (527)
27 analges$.tw. (19712)
28 caffeine.tw. (1704)
29 local anaesth$.tw. (1915)
30 corticosteroid$.tw. (6894)
31 (counselling or counseling).tw. (4514)
32 iucd.tw. (21)
33 transcutaneous nerve stimulation.tw. (73)
34 exp complementary therapies/ or exp acupressure/ or exp acupuncture therapy/ or exp electroacupuncture/ or exp moxibustion/ or exp holistic health/ or exp medicine, traditional/ or exp mind-body therapies/ or exp "biofeedback (psychology)"/ or exp hypnosis/ or exp "imagery (psychotherapy)"/ or exp meditation/ or exp relaxation therapy/ or exp yoga/ or exp phytotherapy/ or exp reflexotherapy/ (10237)
35 exp anesthetics, local/ or exp lidocaine/ (8493)
36 local anesthetic$.tw. (2318)
37 referral$.tw. (2888)
38 magnetic field$.tw. (275)
39 sertraline.tw. (1089)
40 medroxyprogesterone$.tw. (1246)
41 emotional disclosure.tw. (62)
42 reinforcement.tw. (1178)
43 goserelin.tw. (333)
44 dihydroergotamine.tw. (294)
45 lofexidine.tw. (62)
46 (chinese medicine$ or chinese herb$).tw. (1599)
47 pain relief.tw. (5639)
48 gonadotropin-releasing hormone analogue$.tw. (64)
49 or/1-48 (370766)
50 exp Pelvic Pain/ (507)
51 (Pelv$ adj1 Pain$).tw. (390)
52 (Pelv$ adj1 congest$).tw. (11)
53 abdomin$ pain$.tw. (1687)
54 or/50-53 (2412)
55 49 and 54 (2000)
56 limit 55 to yr="2009 -Current" (275)

This search was updated on 15 May 2013, and again on 5 February 2014.

Appendix 5. AMED (Allied and Complementary Medicine)

1 (Pelv$ adj1 Pain$).tw. (105)
2 (Pelv$ adj1 congest$).tw. (4)
3 1 or 2 (109)
4 random.tw. (1984)
5 control.tw. (18120)
6 double-blind.tw. (1482)
7 clinical trials/ (1669)
8 placebo/ (517)
9 or/4-8 (22380)
10 3 and 9 (14)

This search was updated on 15 May 2013, and again on 5 February 2014.

Appendix 6. Search strategy

YC816 Search string 09.09.09

Keywords CONTAINS "pelvic congestion" or "pelvic venous congestion" or "pelvic pain" or "chronic pain" or "chronic pelvic pain" or "pain-pelvic" or Title CONTAINS "pelvic congestion" or "pelvic venous congestion" or "pelvic pain" or "chronic pain" or "chronic pelvic pain" or "pain-pelvic"

The MEDLINE search was combined with the Cochrane highly sensitive search strategy for identifying randomized trials which appears in the Cochrane Handbook of Systematic Reviews of Interventions (Version 5.0.2 chapter 6, 6.4.11)
The EMBASE search is combined with trial filters developed by the Scottish Intercollegiate Guidelines Network (SIGN) http://www.sign.ac.uk/methodology/filters.html#random

There is no language restriction in these searches.

History

Protocol first published: Issue 11, 2010
Review first published: Issue 3, 2014

DateEventDescription
30 October 2009New search has been performedThis review was previously part of the review 'Interventions for treating chronic pelvic pain in women'. Due to the increase in the total number of studies, this review will now focus only on the non-surgical management of chronic pelvic pain. Another review on surgical management is also planned.

Contributions of authors

YCC performed the analysis and was the lead author in the writing of the review. GS contributed to the methodology and content of the review. AW contributed to the content and acted as a moderator.

Declarations of interest

None known.

Sources of support

Internal sources

  • University of Southampton, UK.

  • University of Auckland, New Zealand.

External sources

  • No sources of support supplied

Differences between protocol and review

This review revises and updates the previous review entitled 'Interventions for women with chronic pelvic pain', which included only studies involving non-surgical interventions. Surgical interventions will be covered in a separate review.

In the published protocol, we planned to consider the following six intervention groups.

  • Medical interventions.

  • Alternative/complementary therapies (such as magnetic field therapy, therapies encompassed in traditional Chinese medicine (acupuncture, herbal therapy, moxibustion), transcutaneous nerve stimulation and transcranial current stimulation).

  • Psychological therapies (such as ultrasonography as a reassurance tool, written or oral emotional disclosures, counselling, cognitive therapy and biofeedback).

  • Physical therapy (such as massaging and stretching).

  • Lifestyle (such as exercise and diet).

  • Multidisciplinary/integrated approach: interventions combining two or more of the approaches described in the categories above.

In the review, we considered the following three intervention groups.

  • Medical interventions.

  • Psychological treatments versus placebo/no treatment, or other interventions.

  • Complementary treatments versus no treatment/sham or placebo or other interventions.

Rationale for change

Interventions were regrouped using broader principles than those used in the protocol. Complementary and physical therapies were grouped together, as they aim to make a physical change to reduce pain, thereby achieving improved quality of life; psychological, educational and rehabilitative treatments were grouped together, as they aim to enable the person with CPP to manage the pain better, thereby achieving a better quality of life.

This regrouping is consistent with handling of physical, psychological and rehabilitative therapies in the Pain, Palliative and Supportive Care CRG (PaPaS) and with the rationales of the interventions. It allows some combination of studies, which otherwise would all be single studies, from which we could learn little. It is rare if not impossible for these interventions, which rely much more on the skills, training and orientation of the therapist than on a highly quality-controlled substance, to resemble one another much in practice.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abbott 2006

MethodsRandomised controlled trial
Participants

N = 60 (30 each group)

Women aged 18 to 55 years who had more than two years of chronic pelvic pain that caused disruption to their daily activities

Women were excluded if they were breastfeeding, pregnant or desiring pregnancy during the study period, were unwilling to use contraception during the study period or had previously received botulinum toxin type A injections to the pelvic floor. Palpable pelvic pathology, current use of aminoglycoside antibiotics, history of neurological or bleeding disorders and known sensitivity to the formulation of botulinum toxin type A were also reasons for exclusion

Interventions

Women were randomly assigned to receive 80 units of botulinum toxin type A at a concentration of 20 units/mL or saline injections (placebo group)

FU 26 weeks after injections

OutcomesVAS, EuroQOL-5D (EQ-5D), SF-12, Sexual Activities Questionnaire
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated sequence
Allocation concealment (selection bias)Low riskCentral telephone randomisation
Blinding of participants and personnel (performance bias)
All outcomes
Low riskPlacebo injection given
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Less than 10% dropout

Two from placebo; one from botulinum group

Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Brown 2002

Methods

Method of allocation: unclear

Power calculation: yes

Exclusion postrandomisation: zero

Losses to follow-up: one

Intention-to-treat analysis: no

Source of funding: BIOflex Medical Magnets

Participants

Country: USA

Number of participants: 32

Inclusion criteria: pelvic pain > six months despite other treatment, impaired social function, trigger/circumscribed tender point on examination, normal pelvic examination, normal cervical smears

Age: 18 to 50 years

Source of participants: gynaecology clinic

Exclusion criteria: pregnancy, breastfeeding, medical disorders, metal/electronic device, BMI > 35

Interventions

Treatment: static magnetic fields (n = 16)

Control: no treatment (n = 17)

Duration: two to four weeks

OutcomesThe McGill Pain Questionnaire, Pain Disability Index, Clinical Global Impression Scale
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot specified
Allocation concealment (selection bias)Unclear riskNot specified
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blinded
Incomplete outcome data (attrition bias)
All outcomes
High riskVariable duration of study. Subgroup analysis of women who continued to have four weeks of treatment showed significance. High discontinuation between two and four weeks (41% attrition rate)
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Engel 1998

Methods

Randomisation: unclear

Method of allocation: unclear

Double-blinded

Exclusions postrandomisation: two

Losses to follow-up: zero

Unusual study design: cross-over design

Participants

Country: USA

Number of participants: 25

Age: mean 29

Sex: F

Inclusion criteria: pelvic pain for longer than three months, no psychoactive medication for previous two weeks

Exclusion criteria: laparoscopy within three months, failed seven to 10-day placebo run-in phase

Interventions

Treatments: sertaline 50 mg twice daily

Control: placebo

Duration: six weeks

Follow-up: end of treatment

Outcomes

Composite pain score

SF-36

Hamilton Depression Rating Scale

Social Adjustment Survey

Hopkins Symptoms Checklist Somatization items

Pin

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskMethod not clearly specified
Allocation concealment (selection bias)Unclear riskNot specified
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskDouble-blinded
Incomplete outcome data (attrition bias)
All outcomes
Low risk25 randomly assigned, 23 completed the study
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Farquhar 1989

Methods

Randomisation: blocks of 12

Method of allocation: sealed envelopes

Exclusion postrandomisation: zero

Losses to follow-up: seven

Unusual study design (e.g. factorial)

Participants

Country: England

Number of participants: 102

Age: mean 29.8

Sex: F

Inclusion criteria: pelvic pain for longer than six months, no pathology on laparoscopy, venogram score of five or higher

Exclusion criteria: recent psychiatric disease, history of thromboembolism

Postmenopausal, previous hysterectomy

Interventions

Treatments: medroxyprogesterone acetate (MPA) 50 mg daily (n = 25)

MPA and psychotherapy (n = 26)

Control: placebo (n = 25)

Placebo and psychotherapy (n = 26)

Duration: four months

Follow-up: nine months

Outcomes

Visual analogue scale pain score

Pain improvement rating scale

Side effects

NotesNot blinded to psychotherapy. Quality score A
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskRandomisation by random numbers table
Allocation concealment (selection bias)Low riskNumbered sealed envelopes for medications
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blinded
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskIt was recognised that the women might know whether they were receiving MPA because of its effect on their menstrual cycle. Therefore, all were told that both treatments— MPA and placebo—could induce amenorrhoea or irregular vaginal bleeding or have no obvious effect. In addition, women were asked to stop all forms of hormonal or intrauterine contraception and to use barrier methods throughout the 13 months of the trial
Incomplete outcome data (attrition bias)
All outcomes
High riskOf 102 women, 84 completed the full study (18% attrition). Of the other 18 women, 12 withdrew during the treatment period and six during the follow-up. Reasons cited were pregnancy, failure to attend the clinic and inability to maintain trial protocol
Selective reporting (reporting bias)Low riskLess than 10% loss to follow-up
Other biasLow riskNil

Ghaly 1994

Methods

Closed envelope system

Losses to follow-up: 10

Participants

Country: Scotland

Number of participants: 100 (50 each group)

Age: 21 to 55

Sex: F

Inclusion criteria: > six months' pain, negative laparoscopy

Exclusion criteria: previous malignant disease, mental retardation, medical treatment for pelvic pain at first visit, suspicion of malignant disease on pelvic examination, abnormal pelvic examination

Interventions

Treatments: US scan and education/counselling sessions

Control: 'wait and see' policy (standard treatment)

Duration: four to nine months' reassessment

Outcomes

McGill Pain Scale score: at least five-point improvement

Hospital Anxiety Depression Scale: improvement in category (normal, borderline, depressed)

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot specified, quote: 'random allocation to groups'
Allocation concealment (selection bias)Low riskClosed envelope system
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot possible because of the nature of the study
Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessed blind to allocation
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskOf 100 randomly assigned, 10 failed to attend for follow-up
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Haugstad 2008

MethodsRandomised trial
ParticipantsWomen between the ages of 20 and 50 years with deep pelvic pain lasting between one and 10 years
Interventions

Treatment group received 10 treatment sessions with the Mensendieck therapist (Haugstad 2007) of one hour’s duration over 90 days, and the control group received standard gynaecological advice at inclusion and again during the treatment period. This therapeutic approach can be seen as a mixture of physiotherapy and psychotherapy. It teaches patients to change their posture, breathing patterns and the way they move to reduce their pain. It uses a cognitive approach to allow women to have an improved understanding and experience of their body

Treatment period: three months

FU: one year

16 study groups, 18 controls

OutcomesVAS, GHQ-30
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Low riskRandomisation occurred by drawing a folded piece of paper with the participant's name from a jar, thus allocating the name to a previously chosen treatment group. Randomisation was performed by a person external to the study
Blinding of participants and personnel (performance bias)
All outcomes
Low riskNot possible in this case, unclear whether assessors blinded
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskNo attrition figures stated, but at one year, only 13 women in each group had completed the questionnaires
Selective reporting (reporting bias)Low risk 
Other biasLow riskNil

Heyman 2006

Methods

Allocation concealment: sealed envelope system, blocks of four (balanced)

Blinding: no

Exclusion postrandomisation: zero

Losses to follow-up: five (three/two)

Power calculation: yes

Intention-to-treat analysis: none

Participants

Country: Sweden

No. of participants: 50 (25 each group)

Age: median 33 (19 to 54)

Sex: F

Inclusion criteria: pelvic pain in fertile women > 19 years of age with a duration of at least six months, continuous or intermittent pain at least two days/wk

Exclusion criteria: known disease of abdomen, pelvis or lumbar spine; pregnancy; STI; severe mental illness; substance abuse; previous treatment with distension of painful structures in the pelvic floor

Interventions

Treatment: The participant lay in a prone position; the physician placed his index finger deep into the participant's rectum, and previously identified painful structures were treated in the following order: At a point two finger-widths lateral of the sacrum, the physician used his index finger to exert strong pressure against the sacrotuberous/spinal ligaments for 15 s to elicit pain. Thereafter, the musculature of the pelvic floor and the joint between the coccyx and the sacrum were concurrently forcefully distended dorsally for 60 s with the index finger. This procedure was repeated after two to three weeks

Control: standard care (counselling)

Duration: four to six weeks

OutcomesVAS
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskRandomisation method not stated
Allocation concealment (selection bias)Low riskBy drawing an envelope, assignment to treatment or control group was performed in blocks of four (i.e. the number of participants in each group was balanced after each fourth participant)
Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding not possible, unclear whether assessors blinded
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskThree of 25 (> 10%) dropped out from each group
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Norman 2004

Methods

Method of allocation: randomly assigned in blocks of two

Power calculation: no

Intention-to-treat analysis: no

Participants

Country: United States

Number of participants: 48 (28 disclosure, 20 control)

Age: 18 to 64

Sex: F

InterventionsTreatments: Two groups of women wrote about their positive (control group) and their negative (disclosure group) experience of pain and had their health status assessed at the end of two months
OutcomesMcGill Pain Questionnaire
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk'Randomised in blocks of 2' into sealed packets
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
High riskNot stated
Blinding of outcome assessment (detection bias)
All outcomes
Low riskQuote: 'interviewer was blind to group assignment'
Incomplete outcome data (attrition bias)
All outcomes
High risk60 randomly assigned, 12 dropped out (four intervention, eight control group). Reasons obtained; > 10% attrition
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Peters 1991

Methods

Methods of allocation: sealed envelope

Outcome assessor blind to allocation

Losses to follow-up: six unsuitable for laparoscopy

Participants

Country: Netherlands

Participants: 106 (57 treatment, 49 control)

Age: 16 to 58

Sex: F

Inclusion criteria: chronic pelvic pain > three months, no problem with Dutch, no mental retardation

Exclusion criteria: no malignancy/disease requiring prompt gynaecological intervention, no history of psychiatric/psychotherapeutic treatment for abdominal pain, no elaborate medical analysis re abdominal pain in the past two years

Interventions

Treatment: integrated (guided by pain model by Loeser 1980, which comprises four components: nociception, pain sensation, pain suffering and pain behaviour; equal attention was devoted to possible organic, psychological, dietary and environmental causes of pain)

Control: standard treatment (includes laparoscopy)

Duration of treatment: six months

Follow-up: one year

Outcomes

General pain experience

Disturbance of daily activities

Associated symptoms

McGill VAS score

Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Low riskQuote: 'randomisation was done by means of closed envelope procedure'
Blinding of participants and personnel (performance bias)
All outcomes
High riskBlinding not possible, but unclear whether assessors blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessor blind to allocation
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Sator-Katzenschlager 2005

MethodsRandomisation methods not specified
ParticipantsCPP longer than six months
Interventions

Gabapentin (n = 20), amytriptyline (n = 20) or combination (n = 16)

Dose of amytriptyline was increased from an initial dose of 25 mg per day up to a maximum dose of 150 mg per day in 25-mg increments each week until sufficient pain relief or the occurrence of side effects such as somnolence, dizziness, orthostatic hypotension, palpitations, dry mouth and weight gain. The dose of gabapentin was increased from 300 mg per day up to a maximum dose of 3600 mg per day in 300-mg increments each week until sufficient pain relief or the occurrence of side effects

OutcomesVAS
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot stated
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
High riskNot blinded as open-label trial, unclear whether assessors blinded
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskSeven participants dropped out because of side effects; > 10% dropout
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasUnclear riskSeven participants excluded after randomisation, so not analysed by intention-to-treat, but same number of dropouts from gabapentin (three) or amytriptyline group (three)

Soysal 2001

MethodsMethod of allocation: computer-generated numbered opaque sealed envelopes
Participants

Country: Turkey

47 women with pelvic pain and venographically demonstrated pelvic congestion

InterventionsGoserelin 3.6 mg subcutaneous implant monthly for six months versus medroxyprogesterone acetate tablets 30 mg daily for six months
OutcomesVenography score; pelvic symptom and physical examination score (modified from Biberoglu and Behrman); Hospital Anxiety, Depression and Total scores; revised Sabbatsberg Sexual Rating Scale
NotesNote: NO dropouts
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskComputer-generated randomisation sequence
Allocation concealment (selection bias)Low riskOpaque sealed envelopes
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskBlinding: some outcomes assessed double-blind. Participants not blind owing to modes of drug administration
Blinding of outcome assessment (detection bias)
All outcomes
Low riskAt final assessment of periuterine venography, operators were blinded
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Exclusion postrandomisation: zero

Losses to follow-up: zero

Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Stones 2001

Methods

Sealed envelope system. Double-blinded

Power calculation: yes

Number of participants randomly assigned: 39

Participants

Country: England

Number of participants: 39

Age: 25 to 35

Sex: F

Inclusion criteria: pelvic pain > six months, laparoscopy identified no pathology

Exclusion criteria: hysterectomised women

Interventions

Treatment: lofexidine 200 mcg twice daily, increasing to 600 mcg twice daily (first three weeks)

Control: placebo tablets

Duration: eight weeks

Follow-up: until the end of treatment

OutcomesVisual analogue scale pain score. Participant's self rating of pain as worst, unchanged, somewhat relieved, considerably relieved or completely relieved
NotesNote high dropout rate in treatment group (nine of 19 completed eight weeks of treatment)
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskQuote: "Women were randomised using a sealed envelope system to receive lofexidine hydrochloride or placebo''
Allocation concealment (selection bias)Low riskSealed envelope
Blinding of participants and personnel (performance bias)
All outcomes
Low riskDouble-blinded, unclear whether assessors blinded
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate, > 10% dropout
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Walton 1992

Methods

Methods of allocation: not stated.

Blinding: not stated

Exclusion postrandomisation: zero

Participants

Country: UK

Number of participants: 165

Age: not given

Sex: F

Inclusion criteria: pelvic pain for longer than six months

No pathology on laparoscopy

Exclusion criteria not given

Interventions

Treatment: medroxyprogesterone acetate 50 mg daily

Control: placebo tablets

Duration: four months

Follow-up: only until end of treatment

Outcomes

Visual analogue scale pain score

Pain improvement rating: better/not better

NotesNote very high dropout rate in MPA and placebo groups. Published report does not give SD for mean VAS, so data entered in Table are the numbers reporting 50% reduction in VAS at completion of the study. This allowed comparison with Farquhar 1989, as the drug, dose and duration of therapy are the same. Complete study report obtained by the review authors
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskQuote: "Two patients were allocated, at random, to the treatment group for each one given placebo"
Allocation concealment (selection bias)Unclear riskNot stated
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot stated
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot stated
Incomplete outcome data (attrition bias)
All outcomes
High riskHigh dropout rate, reasons obtained; commonest is non-compliance; losses to follow-up: 64% of those taking active drug and 57% of those taking placebo completed the study
Selective reporting (reporting bias)Low riskAll outcomes reported
Other biasLow riskNil

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Brown 2008Open-label trial. Lack of placebo control group, lack of randomisation
Elcombe 1997Participants entered and evaluated at different time points in control and active groups, making comparison between groups difficult
Fenton 2008Cross-over trial with no washout period
Onwude 2004Includes surgery
Pearce 1986Abstract only. No data available
Reginald 1987Not an RCT
Simsek 2007Randomised cross-over trial without washout period

Characteristics of studies awaiting assessment [ordered by study ID]

Horne 2012

MethodsRandomised controlled trial (pilot feasibility study)
Participantsn = 60 women recruited from NHS UK hospital
InterventionsWomen randomly assigned to gabapentin versus placebo
OutcomesPrimary objective is to assess recruitment and retention rates. Secondary objectives are to determine the effectiveness and acceptability to participants of proposed methods of recruitment and randomisation, drug treatments and assessment tools and to perform a pretrial cost-effectiveness assessment of treatment with gabapentin
Notes