{"paper_id":"4b0533b9-a615-47b9-9361-500f805a91b7","body_text":"Manuscript accepted for publication\n \n 1 \nProvisionally accepted for publication \nNARRATIVE REVIEW \nComplementary pain management in endometriosis: a scoping review \nShort title: Complementary management pain in endometriosis \n \nDoi: 10.36129/jog.2022.68 \n \nMaría Alejandra Sanchez Vera 1, Olga Isabel Restrepo Castro 2*, Sofía Ortiz Zornosa 3, Juanita \nDíaz Bruce 3, Zulied Yurany Sierra Rodríguez 4, Oscar Fernando Caro Durán4 \n \nAuthors’ institutional affiliations: \n1 Physiotherapy, epidemiology/Universidad de La Sabana, Chía, Colombia \n2 Gynecology and Obstetrics/ Universidad de La Sabana, Chía, Colombia \n3 Medical student/ Universidad de La Sabana, Chía, Colombia \n4 Physiotherapy student/ Universidad de La Sabana, Chía, Colombia \n \n*Corresponding author: Olga Isabel Restrepo Castro , Gynecology and Obstetrics/ Universidad de \nLa Sabana, Chía, Colombia, olga.restrepo@unisabana.edu.co \n \nORCIDs: \nOlga Isabel Restrepo (0000-0002-1843-091X) \nMaría Alejandra Sánchez ( 0000-0002-6016-8177) \nSofía Ortiz (0000-0002-6362-0114) \nJuanita Díaz (0000-0003-3683-0703) \nZulied Sierra ( 0000-0002-5072-2832) \nOscar Fernando Caro ( 0000-0001-5830-1031)  \n\nManuscript accepted for publication\n \n 2 \nABSTRACT \nEndometriosis is a gynecological disease characterized mainly by infertility, chronic pelvic as well by \nthe disability that generates. In 2020, the WHO established that it affects approximately 10% of \nwomen and girls of reproductive age worldwide. Multiple surgical and pharmacological treatments \nhave been recommended by different clinical practice guidelines for pain relief. Complementary \ntherapies such as acupuncture, electrotherapy, massage, physical exercise, or diet have not been \nestablished as strong recommendation Nevertheless studies demostrated significant decrease in \npain that support its use as an adjunct pain managment.  \nObjective. To understand and expose the contribution of complementary therapies to pain relief in \npatients with endometriosis.  \nMethodology. For the study, a search was carried out in: PubMed, Web of Science, Scopus, and \nOvid databases with controlled descriptors in health, filtering 994 articles and including 12.  \nResults. It was found that medical management for pain relief in patients with endometriosis is the \nbasis of the treatment of this health condition. However, with complementary therapies a decrease \nin pain was demonstrated. This include: Transcutaneous electrical stimulation, neuromuscular pelvic \nfloor manipulation, complementary alternative medical therapy, acupuncture technique on Ah Shi \npoints, cognitive behavioral therapy, physical activity, diet and physioterapy. Information was found \nin 16 articles of experimental, observational studies and narrative reviews which support the use of \ncomplementary therapy as an adjunct in the management of pelvic pain. \nConclusions. The use of complementary therapies are effective interventions for pain control in \npatients with endometriosis and should be recommended for pain improvements and quality of life.  \nKey words \nEndometriosis; pelvic pain; complementary therapies, physical therapy.   \n\nManuscript accepted for publication\n \n 3 \nIntroduction \nEndometriosis is a disease defined by the presence of active endometrial tissue outside the uterus. \nThe condition affects quality of life of the patient mostly because of pain, incapacity, infertility and \nobstetric complications [1][2][3]. It mainly affects women of reproductive age, causing infertility in \n30% of them [4].  Although its etiology is not completely elucidated, there are different theories that \ntry to explain its origin [5]. Retrograde menstruation with transplantation of shed endometrium i s \nconsidered the primary etiopathogenic mechanism. However, its understanding is still incomplete \n[6-8]. Activity of macrophages causing proliferation of fibroblasts, formation of adhesive lesions and \nangiogenesis due to the inflammatory cascade has been reported [9].  Numerous biomarkers are \npotentially involved in the development of endometriosis including IL-31,IL-33, IL6,IL8, CD68, CD14  \nTGF- β1, COX -2, VEGF, ER -1β, aromatase, alarmins, CA -125,ABCG2, CD133 [10-13], TNF-α , \nMCP-1 [9] by causing an inflammatory response and some of them angiogenesis and growth of \nendometrial lesions potential. Their use as tool for diagnosis is limited by their lack of specificity and \nsensivity for endometriosis [14]. Currently the diagnosis is primally made through laparoscopy \nvisualization [5]. Ultrasound is also used as an effective tool to detect and characterize lesions on \nthe uterosacral ligament, parametrium and paracervix [3][15]. Other methods being investigated as \nalternatives include measurement of anogenital distance length(22.8 ± 4.6mm) and anti -Müllerian \nhormone (AMH) levels [16-17] instead of surgical procedures which can cause pelvic adhesions and \ninflammation [18]. Before a definitive diagnosis is made women often endure symptoms for years \nwhile negative effects on wellbeing and quality of life accumulate [5]. Scales such as the Depression \nAnxiety Stress Scales (DASS-21), the Visual Analogue Scale (VAS) and the Endometriosis Health \nProfile-5 (EHP-5) have demonstrated that infertility and pain had the highest possible negative \nimpact on quality of life [19-20].  Within the spectrum of current pain treatment are surgical and \npharmacologic modalities. New hormonal treatments such as GnRH antagonists, Aromatase \ninhibitors, SERMs, and SPRMs are currently under investigation.  Nevertheless, there are side \neffects and some precautions and contraindications [21-23].  Some data have shown that non-\nsurgical or pharmacological treatment for chronic pelvic pain in endometriosis is safe, has hardly any \nadverse effects and improves the quality of life. These include physical therapy, acupuncture, \n\nManuscript accepted for publication\n \n 4 \nmassage, Pilates, diet, and cognitive behavioral therapy. The few publications that are found in this \nregard on complementary therapies show positive and promising results over this topic [24-26]. \nGiven the above, this study aims to describe and analyze the effects of complementary therapies for \npain management in endometriosis. \n \nMaterials and Methods \nThis research is a scoping review, where a search for information on complementary treatment (non-\npharmacological or surgical) of endometriosis was done in 4 databases in May 2022, following the \nPreferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping \nReviews (PRISMA -ScR). The following databases were searched: PubMed, Web of science, \nScopus, and Ovid. A total of 941 articles were found. For the information search, the PICOT strategy \nwas considered, where the population corresponded to patients with endometriosis, the intervention \nconsisted of non-pharmacological or surgical treatment, without the presence of a comparator and \nthe primary outcome to be measured was pain.  \nThe inclusion criteria were articles in English or Spanish, publications with empirical data \n(experimental, quasi-experimental, observational) and narrative (systematic, panoramic, integrative \nreviews, case studies), research on patients diagnosed with endometriosis who had  some type of \nnon-pharmacological treatment such as: physiotherapy, acupuncture, physical exercise, alternative \ntherapy, among others, taking pelvic pain as the main outcome. The exclusion criteria were articles \nwithout full text available, research focused on the treatment of other pathologies such as \ndyspareunia or dysmenorrhea, as well as clinical trial protocols and systematic review protocols. \nThe search equation was performed by a person with review training and is condensed as follows: \nendometriosis AND (“Non-pharmacological treatment” OR physiotherapy OR acupuncture OR \n“physical exercise” OR “physical activity”) AND pain. All the results were initially filtered through the \nRayyan free software, where two independent reviewers evaluated all the articles by title and \nabstract and in case of disagreement, a third party intervened to make the inclusion decision. 44 \nduplicates were eliminated for a total of 894 articles analyzed, of which 22 were included. The second \nfilter consisted of reading the full text where 14 investigations were selected, 2 were discarded \n\nManuscript accepted for publication\n \n 5 \nbecause they did not meet all the inclusion criteria, for a total of 12 articles included in this review \n(Figure 1) The results were condensed in a table on the Microsoft Excel program, where the \nvariables of author, year, country, objective of the study, and conclusions were analyzed.  \nFigure 1. Flowchart of the article selection process (PRISMA) \n \nResults \nFour experimental studies and eight observational studies and/or systematic reviews were included \n(n=12). \nSynthesis of the findings of the included publications \nRandomized controlled trials (n=2), narrative reviews (n=5), retrospective cohort study (n=1), a \nquasi-experimental study (n=1), systematic reviews (n=2), and a case report were found (n=1). The \ncountries of origin of the studies were Australia (n=1), Switzerland (n=1), United States (n=2), Italy \n(n=1), Germany (n=1), England (n=1), China (n=2) and Brazil (n=1). \n \nExperimental studies (Table 1 and 2) \nOf the controlled clinical trials found  Mikocka, A et al. [25] states that cognitive behavioral therapy \nand yoga may have benefits in alleviating the general well -being of patients with pain caused by \nendometriosis. Similarly, Mira, T et al. [26] in their trial that included 101 patients showed \nimprovement in chronic pelvic pain p < 0.001 with a decrease of 36% in the intervention group, \nthrough transcutaneous electrical stimulation. This reduction in pain was observed from the third \nweek to the end of treatment, as well as improvements in dyspareunia, sexual function, and quality \nof life of the participants. \nIn turn, Ling Bi, X et al. [27] carried out a retrospective cohort study, highlighting the effect and safety \nof neuromuscular electrical stimulation (NES) in patients suffering from endometriosis after 10 \nweeks, P < 0.01. However, the efficacy of NES was not studied, as a placebo control group was not \nincluded. \nBenedict, O et al. [28] conducted a quasi -experimental study in which it was shown that strength \nexercises have an effect of lowering the pain threshold in symptomatic patients with endometriosis \n\nManuscript accepted for publication\n \n 6 \ncompared to healthy women who did not have a long-term decrease in the pain threshold. They had \nthe lowering of pain 20 minutes after performing strength exercise returning to normal values after \nthis time compared with the decrease in pain threshold in symptomatic women with endometriosis \nwhich was evidenced in the first week. However, after this time in symptomatic women the thresholds \nremained stable, but still lower than those of healthy patients.  \n \nObservational studies and systematic reviews (Table 3) \nWithin the observational studies and systematic reviews,  the use of complementary therapies is \nhighlighted, where two of the studies included in this review analyzed transcutaneous electrical \nstimulation (TENS); acupuncture techniques were included in four studies, the prescription of activity \nand physical exercise was the focus of discussion in three investigations, as well as diet control was \nalso described in three articles, osteopathic manipulative therapy was present in one study as well \nas the yoga respectively. \nAgarwal S, et al [29] in his narrative review, gives a multidisciplinary perspective to intervene \nendometriosis, within this proposal, the pelvic floor approach performed by physiotherapy in synergy \nwith the prescription of analgesics such as gabapentin for the management of endometriosis is \nmentioned. It highlighted the importance of an early intervention in mental health to prevent and, if \nnecessary, treat clinical symptoms of anxiety and depression. On the other hand, Mechsner et al. \n[30] describes a multimodal approach with a series of interventions for pain management in patients \nwith endometriosis. It exposes in the first place the use of pharmacology in acute stages of pain, \nmentioning the use of ibuprofen, naproxen and metamizole; On the other hand, a great emphasis is \nplaced on diet control, suggesting a reduction in the consumption of gluten industrial sugars and \nmeat to reduce the \"endo-belly\" syndrome, which refers to intestinal swelling, constipation or \ndiarrhea with abdominal distention. Finally, it proposes a physiotherapeutic approach. Muscle \nchanges in the pelvic floor need to be managed because of trigger points and increased muscle \ntone, the above through manual therapy techniques, therapeutic exercise, and electrostimulation. \nYang X, et al. [31] in his systematic review analyzed the use of acupuncture techniques finding a \nsignificant decrease in pain. This strategy creates a type of analgesia which suppresses serum levels \n\nManuscript accepted for publication\n \n 7 \nof estradiol, inhibits the growth of the ectopic endometrium, and allows the release of neurological \nfactors humoral such as adenosine, γ-aminobutyric acid, opioid peptide, acetylcholine, nitric oxide, \nnorepinephrine, and dopamine. Additionally, Payne J, et al. [32] support what was found by Yang et \nal. It is described that the use of acupuncture and the Ah Shi technique on pelvic floor trigger points \nsubstantially improves pain and pelvic perineal muscle tone. \nBuggio, L et al. [33] expose physical activity as a protective factor against the pain presented in \nendometriosis since high-intensity exercise can reduce the level of estrogen, and it helps to reduce \nthe proliferation, migration, and differentiation of endometriotic tissue. The odds ratio for \nendometriosis for any physical activity versus no physical activity was 0.85 (95% confidence interval \n[CI] 0.67-1.07). Similarly, they stated that, through the practice of yoga, through learning postures, \nbreathing techniques and meditation, patients improved their ability to relief pain and thus control \ntheir symptoms. However, they propose another series of alternative interventions  such as \nosteopathic manipulative therapy and massage. This is mainly based on the control of inflammation \nof internal organs that can cause symptoms in the musculoskeletal system. Jointly electro \nacupuncture is proposed where the use of acupuncture is combined with electrostimulation, this is \nbased on the pituitary stimulation and production of cortisol and adrenocorticotropic hormone \ngenerating an anti-inflammatory effect. In the same way, the use of non-invasive TENS is suggested, \nwith the main objective of performing nerve stimulation to control pain and generate a release of \nendogenous opioids. \n \nTable 1. Characterization of experimental studies \nTable 2. Description of intervention and results of experimental studies \nTable 3. Characteristics of observational studies and systematic reviews \n \nDiscussion \nThis Scoping review describes complementary therapeutic strategies and their effect on pain \nmanagement in patients with endometriosis. Within the heterogeneity of these interventions, is \nevident that non-pharmacological treatment for pain management works as an adjuvant to main \n\nManuscript accepted for publication\n \n 8 \nmedical treatments such as combined oral contraceptives, progestogens, anti -inflammatories, and \nlaparoscopic surgery. Although in this review only one case report is exposed where the efficacy of \nacupuncture and herbal therapy for pain in endometriosis is seen after 6 months, being the only \ntherapeutic strategy, most of the clinical trials and reviews describe the efficacy mainly of \nacupuncture and electrical stimulation after a treatment time greater than 4 weeks. This as a \ncomplement of  medical or/and pharmacological treatment, mentioning that it is not replaced in any \ncircumstance due to its limited evidence. However, other alternative therapies such as cognitive \nbehavioral therapy, yoga, low-red meat diet, exercise and psychological interventions not only help \nimprove pain but also improve the quality of life of patients. \nThis wide range of therapeutic possibilities stems from the different mechanisms that can harm \nwomen with endometriosis. Endometriomas activate nociceptive fibers from all the inflammation they \ngenerate through a localized inflammatory response [5] which, over a long period of time can cause \ncentral sensitization and thus lower pain thresholds leading to a pathology of stress and chronic pain \n[34] This leads to problems that are triggered by the chronicity of pain and chronic inflammatory state \nsuch as the adoption of incorrect postures due to muscle spasms, inflammation at the \ngastrointestinal systemic level and psychological symptoms with a consequent decrease in quality \nof life. Chronic pain and consequent stress have been seen to decrease muscle tone and strength \nas well as decrease muscle relaxation capacity, generating changes in the pelvic floor due to muscle \nhypertonicity, causing trigger points of myofascial pain. This being one of the reasons why electrical \nstimulation and acupuncture can work [35]. \nOn the other hand, it has been postulated that the chronic proinflammatory state generates changes \nin the microbiota that lead to symptoms of diarrhea, abdominal distention, vomiting, or cyclical \nconstipation. Taking this into account, diet has an important role. It has been postulated that the \nconsumption of vegetarian products rich in fiber, fruits and vegetables has an anti-inflammatory role \ncompared to a diet rich in protein, which has a pro-inflammatory role emphasizing pork and red \nmeats [36]. Many times, these symptoms cause additional abdominal pain, discomfort and a feeling \nof heaviness. Therefore, diet can be a point of help to manage these symptoms and impact quality \nof life.  \n\nManuscript accepted for publication\n \n 9 \n \nThe complementary treatment exposed above could be a strong point of help in pain in patients with \nthe most difficult medical conditions to treat such as deep endometriomas and extrapelvic \nendometriosis [37] It represents a clinical and surgical challenge, considering that therapeutic \nstrategy should be modulated and tailored on patient’s characteristics. Surgeon has to look for deep-\nseated lesions in the uterus, uterosacral ligaments, pelvic peritoneum, ovaries and ureters, sigmoid \ncolon, and the upper rectum being the extraperitoneal surgical approach sometimes necessary [38]. \nTo prevent recurrence rates, formation of postoperative lesions and improve fertility a total removal \nof endometrial implants without compromising ovarian function, protect and preserve the vasculature \nand nerve structures is mandatory [39-40],  what can be a winding road for patients.  \nFinally, it has been seen that 15-87% of patients with endometriosis have depressive and 29-88% \nanxious symptoms [4-42]. This is where the effectiveness of cognitive behavioral therapy, yoga and \nexercises of self-modulation of pain are postulated. It is assumed that it helps with acupuncture to \nrelease endogenous opioids (pain reduction) and endogenous cortisol (anti -inflammatory) \ndeactivating brain areas linked to pain perception. It also helps to release adenosine and to modulate \nthe brain local blood flow which can contribute to pain modulation [43]. \nThis is how, based on what can trigger the disease, the need arises for a multidisciplinary care \napproach that comprehensively manages women from the moment of diagnosis and the first \nsymptoms, involving, in turn, the participation of different bodies of knowledge in health, such as \ngynecology, nutrition, physiotherapy, psychiatry and psychology, as well as urology and \ngastroenterology. The foregoing suggests that the use of complementary therapies is not exclusively \nlimited to being an adjunct to traditional management, on the contrary, alternative interventions to \nthe usual praxis may have a potential leading role in pain management and therefore in the \nprevention of pain, optimization of the well-being and quality of life in women with endometriosis. \nThis review exposes the need of randomized clinical trials and studies of high methodological quality \nwhich representatively evaluate the efficacy of the different complementary interventions. Also, we \nhighlight the importance of doing investigations where the percentage of patient satisfaction \nregarding the therapeutic complementary management can be shown vs the conventional one or \n\nManuscript accepted for publication\n \n 10 \ncombining those. On the other hand, it is necessary to delve into the impact of a complementary \ntherapeutic arsenal as a primary option for treating pain in endometriosis with medical and surgical \ntreatment and not leave them as an option.  However, we need more information about its side  \neffects, recommendations, and long-term effectiveness. Additionally, this review denotes the \nabsence of recommendations from clinical practice guidelines for non-pharmacological strategies \nfor endometriosis, limiting the external validity of its implementation due to the lack of a prescription \nsupported by high standards of evidence.  \n \nConclusions \nThe use of complementary strategies such as physical exercise, acupuncture, electrostimulation, \ncognitive behavioral therapy and diet are effective interventions  for pain control in patients with \nendometriosis. More interdisciplinary research is required to promote understanding and the long-\nterm effects of these currents of intervention, but its implementation should be recommended for \npain improvements and quality of life in endometriosis patients from the beginning.   \n  \n\nManuscript accepted for publication\n \n 11 \nCompliance with Ethical Standard - ethical responsibilities \nProtection of people and animals. The authors declare that no experiments have been performed on \nhumans or animals for this research. \nData confidentiality. The authors declare that no patient data appear in this article. \nRight to privacy and informed consent. The authors declare that no patient data appear in this article. \nAuthor's contribution: \nMASV: Methodology, project administration, supervision, writing original draft, writing review & \nediting \nOIRC: Project administration, supervision, writing- review & editing \nSOZ: Investigation, supervision, writing -original draft, writing review & editing \nJDB: Investigation, writing original draft  \nZYSR: Investigation, writing original draft \nOFCD: Investigation, writing original draft \nFunding:  \nThis research does not have any funding for its development.   \nStudy registration:  \nDoes not apply. \nDisclosure of Interests:  \nThe authors declare no conflict of interest. \nData sharing. \n- Numbered pages. \n18 pages.  \n- Numbered lines. \n \n- Figure/Table legend.  \nReferences: \n\nManuscript accepted for publication\n \n 12 \n1. Laganà AS, Garzon S, Götte M, Viganò P, Franchi M, Ghezzi F, et al. The Pathogenesis of \nEndometriosis: Molecular and Cell Biology Insights. Int. 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Mira TAA, Yela DA, Podgaec S, Baracat EC, Benetti-Pinto CL.  Hormonal treatment isolated \nversus hormonal treatment associated with electrotherapy for pelvic pain control in deep \nendometriosis: Randomized clinical trial. European Journal of Obstetrics and Gynecology \nand Reproductive Biology. 2020;255(5)134–141. doi:10.1016/j.ejogrb.2020.10.018 \n \n27. Bi  XL,  Xie CX. Effect of neuromuscular electrical stimulation for endometriosis -Associated \npain. Medicine (United States), 2018. doi:10.1097/MD.0000000000011266 \n \n28. Poli-Neto OB, Oliveira AMZ, Salata MC, Rosa-E-Silva JC, Mac hado DRL, Salata MC, et al. \nStrength exercise has different effects on pressure pain thresholds in women with en-\n\nManuscript accepted for publication\n \n 15 \ndometriosis-related symptoms and healthy controls: A quasi -experimental study. Pain Me -\ndicine (United States). 2020;21(10):2280–2287. doi: 10.1093/PM/PNZ310 \n \n29. Agarwal SK, Foster WG, Groessl EJ.  Rethinking endometriosis care: Applying the chronic \ncare model via a multidisciplinary program for the care of women with endometriosis. In \nInternational Journal of Women’s Health. 2019;11:405-410. doi:10.2147/IJWH.S207373.     \n \n30. Mechsner, S. Endometriosis, an Ongoing Pain—Step‐ by‐Step Treatment. In Journal of \nClinical Medicine 2022.  doi: 10.3390/jcm11020467. \n \n31. Xu Y, Zhao W, Li T, Zhao Y, Bu H, Song S. Effects of acupuncture for the treatment of \nendometriosis-related pain: A systematic review and meta -analysis. PLoS One. 2017. doi: \n10.1371/journal.pone.0186616.  \n32. Payne JA. Acupuncture for Endometriosis: A Case Study. Medical Acupuncture 2019. doi: \n10.1089/acu.2019.1379.6 \n33. Buggio L, Barbara G, Facchin F, Frattaruolo MP, Aimi G, Berlanda N, et al. Self-management \nand psychological -sexological interventions in patients with endometriosis: strategies, \noutcomes, and integration into clinical care. Int J Womens Health. 2017;2(9):281-293. doi: \n10.2147/IJWH.S119724.  \n34. Borrelli GM, Carvalho KI, Kallas EG, Mechsner S, Baracat EC,  Abrão MS, et al. Chemokines \nin the pathogenesis of endometriosis and infertility. In Journal of Reproductive Immunology. \n2013;98(1-2):1-9. doi:10.1016/j.jri.2013.03.003. \n35. Finas D, Hüppe M, Diedrich K, Kowalcek I. Chronischer Unterbauchschmerz Am. Beispiel \nder EndometrioseProblempatientin in der Gynäkologie?  Geburtshilfe Frauenheilkd. \n2005;65(2):156-163 doi: 10.1055/s-2004-830535 \n36. Ata B, Yildiz S, Turkgeldi E, Brocal VP, Dinleyici EC, Moya A.,et al. The Endo-biota Study: \nComparison of Vaginal, Cervical and Gut Microbiota Between Women with Stage 3/4 \nEndometriosis and Healthy Controls. Scientific Reports.  2019. doi:10.1038/s41598-019 -\n39700-6 \n\nManuscript accepted for publication\n \n 16 \n37. Antonio Simone L, Salvatore Giovanni V, Roberta G, Vittorio P, Helena Ban F, Eda V, et al. \nBenito C. and & Onofrio Triolo. Clinical dynamics of Dienogest for the treatment of \nendometriosis: from bench to bedside, Expert Opinion on Drug Metabolism & Toxicology. \n2017;13(6):593-596, doi: 10.1080/17425255.2017.1297421 \n38. Sansone A, De Rosa N, Giampaolino P, Guida M, Laganà AS, Di Carlo C, et al. Effects of \netonogestrel implant on quality of life, sexual function, and pelvic pain in women suffering \nfrom endometriosis: results from a multicenter, prospective, observational study. Arch \nGynecol Obstet. 2018;298(4):731-736. doi: 10.1007/s00404-018-4851-0.  \n39. Laganà AS, Vitale SG, Trovato MA, Palmara VI, Rapisarda AM, Granese R, et al.   Full -\nThickness Excision versus Shaving by Laparoscopy for Intestinal Deep Infiltrating \nEndometriosis: Rationale and Potential Treatment Options. Biomed Res Int. 2016. doi: \n10.1155/2016/3617179. \n40. Campo S, Campo V, Benagiano G. Adenomyosis and infertility. Reproductive Biomedicine \nOnline. 2012. doi: 10.1016/j.rbmo.2011.10.003. \n41. Chapron C, Pietin-Vialle C, Borghese B, Davy C, Foulot H, Chopin N, et al. Associated \novarian endometrioma is a marker for greater severity of deeply infiltrating endometriosis. \nFertil Steril. 2009;92(2):453-457. doi: 10.1016/j.fertnstert.2008.06.003.  \n42. Cousins FL, O DF, Gargett CE. Endometrial stem/progenitor cells and their role in the \npathogenesis of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2018. doi: \n10.1016/j.bpobgyn.2018.01.011.  \n43. Berman BM, Langevin HM, Witt CM, Dubner R. Acupuncture for chronic low back pain. New \nEngland Journal of Medicine. 2010;363(5):454-61. doi: 10.1056/NEJMct0806114.  \n \n \n \n \n \n\nManuscript accepted for publication\n \n 17 \nTable 1. Characterization of experimental studies   \nAuthor(\ns) \nYea\nr \nCountr\ny \nDesign Age \n(year\ns) \nPopulation \ncharacteristi\ncs \nNumb\ner of \nsubjec\nts in \nthe \nstudy \nThe \npurpose of \nthe study \n \nMikocka\n, A et al.   \n \n \n202\n1 \n \nAustrali\na \n \nRandomize\nd and \nparallel \ncontrolled \ntrial. \n \n>18  \n \nWomen >18 \nyears old, \nwith high \nlevel of \nEnglish, \ninternet \naccess and \nendometriosi\ns diagnosed  \nin the last 6 \nmonths by \nUS, histology \nor clinically. \nPain \nincluded: \ndysmenorrhe\na, dyschezia, \ndysuria or \ncyclic pain. \nDrug \ntreatment \nwas \ncontinued \nduring the \ninterventions. \n \n \n258 \n \nTo compare \nthe cost-\neffectiveness \nand efficacy \nof cognitive \nbehavioral \ntherapy and \nyoga vs. \neducation in \nthe \ntreatment of \nendometriosi\ns.   \nMira, T \net al.   \n \n202\n0 \nNot \navailabl\ne  \nMulticenter \nrandomized \ncontrolled \ntrial. \n28 to \n43  \nMenstruating \nwomen who \npresent deep \ninfiltrative \nendometriosi\ns, in \ncontinuous \nhormonal \ntreatment for \nthe least 3 \nmonths and \nreport \nsymptoms of \nchronic \npelvic pain or \ndeep \ndyspareunia.  \n \n101 To evaluate \nthe clinical \neffectiveness \nof \ncomplement\nary self-\napplied \nelectrotherap\ny treatment \nfor pain \ncontrol \ncompared to \nstandard \nhormonal \ntreatment \nalone for \nendometriosi\ns and to \ndescribe its \ninfluence on \nquality of life \n\nManuscript accepted for publication\n \n 18 \nand sexual \nfunction in \nwomen with \ndeep \ninfiltrative \nendometriosi\ns. \n \nLing Bi, \nX et al.   \n \n201\n8 \nChina Retrospecti\nve cohort \nstudy   \n18 to \n42  \nWomen aged \n18 to 42 \nyears with a \nconfirmed \ndiagnosis of \nendometriosi\ns-associated \npain (EAP) \nand chronic \npelvic pain \n(CPP). \n \n154 To assess \nthe effect of \nneuromuscul\nar electrical \nstimulation \n(NMES) for \nthe \ntreatment of \nEAP \nBenedic\nto, O et \nal. \n202\n0 \nBrazil Quasi-\nexperiment\nal study   \n18 to \n50  \nSedentary \nwomen with \nchronic \npelvic pain \n(CPP) \nassociated \nwith \nsignificant \ndysmenorrhe\na for the \nleast 6 \nmonths.   \n21 To evaluate \nthe influence \nof strength \nexercise on \nremote pain \nsensitivity in \nwomen with \nendometriosi\ns-related \nsymptoms. \n \n \n \n \n \n \n \n \n \n \n \n \n\nManuscript accepted for publication\n \n 19 \nTable 2. Description of intervention and results of experimental studies   \nAutho\nr(s) \n Control \nintervention \nExperimental \nintervention \nMain \noutcomes  \nPain \nmeasureme\nnt scale \n \nResults \nMikoc\nka, A \net al. \nEducation \nbrochures \nvia email \nwith \neducation \nabout \nendometriosi\ns: symptoms \nand their \ncauses, \ndiagnosis, \nmanagemen\nt and \ntreatment, \nfertility and \npregnancy, \nemotions, \ncomplication\ns and risks, \nrelationships\n, and \nsexuality. \nCognitive \nbehavioral \ntherapy: Weekly \n120-minute \ntherapy with \ngroups of 10-13. \nThey were \nencouraged to \nunderstand, \neducate, and \nmanage pain. \nThey were also \nrequired to have \nat least 3 times a \nweek 20 minutes \nof practice at \nhome. \n \nYoga: Yoga \nclasses once a \nweek of 60 \nminutes in \ngroups of 10-13 \npeople. Physical \npostures, \nconscious \nbreathing \ntechniques, \nrelaxation and \nmeditation were \ndone. \nParticipants were \nrequired to \ncomplete at least \n20 sessions at \nhome 3 times a \nweek of \nmovements and \nbreathing \ntechniques. \n \n1. Quality of \nlife 2. Quality \nof sleep 3. \nPsychologica\nl symptoms, \n4.Fatigue, \n5.Menstrual \nsymptoms, \n6.Pain, \n7.Functionali\nty and pain, \n8.Catastroph\nic pain \n9.Self-\nefficacy \n10.Central \nsensitization. \nPain: VAS \n(0-10)  \nPain and \nfunctionality: \nBrief Pain \nInventory  \nPain \ncatastrophizi\nng: Pain  \nCatastrophizi\nng Scale  \nPain Self-\nEfficacy: \nPain Self-\nEfficacy \nQuestionnair\ne Central \nSensitization: \nE \nFibromyalgia \nCriteria-2016 \nCognitive \nbehavioral \ntherapy and \nyoga improve \ngeneral well-\nbeing, pain, \npsychological \nsymptoms, \nand \nsatisfaction in \npatients with \nendometriosis\n.  \n  \nYoga and \ncognitive \nbehavioral \ntherapy were \nfound to be \nmore effective \nthan \neducation in \nimproving \nquality of life \nin patients \nwith \nendometriosis\n. \n\nManuscript accepted for publication\n \n 20 \nMira, \nT et \nal. \nHormonal \ntreatment   \nTranscutaneous \nelectrical nerve \nstimulation \n(TENS) in the \npresacral region \n(S3-S4 position) \ntwice a day, 20 \nmin per \napplication + \nhormonal \ntreatment.   \n1. Chronic \npelvic pain \n(EVA) 2. \nDeep \ndyspareunia \n(DDS) 3. \nDyschezia \n(EVA) 4. \nFrequency of \nbowel \nmovement \n(per week) 5. \nDysuria \n(EVA) 6. \nPain during \nspotting \n(EVA) 7. \nQuality of life \n(Endometrio\nsis Health \nProfile \nEndometriosi\ns Health \nProfile (EHP-\n30) \n8. Sexual \nFunction \n(Female \nSexual \nFunction \nIndex (FSFI) \n \nEVA The TENS \nproved to be \na good \ncomplement \nfor the \nreduction of \nchronic pelvic \npain and \ndeep \ndyspareunia. \nAlso it has an \nimprovement \nin quality of \nlife and \nsexual \nfunction of \npatients.  It \ncan be \nconsidered a \ngood \ncomplementa\nry tool for the \ntreatment of \ndeep \ninfiltrative \nendometriosis \nin this case in \nmenstruating \nwomen. \nLing \nBi, X \net al.   \n \nNo \nintervention \nNeuromuscular \nelectrical \nstimulation in \nacupuncture \npoints at the \nlevel of the \nabdomen and \nlower limb. From \n2 to 100 Hz for \n30 minutes, once \na day, 3 weekly \nsessions for a \ntotal of 10 \nweeks. \nPain: \nMeasured by \nnumerical \nrating scale \n(NRS) and \nendometriosi\ns symptom \nseverity \nscore \n(ESSS).  \nQuality of \nlife: \nMeasured by \nthe 36-item \nShort Form \nHealth \nSurvey (SF-\n36). It \nincluded 2 \nmain \nsubscales of \nphysical \ncomponent \nsummary \nNRS Neuromuscul\nar electrical \nstimulation \n(NMES) is \nshown to be \neffective in \nChinese \nwomen with \nendometriosis\n-associated \npain after 10 \nweeks of \ntreatment. \nMore studies \nare needed to \ncorroborate \nthis result.   \n\nManuscript accepted for publication\n \n 21 \n(PCS) and \nmental \ncomponent \nsummary \n(MCS).   \n \nBene\ndicto, \nO et \nal.\n \n \nChair leg \nextension \nstrength \nexercises \nwere \nperformed in \nhealthy \nwomen. The \nphases were \npreparation \nand \nexperimentat\nion. In the \npreparation \nphase, a \nmock \nsession was \nperformed to \nacquire a \ncorrect \nposture; in \nthe \nexperimental \nphase, a \nlight warm-\nup of 3 \nminutes was \nstarted, and \nwhen the \nexercise was \nperformed, a \n1RM test \nwas \nestimated, \nconsisting of \n10 \nrepetitions to \nmeasure \nsub-maximal \nstrength with \na load of \n60%. The \nprotocol \nincluded 4 \nsets of 15 \nrepetitions \nwith intervals \nof 1 to 2 \nminutes.  \n  \nLeg extension \nstrength \nexercises in a \nchair were \nperformed in \nsymptomatic \nwomen with \nendometriosis. \nThe phases were \npreparation and \nexperimentation, \nin the \npreparation \nphase a mock \nsession was \nperformed to \nacquire a correct \nposture, in the \nexperimentation \nphase it began \nwith a light \nwarm-up of 3 \nminutes, when \narriving to the \nexercise a 1RM \ntest was \nestimated, \nconsisting of 10 \nrepetitions to \nmeasure sub \nmaximal strength \nwith a load of \n60%. The \nprotocol included \n4 series of 15 \nrepetitions with \nintervals of 1 to 2 \nminutes.  \n \nSub-maximal \nstrength \n(1RM), \nPressure \npain \n(algometry), \nHeart rate, \nBlood \npressure.   \nVisual \nAnalog Scale \n(VAS)   \nThe results of \ntwo groups \nwith the same \nintervention \nwere \nconsidered. It \nwas observed \nthat women \nwith \nendometriosis\n-related \nsymptoms \nhad lower \npain \nthresholds \nthan women \nin the control \ngroup who \nwere \nasymptomatic \nand healthy. \nIn the control \ngroup the \npressure pain \nthresholds \nincreased \nimmediately \nafter exercise \nand returned \nto baseline \nafter 20 \nminutes. In \nthe \nexperimental \ngroup, there \nwere \nincreases in \nheart rate and \nsystolic \npressure \nimmediately \nafter exercise, \nbut significant \nalterations in \nthe pressure \npain threshold \nwere not seen \nuntil the first \nweek when \n\nManuscript accepted for publication\n \n 22 \nthe threshold \ndecreased. \n \n \n \nTable 3. Characteristics of observational studies and systematic reviews \nAuthors Year Country Design Objective Conclusions \nKalaitzopou\nlos D, et al \n \n2021 Switzerla\nnd \nNarrative \nreview \nGive an \noverview of \ntherapeutic \napproaches \nfrom eight \nwidely used \nnational and \ninternational \nguidelines. \nAll the guidelines of \ndifferent gynecology and \nobstetrics associations \nagree that the combined \noral contraceptive pill \nand progestogens are \nrecommended therapies \nfor pain associated with \nendometriosis.  \nAcupuncture proved to \nbe effective as a \ncomplementary therapy \nfor the significant \nreduction of pelvic pain \nand improvement in the \nquality of life of patients. \nLikewise, \nTranscutaneous \nElectrical Nerve \nStimulation (TENS) is \nthe most widely used \nelectrical stimulation for \npain therapy by directly \nblocking the \ntransmission of pain \nsignals along the \nnerves. \n \nAgarwal S, \net al \n \n2019 United \nStates \nNarrative \nreview \n \nDescribe long-\nterm clinical \noutcomes for \nwomen with \nendometriosis-\nassociated \npain. The \nmultidisciplinary \nmodel of care is \nconsidered as \nan alternative to \nthe single \nprovider model \nand also is \nconsidered to \noffer counseling \nas part of \nTo improve long-term \nclinical outcomes, a \nmultidisciplinary \napproach, including pain \nmedicine, psychology, \npelvic physiotherapy, \nnutrition, and other \ndisciplines, will be \nhelpful. Pelvic \nphysiotherapy \nintervention can improve \npelvic pain by internal \nmanipulation of the \npelvic floor muscles and \nligaments. \n\nManuscript accepted for publication\n \n 23 \ntreatment. \n \nTennfjord \nMK, et al.   \n \n2021 Carpente\nr et al \nUnited \nStates   \nFiggi \nSebe \nPetrelluzz\ni et al \nBrazil \nGoncalve\ns et al \nBrazil \nSystema\ntic \nreview \nTo determine \nthe effect of \nphysical activity \n(PA) in patients \nwith \nendometriosis. \nThere may be a \nbeneficial association \nbetween physical \nactivity and \nendometriosis \nsymptoms, however the \nexact impact cannot be \ndetermined from the \nexisting literature.  The \nbenefits of PA should be \ncommunicated to \npatients with \nendometriosis and \nfuture studies should be \nRCTs that measure and \nreport pain, quality of life \nand patient satisfaction.   \n \nBall E, et al.   \n \n2020 Not \navailable  \nNarrative \nreview \n \nTo disseminate \nscientific and \ninnovative \ninformation on \nthe approach to \nchronic pelvic \npain. \nHolistic, self-care and \npsychological \napproaches were shown \nto have positive or \nprotective factors for \nendometriosis. Low red \nmeat diet and exercise \nare a protective factor \nfor endometriosis and \nacupuncture and \npsychological \ninterventions were \neffective for pain relief \nand quality of life. \n \nBuggio L, \net al. \n \n2017 Italy Narrative \nreview \n \nTo examine the \nevidence for \nnew alternative \napproaches \nsuch as \nosteopathic \nmanipulative \ntherapy (OMT), \nmassage, \nacupuncture, \ntranscutaneous \nelectrical nerve \nstimulation \n(TENS), \nvitamins, and \ndietary \nsupplementatio\nn for the \nmanagement of \nendometriosis. \nIt is observed within the \nreview the importance of \nfactors such as diet and \nphysical exercise, \ncomplementary \nalternative medical \ntherapy (CAMT) could \nbe a good complement \nto hormonal therapy \neven more in those \npatients with some \ncontraindication. Finally, \nthe importance of an \ninterdisciplinary \nintervention to obtain \nintegral results in the \ntreatment is analyzed.   \n \n\nManuscript accepted for publication\n \n 24 \nMechsner, \nS et al. \n \n2022 Germany Narrative \nreview \n \nTo describe the \ndifferent \ninterventional \ntechniques for \nchronic \nendometriosis \nand to give an \noverview of the \npathology. \nThe main cause of pain \nwas analyzed as \nperipheral and central \nsensitization leading the \npatient to suffer chronic \npain. Pelvic myofascial \npain reduces the quality \nof life of patients and \ncan overlap with other \ntypes of chronic pain \nsuch as irritable bowel \nsyndrome, vulvodynia, \nand painful bladder \nsyndrome. In these \ncases, it is recognized \nby a very low pain \nthreshold and \nmultimodal therapy is \nneeded. \n \nYang X, et \nal.   \n \n2017 China Systema\ntic \nreview \nand \nmeta-\nanalysis \nTo determine \nthe \neffectiveness of \nacupuncture as \na treatment for \nendometriosis \npain. \n \nAcupuncture reduces \npain and serum CA-125 \nlevels. There is very little \nevidence from \nrandomized blinded \nclinical trials.   \nPayne J, et \nal. \n2019 United \nStates \nCase \nReport \nTo detail the \npossible effects \nof Traditional \nChinese \nMedicine on \npelvic pain \nsecondary to \nendometriosis \nthrough the \npresentation of \na single case. \nSignificant changes in \npain levels were \nobserved after the \npatient underwent \nacupuncture using Ah \nShi points. However, the \npatient used a series of \nformulations and \nmedications, and no \nway was found to \ndetermine the \neffectiveness of these \nfor the reduction of \nfibroids and bleeding. \nThe use of points other \nthan Ah Shi is being \nconsidered for future \nstudies.   \n \n \n \n \n \n \n \n \n\n \n 25 \n \nManuscript accepted for publication","source_license":"CC0","license_restricted":false}