{"paper_id":"a0a5a0fa-d85a-4511-b23b-b7fc13b09ab3","body_text":"BACKGROUND\nAdenomyosis is the presence of endometrial-\nlike tissue and stroma within the myometrium. \nHistorically, the diagnosis of adenomyosis was \nmade on the basis of histopathology following \nhysterectomy, meaning the community \nprevalence of adenomyosis and prevalence in \nyounger women are unknown.1,2\nThe likelihood of identifying adenomyosis \nfollowing hysterectomy varies widely, \nwith reports ranging from 8.8% to 61.5%.2 \nThere is no unified histological diagnostic \ndefinition of adenomyosis.1 Rates are likely \ninfluenced by care setting variables, for \nexample, access to or indications for surgery. \nThe evolution of alternative treatments \nto hysterectomy, including less invasive \nsurgery (for example, endometrial ablation \ntechniques) and hormonal coil treatments, \ninfluence hysterectomy rates,3 which in turn \nwill impact on histology-based adenomyosis \ndiagnoses.2,4\nDiagnosis without surgery has become \npossible through imaging (transvaginal \nultrasound (TVUS) or MRI). Changes \ncompatible with possible adenomyosis are \nincreasingly described radiologically, but \nare dependent on the specialist performing \nthe scan.2 As with histology, there is no \nstandardised radiological diagnostic criterion \nfor adenomyosis.1 Adenomyosis prevalence \non TVUS in specialist clinics is estimated at \n20.9% to 34%.2\nLittle is known about how often \nadenomyosis is documented, encountered, \nor managed in GP settings.\nThe aetiology of adenomyosis is unclear. \nIt was originally thought to develop after \ndisruption of the endometrium–myometrium \njunction (for example, during uterine surgery, \npregnancy, or labour) allowing endometrial \ncells to invade the myometrium.2 However, \nimaging identifies the condition in younger \nand nulliparous women, suggesting additional \nmechanisms. It is likely that factors associated \nwith endometriosis development may also \napply to adenomyosis, including genetic \ncontributions, oestrogen dependence, and \nmetaplasia of Müllerian remnants.5\nASSOCIATED SYMPTOMS \nAdenomyosis can contribute to heavy \nmenstrual bleeding, intermenstrual bleeding, \npainful periods, and pelvic pain. 1,2,5 The \nuterus may feel enlarged or bulky to the \npatient or identified during examination.4 \nWhile it is often cited that approximately \none-third of patients with adenomyosis \nhave no associated symptoms,1,4,5 this figure \nis uncertain.2 It derives from retrospective \nreviews of hysterectomy indication, whereby \na hysterectomy performed for prolapse was \ncategorised as asymptomatic, although \nthe patient may have experienced relevant \nundocumented symptoms. Newer evidence \nsuggests that most patients with adenomyosis \nexperience symptoms.2\nAdenomyosis can be identified alongside or \ncoexist with other gynaecological conditions, \nincluding endometriosis and fibroids. 1 \nApproximately 35%–55% of patients with \nadenomyosis also have fibroids4 and 16%–\n62% of women having surgery for fibroids \nare reported to have adenomyosis.2 These \nassociations complicate understanding \npossible relationships between symptoms \nand adenomyosis, 6 and may reflect \naetiological or symptomatic overlap, or access \nto diagnoses.2\nIn patients with endometriosis having \nsurgery, 15%–31% also have adenomyosis \nwith higher rates of coexistence reported in \npatients with endometriosis and symptoms \nof subfertility or pelvic pain.2 Conversely, in \npatients having surgery for adenomyosis, a \ncase-series reports coexistent endometriosis \nin 28.6% of cases.7 A US population study \nUterine adenomyosis: \nan update for GPs\nSharon Dixon, Nura Fitnat Topbas Selcuki, Thomas Round, Gail Hayward and Katy Vincent\nClinical Practice\nS Dixon (ORCID: 0000-0002-7469-6093), \nMBBS, MSc, MRCGP, GP and National Institute \nfor Health and Care Research doctoral \nresearch fellow; G Hayward, (ORCID: 0000-\n0003-0852-627X), DPhil, MRCGP, associate \nprofessor, Nuffield Department of Primary \nCare Health Sciences, University of Oxford, \nOxford. NF Topbas Selcuki (ORCID: 0000-0002-\n5749-9987), MD, DPhil candidate; K Vincent \n(ORCID: 0000-0001-9249-2492), DPhil, \nMRCOG; associate professor, senior fellow \nin pain in women, and honorary consultant \ngynaecologist, Nuffield Department of Women’s \nand Reproductive Healthcare, University of \nOxford, Oxford. T Round, (ORCID: 0000-0003-\n4382-1629), MRCGP, GP and Academic Clinical \nFellow, Population Health Sciences, King’s \nCollege London, London. \nCorrespondence\nSharon Dixon, Radcliffe Primary Care Building, \nRadcliffe Observatory Quarter, Woodstock \nRoad, Oxford OX2 6GG, UK.\nEmail: sharon.dixon@phc.ox.ac.uk\nSubmitted: 21 September 2023; Editor’s \nresponse: 23 September 2023; final \nacceptance: 23 September 2023.\n©British Journal of General Practice 2023; 73: \n524–525.\nDOI: https://doi.org/10.3399/bjgp23X735549\n524  British Journal of General Practice, November 2023\nBox 1. Case\nJo is 42. They came to the GP with increasingly \nheavy, painful periods. They are not on HRT \nor hormonal contraception. A colleague \narranged a pelvic USS, which suggests possible \nadenomyosis, with no other worrying features. \nThey have come to see you to ask what this \nmeans and what could happen next.\nbjgpnov-2023-73-736-524.indd   1bjgpnov-2023-73-736-524.indd   1 06/10/2023   16:3506/10/2023   16:35\n\nincluding 333 693 patients with adenomyosis \nfound that 18% had a concurrent \nendometriosis diagnosis.8\nDespite their similarity and potential \noverlap, endometriosis and adenomyosis \nare considered different conditions that can \ncoexist or occur independently. It is important \nto be aware of their potential coexistence \nwhen counselling about treatments for \nsymptoms, including careful safety netting, \nencouraging patients to report the impact of \ntrials of hormonal treatment for symptomatic \nbenefit including returning for review if these \nare not adequately tolerated or effective.\nAlthough adenomyosis was considered \nan association of multiparity, the advent \nof imaging diagnosis highlights growing \nawareness of a potential association with \nsubfertility. A 2023 systematic review \nreported that approximately 10% of patients \nassigned female at birth with subfertility \nhad adenomyosis alone (without coexistent \nfibroids or endometriosis).9\nFindings that may look like adenomyosis \ncan be reported in adolescents with menstrual \npain or heavy bleeding.10,11 Any adolescent \nwith atypical ultrasound scan appearances \nshould be referred for specialist assessment.\nIn general practice, as in the scenario \n(Box 1), an ultrasound scan is typically \narranged in the context of a clinically relevant \nconcern, with subsequent management in \nline with symptoms and the patient’s priorities. \nHowever, possible adenomyosis may be \nencountered incidentally in the context of \nimaging done for another reason. This offers \nan opportunity to proactively ask about \nsymptoms and consider support options.\nMANAGEMENT IN PRIMARY CARE\nTrials of empirical treatment are a mainstay \nof primary care for adenomyosis. These need \nto be supported by shared decision making, \nincluding acknowledging uncertainty and \npossible next steps. Ensuring patients know \nwhen to come back and the importance of this \nis central to adenomyosis care. Proactively \narranging or enabling routes for follow-up \nand continuity of care may help.\nGuidance about how to manage \nadenomyosis is usually embedded in \nsymptom-focused pathways (for example, \nheavy menstrual bleeding or dysmenorrhoea), \nrather than guidance specific to adenomyosis. \nOffering treatments that mitigate against \npain and bleeding are typically first line, \ntailored against patient preferences, medical \ncontext, and previous experiences. While \nnot trialled specifically in adenomyosis, \na trial of NSAIDs or medications to reduce \nmenstrual flow (tranexamic acid, hormonal \ncontraception) is appropriate if not \ncontraindicated.1 Medications that alter \nmenstrual bleeding (contraceptive or non-\ncontraceptive hormonal therapies) can be \nbeneficial if acceptable and tolerated. The \nhormonal IUS is well studied in adenomyosis \nand is a first-line recommendation for heavy \npain and bleeding, if acceptable or tolerable \nto the patient.1 Rates of IUS expulsion are \nreported to be higher in patients with \nadenomyosis or fibroids.12\nIf any symptoms (pelvic pain, \ndysmenorrhoea, heavy bleeding) are not \nmanaged effectively or adequately with a \nprimary care trial of treatment, or there are \nongoing concerns, referral for specialist \nevaluation is appropriate. This is in part \nbecause of the potential overlap between \nadenomyosis and endometriosis but is \nequally applicable for anyone experiencing \nintractable or difficult symptoms. This \nincludes adolescents, and those concerned \nabout fertility.\nThe presence of adenomyosis can \ncomplicate interpreting ultrasound reports \nabout the endometrium in patients with \nirregular bleeding. If there is any uncertainty \nin primary care, especially if perimenopausal \nor menopausal, referring for specialist \nassessment is appropriate.\nSUPPORT FROM SPECIALIST CARE\nIf patients are referred on, subsequent \ntreatment will be guided by further \nassessment, which may include further \nimaging (MRI), laparoscopy, or hysteroscopy \nand biopsy.\nGynaecology services may advise using \nnon-contraceptive hormonal treatment \n(for example, non-contraceptive dose \nnorethisterone or medroxyprogesterone \nacetate) or GnRHa treatment before or while \nwaiting for specialist review. In this case, \nasking for guidance that includes duration \nof treatment and any monitoring or addback \ntherapy advised is important. Other specialist \nmedications trialled in adenomyosis include \ndanazol and SERMs,1 although their use is \nless widespread.\nSpecialist centres may offer \nmultidisciplinary support for pelvic pain \n(including physiotherapy and psychological \ninput). Trials of treatment may include \nsupervised use of GnRH analogues. Specialist \nsurgical treatments may include hysterectomy \nwith or without oophorectomy depending on \nthe patient’s age. Hysterectomy is the only \ncurative treatment for adenomyosis.\nNICE identifies the long-term outcomes \nof pharmacological or uterine-sparing \ntreatments for heavy menstrual bleeding \nassociated with adenomyosis as a research \npriority evidence gap.13\nBritish Journal of General Practice, November 2023  525\nREFERENCES\n1. Dason ES, Maxim M, Sanders A, et al. Guideline \nNo. 437: diagnosis and management of \nadenomyosis. J Obstet Gynaecol Can 2023; \n45(6): 417–429.e1.\n2. Upson K, Missmer SA. Epidemiology of \nadenomyosis. Semin Reprod Med 2020; 38(2-\n03): 89–107.\n3. Hammer A, Rositch AF, Kahlert J, et al. Global \nepidemiology of hysterectomy: possible impact \non gynecological cancer rates. Am J Obstet \nGynecol 2015; 213(1): 23–29.\n4. Peric H, Fraser IS. The symptomatology of \nadenomyosis. Best Pract Res Clin Obstet \nGynaecol 2006; 20(4): 547–555.\n5. Vannuccini S, Tosti C, Carmona F, et al. \nPathogenesis of adenomyosis: an update on \nmolecular mechanisms. Reprod Biomed Online \n2017; 35(5): 592–601.\n6. Gordts S, Grimbizis G, Campo R. Symptoms and \nclassification of uterine adenomyosis, including \nthe place of hysteroscopy in diagnosis. Fertil \nSteril 2018; 109(3): 380–388.e1.\n7. Naphatthalung W, Cheewadhanaraks S. \nPrevalence of endometriosis among patients \nwith adenomyosis and/or myoma uteri \nscheduled for a hysterectomy. J Med Assoc Thai \n2012; 95(9): 1136–1140.\n8. Yu O, Schulze-Rath R, Grafton J, et al. \nAdenomyosis incidence, prevalence and \ntreatment: United States population-based study \n2006–2015. Am J Obstet Gynecol 2020; 223(1): \n94.e1–94.e10.\n9. Mishra I, Melo P, Easter C, et al. Prevalence \nof adenomyosis in women with subfertility: \nsystematic review and meta analysis. Ultrasound \nObstet Gynecol 2023; 62(1): 23–41.\n10.\t Kapczuk\tK,\tFriebe\tZ,\tIwaniec\tK,\tKędzia\tW.\t\nObstructive Müllerian anomalies in menstruating \nadolescent girls: a report of 22 cases. J Pediatr \nAdolesc Gynecol 2018; 31(3): 252–257.\n11. Itam SP 2nd, Ayensu-Coker L, Sanchez J, et al. \nAdenomyosis in the adolescent population: a \ncase report and review of the literature. J Pediatr \nAdolesc Gynecol 2009; 22(5): e146–e147.\n12. Youm J, Lee HJ, Kim SK, et al. Factors affecting \nthe spontaneous expulsion of the levonorgestrel-\nreleasing intrauterine system. Int J Gynaecol \nObstet 2014; 126(2):\t165‒169.\n13.  NICE. Heavy menstrual bleeding: assessment \nand management. NG88. 2018.\nFunding\nThis study was funded as part of Sharon \nDixon’s NIHR doctoral research fellowship \nNIHR301787. The views expressed are those \nof the author(s) and not necessarily those of \nthe NIHR or the DHSC.\nProvenance\nFreely submitted; not externally peer reviewed.\nCompeting interests\nKaty Vincent has received research funding \nfrom Bayer HealthCare (BH) and honoraria for \ntalks and consultancy fees from BH, AbbVie, \nand Eli Lilly. Thomas Round is BJGP Associate \nEditor and Clinical Lead for the RCGP Essential \nKnowledge Updates programme.\nDiscuss this article: bjgp.org/letters\nbjgpnov-2023-73-736-524.indd   2bjgpnov-2023-73-736-524.indd   2 06/10/2023   16:3506/10/2023   16:35","source_license":"public-domain-us","license_restricted":false}