{"paper_id":"ec4cab35-4a8b-49e2-b242-a0f7cdd5e25d","body_text":"Gynecological Endocrinology\nISSN: 0951-3590 (Print) 1473-0766 (Online) Journal homepage: www.tandfonline.com/journals/igye20\nTreatment strategies for pelvic pain associated\nwith adenomyosis\nV. E. Radzinsky, M. B. Khamoshina, E. N. Nosenko, A. O. Dukhin, M. A.\nSojunov, A. A. Orazmuradov, M. G. Lebedeva & M. R. Orazov\nTo cite this article: V. E. Radzinsky, M. B. Khamoshina, E. N. Nosenko, A. O. Dukhin, M. A.\nSojunov, A. A. Orazmuradov, M. G. Lebedeva & M. R. Orazov (2016) Treatment strategies for\npelvic pain associated with adenomyosis, Gynecological Endocrinology, 32:sup2, 19-22, DOI:\n10.1080/09513590.2016.1232673\nTo link to this article:  https://doi.org/10.1080/09513590.2016.1232673\n© 2016 The Author(s). Published by Informa\nUK Limited, trading as Taylor & Francis\nGroup.\nPublished online: 19 Oct 2016.\nSubmit your article to this journal \nArticle views: 3799\nView related articles \nView Crossmark data\nCiting articles: 1 View citing articles \nFull Terms & Conditions of access and use can be found at\nhttps://www.tandfonline.com/action/journalInformation?journalCode=igye20\n\nhttp://informahealthcare.com/gye\nISSN: 0951-3590 (print), 1473-0766 (electronic)\nGynecol Endocrinol, 2016; 32(S2): S19–S22\n! 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.\nDOI: 10.1080/09513590.2016.1232673\nORIGINAL ARTICLE\nTreatment strategies for pelvic pain associated with adenomyosis\nV. E. Radzinsky, M. B. Khamoshina, E. N. Nosenko, A. O. Dukhin, M. A. Sojunov, A. A. Orazmuradov, M. G. Lebedeva,\nand M. R. Orazov\nDepartment of Obstetrics and Gynecology with a Course in Perinatology, Faculty of Medicine, Peoples’ Friendship University of Russia, Moscow,\nRussia\nAbstract\nObjective: To observe the effects of levonorgestrel-releasing intrauterine system (LNG-IUS)\nin treatment of chronic pelvic pain associated with adenomyosis (AM) and in prevention of its\nrecurrence.\nMethods: A prospective continuing study including 180 patients with chronic pelvic pain\nassociated with AM who received insertion of LNG-IUS who were divided into three groups\ndepending on the pain severity. The visual analog scale (VAS) was used for pain assessment\nbefore and during the treatment and transvaginal ultrasonic measurement of the uterine size,\nwhile various side effects, were observed and recorded.\nResults: After placement of LNG-IUS, scores of pain and ratio of severe pelvic pain decreased\nsignificantly compared with baselines ( p50.01), the scores of VAS were 9.0 ± 0.8, 6.5 ± 2.8,\n4.3 ± 1.8, 3.3 ± 2.2, 2.2 ± 2.1, 2.2 ± 1.8, 1.4 ± 1.6 and 1.3 ± 1.3 at 0, 3, 6 and 12 months,\nrespectively. During 12 months after placement of LNG-IUS, scores of pain had improved\nsignificantly compared with preceding period ( p50.01). We found no universal dependent\nfactors predicting improvement of pain, which was neither relevant with simultaneous changes\nof menstruation patterns nor with adverse effects ( p40.005).\nConclusion: The obtained results allowed to confirm the possibility of using LNG-IUS in the\ntreatment of pelvic pain syndrome associated with AM, particularly with mild and moderately\nsevere pelvic pain syndrome. This is a cost effective, reversible and long-term treatment for\nwomen with pelvic pain associated with AM, which reduces the need for surgical interventions.\nKeywords\nAdenomyosis, chronic pelvic pain,\ndysmenorrhea, levonorgestrel releasing\nintrauterine system\nIntroduction\nAdenomyosis (AM) is a widespread disease that affects women\nof the reproductive age [1]. This is a gynecological disorder\ncharacterized by a benign invasion of ectopic endometrium tissue\nwithin the wall of the uterus with the adjacent smooth muscle\nhyperplasia [2]. But, today the definition of AM is characterized\nby the presence of heterotopic endometrial glands and stroma\nwithin the myometrium, 42.5 mm in depth in the myometrium or\nmore than one microscopic field at 10 times magnification from\nthe endometrium–myometrium junction and a variable degree of\nadjacent myometrial hyperplasia, causing globular and cystic\nenlargement of the myometrium, with some cysts filled with\nextravasated, hemolyzed red blood cells, and siderophages. The\netiology is unclear, but as risk factors, in addition to hereditary\nones, include uterine trauma during the delivery or abortion,\nchronic endometritis and hyperestrogenemia [3].\nIn various sources, its prevalence is estimated from 5 to 70%,\nbut it is difficult to be precisely determined for many reasons. In\none third of the cases, AM is an asymptomatic disease and\nconsequently can be occasionally diagnosed by pelvic ultrasound\nor it is found in hysterectomy specimens performed for other\nmedical reasons. In these cases, diagnosis can be also mistaken\nfrom 10 to 90% among pathologists if histological criteria are not\nstrictly followed. AM does not present pathognomonic clinical\nfeatures: enlarged uterus, dysmenorrhea (30%) and menorrhagia\n(50%) can be associated with other diseases [1].\nChronic pelvic pain has recently been defined as ‘‘chronic or\npersistent pain perceived in structures related to the pelvis of\nwomen. It is often associated with negative cognitive, behav-\nioural, sexual and emotional consequences as well as with\nsymptoms suggestive of lower urinary tract, sexual, bowel, pelvic\nfloor or gynaecological dysfunction’’. Despite this definition\nacknowledging that the patient and clinician localize the pain as\nbeing perceived in the specified anatomical area, the conscious\nexperience of pain is the result of co-ordinated activity within the\ncentral nervous system (CNS). If the focus is shifted away from\nthe pelvis and onto the CNS, it can be seen that women with CPP\ndo exhibit central changes analogous to those observed in other\nchronic pain conditions.\nIt is an important cause of chronic pelvic pains, dysmenorrhea\nand heavy menstrual bleeding (HMB), which occur in /C24 65% of\nwomen with AM and can result in a poor quality of life [4].\nThis is an Open Access article distributed under the terms of the Creative\nCommons Attribution License (http://creativecommons.org/licenses/by/\n4.0/), which permits unrestricted use, distribution, and reproduction in\nany medium, provided the original work is properly cited.\nAddress for correspondence: Mekan Orazov Rahimberdievich,\nDepartment of Obstetrics and Gynecology with course Perinatology,\nPeoples’ Friendship University of Russia, Moscow 117198, Russia.\nE-mail: omekan@mail.ru\n\nTraditionally, the diagnosis of AM was based on clinical findings\nand pathologic confirmation after hysterectomy. However, transva-\nginal ultrasonography (TVS) and magnetic resonance imaging have\nbeen shown to be accurate, noninvasive methods for diagnosis [5].\nHysterectomy is a ‘‘gold standard’’ and definitive therapy for\nuterine AM associated with pelvic pain, and many cases of AM\nhave been diagnosed by pathological review retrospectively. As\nsuch, the diagnosis of AM is difficult, and this subsequently\nresults in difficulty in the management of these patients,\nparticularly those who are symptomatic but have a strong desire\nto preserve their uterus. The use of uterine-sparing surgery in the\nmanagement of uterine AM still remain controversial, however,\nsome data support its feasibility. This is why conservative\ntreatment is still needed in the group of patients with pelvic\npain syndrome that requires preservation of fertility and improve-\nment of quality of life. However, studies focusing on the topic of\nmedical treatment for AM are rare.\nMedical treatment for AM always follows the principles of the\nmanagement of endometriosis, which are usually aimed at\nreducing the production of endogenous estrogen or inducing\nendometrial differentiation with progestins. Clinical evidence\npoints to the clear and deleterious effect of uninterrupted\novulatory cycles on the development and persistence of AM;\nsymptoms of AM usually appear after menarche and vanish after\nmenopause. The objectives of medical treatment are the inhibition\nof ovulation, abolition of menstruation and achievement of a\nstable steroid hormone milieu, based on the concept that the\nresponses of the eutopic and ectopic endometria are substantially\nsimilar [6]. Medical therapies primarily aimed at the relief of\npelvic pain and commonly used in the treatment of AM, similar to\nthose for endometriosis, are mainly based on the fact that the\nhypothalamic–pituitary–gonadal axis plays a pivotal role in every\nphase of mammalian reproduction, and include gonadotropin-\nreleasing hormone agonist (GnRH agonist), oral contraceptives\n(OCs), progestins, danazol, and recently, selective estrogen\nreceptor modulators (SERMs), selective progesterone receptor\nmodulators (SPRMs) or aromatase inhibitors (AIs). These agents\ncreate a hypoestrogenic (GnRH agonists, AIs), hyperandrogenic\n(danazol, gestrinone), or hyperprogestogenic (OCs, progestins)\nenvironment, with suppression of endometrial cell proliferation\n[6]. However, medical treatments are symptomatic and not\ncytoreductive: lesions survive the use of any drug, at any dose,\nfor any length of time, and are ready to resume their metabolic\nactivity at treatment discontinuation [7]. Medical treatments of\npelvic pain caused by AM may represent hormonal therapies but\nare associated with adverse events impacting long-term use and\nadherence this is why the use of drugs with minimal systematic\nside effects is the target basis of the modern therapy of pelvic pain\nassociated with AM.\nThe aim of the study was to study immediate and remote\nresults of the relief of chronic pelvic pain in women of\nreproductive age with AM, with the use of the levonorgestrel-\nreleasing intrauterine system.\nMaterials and methods\nA total of 180 reproductive age patients (31–46 years) 31, 56 ± 2,\n32 years participated in a retrospective study conducted from\nJanuary 2014 to December 2015 on the basis of the Peoples’\nFriendship University of Russia, Department of Obstetrics and\nGynecology with a Course in Perinatology of the Faculty of\nMedicine. The patients were diagnosed with AM using TVS and\nhad a uterine size /C21 12 gestational weeks during the pelvic\nexamination along with chronic pelvic pains. The diagnostic\ncriteria for AM with TVS were as follows: globular and/or\nasymmetric thickening of the uterine wall, myometrial cysts,\ndistorted and heterogeneous myometrial echotexture, focal or\ndiffuse heterogeneous myometrial echotexture, a poorly defined\nendometrial–myometrial junction, and a poorly defined focus\nof abnormal myometrial echotexture. The uterine volume\nwas calculated using the formula for an ellipsoid (volume ¼\n0.52 /C2 length /C2 anteroposterior diameter /C2 transverse diameter).\nAll patients refused to undergo hysterectomy or use oral\ncontraceptives, and provided informed consent for treatment of\nsymptomatic AM with the LNG-IUS.\nThe inclusion criteria in the group was the lack of hormonal\ntherapy for six cycles prior to installation and the use of LNG-\nIUS, the presence of varying severity pelvic pain associated with\nAM.\nExclusion criteria were the presence of fibroids of the uterus,\nacute inflammatory diseases of the pelvic organs, external\nendometriosis, ovarian formation, deformation of the uterine\ncavity and the generally accepted contraindications for the\ninstallation of LNG-IUD.\nThe duration of the presence of symptoms of chronic pelvic\npain ranged from 1 to 15 years.\nDepending on the severity of pelvic pain patients were equally\nallocated to three groups:\nGroup I – 60 ( n ¼ 60) women with a pelvic pain syndrome low\ndegree of severity;\nGroup II – 60 ( n ¼ 60) women with a pelvic pain syndrome of\nmoderate severity;\nGroup III – 60 ( n ¼ 60) women with severe pelvic pain.\nThe LNG-IUS was installed into the uterine cavity during days\n5–7 of the menstrual cycle of all patients. After the installation of\nthe LNG-IUS, we recommended follow-up visits every 3–6–12\nmonths during the first year. Each follow-up visit typically\nentailed TVS examinations to confirm the uterine volume and\nlocation of the LNG-IUS. Pain assessment was done with a visual\nanalog scale (VAS). Pre insertion symptoms of pelvic pain were\nassessed using a linear scale, with the left extreme defined as ‘‘no\npain or no bleeding’’ (0 mm) and the right extreme defined as\n‘‘worst pain I have ever felt’’ (100 mm). The score itself was\ndetermined by measuring the distance from the left side of the\nscale to the point marked by patients as their level of pain. All\nfollow-up data (i.e. symptomatic changes, side effects and TVS\nfindings) were retrospectively collected and analyzed.\nStatistical analyses were performed using SPSS software for\nWindows version 20 (SPSS Inc., Chicago, IL). The Shapiro–Wilk\ntest was used to test the normality of the data. Descriptive data were\nexpressed as the mean ± standard deviation. Skewed data were\nwithin the median and range. A Wilcoxon signed rank test was used\nto compare the subjective changes in symptoms and the uterine\nvolume prior to and after the LNG-IUS insertion. Statistical\nsignificance was set at p50.05. All statistical tests were two-sided.\nResults\nOf the 180 ( n ¼ 180) patients 178 (98.8%) completed the study.\nTwo (1.25%) patients refused from the study due to the non-\neffectiveness of treatment within the first month. Expulse IUD\noccurred in two women during the first three months (1.1%) and\nthey produced re-introduction of the LNG-IUD.\nThe main emphasis was on the reduction of pain syndrome.\nTotally 180 women meet inclusion criteria, among which 178\ncases (98.8%) had pelvic pains of varying severity, with median\nfollow-up period of 12 months (range 1–12 months). After\nplacement of LNG-IUS, scores of pain and ratio of severe pelvic\npain decreased significantly compared with baselines ( p50.01),\nthe scores of VAS were 9.0 ± 0.8, 6.5 ± 2.8, 4.3 ± 1.8, 3.3 ± 2.2,\n2.2 ± 2.1, 2.2 ± 1.8, 1.4 ± 1.6 and 1.3 ± 1.3 at 0, 3, 6 and\nS20 V. E. Radzinsky et al.\nGynecol Endocrinol, 2016; 32(S2): S19–S22\n\n12 months respectively. During 12 months after placement of\nLNG-IUS, scores of pain had improved significantly compared\nwith preceding period ( p50.01). We found no universal depend-\nent factors predicting improvement of pain, which was neither\nrelevant with simultaneous changes of menstruation patterns nor\nadverse effects ( p40.005).\nIn the group with pain of low intensity, improvement was\nobserved already at the end of the first (20%) month in 12\npatients, at the end of the second month – in 38 (66.3%) patients\nand in the remaining 10 (16.65) patients – at the end of the third\nmonth, thus a complete pain syndrome reduction was registered\nalready at the end of the third month in all patients. In the group\nwith moderate pelvic pain, reduction of pain was observed in\n15 (25%) patients at the end of the third month, in 32 (53.3%)\nwomen on the sixth month of treatment, in 13 (21.6%) patient’s\npain persisted until the 12th month.\nIn the group with severe pelvic pain syndrome, a reduction of\npain was observed in 14 (24.1%) patients at the end of the third\nmonth, in 27 (46.5%) patients – at the end of the sixth month, and\nin 6 (10.3%) patients – at the end of 12th month. Unfortunately,\nof the 58 patients of this group, pain persisted in the remaining\n11 patients and this was the basis for changing of the treatment\ntactics.\nBy the end of the 12th month of observation in the first and in\nthe second group of 36 women on the background of the therapy\namenorrhea was registered.\nDuring the year of observation no patient became pregnant,\nwhat demonstrates the high-contraceptive effectiveness of the\nmethod.\nSide effects were as follows: the most frequent of them was a\nviolation of the menstrual cycle by the type intermenstrual\nbleeding and also in the follow up period after 1 year of the\nbeginning of treatment with LNG-IUD, 3.3% of patients regis-\ntered headache and acne vulgaris.\nThe mean uterine volume was 162 mm\n3 (range 39–842 mm3).\nAmong the total participants, 2 (1.25%) discontinued the treat-\nment prematurely. However, there was significant difference in\nuterine volume between Group 1 and Group 2 (176 ± 12.5 and\n138 ± 6.2 mm\n3, p ¼ 0.010). Based on the receiver operator\ncharacteristic analysis, the optimum cutoff value of uterine\nvolume less than 140–148 mm\n3 was observed in the group with\na moderate pelvic pain ( p40.005).\nDiscussion\nThe natural desire to preserve the specific function of the\nreproductive system in women requires addressing the discussion\nquestion about the possibilities of conservative therapeutic\nmethods of pelvic pain, place and time of the surgery.\nThe modern concept of conservative treatment is the basis for\nthe use of a rather broad spectrum of therapeutic measures as with\nisolated in the mono-therapy mode, and in combined therapy;\nfrom direct or indirect impacts on the centers governing\nthe reproductive system, including the application of agonists\nGN-WP, antigonadotropins or synthetic analogs of progesterone.\nDue to the high frequency of comorbidity and the development of\na number of side effects, the use of these hormonal drugs may be\nlimited. One of the possible solutions is to define algorithm of\ncomplex conservative therapy including long-acting drug inhibit-\ning the pathogenic mechanisms and providing a stable effect.\nIn this regard, the development of a comprehensive, personalized\nmanagement of reproductive age patients with pelvic pain\nassociated with AM remains a challenge.\nThis study shows that there is a vast number of scientific\nliteratures, which recommends different groups of hormonal\ndrugs for reduction of pelvic pain caused by AM, each of them\nhaving its limitations, both in the effectiveness and safety criteria\nand side effects. Chronic pelvic pain restricts and modifies the\ndaily routine of these patients, directly affecting their quality\nof life. Despite the use of instruments to measure pain, such\nanalysis is complex due to its subjective nature and the influence\nof factors, such as personality, psychiatric disorders (depression)\nand psychosocial factors. The severity of pain may be related to\nthe degree of depression and anxiety, present in 90% of women\nwith endometriosis, namely with AM, this is why all hormonal\ndrugs must be prescribed in the way excluding neurotic disorders\n(such as depression and anxiety). Some authors indicate that\ndepression is a direct consequence of chronic pelvic pain, but\nthere is no consensus on this temporal issue when defining which\ncondition precedes the other [7]. However, it is possible to affirm\nthat the two conditions coexist, and that one worsens the\nexperience of the other [8]. Whenever endometriosis patients\nexhibit depression, it is clinically important to assess the\ncondition and start appropriate treatment as soon as possible.\nDepression, if left untreated, has a negative effect on the patient’s\nability to deal with the chronic pelvic pain, daily functioning and\nespecially their quality of life. In addition, the impact of a chronic\ndisease, such as endometriosis, associated with persistent painful\nsymptoms in the pelvic area, causes the patient to become\nisolated, damaging relationships given that women with endo-\nmetriosis are labeled as ‘‘hypochondriac’’ and their circle of\nfriends ends up getting tired of so many complaints [5]. In this\nstudy, we found that LNG-IUS was an effective and simple\nalternative method for the treatment of chronic pelvic pain. Our\nfinding was in accordance with many previous studies [2–4]. With\nLNG-IUS local endometrial concentration of levonorgestrel is\nhigh and uniform as compared to blood concentration and this\naccount for lesser side effects. Four women achieved amenorrhea\nafter 12 months and many complained of intermittent spotting at\n3 months, which further decreased at 6 and 12 months post\ninsertion. The treatment with LNG-IUS seemed to be an\nappropriate alternative to hysterectomy for all women who\nperceived with chronic pelvic pain of varying severity.\nConclusion\nThus, the obtained results allowed to confirm the possibility of\nusing LNG-IUS in the treatment of pelvic pain syndrome\nassociated with AM, particularly with mild and moderately\nsevere pelvic pain syndrome. This is a cost effective, reversible\nand long-term treatment for women with pelvic pain associated\nwith AM, which reduces the need for surgical interventions.\nDeclaration of interest\nThe authors declare that they have no competing interests.\nReferences\n1. Li L, Leng JH, Dai Y, Zhang JJ. A prospective cohort study on\neffects of levonorgestrel-releasing intrauterine system for adeno-\nmyosis with severe dysmenorrhea. Zhonghua Fu Chan Ke Za Zhi\n2016;51:345–51.\n2. Byun JY, Kim SE, Choi BG, et al. Diffuse and focal adenomyosis:\nMR imaging findings. Radiographics 1999;19:161–70.\n3. Atri M, Reinhold C, Mehio AR, et al. Adenomyosis: US features\nwith histologic correlation in an in-vitro study. Radiology 2000;215:\n783–90.\n4. Azziz R. Adenomyosis: current perspectives. Obstet Gynecol Clin\nNorth Am 1989;16:221–35.\n5. Fong YF, Singh K. Medical treatment of a grossly enlarged\nadenomyotic uterus with the levonorgestrel-releasing intrauterine\nsystem. Contraception 1999;60:173–5.\nDOI: 10.1080/09513590.2016.1232673 Treatment strategies for pelvic pain associated with adenomyosis S21\n\n6. Dueholm M, Lundorf E. Transvaginal ultrasound or MRI for\ndiagnosis of adenomyosis. Curr Opin Obstet Gynecol 2007;19:\n505–12.\n7. Lee KH, Kim JK, Lee MA, et al. Relationship between uterine\nvolume and discontinuation of treatment with levonorgestrel-\nreleasing intrauterine devices in patients with adenomyosis. Arch\nGynecol Obstet 2016;294:561–6.\n8. Vercellini P, Vigano ` P, Somigliana E, Fedele L. Endometriosis:\npathogenesis and treatment. Nat Rev Endocrinol 2013;10:\n261–75.\nS22 V. E. Radzinsky et al. Gynecol Endocrinol, 2016; 32(S2): S19–S22","source_license":"CC0","license_restricted":false}