{"paper_id":"0ce92c5d-e032-4498-b7a6-64e39f68eb7d","body_text":"ORIGINAL RESEARCH ARTICLE\nExperience of Symptoms and Disease Impact in Patients\nwith Adenomyosis\nLinda M. Nelsen 1 • William R. Lenderking 2 • Robin Pokrzywinski 3 •\nZaneta Balantac 3 • Libby Black 1,4 • Shibani Pokras 1 • Mary Beth Enslin 5 •\nMelisa Cooper 5 • Andrea S. Lukes 6\nPublished online: 2 December 2017\n/C211 The Author(s) 2017. This article is an open access publication\nAbstract\nBackground Adenomyosis is a poorly understood, benign\ndisease of the uterus.\nObjective In this study, patient interviews were conducted\nto characterize the symptoms and impact of adenomyosis.\nMethods This was a cross-sectional study in which women\nwith adenomyosis were recruited from five US clinics and\na health-related social network forum. Participants (aged\n18–55 years) were pre-menopausal with a history of reg-\nular menstrual cycles. Participants were interviewed about\ntheir experiences with adenomyosis, symptoms and\nimpacts on day-to-day activities (concept elicitation), and\nsubsequently about the occurrence, relative severity, and\nimpact of symptoms (card-sorting exercise).\nResults In total, 31 women were interviewed. Mean\nduration since onset of first adenomyosis symptom was\n5.7 years; 41.9% reported severe/very severe adenomyosis.\nOver 50 symptoms and 30 impacts of adenomyosis were\nreported in the concept elicitation; 87% of symptoms were\nreported after 7 interviews and 78% of impacts after 5\ninterviews, indicating a condition with a significant\nsymptom burden and a consistent presentation. The most\ncommon symptoms were heavy menstrual bleeding (87%),\ncramps (84%), and blood clots during menstrual bleeding\n(84%). The most common impacts were burdensome self-\ncare hygiene (71%), and fatigue/low energy (71%). In the\ncard-sorting exercise, the most commonly endorsed\nsymptoms were pain during menstruation/menstrual\ncramps and heavy menstrual bleeding (both frequently\nrated as severe). The symptom with the highest impact was\nheavy menstrual bleeding.\nConclusion Initiatives to understand women’s experiences\nwith adenomyosis may improve management of the con-\ndition. This study provides a first step in understanding\ntheir experience and new information on the symptom\nprofile of adenomyosis.\nElectronic supplementary material The online version of this\narticle ( https://doi.org/10.1007/s40271-017-0284-2) contains supple-\nmentary material, which is available to authorized users.\n& Linda M. Nelsen\nlinda.m.nelsen@gsk.com\n1 Value Evidence and Outcomes, GSK, 1250 South\nCollegeville Road, Building 4, 4th floor, Collegeville, PA\n19426, USA\n2 Evidera, Waltham, MA, USA\n3 Evidera, Bethesda, MD, USA\n4 Present Address: Recro Pharma, Inc., Malvern, PA, USA\n5 Alternative Discovery and Development, GSK,\nKing of Prussia, PA, USA\n6 Carolina Women’s Research and Wellness Center, Durham,\nNC, USA\nPatient (2018) 11:319–328\nhttps://doi.org/10.1007/s40271-017-0284-2\n\nKey Points for Decision Makers\nLimited information is available from the patient\nperspective regarding the signs, symptoms, and\nimpacts of adenomyosis. A better understanding is\nrequired to improve the management of the\ncondition.\nInterviews with women with adenomyosis found that\nthe most common symptoms were heavy menstrual\nbleeding, cramps, and blood clots during menstrual\nbleeding. The most commonly reported impacts of\nadenomyosis were burdensome self-care hygiene,\nfatigue/low energy, and impacts on leisure/social\nactivities, household/activities of daily living, travel,\nand physical activities.\nFor both symptoms and impacts, saturation (the\ninterview at which no novel concepts were gathered)\nwas reached after a small number of interviews,\nindicating a condition with a consistent presentation.\n1 Introduction\nAdenomyosis is an under-diagnosed disease of the uterus\ncharacterized by the abnormal presence of endometrial\nglands and stroma within the myometrium. This results in\nan enlarged uterus that microscopically exhibits ectopic,\nnon-neoplastic endometrial glands and stroma surrounded\nby the hypertrophic and hyperplastic myometrium [ 1, 2].\nAlthough the condition was first defined nearly 50 years\nago, it remains both under-diagnosed and poorly under-\nstood due to the lack of a consensus definition, diagnostic\ndifficulties, and inadequately defined symptoms [ 3]. The\nresults of epidemiologic studies of adenomyosis are diffi-\ncult to interpret due to the difficulties with diagnosis. Until\nrelatively recently, diagnosis of adenomyosis was only\npossible on histologic examination of a uterus following a\nhysterectomy [ 4], and it has been reported to occur in\n20–30% of women undergoing hysterectomy [ 5]. The\nsymptoms of adenomyosis can include heavy menstrual\nbleeding, dysmenorrhea, abnormal uterine bleeding,\nbloating, dyspareunia, pelvic pain, infertility, and miscar-\nriage [ 3, 6].\nNo drugs have been approved by the US FDA for the\ntreatment of adenomyosis. Healthcare prescribers may\nprescribe nonsteroidal anti-inflammatory drugs or stronger\npain medications, oral contraceptives, anti-prostaglandins,\ntranexamic acid, danazol, aromatase inhibitors, gonado-\ntropin-releasing hormone analogs, or a levonorgestrel-\nreleasing intrauterine device system to treat symptoms\n[7–9]. Therapeutic minimally invasive procedures, such as\nendometrial ablation, may have a higher rate of failure for\nwomen with adenomyosis [ 10]. When there is focal\nadenomyosis, laparoscopic myometrial electrocoagulation\nor excision can be used [ 8]. Hysterectomy is an option if\nfertility is not an issue, given other treatments may fail [ 8].\nBased on a targeted literature review, no patient-reported\noutcome (PRO) measures for adenomyosis have been\ndeveloped, and information regarding its specific signs,\nsymptoms, and impacts characterized by women with\nadenomyosis is limited. Given the increasing emphasis of\nthe FDA on patient-centred outcomes [ 11], a validated\nPRO measure could be highly supportive of regulatory\napproval of novel treatments.\nImproved understanding of women’s experience with\nadenomyosis will support the development of informed,\nresponsive PRO measures to help characterize the response\nto novel treatment approaches for adenomyosis. The\nobjective of this study was to conduct qualitative inter-\nviews to characterize the symptoms, impacts, and disease\nexperience of women with adenomyosis.\n1.1 Methods\n1.1.1 Study Design\nThis was a qualitative, cross-sectional, descriptive study in\nwomen with adenomyosis (GSK study: HO-15-15667).\nQualitative analyses were conducted that followed the\nprinciples of the grounded theory method [ 12] as well as\nmethods suggested by Patton [ 13]. The key tenet of the\ngrounded theory method (originally developed by Glaser\nand Strauss [ 14]) is that the concepts that emerge through\nanalysis of the data are ‘ ‘grounded’ ’ in the experiences of\nthe respondents, and the results can be used to develop a\ntheoretical understanding of the content areas under\ninvestigation. In this study, the preliminary stage of con-\ncept analysis was performed to identify the concepts/\nsymptoms of interest. A card-sorting exercise based on pre-\nidentified symptoms (from literature review) was con-\nducted to provide additional structured information\nregarding symptom severity and impact.\nInstitutional review board approval was received from\nthe Western Institutional Review Board, Puyallup, WA,\nUSA, and Ethical Independent Review Services, Indepen-\ndence, MO, USA; all participants provided written\ninformed consent prior to being interviewed. The study was\nconducted in alignment with the recommendations of the\nFDA PRO guidance [ 11] and the International Society for\nPharmacoeconomics and Outcomes Research (ISPOR)\nGood Research Practices Task Force for establishing and\nreporting the content validity of PRO instruments [ 15].\n320 L. M. Nelsen et al.\n\nParticipants took part in a single 1:1 face-to-face or\ntelephone interview, conducted between September and\nDecember 2015 by employees of Evidera (Table 1 in the\nElectronic Supplementary Material [ESM]). Participants\nwere informed of the aims of the study, the study sponsor,\nand the role of the interviewer in the study. Participants had\nno relationship with the interviewer prior to the interview;\nthe interviewer asked some condition-specific questions at\nthe beginning of the interview to gain a high-level under-\nstanding of the participants clinical history. Interviews\nfollowed a semi-structured interview guide developed\nbased on a targeted literature review to identify adeno-\nmyosis symptoms and impacts, and feedback from two\nexpert physicians and two patients. Interviews consisted of\nconcept elicitation, a card-sorting exercise, and completion\nof a sociodemographic form, and lasted up to 2 h. For the\nconcept elicitation, women were asked about their general\nexperiences with adenomyosis signs and symptoms and\nhow adenomyosis impacts their day-to-day activities. Ini-\ntially, women were encouraged to spontaneously report\ntheir experiences; interviewers then probed participants\nusing a pre-specified list. To ensure that all concepts\nimportant to the participants were included, and to mini-\nmize bias, concept saturation for the concept-elicitation\nphase was determined using a saturation grid [ 15, 16].\nFor the card-sorting exercise, participants were provided\nwith 41 cards (Table 2 in the ESM), each listing a symp-\ntom of adenomyosis (identified from literature and the prior\npatient and physician expert interviews). For participants\ntaking part in telephone interviews, the cards were sent\nprior to the interview. Participants were asked to sort the\ncards by symptoms that they did and did not experience.\nFor the symptoms they did experience, they were asked to\nsort the cards three times; by severity, by the level of\nimpact in their daily lives, and by occurrence in relation to\ntheir menstrual cycle. For the telephone interviews, par-\nticipants provided the order of the cards in response to the\nquestions over the phone.\n1.2 Participants\nWomen were recruited from five clinics across the USA\n(Philadelphia, PA; Boise, ID; Durham, NC; New Bruns-\nwick, NJ; Virginia Beach, VA) and through targeted pop-\nup advertisements on HealthUnlocked, a social network\nsite that provides a forum for patients to discuss health-\nrelated issues. Participants were aged 18–55 years and pre-\nmenopausal with a history of regular menstrual cycles\n(occurring every 21–35 [ ± 5] days). Participants recruited\nat clinics had a diagnosis of adenomyosis according to\ntransvaginal ultrasound or magnetic resonance imaging\n(MRI). For participants recruited at a clinical site, the clinic\ncompleted a clinical case report form that included the\nparticipant’s clinical history and comorbid medical condi-\ntions. Participants recruited through advertisements self-\nreported their adenomyosis that had been diagnosed by\ntheir physicians. Key exclusion criteria for participants\nrecruited at clinics included history of an endometrial\nablation or uterine artery embolization within 6 months of\nenrollment; currently pregnant or less than 6 months\npostpartum; confirmed rectovaginal endometriosis; MRI\ndemonstrating uterine fibroids as the dominant process\n(presence of sub-mucosal fibroids or intramural fibroids\nC 10 cm; sub-serosal uterine fibroids were acceptable);\nmalignant disease of the uterus, ovary or cervix; ovarian\nlesions suggestive of endometriosis [3 cm in diameter; or\nthe presence of uterine polyps. In addition, participants\nrecruited through advertising with any diagnosis of uterine\nfibroids were excluded.\n1.3 Data Analysis\nInterviews were digitally recorded, and audio recordings\nwere transcribed. Participant-identifying information was\nremoved before analysis. Data were analyzed using\nATLAS.ti qualitative data analysis software, version\n7.1.6. Transcripts were not provided to participants, and\nparticipants were not asked to provide feedback on the\nfindings.\nA coding dictionary was developed for the study based\non the interview guide. All transcripts were coded and\nreviewed by three trained personnel according to the fol-\nlowing protocol. Two of the personnel independently\ncoded each interview transcript. A post-coding comparison\nand reconciliation was conducted by the third member of\nthe team. Relevant codes were attached to each concept\nmentioned within each transcript; where necessary, new\ncodes were added to the coding dictionary. Once all tran-\nscripts were coded, a quality-control check was performed.\nAll utilized codes were then entered into a saturation grid\nto track the concepts identified in each interview and to\ndetermine when saturation (the interview at which no novel\nconcepts were gathered) was reached [ 17].\n2 Results\n2.1 Study Population\nIn total, 31 women participated in the study; 27 were\nrecruited from clinical sites and four were recruited\nthrough HealthUnlocked (Table 1). Two participants took\npart in face-to-face interviews; the remaining 29 interviews\nwere undertaken over the telephone. With the exception of\nWilliam R. Lenderking (a senior clinical psychologist and\nthe project director), all interviewers were women. Dr.\nPatient-Reported Symptoms and Impact of Adenomyosis 321\n\nLenderking conducted 8 interviews over the telephone;\nthese participants were explicitly asked whether they were\nuncomfortable being interviewed by a male, and they\nraised no issues. No effect on the women’s candor was\nnoted as a function of the sex of the interviewer.\nParticipants reported the mean (range) duration since\nthey first experienced adenomyosis symptoms as 5.7\n(0–23) years, and 41.9% rated their adenomyosis as severe\nor very severe (Table 2). For participants recruited from\nclinics, clinicians reported a mean (range) duration since\nadenomyosis diagnosis of 1.2 (0–6) years. The majority of\nwomen (88.9%; n = 24/27) were diagnosed via\ntransvaginal ultrasound, and 11.1% ( n = 3/27) were diag-\nnosed via MRI.\n2.2 Concept Elicitation: Symptoms\nMore than 50 different symptoms of adenomyosis were\nreported, the most common of which were heavy menstrual\nbleeding (87%), cramps (84%), blood clots during men-\nstrual bleeding (84%), bloating (55%), and low\nenergy/fatigue (52%) (Table 3). The saturation grid\ndemonstrated that 87% of concepts were reported after 7\ninterviews, and saturation was reached after 30 interviews\n(Table 3 in the ESM). New symptoms after the seventh\ninterview included blood in the urine, constipation, difficult\nor painful defecation, ovarian pain, and diarrhea.\n2.3 Concept Elicitation: Impacts\nMore than 30 impacts of adenomyosis were reported; the\nmost common were burdensome self-care hygiene (71%),\nfatigue/low energy (71%), and impacts on leisure/social\nactivities (65%), household/activities of daily living (61%),\ntravel (61%), and physical activities (61%) (Table 3).\nMany participants reported that fatigue was more of an\nissue during their menstrual periods. Saturation on impacts\nwas reached after 25 interviews, and 78% of impacts had\nbeen reported after 5 interviews (Table 4 in the ESM). New\nimpacts after the fifth interview included eating (primarily\nfeeling too nauseous to eat), stress, anxiety (e.g., the fear of\nhaving a bleeding accident, and concern that they may have\na condition more severe than adenomyosis), and loss of\ncontrol/helplessness.\n2.4 Card Sorting\nAll 41 symptoms presented in the card-sorting exercise\nwere experienced by at least one participant (Fig. 1a). The\nmost commonly endorsed symptoms, pain during men-\nstruation/menstrual cramps (dysmenorrhea) and heavy\nmenstrual bleeding, were also the symptoms most fre-\nquently rated as severe (70% [ n = 21/30] and 76%\n[n = 22/29], respectively), along with longer cycles (84%\n[n = 16/19]; Fig. 1b).\nThe symptoms with the highest impact were heavy\nmenstrual bleeding (68% [ n = 19/28]), pain (64% [n = 16/\n25]), longer cycles (63% [ n = 12/19]), and pain during\nmenstruation/menstrual cramps (60% [n = 18/30]; Fig. 1c).\nSymptoms most commonly reported to be present all\nmonth regardless of menstruation included pain during\nintercourse (dyspareunia 88% [ n = 15/17]); bleeding or\nspotting between periods (79% [ n = 11/14]); waking at\nnight to urinate (76% [ n = 13/17]); dryness/tightness in the\nvaginal region (70% [ n = 7/10]); and tingling or numbness\nin hands or feet (69% [ n =\n9/13]). The symptoms reported\nby the highest proportion of women as being experienced\nonly during menstruation included heavy menstrual\nbleeding (100% [ n = 29/29]), blood clots during menstrual\nbleeding (100% [ n = 28/28]), and difficulties with men-\nstruation (100% [ n = 24/24]).\n3 Discussion\nAdenomyosis is not well characterized and likely under-\ndiagnosed by clinicians. A literature search revealed a\nlimited understanding of the signs, symptoms, and impacts\nTable 1 Participant demographics\nParticipant-reported demographic\ncharacteristics\nParticipants ( N = 31)\nAge, years 40.9 ± 5.8 (range 28–52)\nRacial background\nWhite 14 (45.2)\nBlack or African American 11 (35.5)\nAsian 4 (12.9)\nOther 2 (6.5)\nEmployment status\nEmployed, full time 20 (64.5)\nEmployed, part time 5 (16.1)\nHomemaker 4 (12.9)\nStudent 1 (3.2)\nUnemployed 1 (3.2)\nHighest level of education\nElementary/primary school 1 (3.2)\nSecondary/high school 3 (9.7)\nTechnical or vocational degree 2 (6.5)\nSome college/university 7 (22.6)\nCollege/university degree 13 (41.9)\nPostgraduate degree 4 (12.9)\nOther 1 (3.2)\nData are presented as mean ± standard deviation or n (%) unless\notherwise indicated\n322 L. M. Nelsen et al.\n\nTable 2 Participant clinical\ncharacteristics\nParticipant self-reported clinical characteristics Participants ( N = 31)\nCurrently sexually active 29 (93.5)\nGeneral health status within the past week\nExcellent 3 (9.7)\nVery good 13 (41.9)\nGood 12 (38.7)\nFair 2 (6.5)\nPoor 1 (3.2)\nSeverity of adenomyosis\nMild 5 (16.1)\nModerate 12 (38.7)\nSevere 9 (29.0)\nVery severe 4 (12.9)\nMissing 1 (3.2)\nYears since first experience of adenomyosis symptom 5.7 ± 6.5 (range 0–23)\nFrequency of bleeding between periods\nNone of the time 16 (51.6)\nSome of the time 10 (32.3)\nMost of the time 4 (12.9)\nNearly all of the time 1 (3.2)\nDaily 0\nSeverity of bleeding between periods\nNone of the time 16 (51.6)\nLight 10 (32.3)\nModerate 2 (6.5)\nHeavy 3 (9.7)\nClinician-reported clinical characteristics N = 27\na\nYears since adenomyosis diagnosis 1.2 ± 1.91 (range 0–6)\nImaging of suspected adenomyosis b\nTransvaginal ultrasound 24 (88.9)\nMRI 3 (11.1)\nComorbid health conditions\nOvarian cysts or other ovarian disorders 7 (25.9)\nAnemia 4 (14.8)\nAnxiety 4 (14.8)\nEndometriosis 4 (14.8)\nUterine fibroids 4 (14.8)\nCervical polyps 1 (3.7)\nDepressive disorder 1 (3.7)\nAny other gynecological conditions\nc 2 (7.4)\nOtherd 7 (25.9)\nNone 5 (18.5)\nData are presented as mean ± standard deviation or n (%) unless otherwise indicated\nMRI magnetic resonance imaging, SD standard deviation\na No clinically provided data were available for four participants recruited through advertising\nb Neither ultrasound nor MRI ( n = 1); includes one participant with both ultrasound and MRI\nc Herpes ( n = 1) and history of abnormal pap smear ( n = 1)\nd Abnormal uterine bleeding ( n = 2), carpal tunnel ( n = 1), free fluid in pelvis ( n = 1), hyperthyroidism\n(n = 1), multiple sclerosis ( n = 1), pelvic pain ( n = 3), and seasonal allergies ( n = 1)\nPatient-Reported Symptoms and Impact of Adenomyosis 323\n\nTable 3 Concept elicitation: symptoms and impacts described by participants\nSigns, symptoms, and impacts\nmentioned by C 10% of participants\nParticipants\n(N = 31), n (%)\nRepresentative quotes\nSigns/symptoms\nBleeding characteristics ‘I get just very heavy bleeding—I stand up and it feels like a waterfall, I mean it\nsounds disgusting, but that’s exactly how it feels—like, it gets so bad that I have to\nuse the super-duper overnight pads during the day, and I change them quite\nfrequently.’\n‘Yes, during my cycle it’s very heavy, so the first couple of days, you know, I spot\nand then day 1 and day 2 I spot mostly, and then it just kind of comes full force. I\nmean I get clotting, I get just very heavy bleeding’\nHeavy menstrual bleeding 27 (87)\nBlood clots during menstrual\nbleeding\n26 (84)\nBleeding or spotting between\nperiods\n15 (48)\nLonger menstrual bleeding 12 (39)\nPain ‘I would say like contractions almost, the first couple of days it feels like I’m\nactually in labor a little bit, yeah, and it’s like sometimes—the first two days\nthey’re pretty intense’\n‘In terms of cramping I would have pain, you know, because those cramps would\nfeel like, you know, like somebody is cutting me or my, you know, my uterus is\nbeing squished or in like a clamp or something, you know, like there’s pressure’\n‘… with the adenomyosis it’s not so much a burning sensation, but like pulses of\npain, I mean it’s kind of hard to describe, but it doesn’t burn, it just hurts, it’s like\nsharp, stabbing pains, that’s what it feels like to me—and it’s always in the same\nsection, always towards my left side … it’s a pain in the rear’\n‘The vaginal, it’s like with the part that the baby comes out, and then the lower belly,\nit’s like you have the cramps, and the back, it’s like with the, what do you call it,\nthe ribs on the left and right, something like that—it’s like the muscle’\nCramps (dysmenorrhea) 26 (84)\nAbdominal pain 13 (42)\nLower back pain 12 (39)\nPain (general or unspecified) 9 (29)\nPain during intercourse\n(dyspareunia)\n8 (26)\nAbdominal pressure 8 (26)\nPelvic pain 7 (23)\nCramps (non-menstrual) 7 (23)\nPain radiating down the legs 7 (23)\nTenderness (breast and/or\nabdominal)\n6 (19)\nPain or aches in muscles or joints 5 (16)\nHeadaches 5 (16) ‘I get headaches during the day preceding when—before my period starts and the\nfirst day, but I don’t know if it’s due to a regular menstrual headache or is it\nhormonal or is it due to adenomyosis—that I don’t know’\nBloating 17 (55) ‘I’d say the bloating starts like right around when I’m getting breast tenderness. I\nknow my period is coming, so like the week—like a couple days in the week\nbefore, and bloating throughout that whole time that I would have my period’\nEnlarged uterus to the point where\nyou look pregnant\n5 (16)\nSwelling or heaviness in the legs/\nfeet\n7 (23)\nLow energy/fatigue 16 (52) ‘I would say at least two full days where I just want to lay around—and if I could, I\nwouldn’t go to work; I would just lay around for those two days, at least two good\ndays’\nAnemia-related fatigue 3 (10)\nNausea 9 (29) ‘I just get very sick where you are nauseous, really can’t function, throw up, you\nknow, and just overall just not feeling well’\nDifficulties with urination ‘Some days I will have that symptom that I have to go to the bathroom—I feel like I\nhave to go to the bathroom all the time’\n‘… that comes in waves, too. Sometimes I will wake up four or five times at night,\nand sometimes it will only be once’\nPassing urine frequently 5 (16)\nLeaking urine/incontinence 3 (10)\nFeeling sudden urge to urinate 3 (10)\nWaking at night to urinate 3 (10)\nDifficulties with defecation ‘Oh, sometimes I’m scared, and then I ask my primary doctor to give me some\nmedicine for if I feel constipated. If I’m not mistaken it’s about 3 times a month or\n4 times a month—and also if I have a heavy period, that’s when I have the time\nthat I pee and then at the same time I poop, something like that, I need to rush to\nthe bathroom—it’s like I feel excited and I need to go to the bathroom, especially\nwhen I get a pain’\nIrregular bowel movement 5 (16)\nConstipation 3 (10)\nDryness/tightness in the vaginal\nregion\n4 (13) ‘I have experienced dryness, and I know some of that is psychological or can be as\nwell, because I’m not in the mood, nothing excites me, so I thought part of that\nmight also be because I’m psychologically not in it’\nOvarian pain 3 (10) ‘Um, a pain that would come and go, that is almost like a gnawing sensation, like\nsomething is gnawing at you. My left side, lower, um, sort of like below my uterus,\nbetween my uterus and ovary, left ovary. Kind of like a scratching sensation or\ngnawing, like something’s digging in me’\n324 L. M. Nelsen et al.\n\nTable 3 continued\nSigns, symptoms, and impacts\nmentioned by C 10% of participants\nParticipants\n(N = 31), n (%)\nRepresentative quotes\nImpacts\nBurdensome self-care hygiene 22 (71) ‘I try not to go out and if I do I panic basically because I don’t know when I’ll get a\nchance to change and I some—I—those times when I have to go out I use a tampon\nand an under pad—second pad because I put on two [laughter] under one of that.\nI’ve had—I’ve had to line, you know, put plastic and stuff on my car seat just in\ncase. And there have been times where it comes right through my pants through to\nthe—to the car seat and everything. I had it happen at work where it came right\nthrough to the—my chair. And I had to go home and change’\nFatigue/low energy 22 (71) ‘ … when I have so much pain, it’s exhausting, so, you know, I don’t want to do\nanything or I don’t want to get up off the couch because I’m so tired, the littlest\nthings tire me out’\nLeisure/social 20 (65) ‘Any social activity whether it’s going to the movies, hanging out with friends. No, I\n… I’m not doing any of that because I’m too worried about if I’m going to mess\nup, if I’m going to able to use the public bathroom to change and that type of stuff’\nHousehold/activities of daily living 19 (61) ‘Cleaning is troublesome, because of the bending’\nTravel 19 (61) ‘ … there are certain times where I won’t go like on a trip or anything because of it\nor, you know, because it’s just, you know, am I going to be able to use the\nbathroom or sometimes you just don’t, you know, you’re not feeling it’\nPhysical activities 19 (61) ‘I mean I don’t really do very many physical things, I mean I joined a gym, but I\ndon’t actually go to the gym during my period, because it just would never work’\nSleep 18 (58) ‘I mean the first three days I get no sleep, I am exhausted, because I don’t want to\nhave any accidents, you know, which I wind up having anyway, because\nsometimes I fall asleep because I’m so exhausted, and like an hour later the bed is\nsoaked, change my underwear and nightgown—it’s terrible—it’s terrible’\nWork/school 17 (55) ‘So not being able to lift things—every once in a while, like I work at a bank, so, you\nknow, boxes of coins, you know, they’re pretty heavy or I have the pain I can’t do\nit. I can’t stand for an extremely long period of time, usually my boss doesn’t like\nwhen you sit and you help the customers, but when I have the pain I don’t have\nmuch of a choice’\nRelationships 16 (52) ‘He doesn’t quite understand what’s going on with the pain, so he’ll say things like\n‘ ‘oh, are you in pain today,’ ’ but he says it like he doesn’t know what to do kind of\nthing, so it kind of puts a strain on us a little bit, because I’m over here in pain and\nI’m not in such a good mood, and he’s over there trying to make me feel better,\nand it’s definitely not working’\nQuality of life 13 (42) ‘I would say that it does have a big effect on the quality of life, because it minimizes\ncertain things that I can do and when I can do it, things like that’\nFinancial 12 (39) ‘Well, it has definitely increased the cost of feminine hygiene products. Oh, and not\njust that, and the cost of the medical care. I just got the bill from the procedure,\n$US1800 is my portion I need to pay’\nPsychological/emotional ‘Yeah, so my pain definitely dictates how I’m feeling that day and, you know, I can\nbe a lot harder to deal with, I know. I get angrier quicker when I’m in a lot of pain’\n‘My mood swings all over the place. Oh, goodness, very emotional, my gosh, it’s the\nworst, very moody, very emotional’\n‘It even gets me like anxious, because I don’t know, maybe it’s my personality, I\ndon’t know. I like to be doing a lot of stuff, but I feel like I can’t—that I can’t do\nall I want at work and in my house’\nFrustration 11 (35)\nMoody/mood swings 10 (32)\nDepression 9 (29)\nWorry 9 (29)\nAnxiety 3 (10)\nMobility 10 (32) ‘I can’t even stand up straight, it’s very painful, I have to take medication or I’m\ngoing to the emergency room’\nEating 9 (29) ‘Oftentimes like it just makes it hard to want to eat and like it just sort of becomes\nlike a vicious cycle a little bit that, I will get nauseous. So it’s hard for me to eat\nand take my pain meds, but if I, you know, don’t, then I’m in a cycle of pain’\nPatient-Reported Symptoms and Impact of Adenomyosis 325\n\na\nb\nc\nFig. 1 Card sorting exercise results: a the 30 most frequently endorsed symptoms ( C 10 women), b their severity and c their impact\n326 L. M. Nelsen et al.\n\nof the condition, with little evidence derived directly from\nwomen with adenomyosis. To improve management of\nadenomyosis, it is important to understand the experiences\nof women with this condition. This study reports the\nsymptoms and impacts of adenomyosis from the patient\nperspective.\nThe 31 participants in the study reported over 50 dif-\nferent symptoms, and all reported multiple symptoms. The\nmost common symptoms were associated with bleeding\nand pain. The biggest impacts for women concerned self-\ncare hygiene, fatigue/low energy, and leisure/social activ-\nities. In spite of the variability of symptoms and impacts\nreported, 87% of symptoms were reported after 7 partici-\npant interviews, and 78% of impacts were reported after\njust 5 interviews. This suggests that, although there is\nvariability and a wide range of symptoms and impacts, the\noverall symptom profile of adenomyosis was fairly con-\nsistent in this study population.\nIn addition to the concept elicitation, the card-sorting\nexercise enabled us to ask women to review a predefined\nlist of symptoms. Given the time constraints of the inter-\nviews and the wide range of symptoms, this allowed us to\ninvestigate symptoms that women may not have originally\nreported during the concept elicitation but did associate\nwith their adenomyosis when prompted by the cards. The\nresults of the card-sorting exercise reinforced the concept-\nelicitation findings.\nAlthough there are some similarities in the pathogenesis\nof adenomyosis and endometriosis [ 6], adenomyosis results\nfrom the infiltration of basal endometrium into the under-\nlying myometrium [ 18], whereas in endometriosis there is\nendometrial gland and stroma-like tissue outside of the\nuterus [ 19]. In reviewing the literature, the authors are not\naware of other studies that have comprehensively investi-\ngated the symptoms and impacts of adenomyosis from the\npatient perspective. However, previous studies in women\nwith endometriosis have identified similar symptoms,\ndemonstrating overlap between the two conditions.\nSymptoms of adenomyosis, such as pain, fatigue, bloating,\nand abnormal uterine bleeding are commonly reported by\nwomen with endometriosis [ 20, 21]. Although there is\noverlap between the type of symptoms, particularly pain,\nexperienced in adenomyosis and endometriosis, there may\nbe substantial differences in the character of the pain;\nfurther research is required to determine whether this is the\ncase.\nMany of the physical and psychological impacts of\nadenomyosis are also experienced by women with\nendometriosis. Importantly, burdensome self-care/hygiene,\nthe most commonly reported impact of adenomyosis, has\nnot been associated with endometriosis and is likely due to\nheavy menstrual bleeding. Furthermore, fatigue/low\nenergy, another highly reported impact of adenomyosis,\nappears to be a less common impact of endometriosis [ 21].\nIn contrast, both adenomyosis and endometriosis have been\nshown to negatively impact overall quality of life, activities\nof daily living, social activities, work/education, finances,\nand sleeping, as well as psychological well-being in terms\nof frustration, depression, and anxiety [ 20, 21].\nThis study provides important information regarding the\nsymptoms and impacts of adenomyosis from the perspec-\ntive of women; however, it does have some limitations.\nThe majority of women in the study were diagnosed with\nadenomyosis using transvaginal ultrasound or MRI; how-\never, diagnostic information was not available for the small\nnumber of participants ( n = 4) recruited through\nHealthUnlocked, which could affect the reliability of the\ncase definition. The requirement for women recruited from\nclinics to have a diagnosis confirmed by imaging may have\nresulted in the exclusion of patients with mild adenomyosis\n(43% of the study population had severe/very severe\nadenomyosis); therefore, the results may be less represen-\ntative of women with mild adenomyosis. A small number\nof participants (four recruited from clinics and two from\nHealthUnlocked) had diagnoses of both adenomyosis and\nendometriosis, so not all of the symptoms and impacts\nreported by these participants may have been due purely to\nadenomyosis. The small number of participants with both\nconditions means it was not possible to compare the\nsymptoms of these patients with those of patients with\nadenomyosis alone. Furthermore, some of the women with\nadenomyosis may have undiagnosed endometriosis.\nIndeed, there is a recognized association between having\nadenomyosis and endometriosis [ 19]. Finally, the study\npopulation consisted of women in the USA only; therefore,\nthe findings may not be generalizable to women from other\ncountries.\n4 Conclusion\nInitiatives to understand women’s experiences with ade-\nnomyosis will support the development of informed,\nresponsive PRO measures to help characterize the response\nto novel treatment approaches. This study provides a first\nstep in understanding the perspectives and experiences of\nwomen with adenomyosis.\nAcknowledgements The authors thank all women who participated\nin the interviews.\nAuthor contributions LMN, LB, SP, MBE and MC contributed to\nthe conception/design of the study and analyis/interpretation of the\nresults. WRL, RP and ZB contributed to the conception/design of the\nstudy, acquisition of data (including conducting interviews with the\nstudy participants), and analyis/interpretation of the results. ASL\ncontributed to the conception/design of the study, acquisition of data,\nPatient-Reported Symptoms and Impact of Adenomyosis 327\n\nand analyis/interpretation of the results. All authors contributed to the\npreparation of this manuscript. Editorial assistance (in the form of\nwriting assistance, assembling tables and figures, collating author\ncomments, grammatical editing, and referencing) was provided by\nKatie White, PhD, Fishawack Indicia Ltd, UK, and was funded by\nGSK.\nCompliance with ethical standards\nFunding This study was funded by GlaxoSmithKline (GSK). Evi-\ndera, funded by GSK, and GSK contributed to the design of the study\nand the acquisition, analysis, and interpretation of the data.\nConflict of interest Linda M. Nelsen, Shibani Pokras, Mary Beth\nEnslin, and Melisa Cooper are employees of GSK. William R. Len-\nderking, Robin Pokrzywinski, and Zaneta Balantac are full-time\nemployees of Evidera, a company that provides works for hire to the\npharmaceutical industry. William R. Lenderking owns stock in Pfizer\nInc. as a former employee. Libby Black is a Global Health Outcomes\ncontract researcher for Recro Pharma, Inc. and was employed as a\ncontractor by GSK at the time the study was conducted. She owns\nstock in GSK. Andrea S. Lukes has acted as a consultant for and\nreceived grants from GSK.\nOpen Access This article is distributed under the terms of the\nCreative Commons Attribution-NonCommercial 4.0 International\nLicense (http://creativecommons.org/licenses/by-nc/4.0/), which per-\nmits any noncommercial use, distribution, and reproduction in any\nmedium, provided you give appropriate credit to the original\nauthor(s) and the source, provide a link to the Creative Commons\nlicense, and indicate if changes were made.\nReferences\n1. Bird CC, McElin TW, Manalo-Estrella P. 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Kunz G, Beil D, Huppert P, Noe M, Kissler S, Leyendecker G.\nAdenomyosis in endometriosis—prevalence and impact on fer-\ntility. Evidence from magnetic resonance imaging. Hum Reprod.\n2005;20:2309–16.\n19. Sourial S, Tempest N, Hapangama DK. Theories on the patho-\ngenesis of endometriosis. Int J Reprod Med. 2014;2014:179515.\n20. Moradi M, Parker M, Sneddon A, Lopez V, Ellwood D. Impact of\nendometriosis on women’s lives: a qualitative study. BMC\nWomen’s Health. 2014;14:123.\n21. Culley L, Law C, Hudson N, Denny E, Mitchell H, Baumgarten\nM, et al. The social and psychological impact of endometriosis on\nwomen’s lives: a critical narrative review. Hum Reprod Update.\n2013;19:625–39.\n328 L. M. Nelsen et al.","source_license":"CC0","license_restricted":false}