{"paper_id":"69264df5-dc33-4911-8cdc-b2f0147d0a24","body_text":"4 December 2022 Women’s Healthcare  NPWomenshealthcare.COM  \nCONTINUING EDUCATION\nFaculty: Gay L. Goss is Professor and nurse practitioner at the \nUnited States University in San Diego, California. Beth M. Kelsey \nis editor in chief of Women’s Healthcare: A Clinical Journal for NPs, and \nDirector of Publications for the National Association of Nurse Prac-\ntitioners in Women’s Health. Heidi Collins Fantasia is Associate \nProfessor and Department Chair at the Solomont School of Nursing \nin Lowell, Massachusetts, and editor of Nursing for Women’s Health. \nAllyssa L. Harris is Dean and Professor, College of Nursing, at Prairie \nView A&M University in Prairie View, Texas. Shelagh B. Larson is \na provider in the Department of Women and Infants at the Acclaim \nMulti-Specialty Group, Tarrant County Hospital District, in Fort Worth, \nTexas. Jennie Mastroianni is a nurse practitioner in the Depart-\nment of Obstetrics & Gynecology at Tufts Medical Center and Assis-\ntant Clinical Professor in the Department of Obstetrics & Gynecology \nat Tufts University School of Medicine in Medford, Massachusetts. \nContinuing education approval: This activity has been evalu-\nated and approved by the Continuing Education Approval Program \nof the National Association of Nurse Practitioners in Women’s Health \n(NPWH) for 1.0 continuing education contact hours including 0.50 \ncontact hours of pharmacology content now through December 31, \n2024. \nIntended audience: This continuing education (CE) activity has \nbeen designed to meet the educational needs of nurse practitioners \nand other clinicians who provide healthcare for women. \nGoal statement: Nurse practitioners and other clinicians who pro-\nvide healthcare for women will increase their knowledge about the \ndiagnosis and management of endometriosis. \nNeeds assessment: Endometriosis is associated with pelvic pain, \ndysmenorrhea, dyspareunia, infertility, and lower health-related \nquality of life. It has a prevalence rate of 10% in reproductive-age \nwomen and is often chronic and progressive. Unfortunately, it takes \nan average of 8 to 10 years between initial presentation of symptoms \nand diagnosis. An understanding of recommended assessment, diag-\nnostic criteria, and management options for endometriosis is essential \nto provide care that is appropriate and attentive to individual needs \nand desires. \nEducational objectives: At the conclusion of this educational ac-\ntivity, participants should be able to: \n1.  Identify clinical indicators and imaging studies helpful in the diag-\nnosis of endometriosis. \n2.  Discuss a patient-centered approach for relief from symptoms and \nimproved quality of life.\n3.  Describe indications, mechanism of action, efficacy, adverse \nevents, and contraindication for pharmacologic options in treating \nendometriosis. \nThe authors have no actual or potential conflicts of interest in relation \nto the contents of this article, but as journal editor in chief, Dr. Kelsey \ndid not participate in any aspects of peer review or decision on ap-\nproval of this manuscript.\nDisclaimer: Participating faculty members determine the editorial \ncontent of the CE activity; this content does not necessarily represent \nthe views of NPWH. This content has undergone a blinded peer re-\nview process for validation of clinical content. Although every effort \nhas been made to ensure that the information is accurate, clinicians \nare responsible for evaluating this information in relation to generally \naccepted standards of care and integrating the information in this ac-\ntivity with that of established recommendations of other authorities, \nnational guidelines, and individual patient characteristics. \nCommercial support:  This activity is supported by an educational \ngrant from Myovant Sciences and Pfizer Inc. \nSuccessful completion of the activity: Successful completion of \nthis activity, J-22-06, requires participants to do the following: \n1.  “Sign in” at the top right-hand corner of the page pathims.com/\nnpwh/courses/48068  if you have an NPWH account. You must \nTo participate in this CE program, click hereA.\nEndometriosis care:  \nWomen’s health nurse \npractitioners share \nperspectives\nBy Gay L. Goss, PhD, APRN-BC, WHNP; Beth M. Kelsey, EdD, APRN, WHNP , \nFAANP; Heidi Collins Fantasia, PhD, RN, WHNP-BC, FNAP; Allyssa L. Harris, \nPhD, RN, WHNP-BC; Shelagh B. Larson, DNP , APRN, WHNP-BC, NCMP; and  \nJennie Mastroianni, DNP , WHNP-BC, NCMP\n\nNPWomenshealthcare.COM December 2022 Women’s Healthcare  5 \nbe signed in to receive credit for this course. If you do not remem-\nber your username or password, please follow the “Forgot Pass-\nword” link and instructions on the sign-in page. If you do not have \nan account, please click on the “Create an Account. ”*\n2.  Read the learning objectives, disclosures, and disclaimers.\n3.  Study the material in the learning activity during the approval  \nperiod (now through December 31, 2024). \n4.  Complete the post-test and evaluation. You must earn a score of \n70% or higher on the post-test to receive CE credit. \n5.  Print out the CE certificate after you have successfully passed the \npost-test and completed the evaluation. \n*If you are an NPWH member, were once a member, or have com-\npleted CE activities with NPWH in the past, you have a username and \npassword in our system. Please do not create a new account. Creation \nof multiple accounts could result in loss of CE credits as well as other \nNPWH services. If you do not remember your username or password, \neither click on the “Forgot Username” or “Forgot Password” link or call \nthe NPWH office at (202) 543-9693, ext. 1. \nA panel of six experienced women’s \nhealth nurse practitioners convened \nfor two roundtable discussions \nto share insights and expertise \non essential aspects of endome-\ntriosis care. They agreed that key \ncomponents were being astute at \nidentifying at-risk patients for early \ndiagnosis and treatment, conduct-\ning a thorough assessment, individ-\nualizing evidence-based treatments \nto meet patient goals, and providing \nattentive follow-up to assess treat-\nment efficacy and patient satisfac-\ntion. The impact of endometriosis \non quality of life underscored their \ndiscussion. They agreed that nurse \npractitioners (NPs) have an import-\nant role in providing adolescents \nand adult women with supportive \ncommunication. Knowledge about \nmenstruation is needed so that \npatients understand what is normal \nand what symptoms suggest the \nneed to see a healthcare provider. \nThis article provides an overview of \nendometriosis, reviews current mo-\ndalities for assessment and diagno-\nsis, discusses medication therapies, \nand addresses the importance of \nquality of life, patient education, and \nshared decision making. \nEndometriosis \noverview\nEndometriosis is an estrogen- \ndependent gynecologic disorder \ncharacterized by the presence of en-\ndometrial tissue outside the endo-\nmetrial cavity. Endometriotic lesions \ntypically occur on the ovaries, pelvic \nperitoneum, and uterosacral liga-\nments. Lesions also can be identified \non the bladder, ureter, or extra pelvic \nsites.1 Endometriosis is associated \nwith pelvic pain, dysmenorrhea, \ndyspareunia, and infertility.1,2 The \ncause of endometriosis is not clearly \nunderstood and likely multifacto-\nrial.1,2 Possible risk factors include \nearly age at menarche, low body \nmass index, short menstrual cycles, \nincreased menstrual flow, nulliparity, \nand family history.1,3 Endometriosis \nhas a strong familial component. \nThe individual with a first-degree rel-\native with endometriosis has a 7- to \n10-fold increased risk of having the \ncondition.1 Endometriosis is a dis-\norder primarily affecting reproduc-\ntive-age females with a prevalence \nrate of 10%. Estimates vary but up to \n21% of women hospitalized for pain \nand 50% of women with infertility \nare diagnosed with endometriosis.3 \nIt is the most common cause of \nsecondary dysmenorrhea in adoles-\ncents.4 Although endometriosis can \nremain stable or improve over time, \nit is often a chronic and progressive \ncondition.5 \nStudies have demonstrated that \nendometriosis is associated with \nlower health-related quality of life \n(HRQL). Women with symptom-\natic endometriosis have reported \nsignificant disruptions in everyday \nactivities; negative impact on sexual, \nsocial, and emotional wellbeing; \npoor sleep quality; loss of sense of \ncontrol; feelings of uncertainty with \ndiagnostic delays; increased stress \nand anxiety; and feelings of lack \nof support or understanding.6–9 \nWomen who experience dyspareu-\nnia report feelings of being an in-\nadequate partner, guilt and shame, \nlow self-esteem, fear of pain, and \nE\nndometriosis is associated with pelvic pain, dysmenorrhea, \ndyspareunia, infertility, and lower health-related quality of life. \nUnfortunately, it takes an average of 8 to 10 years between initial \npresentation of symptoms and diagnosis of this often chronic and \nprogressive condition. Nurse practitioners in primary care settings who \nhave comprehensive knowledge about endometriosis are key to early \ndiagnosis and initiation of treatment. Attention to quality of life, patient \neducation, and shared decision making is essential.\nKey  words : endometriosis, endometriosis-related pain, pelvic pain, \ndysmenorrhea, dyspareunia\nW omens Healthcare. 2022;10(6):4-10. doi: 10.51256/WHC122208 \n© 2022 HealthCom Media. All rights reserved.\nBefore reading the article, click hereA to take the pretest. \n\n6 December 2022 Women’s Healthcare  NPWomenshealthcare.COM  \nwillingness to endure pain to please \nthe partner or achieve pregnancy.10 \nThe potential for infertility caused by \nendometriosis also impacts HRQL.5,9 \nDelay in diagnosis remains prob-\nlematic. It takes an average of 8 to 10 \nyears between initial presentation of \nsymptoms and diagnosis.1,5 The de-\nlay in diagnosis is longer in adoles-\ncents, averaging 12 years from onset \nof symptoms.11 Such delays may in \npart be attributed to a lack of knowl-\nedge about menstruation in general \nand specifically endometriosis, per-\nceptions that pelvic pain is normal, \nand embarrassment in discussing \nsymptoms with healthcare provid-\ners.5 The delay in diagnosis also is \nattributed to healthcare providers’ \nlack of knowledge about the disease \nand its possible symptoms, includ-\ning the overlap of symptoms with \nother pain-associated syndromes. \nDelays in the diagnosis and treat-\nment of endometriosis also occur \nwhen healthcare providers are hesi-\ntant to establish the diagnosis based \non clinical findings without direct \nlaparoscopic confirmation and tis-\nsue biopsy of visible lesions.1,9,12,13 \nDelays in diagnosis and initiation of \ntreatment increase negative symp-\ntoms and can result in a disease \nstate more difficult to treat.5\nQualitative studies have demon-\nstrated that diagnosis of the disease \ncan result in feelings of relief, legitima-\ntion, and empowerment. A diagnosis \nof endometriosis validates a woman’s \nsymptoms and allows for the start of \ntargeted treatment.9 Early diagnosis \nand treatment have the potential to \navoid central sensitization, a compli-\ncated response causing pain hyper-\nsensitivity. In addition, early diagnosis \nand treatment reduces chronic pain \nand infertility and changes the trajec-\ntory of patients' lives.13 \nAssessment and \ndiagnosis\nTo prevent delays in diagnosis and \ntreatment, the inclusion of a thor-\nough menstrual history to screen \nfor symptoms and risk factors is es-\nsential. The patient may not always \nreport such clues unless asked, and \nit provides an excellent opportunity \nfor the NP to share information \nabout normal menses. An important \npart of the menstrual history is to \nask about a family history of endo-\nmetriosis or painful periods. The sex-\nual, obstetric, and pelvic-abdominal \nsurgery history and review of sys-\ntems can further identify symptoms \nand other factors that trigger the \nneed for further investigation.\nPatients who present with dys-\nmenorrhea that negatively impacts \ndaily activities and quality of life, \ndyspareunia with deep penetration, \ncyclic gastrointestinal or genitouri-\nnary symptoms, chronic pelvic pain, \nor infertility in association with one \nor more these symptoms should \nalert the NP to include endometrio-\nsis in the differential diagnosis.5 As \nthese symptoms are not disease spe-\ncific, it is essential to consider other \ndiagnoses that may be a primary or \ncontributing etiology of the patient’s \npain. Table 1 displays differential di-\nagnoses for consideration.1,13,14\nAn abdominal and pelvic exam-\nination may reveal findings sug-\ngestive of endometriosis and aid \nin eliminating other etiologies and \ncoexisting pain syndromes. Physical \nexamination findings consistent \nwith endometriosis include bluish \nlesions on the cervix or upper va-\ngina, tenderness and/or palpable \nnodules in the uterosacral ligaments \nor posterior cul-de-sac, and a fixed \nretroverted uterus.1,15 It is import-\nant to note that the individual with \nendometriosis may or may not have \nphysical examination findings indic-\native of endometriosis. Adolescents \nTable 1. Differential diagnoses for endometriosis 1,13,14\nSymptom Differential diagnoses Endometriosis \ncharacteristics\nChronic pelvic-abdominal pain \n(noncyclic)\nAdnexal mass, pelvic \ninflammatory disease, \npelvic adhesions, IBS, IC/\nBPS, abdominal wall nerve \nentrapment syndromes, \nneuropathic pain \nPain exacerbated during \nmenses; pain worsens over \ntime\nDysmenorrhea Adenomyosis, primary \ndysmenorrhea; congenital \nobstructive anomalies of \nreproductive tract\nSeverity that affects daily \nactivities and quality of life\nDyspareunia Vaginal atrophy, vaginal \ninfection, dermatologic \nconditions, vulvodynia, \npelvic floor disorders\nDeep pain during or after \nsexual intercourse\nPainful bowel movements Constipation, hemorrhoids, \nIBS, anal fissures; pelvic \nfloor disorders\nAssociated with or worse \nduring menses\nPainful urination UTI, IC/BPS, pelvic floor \ndisorders \nAssociated with or worse \nduring menses\nIBS, irritable bowel syndrome; IC/BPS, interstitial cystitis/bladder pain; UTI, urinary tract infection.\n\nNPWomenshealthcare.COM December  2022 Women’s Healthcare  7 \nwho have not had sexual intercourse \nmay or may not be able to tolerate a \nvaginal examination. Discussion and \ninformed consent are critical.\nIn patients with suspected endo-\nmetriosis, further diagnostic steps \nshould be considered even if the \nclinical examination is normal.5,12,15 \nLaparoscopy was once regarded \nas the diagnostic gold standard for \nendometriosis. With advances in \nthe quality and availability of im-\naging modalities, ultrasound can \nbe utilized with less risk and cost to \npatients.12 Transvaginal ultrasound \n(TVU) is an effective technique for \nconfirming or excluding the diagno-\nsis of endometriosis and also can aid \nin detecting other causes for pelvic \npain such as adenomyosis.1,5,12,15 \nThe sensitivity of TVU, however, is \nvariable depending on the location \nand size of endometrial lesions.12 \nA negative finding on ultrasound \ndoes not exclude endometriosis, \nparticularly superficial peritoneal \ndisease.12 If a TVU is not appropriate \ndue to age, inability to tolerate vag-\ninal examinations, or other factors, \ntransabdominal ultrasound or mag-\nnetic resonance imaging (MRI) may \nbe considered.5,12 When imaging \nwith ultrasound or MRI is negative, \nempiric medical treatment is unsuc-\ncessful, or if it is the patient’s prefer-\nence, laparoscopy is recommended \nfor the diagnosis and treatment of \nsuspected endometriosis.5,12,15 \nTreatment of \nendometriosis-related \npain\nKey to successful treatment of \nendometriosis-related pain is a pa-\ntient-centered approach that meets \npatient goals for relief from symp-\ntoms and improvement of HRQL. \nChanges should be made as needed \nbased on patient response to treat-\nment and personal and reproductive \ngoals. All treatment options should \nbe discussed with review of the \nbenefits, risks, and potential side \neffects. Patients should be informed \nthat both medical and surgical treat-\nments may offer complete or partial \nrelief of pain symptoms. However, \nsymptoms often recur after discon-\ntinuation of hormonal suppressive \ntherapy or a period of time after \nsurgical treatment.12,15 Baseline and \nrepeated assessment of pain levels \nand HRQL aid in the ongoing deter-\nmination of treatment effectiveness. \nThe frequency and type of follow-up \nshould be individualized based on \nsymptom severity. Pain levels can be \ndocumented using a scale of 0 to 10. \nWhat may be more important than \nassigning a number, however, is to \ntalk with the patient about how pain \nis affecting all aspects of their daily \nlife.1 The EHP-30 [Endometriosis \nHealth Profile-30] has demonstrated \nreliability and validity for assessment \nof HRQL.16 The generic quality-of-life \nquestionnaire SF-36 also has been \nvalidated for use in endometriosis.17 \nIndividual circumstances and priori-\nties should guide referrals for coun-\nseling and other support services. \nThe most commonly prescribed \npharmacologic treatments for en-\ndometriosis include nonsteroidal \nanti-inflammatory drugs (NSAIDs) \nand drugs that modify the hormonal \nenvironment either by suppressing \novarian activity or acting directly \non steroid receptors and enzymes \nfound in the lesions. These include \ncombined hormonal contraceptives \n(CHCs), progestins, gonadotropin- \nreleasing hormone (GnRH) agonists, \nand GnRH antagonists. Aromatase \ninhibitors, although not approved \nby the US Food and Drug Admin-\nistration for this indication, are an \noff-label option for severe endo-\nmetriosis-related pain refractory to \nother medical or surgical treatments. \nThey may be used in combination \nwith hormonal medications because \nthey suppress extraovarian estro-\ngens.12\nThree European-based groups \nhave provided guidelines for the di-\nagnosis and management of endo-\nmetriosis based on scientific reviews \nof evidence regarding efficacy and \nsafety. These groups are the National \nInstitute for Health and Care Excel-\nlence (NICE), European Society of \nHuman Reproduction and Embry-\nology (ESHRE), and the French Na-\ntional Authority for Health and the \nFrench College of Gynecologists and \nObstetricians (CNGOF/HAS).5,12,15 \nAll three groups note that the aim of \nclinical practice guidelines is to aid \nhealthcare professionals in everyday \nclinical decisions about appropriate \nand effective care, not precluding \nclinical judgment and individual \npatient preference. Table 2 compares \ntheir recommendations. It is import-\nant to note that the timing of the \nNICE and CNGOF/HAS review of ev-\nidence preceded some of the most \nrecent available study results on oral \nGnRH antagonists.5,12,15\nThe NP in a primary care prac-\ntice can initiate first-line therapies \n(NSAIDs, CHCs, progestins) when the \npatient exhibits mild-to-moderate \nsymptoms consistent with endome-\ntriosis.  First-line therapies are those \ncombining known efficacy with \ngood safety profiles, minimal side \neffects, ease in administration, and \nlower cost. For patients who have \npreviously tried one or more of the \nfirst-line therapies without apprecia-\nble pain relief or with unacceptable \nside effects, other options should \nbe considered. These patients may \nbenefit from second-line medication \ntherapies such as GnRH agonists, \nGnRH antagonists, and aromatase \ninhibitors. The use of these medica-\ntions generally requires laparoscopic \nconfirmation of endometriosis. \nSecond-line medication therapies \nhave more potential for side effects, \n\n8 December 2022 Women’s Healthcare  NPWomenshealthcare.COM  \nrelated loss of bone mineral density \n(BMD), and are more expensive than \nfirst-line medications. They should, \nhowever, be considered options for \nindividuals for whom first-line med-\nications have not provided satisfac-\ntory pain relief.\nNSAIDs\nNonsteroidal anti-inflammatory drugs \nare a commonly employed first-line \ntherapy partly because they are readily \navailable and relatively inexpensive. \nThey work by inhibiting cyclooxygenase- \nmediated prostaglandin production. \nProstaglandins are mediators of local-\nized inflammation and are considered \nto be responsible for dysmenorrhea.2 \nEvidence does support the use of \nNSAIDs as an effective treatment for \nmild-to-moderate primary dysmen-\norrhea.18 Nevertheless, available evi-\ndence is limited to support the use of \nNSAIDs for endometriosis-related pain \nmanagement.19 Additionally, these \nmedications do not suppress hormon-\nal-dependent endometrial growths.\nThere are minimal risks to the use \nof NSAIDs although they do have \nside effects, most specifically gas-\ntrointestinal side effects.12 Because \nthey have a general anti-inflamma-\ntory effect, NSAIDs can be used in \nconjunction with hormonal thera-\npies. For women who are attempt-\ning pregnancy, this may be the only \nmedication option for pain relief.\nCombined hormonal \ncontraceptives\nData from two systematic reviews \nhave demonstrated that CHC use \nresults in statistically significant  \nreductions in endometriosis- \nrelated pain and improved quality \nof life.20,21 Although more data are \navailable on combined oral contra-\nceptives, vaginal and transdermal \nCHCs  demonstrated efficacy in \nendometriosis-related pain reduc-\ntion in both systematic reviews. A \nTable 2. Medications for endometriosis-related pain management 5,12,15\nMedication ESRHE (2022) NICE (2017) CNGOF/HAS (2018)\nNSAIDs Weak recommendation Consider short trial (3 months) \nalone or in combination with \nother treatments\nLong-term use not recommended \ndue to gastric and renal side \neffects\nCHCs Strong recommendation\nOral, vaginal, transdermal\nCyclic or continuous\nOffer combined oral \ncontraceptive pill in suspected or \nconfirmed endometriosis\nCHC recommended as first-line \nhormonal therapy\nProgestins Strong recommendation\n52-mg LNG-IUS\nENG implant\nDMPA \nOffer progestin in suspected or \nconfirmed endometriosis\n52-mg LNG-IUS recommended \nfirst-line hormonal therapy \n*Grade C \ndesogestrel low-dose progestin \ncontraception, ENG implant, and \ndienogest recommended second-\nline therapy\nGnRH agonists Strong recommendation\nPrescribe if CHCs or progestins \nineffective\nNo recommendation *Grade C\nrecommended second-line \ntherapy\nGnRH antagonists Recommendation based on data \nfrom phase 3 trials of elagolix\nPrescribe if CHCs or progestins \nineffective \nNo recommendation *Grade C\nData available when  guidelines \nestablished did not justify \nrecommendation for use outside \nclinical trial setting\nAromatase inhibitors Strong recommendation\nin those with endometriosis-\nassociated pain refractory \nto other medical or surgical \ntreatment\nNo recommendation *Grade C\nIn absence of data, aromatase \ninhibitors are not recommended\n Danazol Danazol no longer recommended No recommendation No recommendation\nCHC, combination hormonal contraceptive; DMPA, depot medroxyprogesterone acetate; ENG, etonogestrel; GnRH, gonadotropin-releasing hormone; LNG-IUS, levonorgestrel-releasing intrauterine system; \nNSAIDs, nonsteroidal anti-inflammatory drugs.\n*Grade C CNGOF/HAS recommendations could be revised once results of ongoing clinical trials available.15\n\nNPWomenshealthcare.COM December 2022 Women’s Healthcare  9 \ncontinuous-use regimen appears \nto be more efficacious in regard to \ndysmenorrhea, with nonsignificant \ndifferences between continuous and \ncyclic regimens for chronic pelvic \npain and dyspareunia.22 \nProgestins\nA systematic review including \nprogestin-only pills, the 52-mg \nlevonorgestrel intrauterine system \n(LNG-IUS), etonogestrel (ENG)- \nreleasing subdermal implant, and \ndepot medroxyprogesterone  \nacetate found all to be effective in \nreducing endometriosis-related \npain.19 A recent randomized  \ncontrolled trial reported that both \nthe ENG implant and LNG-IUS \nsignificantly reduced endometriosis- \nrelated pain, dysmenorrhea, and \nchronic pelvic pain.23 \nGnRH agonists\nGonadotropin-releasing hormone \nagonists have demonstrated efficacy \nin relieving endometriosis-related \npain.5,12,15,24 They bind to GnRH \nreceptors on the anterior pituitary, \ncausing a down-regulation of the \npituitary-ovarian axis and profound \nbut reversible hypoestrogenism.24 \nCommonly used GnRH agonists \nthat are FDA approved for up to 12 \nmonths for treatment of endome-\ntriosis-related pain are goserelin SC, \nleuprolide IM, and nafarelin depot \nvia nasal spray.1 There has been no \ndemonstrated difference in efficacy \nor reported side effects related to \nroute of administration.24 The most \nreported side effects are vaginal \ndryness, hot flushes, headaches, and \njoint pain.1 The use of GnRH agonists \nis contraindicated during pregnancy.\nReduction of BMD is a major \nconcern with GnRH agonist treat-\nment continuing for longer than 6 \nmonths. The addition of add-back \ntherapy prevents bone loss and does \nnot affect the efficacy of the GnRH \nagonist treatment.25 Commonly \nused add-back regimens include \nthe progestins medroxyprogester-\none acetate and norethindrone, a \nlow-dose estrogen-progestin com-\nbination, and bisphosphonates.25 \nConsidering the possible impact on \nBMD, GnRH agonists should only be \nused after careful consideration in \nyoung women and adolescents if \nfirst-line treatments are ineffective.12 \nGnRH antagonists\nTwo oral GnRH antagonists have \nbeen FDA approved for the man-\nagement of moderate-to-severe \npain associated with endometriosis. \nElagolix, which is available in two \ndosages, was approved in 2018.26 \nRelugolix combined with estradiol \nand norethindrone acetate was \napproved in 2022.27 GnRH antag-\nonists suppress follicle-stimulating \nhormone, luteinizing hormone, and \nestrogen and may have a quicker \nsymptom relief profile than GnRH \nagonists as well as the advantage \nof oral administration. The most \nfrequently reported side effects \nacross both medications include \nhot flushes, night sweats, and irreg-\nular bleeding.26,27 The use of GnRH \nantagonists is contraindicated in \npregnancy.\nLike GnRH agonists, reduction of \nBMD is a concern with long-term \nGnRH antagonist use. Prescribing \ninformation recommends limiting \nduration of use to 24 months for \nelagolix 150 mg and relugolix com-\nbined with estradiol and norethin-\ndrone acetate.26,27 The higher dose \nof elagolix (200 mg twice daily), \nwhile more effective in pain relief, is \nassociated with more bone loss than \nthe lower dose with recommended \nuse limited to 6 months.26 Consid-\nering the possible impact on BMD, \nGnRH antagonists should only be \nused after careful consideration in \nyoung women and adolescents if \nfirst-line treatments are ineffective.12\nOther considerations\nNeuromodulators such as tricyclic \nantidepressants, selective reuptake \ninhibitors, and anticonvulsants have \nshown promise as a component of \nthe management of endometrio-\nsis-related pain but are associated \nwith dose-limiting side effects. Pel-\nvic physical therapy and cognitive \nbehavioral therapy also may be of \nbenefit to some women.2 \nIt has been suggested that pain \nsyndromes such as endometrio-\nsis may interact with other pain \nsyndromes (eg, irritable bowel \nsyndrome, fibromyalgia, migraine \nheadaches) and that this interaction \nmay feature increased pain sensi-\ntivity stemming from the effects of \nnociceptive inputs on the nervous \nsystem. Perceptual responses to pain \ncan become exaggerated, prolonged, \nand widely spread (central sensitiza-\ntion).28 If central sensitization is sus-\npected, further pain evaluation and \npain management is recommended. \nThis often requires a multidisciplinary \nteam that includes a pain specialist, \nphysical therapist, psychologist, and \nprimary healthcare provider.15  \nFor patients who have undergone \nlaparoscopic surgery, postoper-\native use of a CHC or progestin is \nrecommended to prevent the risk \nof disease recurrence when preg-\nnancy is not desired.12,15 Hormone \nreplacement therapy can be offered \nto postmenopausal women who \nhave undergone surgical treatment, \nalthough endometriosis symptoms \ncould recur.12,15 \nEndometriosis-related infertility \nmanagement should consider cur-\nrent pain as well as the results of \nthe pretreatment infertility evalua-\ntion.5,15 The benefits and risks of sur-\ngery prior to assisted reproductive \ntherapy should be discussed to in-\nclude the potential negative impact \non ovarian reserve.12 There is insuffi-\ncient evidence to support extended \nGnRH agonist, CHC, or progestin use \n\n10 December 2022 Women’s Healthcare  NPWomenshealthcare.COM  \nprior to assisted reproductive thera-\npies to increase live birth rates.12,15 \nImplications for NP \npractice\nNurse practitioners can play a key \nrole in the early diagnosis and treat-\nment of endometriosis. Comprehen-\nsive knowledge of endometriosis \nthat includes risk factors, symptoms, \npotential physical examination \nfindings, and current imaging mo-\ndalities empower the NP to clinically \ndiagnose endometriosis and to \nrecognize when consultation or \ncollaboration is beneficial. Special \nconsiderations should be given to \nadolescent assessment. Providing \npatient education about normal \nmenses and symptoms that require \nhealthcare attention can be incor-\nporated into the patient history. \nA patient-centered approach to \nendometriosis treatment considers \nthe patient’s individual goals, HRQL, \nand follow-up to evaluate for any \nneeded adjustment based on treat-\nment efficacy, patient satisfaction, \nand change in reproductive goals. �\nReferences\n1. Falcone T, Flyckt R. Clinical manage-\nment of endometriosis. Obstet Gynecol. \n2018;131(3):557-571.\n2. Zondervan KT, Becker CM, Missmer \nSA. Endometriosis. N Engl J Med. \n2020;382(13):1244-1256. \n3. Shafrir AL, Farland LV , Shah DK, et al. \nRisk for and consequences of endome-\ntriosis: a critical epidemiologic review. \nBest Pract Res Clin Obstet Gynaecol. \n2018;51:1-15.\n4. American College of Obstetricians and \nGynecologists. Committee opinion \nno. 760: dysmenorrhea and endometri-\nosis in the adolescent. Obstet Gynecol. \n2018;132(6):e249-258.\n5. National Institute for Health and Care \nExcellence. Endometriosis: diagnosis and \nmanagement. NICE guideline. September \n6, 2017. www.nice.org.uk/guidance/ng73.\n6. Pope CJ, Sharma V , Sharma S, Mazmanian \nD. A systematic review of the association \nbetween psychiatric disturbances and  \n \nendometriosis. J Obstet Gynaecol Can. \n2015;37(11):1006-1015.\n7. Marinho MCP, Magalhaes TF, Fernan-\ndez LFC, et al. Quality of life in women \nwith endometriosis: an integrative \nreview. J Womens Health (Larchmt). \n2018;27(3):399-408.\n8. Soliman AM, Coyne KS, Zaiser E, et al. \nThe burden of endometriosis symptoms \non health-related quality of life in women \nin the United States: a cross-sectional \nstudy. J Psychosom Obstet Gynaecol. \n2017;38(4):238-248.\n9. Rush G, Misajon R. Examining subjective \nwellbeing and health-related quality of \nlife in women with endometriosis. Health \nCare Women Int. 2018;39(3):303-321.\n10. Faccine F, Buggio L, Dridi D, et al. The \nsubjective experience of dyspareunia in \nwomen with endometriosis: a systematic \nreview with narrative synthesis of quali-\ntative research. Int J Environ Res Public \nHealth 2021;18(22):12112.\n11. Geysenbergh B, Dancet EAF, D'Hooghe \nT. Detecting endometriosis in adolescents: \nwhy not start from self-report screening \nquestionnaires for adult women? Gynecol \nObstet Invest. 2017;82(4):322-328.\n12. European Society of Human Reproduc-\ntion and Embryology. ESHRE guideline \nendometriosis. February 2, 2022. https://\nwww.eshre.eu/Guidelines-and-Legal/\nGuidelines/Endometriosis-guideline. \n13. Agarwal SK, Chapron C, Giudice LC, \net al. Clinical diagnosis of endometriosis: \na call to action. Am J Obstet Gynecol. \n2019;220(4):354.e1-354.e12.\n14. American College of Obstetricians and \nGynecologists. Practice bulletin no. \n218: chronic pelvic pain. Obstet Gynecol. \n2020;135(3):e98-e109.\n15. Collinet P, Fritel X, Revel-Delhom M, et \nal. Management of endometriosis  \nCNGOF/HAS clinical practice guide-\nlines – short version. J Gynecol Obstet \nHum Reprod. 2018;47(7):265-274.\n16. Pokrzywinski R, Soliman AM, Chen J, et \nal. Responsiveness evaluation and recom-\nmendation for responder thresholds for \nEndometriosis Health Profile-30: analysis \nof two-phase III clinical trials. J Womens \nHealth (Larchmt). 2020;29(2):253-261.\n17. Stoll DE, W asiak R, Kreif N, et al. V alida-\ntion of the SF-36 in patients with endome-\ntriosis. Qual Life Res. 2014;23(1):103-117. \n18. Marjoribanks J, Ayeleke RO, Farquhar C, \net al. Nonsteroidal anti-inflammatory  \n \ndrugs for dysmenorrhoea. Cochrane Data-\nbase Syst Rev. 2015(7):CD001751.\n19. Brown J, Crawford TJ, Allen C, et \nal. Nonsteroidal anti-inflammatory \ndrugs for pain in women with endo-\nmetriosis. Cochrane Database Syst Rev. \n2017;1(1):CD004753.\n20. Grandi G, Barra F, Ferrero S, et al. \nHormonal contraception in women \nwith endometriosis: a systematic review. \nEur J Contracept Reprod Health Care. \n2019;24(1):61-70.\n21. Jensen JT, Schlaff W , Gordon K. Use of \ncombined hormonal contraceptives for the \ntreatment of endometriosis-related pain: \na systematic review of the evidence. Fert \nSteril. 2018;110(1):137-152.e1.\n22. Muzii L, Di T ucci C, Achilli C, et al. \nContinuous versus cyclic oral contracep-\ntives after laparoscopic excision of ovarian \nendometriomas: a systematic review \nand metaanalysis. Am J Obstet Gynecol. \n2016;214(2):203-211.\n23. Margatho D, Carvalho NM, Bahamondes \nL. Endometriosis-associated pain scores \nand biomarkers in users of the etonoges-\ntrel-releasing subdermal implant or the 52-\nmg levonorgestrel-releasing intrauterine \nsystem for up to 24 months. Eur J Contracept \nReprod Health Care. 2020;25(2):133-140.\n24. Brown J, Pan A, Hart RJ. Gonadotro-\nphin-releasing hormone analogues for pain \nassociated with endometriosis. Cochrane \nDatabase Syst Rev. 2010(12):CD008475.\n25. W u D, Hu M, Hong L, et al. Clinical effi-\ncacy of add-back therapy in treatment of \nendometriosis: a meta-analysis. Arch  \nGynecol Obstet 2014;290(3):513-523.\n26. Orilissa [elagolix]. US Food and Drug \nAdministration approved product infor-\nmation. Revised February 2021. https://\nwww.rxabbvie.com/pdf/orlissa_pi.pdf. \n27. Myfembree [relugolix, estradiol, and \nnorethindrone]. US Food and Drug \nAdministration approved product \ninformation. Revised August 2022. \nhttps://www.myovant.com/wp-content/\nuploads/2022/08/Approved-MYFEM-\nBREE-PI-and-PPI_05August2022.pdf.\n28. W oolf CJ. Central sensitization: implica-\ntions for the diagnosis and treatment of \npain. Pain. 2011;152(suppl 3):S2-S15.\nWeb resource\nA. pathlms.com/npwh/courses/48068","source_license":"CC0","license_restricted":false}