This chapter should be cited as follows:
Sasamoto N, Missmer SA, Glob. libr. women's med.,
ISSN: 1756-2228; DOI 10.3843/GLOWM.417643
The Continuous Textbook of Women’s Medicine Series – Gynecology Module
Volume 3
Endometriosis
Volume Editors:
Professsor Andrew Horne, University of Edinburgh, UK
Dr Lucy Whitaker, University of Edinburgh, UK
Chapter
Endometriosis Symptoms and Signs
First published: September 2023
Study Assessment Option
By completing 4 multiple-choice questions (randomly selected) after studying this chapter readers can qualify for Continuing Professional Development awards from FIGO plus a Study Completion Certificate from GLOWM
See end of chapter for details
INTRODUCTION
The symptoms associated with endometriosis, including but not limited to dysmenorrhea (pain with periods or menstrual bleeding), acyclic/non-menstrual pelvic pain (pain occurring sporadically at any time other than menses throughout the menstrual cycle), dyspareunia (pain with vaginal intercourse/penetration), dysuria (painful urination), dyschezia (painful defecation), chronic fatigue, and infertility,1,2 have a substantially negative impact on the physical, mental, sexual, and social well-being of women affected with endometriosis.3,4 In this chapter, we use the terms “woman” and “women”. However, it is important to note that endometriosis can affect all people assigned female at birth.
The visualized volume and anatomic distribution of endometriotic disease can be disproportionate to the type and severity of symptoms.5,6 Endometriosis is most often classified according to criteria formulated by the American Society of Reproductive Medicine (rASRM) into four stages often referred to as minimal (I) to severe (IV).7 However, more “severe” disease according to ASRM staging does not correlate well with symptoms, treatment response, or prognosis.8,9 Women with stage I disease may suffer from severe pain symptoms and/or infertility, whereas some women with stage IV endometriosis may be asymptomatic.8 While surgical visualization is the gold standard for endometriosis diagnosis, using imaging modalities, such as magnetic resonance imaging (MRI), for endometriosis diagnosis is evolving.10 These methods, due to the resolution of the current imaging technology, are more likely to capture endometrioma, deep endometriosis, or stage IV peritoneal disease with large lesion volume and extensive scarring/adhesions, which may in part be contributing to the oversampling of stage III/IV diseases in the current literature. Further, revised guidelines with a goal, in part, of addressing long delays in diagnosis spanning years, have reminded of the validity of a “working diagnosis” of probable endometriosis to initiate life improving treatment.1,3,11 Here, we summarize the reported symptoms and signs that have been associated with endometriosis.
ENDOMETRIOSIS-ASSOCIATED SYMPTOMS
While it is clear that endometriosis presents with various symptoms, the multiple pathways in which women can be diagnosed with endometriosis12,13 creates methodological challenges for valid associative research. Currently surgical visualization is required for a definitive diagnosis, particularly for superficial peritoneal lesions that cannot be captured by transvaginal ultrasound and magnetic resonance imaging (MRI).14 As a result, endometriosis with “classic” symptom presentation (e.g., severe pelvic pain, infertility) are primarily diagnosed/captured, which may introduce diagnostic bias and confounding by indication in studies assessing symptoms associated with endometriosis.13,15 For example, women who have better geographic, financial, and social access to healthcare and thus referral for laparoscopy or frequent users of the medical system are more likely to be surgically diagnosed with endometriosis. Those with more severe symptoms are also more likely to undergo surgical evaluation compared to those with mild to moderate symptoms. This issue is especially relevant for adolescent and young adult patients, among whom severe pelvic pain resistant to hormonal treatment is often necessary to justify referral for surgical evaluation. Another example is endometriosis diagnosed as part of infertility evaluation, as most women experiencing infertility across the globe do not have access to infertility care.16
Pelvic pain
Pelvic pain is the most prevalent symptom among patients diagnosed with endometriosis and is the symptom most often catalyzing a referral for radiologic or surgical evaluation.17 Women with endometriosis experience a variety of pelvic pain symptoms. The most common types of pain experienced in the pelvic area are dysmenorrhea (pain with periods/menstrual bleeding), non-menstrual pelvic pain or general/acyclic pelvic pain (pain occurring at times other than menses), and dyspareunia (pain with vaginal intercourse/penetration). Individuals can present with any combination, and often with substantial overlap among these varying pain symptoms,18 which may or may not be related to the anatomical locations of the endometriosis lesion(s) themselves. Several studies have attempted to correlate endometriotic lesion location with pelvic pain experience, which have suggested that superficial peritoneal endometriosis is more prevalent with dysmenorrhea as the primary presenting symptom, while posterior cul-de-sac and uterosacral lesions are more common among those who experience dyspareunia, bladder and peritoneal lesions with dysuria, and deep vaginal or bowel lesions with dyschezia.9,19,20,21 However, these studies were limited in sample size necessary to examine the multiple fine categories of lesion types/appearance/locations, and most lacked a detailed pain defining data. Further in-depth investigations are needed to understand the correlations more precisely between pain type and characteristics with anatomic sites and types of endometriotic lesions.
Dysmenorrhea
Women diagnosed with endometriosis are more likely to report dysmenorrhea compared to women without, with prevalence of dysmenorrhea among endometriosis ranging from 60 to 75%.9,22,23,24 A study based in the U.S. examining pelvic pain characteristics in 620 women with laparoscopically-confirmed endometriosis and 671 community-based and hospital-based controls reported that 64% of women with endometriosis reported severe dysmenorrhea whereas only 8% reported severe dysmenorrhea among those without.22 When comparing endometriosis diagnosed during adolescence vs. adulthood, endometriosis diagnosed during adolescents were more likely to report pain proximal to their menarche.25 About 50% of those diagnosed during adolescence and about 30% of those diagnosed during adulthood reported their pain started with their very first period (p = 0.002), and adult-diagnosed endometriosis were more likely to report that their pain began more than 2 years after their menarche compared to adolescent-diagnosed endometriosis (25% vs. 12%).
General/acyclic pelvic pain
Non-cyclic or genera/acyclic pelvic pain is another common pelvic pain symptom observed in those with endometriosis, with prevalence ranging from 50 to 70%.22,26 Compared to community-based and hospital-based controls, those with endometriosis had a higher prevalence of having severe (69% vs. 35%), daily (28% vs. 4%), and life interfering general/acyclic pelvic pain (68% vs. 28%).22 Ever experiencing general/acyclic pelvic pain was common in both adolescents (66%) and adults (77%) diagnosed with endometriosis, although the way in which the general/acyclic pelvic pain interfere with life may differ by age at diagnosis.22 Endometriosis symptoms can begin to influence life events in adolescence and continue to have an impact throughout the life course,4,27 interfering with work/school, daily activities at home, social engagement and relationships, and exercise and other healthy behaviors.25,28
Dyspareunia
Dyspareunia or pelvic pain with vaginal intercourse or penetration is reported more often in women with endometriosis compared to those without, with reported prevalence among women with endometriosis being around 50%.9,22,29,30 A study of 473 women ages 18–44 years reported a significantly greater proportion of women with endometriosis reporting vaginal pain and deep pain with intercourse compared to those with normal pelvis (55% vs. 32% and 53% vs. 31% respectively; p < 0.001).9 Life interference attributed to dyspareunia is also significantly higher in women with endometriosis compared to women without, as a greater number of women with endometriosis reported having avoided intercourse or penetration due to dyspareunia (75% vs. 47%) or interrupted intercourse due to dyspareunia (74% vs. 51%) compared to those without.22 In a study that examined sexually active adolescents and young adults with and without surgically-confirmed endometriosis between the ages of 18–25 years (n = 438), young adults with endometriosis were twice as likely to experience dyspareunia compared to controls (79% vs. 40%).29 Recent studies have further elucidated that endometriosis-related dyspareunia presents with heterogeneity in presentation, with ranging severity, location, and timing or onset of pain,31 which may have differing impact on social and emotional well-being. Gendered realities and stigma32 around sexual health and satisfaction and their relationship impact require that healthcare providers consider carefully patient engagement and potentially seek targeted dialogue training to best address this prevalent symptom.
Dysuria
Dysuria or pain with urination has also been reported to be frequently observed in women with endometriosis compared to those without, with a prevalence ranging from 23% to 50%.9,22,25 A study examining 620 surgically-confirmed endometriosis and 671 community-based and hospital-based controls reported that 40% of women with endometriosis reported pain with urination during their periods compared to 10% in women without endometriosis, and 38% of women with endometriosis reported frequent pain with urination while having general/acyclic pelvic pain whereas only 4% in women without endometriosis reported frequent pain with urination.22
Dyschezia
Dyschezia or pain with bowel elimination is observed more frequently in women with endometriosis compared to without (44% vs. 26%).9 Another study reported that 39% of women with endometriosis experienced that their period pain got worse after bowel movement, which was higher compared to that reported from controls (16%), and 37% of women with endometriosis reported their general/acyclic pelvic pain got worse after bowel movement in which only 20% of controls reported this symptom.22
Chronic pelvic pain
Chronic pelvic pain is defined as having cyclical or non-cyclical pelvic pain for at least 6 months’ duration.33 The 6-month cutoff is not necessarily a requirement if central sensitization pain mechanisms are documented (e.g., cognitive, behavioral, and emotional impairment).34 In a systematic review including 1016 women with chronic pelvic pain from nine studies reported that 70% (range 28–93%, CI = 67–73%) were diagnosed with endometriosis.35 Among adolescents with chronic pelvic pain, the reported prevalence of visually diagnosed endometriosis is 49% on average and 75% among those unresponsive to medical treatment.36 Furthermore, approximately 30% of endometriosis patients will develop chronic pelvic pain that is unresponsive to conventional treatments including surgery.2 Emerging evidence suggests the involvement of central sensitization in these endometriosis patients with persistent pain.37,38,39
Overlapping pain conditions or pain outside the pelvis
Pain in endometriosis is modulated by peripheral and central mechanisms, with cross-organ pain sensitization potentially leading to development of multiple systemic, co-morbid pain conditions.38 Previous research has noted an association between endometriosis and co-morbid pain conditions.26,40,41 Among participants with endometriosis in the U.S.-based longitudinal study, The Women’s Health Study: From Adolescence to Adulthood (A2A), 60% reported having two or more other pain conditions in addition to their endometriosis.22 In particular, participants with endometriosis were more likely to report chronic, overlapping pain conditions compared to controls, suggesting that those with endometriosis may be more likely to be impacted by widespread pain or increased sensitization to pain.18,42,43,44,45 Adult endometriosis patients have been reported to present with simultaneous co-occurrence of other chronic pain conditions, such as temporomandibular disorder, fibromyalgia, irritable bowel syndrome, vulvodynia, chronic fatigue syndrome, interstitial cystitis/painful bladder syndrome, migraine headache, and chronic lower-back pain.18 Collectively, these conditions including endometriosis is referred to as “chronic overlapping pain conditions” or widespread pain, which is thought to share a common mechanism of central sensitization.46 Endometriosis co-occurring with these non-pelvic chronic pain conditions may have increased sensitization to pain and therefore a thorough, comprehensive assessment on these pain types may be needed for triaging women with endometriosis to effective pain management.47
Infertility
A large prospective cohort study reported that women with endometriosis have twice the risk for incident infertility compared to women without, with about 30% of women with endometriosis experiencing infertility.48 Other descriptive studies report that about 16–40% of women with endometriosis report having difficulty conceiving.17,48,49 Endometriosis has also been reported to be identified in 30–50% of women undergoing assisted reproductive treatment.50,51 The most obvious causal pathway is via distortions of the normal pelvic anatomy due to lesion-induced scarring and/or adhesions.52,53 However, there are multiple less direct pathways for fertility impairment. Women with superficial and deep endometriosis have well documented increased local inflammation within the peritoneal cavity (i.e., increase in inflammatory cytokines in the peritoneal fluid) that may interfere with normal sperm motility and/or ciliary function of the fallopian tubes.52 Those with endometriomas have reduced oocyte quality, perhaps due to greater inflammation in follicular fluid of the affected ovary.54 Further, as established by Osteen and Bruner-Tran, the eutopic endometrium of women with endometriosis expresses progesterone resistance,55 perhaps driving lower rates of implantation,56 successful conception,56 and also higher rates of spontaneous abortion.57,58
Urinary tract symptoms
About 50% of women with bladder pain syndrome or interstitial cystitis has been reported to co-occur with endometriosis.35,59,60 Women with endometriosis have about four times greater risk of developing bladder pain syndrome compared to women without endometriosis.59,61
Lower urinary tract symptoms are often reported by women with endometriosis. This may be, but is not always, related to the presence of lesions on the bladder or ureter.62 A study examining 1161 women reported a higher prevalence of lower urinary tract symptoms among those with endometriosis compared to those without.63 Compared to women without endometriosis, women with endometriosis were more likely to report difficulty in passing urine (7.9% vs. 2%), still feeling full after urination (18.8% vs. 4.7%), having to urinate again within minutes of urinating (33.1% vs. 17%), and pain when the bladder is full (23% vs. 4.9%).
Gastrointestinal symptoms
Gastrointestinal symptoms are commonly observed among women with endometriosis, including nausea, abdominal bloating, rectal or abdominal pain, rectal bleeding, constipation, diarrhea, and/or changes in bowel frequency,64 which could in part be due to co-existing conditions of irritable bowel syndrome (IBS). IBS has been reported to be more prevalent among those with endometriosis, reported by as high as 75% of adults with endometriosis.65,66,67 A study among 323 adolescents with endometriosis had a five-fold greater odds of having IBS compared to those without endometriosis (OR = 5.26, 95% CI = 2.13–13.0).68 However, endometriosis lesions on the bowel is much less prevalent, with reported frequency being 7.6%.69 Thus, although many with endometriosis present with gastrointestinal symptoms, this is not directly explained by endometriosis lesions involving the bowel. In a study examining symptoms in adolescents vs. adult-diagnosed endometriosis, nausea accompanying general/acyclic pelvic pain was more commonly reported in adolescents (70%) compared to adults (50%; p = 0.004).25 It is important to note that many diagnosed with endometriosis report a long journey including referral for gastroenterologic investigation well before gynecologic intervention.
Fatigue
Fatigue is a frequent symptom of endometriosis – perhaps the most frequent when quantifying across the life course. The proportion of women with fatigue ranges from 46–74%, often accompanied with other symptoms including pelvic pain, anxiety, and stress.70,71,72 In a study examining 1120 women, including 560 with endometriosis, frequent fatigue was observed in 51% of women with endometriosis, and was associated with increased insomnia, depression, and pain.73 In a qualitative study of 22 women with endometriosis-associated pain, fatigue negatively impacted daily life, physical and social activities, mood and emotions, family and intimate relationships, and work and school.74,75 Despite its life-altering impact, fatigue is infrequently documented or addressed within standard endometriosis-focused care.
Symptoms associated with extra-pelvic endometriosis
Endometriosis lesions have been found thriving in extra-pelvic sites distant from gynecological organs, such as the gastrointestinal tract, urinary tract, lung, liver, umbilicus. Symptoms such as pain and pressure at these locations typically coincide with the menstrual cycle, perhaps due to cyclic bleeding in the extra-pelvic location.76,77 These are rare forms of endometriosis that present with diverse symptoms and are referred to non-gynecologic specialists, which greatly impedes and delays diagnosis. Although valid estimates are elusive, involvement of the gastrointestinal tract is the most commonly visualized extra-pelvic site, which could present with cyclic bleeding and/or dyschezia, and even bowel obstructions requiring surgical resection.78 Cyclic hematuria may be caused by bladder or ureter invasion.76,79 Thoracic endometriosis may present with cyclical upper abdominal or chest pain, or hemoptysis or pneumothorax.80 Intrahepatic endometriosis has been reported, presenting with non-cyclical upper right quadrant pain.81 Spontaneous umbilical endometriosis has been reported although rare, presenting with swelling, pain, or bleeding of the umbilicus.82
Adenomyosis
Adenomyosis is characterized by the presence of endometrial glands in the myometrium, defined as non-malignant “invasion of endometrium into the myometrium, producing a diffusely enlarged uterus that microscopically exhibits ectopic, non-neoplastic, endometrial glands and stroma surrounded by the hypertrophic and hyperplastic myometrium”.83 Adenomyosis may often co-exist with endometriosis, however, there are no standardized, uniformly administered diagnostic protocols in women with intact uteri, thus the true prevalence of adenomyosis absent detection bias is unknown.84,85 No prospective data nor biologic marker trajectory data exist for adenomyosis nor its relationship with endometriosis across the life course.84,86 Adenomyosis often presents with severe dysmenorrhea, chronic pelvic pain, menorrhagia, infertility, and pregnancy complications, which are all symptoms that are also commonly observed in endometriosis, and also symptoms without which evaluation for adenomyosis would not occur.84,86,87 Diagnosis of adenomyosis is challenging, and most often is based on pathologic confirmation of endometrial tissue in the uterine myometrium after hysterectomy. While non-invasive imaging-based technologies have been emerging in diagnosing adenomyosis in women with intact uteri, there is still a lack of agreement in the terminology or classification system and the radiologic diagnostic criteria are not agreed.88 Given the substantial overlap in symptoms between these two gynecological disorders involving endometrial-like tissue, it is postulated that a proportion of surgery-resistant pain in endometriosis may actually be unaddressed adenomyosis.1 However, it is challenging to disentangle the causal relationships between endometriosis and adenomyosis, which requires prospective studies incorporating temporality rather than cross-sectional studies reporting co-occurrence of these diseases.85
Symptoms vs. consequences of endometriosis
Women with endometriosis are at high risk of presenting with co-occurrence of other chronic co-morbidities,89,90 including autoimmune diseases, asthma/atopic diseases, cardiovascular diseases, and mental disorders. A study which examined the overlap between molecular processes and biological functions underlying endometriosis and co-morbidities identified 127 genes related to immune responses, inflammation, hormone metabolism, and cell proliferation, suggesting shared underlying pathophysiology between endometriosis and co-occurring chronic diseases.91 Here, we highlight a few of the commonly observed co-occurring co-morbidities of endometriosis, which may share similar underlying pathophysiology, but certainly overlap with respect to endometriosis-associated signs and symptoms.
Obstetrical complications
Studies suggest that pregnant women with endometriosis may be at higher risk for certain adverse pregnancy outcomes.57,92 A meta-analysis of 39 studies reported that compared to women without endometriosis, women with endometriosis had an increased risk of gestational hypertension (OR = 1.14, 95% CI = 1.00–1.31), pre-eclampsia (OR = 1.19, 95% CI = 1.08–1.31), preterm birth (OR = 1.46, 95% CI = 1.26–1.69), placenta previa (OR = 2.99, 95% CI = 2.54–3.53), placental abruption (OR = 1.40, 95% CI = 1.12–1.76), and stillbirth (OR = 1.27, 95% CI = 1.07–1.51).92 There are likely many pathways to these increased risks of adverse pregnancy outcomes among women with endometriosis, including the impact of the endometriosis milieu and pathogenesis on implantation, placental dysfunction, and chronic inflammation.92
Autoimmune conditions
Endometriosis has been associated with immune dysregulation and risk of several autoimmune diseases,93 such as systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), rheumatoid arthritis (RA), autoimmune thyroid disorder, coeliac disease (CLD), multiple sclerosis (MS), inflammatory bowel disease (IBD), and Addison’s disease. Ongoing prospective studies have identified greater risk of psoriasis, particularly psoriatic arthritis.94 Perhaps underlying a portion of the prevalent fatigue reports by patients with endometriosis, much higher frequencies of chronic fatigue syndrome have been reported in women with endometriosis compared to controls (4.6% vs. 0.03%).26 In a study examining reproductive factors in women with and without chronic fatigue syndrome, 19% of women with chronic fatigue syndrome reported endometriosis whereas only 8% of women without chronic fatigue syndrome reported endometriosis.95 A study that examined the prevalence of immune-mediated conditions among a younger population of surgically-confirmed endometriosis (median age = 19) patients and controls never diagnosed with endometriosis (median age = 24) reported that those with endometriosis had greater odds of co-occurrence of allergies (OR = 1.76, 95% CI = 1.32–2.36), chronic fatigue syndrome and/or fibromyalgia (OR = 5.81, 95% CI = 1.89–17.9), and a suggestive greater odds of asthma (OR = 1.35, 95% CI = 0.97–1.88),96 further supporting shared underlying pathophysiology between endometriosis and immune disorders.
High blood pressure, cardio- and cerebrovascular disease
First observed in the U.S.-based Nurses’ Health Study II prospective cohort of 116,430 registered female nurses, endometriosis is associated with greater risk of coronary heart disease (RR = 1.62, 95% CI = 1.39–1,89), including myocardial infarction (RR = 1.52, 95% CI = 1.17–1.98);97 increased risk of hypertension (RR = 1.14, 95% CI = 1.09–1.18);98 and increased risk of stroke (HR = 1.34, 95% CI = 1.10–1.62).99 A study from the UK examining 56,090 women with endometriosis and 223,669 matched controls replicated and expanded upon these findings, confirming that women with endometriosis had an increased risk of cardiovascular disease (HR = 1.24, 95% CI = 1.13–1.37), including ischemic heart disease (HR = 1.40, 95% CI = 1.22–1.61), cerebrovascular disease (HR = 1.19, 95% CI = 1.04–1.36), arrhythmia (HR = 1.26, 95% CI = 1.11–1.43), and hypertension (HR = 1.12, 95% CI = 1.07–1.17).100 This cardiovascular97 and cerebrovascular99 pathology risk is in part attributed to the high rate of hysterectomy with and without bilateral oophorectomy among women with endometriosis, with a growing body of literature independent of endometriosis associating these surgeries with cardiovascular disease.101,102,103
Anxiety/depression
In cross-sectional and prospective studies, women with endometriosis are reported to have higher prevalence of depression and/or anxiety compared to women without, which could be as high as 54%.104,105,106,107 Future discovery must focus on disentangling pathophysiology that causally links endometriosis with emergence of affective disorders from the realities of people who live with life-impacting chronic and often stigmatized symptoms that thrust them along a journey of diagnostic barriers and often imprecise or inadequate treatments. Rigorous longitudinal study that accounts for health system interactions plus comparison to those with persistent chronic pelvic pain or infertility without endometriosis are essential next steps for discovery. Currently it remains unclear whether endometriosis and these mental health disorders have shared underlying pathophysiology, which results in the observed high prevalence of anxiety and/or depression in women with endometriosis, or if this high prevalence is a consequence of the long-term severe symptom burden of endometriosis.
Symptomatology is not sufficient to diagnose endometriosis
Multiple studies have attempted to develop a non-invasive diagnostic model of endometriosis based on signs and symptoms at surgical or radiologic evaluation.108,109 One study developed a prediction model of endometriosis combining symptoms and patient history with ultrasound findings using data from 1396 symptomatic women scheduled for laparoscopy without a prior history of endometriosis, with good accuracy for stage III/IV disease (AUC = 0.849, sensitivity of 82.3% at specificity of 75.8%).110 However, this predictive model was not validated in an independent dataset, and its marginal performance to diagnose all endometriosis including early-stage impedes clinical translation. Impacting symptom-specific diagnostic algorithms is the low specificity of the symptoms associated with endometriosis relative to other gynecologic conditions that are indications for imaging or surgical evaluations, including uterine fibroids. Another barrier is that in studies to date, symptoms are defined proximal to surgical or imaging diagnosis, but they may not be reflective of symptoms most prevalent early in the patient’s journey toward a definitive invasive rASRM stage I/II diagnosis.
UNDERSTANDING ENDOMETRIOSIS SYMPTOMS AND SIGNS FROM A LIFE COURSE PERSPECTIVE
Need for a life course approach to studying endometriosis
While most endometriosis is diagnosed during adulthood, more than 50% of women diagnosed with endometriosis report that the onset of their endometriosis-associated pain symptoms started during adolescence and young adulthood,17 suggesting that adolescence and young adulthood may be a critical time window to understand the initiation and development of endometriosis disease. However, endometriosis diagnosed in adolescence is understudied. Several clinical studies, including a study examining the symptom presentation of adolescents and adults with endometriosis, report differences in clinical presentation between those diagnosed during adolescence vs. adulthood. Those successfully referred for surgical diagnosis during adolescence most often have presented with severe pain111 – severe enough to interfere with social or daily activities,25,112 while those diagnosed during adulthood may present with pain or infertility and are more likely to have deep fibrotic lesions.13,111,113 A study reporting plasma proteomic profiles of adolescent/young adult-diagnosed endometriosis observed some distinct features of systemic biological pathways compared to adult-diagnosed endometriosis,114 which may be due to true differences in pathophysiology by onset of the disease but also may be in part due to the differences in the life course at sample collection. Further research is needed to elucidate the potential similarities and differences in the underlying pathophysiology between adolescent and adult-diagnosed endometriosis. A longitudinal, life course approach is necessary to fully understand the life-stage-specific risk factors and symptoms of endometriosis, in addition to the multiple co-occurring co-morbidities that accumulate as duration of endometriosis exposure accumulates.
Importantly, these findings may be attributed to diagnostic bias in that adolescents with less severe, impactful pain may not be referred for surgical evaluation. In general, given the known delay in endometriosis diagnosis, symptoms at diagnosis could be skewed to those with more severe symptoms (particularly among adolescents), given invasiveness of definitive diagnosis requiring surgery. In adult-focused literature, approximately two-thirds of endometriosis patients reported that pelvic pain was the symptom prompting their diagnosis.17 Women reporting symptoms suggestive of endometriosis often undergo nondiscriminatory investigations (e.g., transvaginal ultrasound)115 that do not detect peritoneal endometriosis, which is more common in young women. Reasonably, surgery is only appropriate when symptoms reach a level of severity to warrant risk, which may result in oversampling of advanced disease (e.g., stage III/IV) and/or bowel-impacting endometriosis relative to stage I/II disease. However, this threshold varies not only by knowledge and normalization of symptoms, but also is impacted by economic and geographic access to care. There is a dramatic shortage of experienced, endometriosis-focused surgeons, and women from large sections of the U.S. live hundreds of miles from the nearest appropriately skilled physician. Consequently, the time between symptom onset and surgically confirmed endometriosis diagnosis averages 7 years.116
Symptom progression vs. persistence or recurrence
For many women with endometriosis, current medical and surgical treatment approaches are ineffective.2 Conventional medical treatments are ineffective for 75% of adolescents with pelvic pain. For women with hormone-resistant endometriosis-associated pain, surgical treatment is the standard and is effective for some but not all women.117 Variability in treatment response and high rate of symptom progression are major challenges of endometriosis, often leading to repeated surgical interventions.118,119 While the reported recurrence of endometriosis after surgery ranges from 6–67%,118,119,120 the definition of “progression” varies between studies (i.e., relapse of pain, absence of improvement in infertility, revisualization of lesion with ultrasonography or surgery), and signs other than pain and infertility may be underreported, leading to hide the true spectrum of endometriosis signs and symptoms. Endometriosis disease progression is often defined based on rASRM staging and not symptoms. A study that conducted subsequent laparoscopy and compared the rASRM stage to the initial surgery among 90 endometriosis patients who had recurrent or worsening pain, reported that there was no stage change observed in 70% of the patients,121,122 highlighting the importance of evaluating endometriosis symptom progression. While new tools are being developed to assess endometriosis symptoms, which will improve communications on symptom burden between patients and healthcare providers and facilitate optimal treatment,123 assessment tools to better capture endometriosis symptoms across the life course is necessary to study and understand the full spectrum of endometriosis symptoms. Moreover, applying such tools to longitudinal studies that follow patients over time regardless of where the patients are receiving care is critical for valid association studies. Understanding the pathophysiology of endometriosis-associated symptom progression will be vital for advancing personalized treatment and discovery of alternative treatment options and novel therapeutics targets.
SUMMARY
Endometriosis is a chronic disease with varied presentation between women and within an individual patient – from development to progression or stabilization and across changing biology and life goals. Therefore, a life course approach is needed to obtain a clear picture of symptoms and signs of endometriosis throughout the endometriosis disease trajectory. Emerging population and molecular evidence suggest that an underlying biological mechanism may differ by symptomatology. Thus, further research is needed to elucidate and cluster symptoms that may share similar underlying biology, which may inform disease pathophysiology and lead to more effective personalized treatment for endometriosis. A symptom-based approach that embraces the heterogeneity of endometriosis aligns with the new ESHRE guidelines that recommend that clinicians consider a “working diagnosis” of probable endometriosis based on presentation of endometriosis-associated signs and symptoms, regardless of imaging results and without requirement of surgical referral.3 While a probable diagnosis should not be equated with a confirmatory diagnosis, especially when superficial peritoneal lesions may be present, it is essential to address as urgently as possible the symptoms that are altering a patient’s health, wellbeing, and quality of life.
PRACTICE RECOMMENDATIONS
- Endometriosis presents with various signs and symptoms, including but not limited to dysmenorrhea (pain with periods or menstrual bleeding), acyclic/non-menstrual pelvic pain (pain occurring sporadically at any time other than menses throughout the menstrual cycle), dyspareunia (pain with vaginal intercourse/penetration), dysuria (painful urination), dyschezia (painful defecation), chronic fatigue, and infertility, which can have a substantially negative impact on the physical, mental, sexual, and social well-being of women affected with endometriosis.
- While endometriosis is most often diagnosed during adulthood, more than 50% of women diagnosed with endometriosis report that the onset of their endometriosis-associated pain symptoms started during adolescence and young adulthood. The 2022 ESHRE guidelines recommend a “working diagnosis” of probable endometriosis, which encourages healthcare providers to urgently address life impacting symptoms and not delay or resist treatment in the absence of a radiologic or surgical evaluation confirming endometriosis.
- A life course approach is needed to obtain a clear picture of symptoms and signs of endometriosis throughout the endometriosis disease trajectory. This is critical for embracing patient goals that evolve at different life windows, advancing personalized treatment, and providing new insights to catalyze discovery of novel therapeutic targets.
CONFLICTS OF INTEREST
NS reports research funding support to her institution from the USA National Institutes of Health (NIH), USA Department of Defense (DoD), and the Marriott Family Foundations; none are related to the content of this chapter. SAM reports research funding support to her institution from the USA NIH, DoD, Marriott Family Foundations, and AbbVie, LLC; SAM has received remuneration as Field Chief Editor for Frontiers in Reproductive Health and for past service on advisory boards for AbbVie, Roche, and Abbot; none are related to the content of this chapter.
Feedback
Publishers’ note: We are constantly trying to update and enhance chapters in this Series. So if you have any constructive comments about this chapter please provide them to us by selecting the "Your Feedback" link in the left-hand column.
REFERENCES
Horne AW, Missmer SA. Pathophysiology, diagnosis, and management of endometriosis. BMJ 2022;379:e070750. | |
Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med 2020;382(13):1244–56. | |
Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Hum Reprod Open 2022;2022(2):hoac009. | |
Missmer SA, Tu FF, Agarwal SK, et al. Impact of Endometriosis on Life-Course Potential: A Narrative Review. Int J Gen Med 2021;14:9–25. | |
Johnson NP, Hummelshoj L, Adamson GD, et al. World Endometriosis Society consensus on the classification of endometriosis. Hum Reprod 2017;32(2):315–24. | |
Vermeulen N, Abrao MS, Einarsson JI, et al. Endometriosis classification, staging and reporting systems: a review on the road to a universally accepted endometriosis classification(). Hum Reprod Open 2021;2021(4):hoab025. | |
Kennedy SH, Bergqvist A, Chapron C, et al. ESHRE guideline on the diagnosis and treatment of endometriosis. Hum Reprod 2005;20:2698–704. | |
Vercellini P, Fedele L, Aimi G, et al. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum Reprod 2007;22(1):266–71. | |
Schliep KC, Mumford SL, Peterson CM, et al. Pain typology and incident endometriosis. Hum Reprod 2015;30(10):2427–38. | |
Nisenblat V, Bossuyt PM, Farquhar C, et al. Imaging modalities for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev 2016;2(2):Cd009591. | |
Taylor HS, Adamson GD, Diamond MP, et al. An evidence-based approach to assessing surgical versus clinical diagnosis of symptomatic endometriosis. Int J Gynaecol Obstet 2018;142(2):131–42. | |
Zondervan KT, Cardon LR, Kennedy SH. What makes a good case-control study? Design issues for complex traits such as endometriosis. Hum Reprod 2002;17(6):1415–23. | |
Shafrir AL, Farland LV, Shah DK, et al. Risk for and consequences of endometriosis: A critical epidemiologic review. Best Pract Res Clin Obstet Gynaecol 2018;51:1–15. | |
Chen-Dixon K, Uzuner C, Mak J, et al. Effectiveness of ultrasound for endometriosis diagnosis. Curr Opin Obstet Gynecol 2022;34(5):324–31. | |
Pascoal E, Wessels JM, Aas-Eng MK, et al. Strengths and limitations of diagnostic tools for endometriosis and relevance in diagnostic test accuracy research. Ultrasound Obstet Gynecol 2022;60(3):309–27. | |
Farland LV, Collier AY, Correia KF, et al. Who receives a medical evaluation for infertility in the United States? Fertil Steril 2016;105(5):1274–80. | |
Nnoaham KE, Hummelshoj L, Webster P, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril 2011;96(2):366–73.e8. | |
Maixner W, Fillingim RB, Williams DA, et al. Overlapping Chronic Pain Conditions: Implications for Diagnosis and Classification. J Pain 2016;17(Suppl 9):T93-t107. | |
Fauconnier A, Chapron C. Endometriosis and pelvic pain: epidemiological evidence of the relationship and implications. Hum Reprod Update 2005;11(6):595–606. | |
Hsu AL, Sinaii N, Segars J, et al. Relating pelvic pain location to surgical findings of endometriosis. Obstet Gynecol 2011;118(2 Pt 1):223–30. | |
Khan KN, Kitajima M, Fujishita A, et al. Pelvic pain in women with ovarian endometrioma is mostly associated with coexisting peritoneal lesions. Hum Reprod 2013;28(1):109–18. | |
Sasamoto N, Shafrir AL, Wallace BM, et al. Trends in pelvic pain symptoms over 2 years of follow-up among adolescents and young adults with and without endometriosis. Pain 2022. | |
Singh S, Soliman AM, Rahal Y, et al. Prevalence, Symptomatic Burden, and Diagnosis of Endometriosis in Canada: Cross-Sectional Survey of 30 000 Women. J Obstet Gynaecol Can 2020;42(7):829–38. | |
Bulletti C, Coccia ME, Battistoni S, et al. Endometriosis and infertility. J Assist Reprod Genet 2010;27(8):441–7. | |
DiVasta AD, Vitonis AF, Laufer MR, et al. Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs. adulthood. Am J Obstet Gynecol 2018;218(3):324.e1-.e11. | |
Sinaii N, Cleary SD, Ballweg ML, et al. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 2002;17(10):2715–24. | |
Van Niekerk L, Johnstone L, Matthewson M. Health-related quality of life in endometriosis: The influence of endometriosis-related symptom presence and distress. J Health Psychol 2022;27(14):3121–35. | |
Mastrangelo M, Turnbull D. The impact of surgically diagnosed symptomatic endometriosis on women's social lives, work and education: An inductive classical content analysis. Aust N Z J Obstet Gynaecol 2022;62(2):274–9. | |
Schneider MP, Vitonis AF, Fadayomi AB, et al. Quality of Life in Adolescent and Young Adult Women With Dyspareunia and Endometriosis. J Adolesc Health 2020;67(4):557–61. | |
Denny E, Mann CH. Endometriosis-associated dyspareunia: the impact on women's lives. J Fam Plann Reprod Health Care 2007;33(3):189–93. | |
Wahl KJ, Imtiaz S, Lisonek M, et al. Dyspareunia in Their Own Words: A Qualitative Description of Endometriosis-Associated Sexual Pain. Sex Med 2021;9(1):100274. | |
Sims OT, Gupta J, Missmer SA, et al. Stigma and Endometriosis: A Brief Overview and Recommendations to Improve Psychosocial Well-Being and Diagnostic Delay. Int J Environ Res Public Health 2021;18(15). | |
Lamvu G, Carrillo J, Ouyang C, et al. Chronic Pelvic Pain in Women: A Review. JAMA 2021;325(23):2381–91. | |
International Association for the Study of Pain. Classification of Chronic Pain, 2nd edn. (revised). Published 2020. Accessed November 18, 2020. | |
Tirlapur SA, Kuhrt K, Chaliha C, et al. The 'evil twin syndrome' in chronic pelvic pain: a systematic review of prevalence studies of bladder pain syndrome and endometriosis. Int J Surg 2013;11(3):233–7. | |
Janssen EB, Rijkers AC, Hoppenbrouwers K, et al. Prevalence of endometriosis diagnosed by laparoscopy in adolescents with dysmenorrhea or chronic pelvic pain: a systematic review. Hum Reprod Update 2013;19(5):570–82. | |
Coxon L, Horne AW, Vincent K. Pathophysiology of endometriosis-associated pain: A review of pelvic and central nervous system mechanisms. Best Pract Res Clin Obstet Gynaecol 2018;51:53–67. | |
Yong PJ, Williams C, Bedaiwy MA, et al. A Proposed Platform for Phenotyping Endometriosis-Associated Pain: Unifying Peripheral and Central Pain Mechanisms. Current Obstetrics and Gynecology Reports 2020;9(3):89–97. | |
Ryan A, Healey M, Cheng C, et al. Central sensitisation in pelvic pain: A cohort study. Aust N Z J Obstet Gynaecol 2022;62(6):868–74. | |
Larrosa Pardo F, Bondesson E, Schelin MEC, et al. A diagnosis of rheumatoid arthritis, endometriosis or IBD is associated with later onset of fibromyalgia and chronic widespread pain. Eur J Pain 2019;23(8):1563–73. | |
Smorgick N, Marsh CA, As-Sanie S, et al. Prevalence of pain syndromes, mood conditions, and asthma in adolescents and young women with endometriosis. J Pediatr Adolesc Gynecol 2013;26(3):171–5. | |
Wolfe F, Butler SH, Fitzcharles M, et al. Revised chronic widespread pain criteria: development from and integration with fibromyalgia criteria. Scand J Pain 2019;20(1):77–86. | |
As-Sanie S, Kim J, Schmidt-Wilcke T, et al. Functional Connectivity is Associated With Altered Brain Chemistry in Women With Endometriosis-Associated Chronic Pelvic Pain. J Pain 2016;17(1):1–13. | |
Grundström H, Gerdle B, Alehagen S, et al. Reduced pain thresholds and signs of sensitization in women with persistent pelvic pain and suspected endometriosis. Acta Obstet Gynecol Scand 2019;98(3):327–36. | |
Phan VT, Stratton P, Tandon HK, et al. Widespread myofascial dysfunction and sensitisation in women with endometriosis-associated chronic pelvic pain: A cross-sectional study. Eur J Pain 2021;25(4):831–40. | |
Williams DA. Phenotypic Features of Central Sensitization. J Appl Biobehav Res 2018;23(2). | |
Till SR, Nakamura R, Schrepf A, et al. Approach to Diagnosis and Management of Chronic Pelvic Pain in Women: Incorporating Chronic Overlapping Pain Conditions in Assessment and Management. Obstet Gynecol Clin North Am 2022;49(2):219–39. | |
Prescott J, Farland LV, Tobias DK, et al. A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod 2016;31(7):1475–82. | |
Abd El-Kader AI, Gonied AS, Lotfy Mohamed M, et al. Impact of Endometriosis-Related Adhesions on Quality of Life among Infertile Women. Int J Fertil Steril 2019;13(1):72–6. | |
Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am 1997;24(2):235–58. | |
Counsellor VS. Endometriosis. A Clinical and Surgical Review. American Journal of Obstetrics and Gynecology 1938;36;887. | |
Tanbo T, Fedorcsak P. Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options. Acta Obstet Gynecol Scand 2017;96(6):659–67. | |
Harris-Glocker M, McLaren JF. Role of female pelvic anatomy in infertility. Clin Anat 2013;26(1):89–96. | |
Yland J, Carvalho LFP, Beste M, et al. Endometrioma, the follicular fluid inflammatory network and its association with oocyte and embryo characteristics. Reprod Biomed Online 2020;40(3):399–408. | |
Bruner-Tran KL, Ding T, Osteen KG. Dioxin and endometrial progesterone resistance. Semin Reprod Med 2010;28(1):59–68. | |
Leone Roberti Maggiore U, Ferrero S, Mangili G, et al. A systematic review on endometriosis during pregnancy: diagnosis, misdiagnosis, complications and outcomes. Hum Reprod Update 2016;22(1):70–103. | |
Farland LV, Prescott J, Sasamoto N, et al. Endometriosis and Risk of Adverse Pregnancy Outcomes. Obstet Gynecol 2019;134(3):527–36. | |
Stern JE, Farland LV, Hwang SS, et al. Assisted Reproductive Technology or Infertility: What underlies adverse outcomes? Lessons from the Massachusetts Outcome Study of Assisted Reproductive Technology. F S Rev 2022;3(4):242–55. | |
Cheng C, Rosamilia A, Healey M. Diagnosis of interstitial cystitis/bladder pain syndrome in women with chronic pelvic pain: a prospective observational study. Int Urogynecol J 2012;23(10):1361–6. | |
Rodríguez MA, Afari N, Buchwald DS. Evidence for overlap between urological and nonurological unexplained clinical conditions. J Urol 2009;182(5):2123–31. | |
Wu CC, Chung SD, Lin HC. Endometriosis increased the risk of bladder pain syndrome/interstitial cystitis: A population-based study. Neurourol Urodyn 2018;37(4):1413–8. | |
de Resende Júnior JAD, Crispi CP, Cardeman L, et al. Urodynamic observations and lower urinary tract symptoms associated with endometriosis: a prospective cross-sectional observational study assessing women with deep infiltrating disease. Int Urogynecol J 2018;29(9):1349–58. | |
Gabriel I, Vitonis AF, Missmer SA, et al. Association between endometriosis and lower urinary tract symptoms. Fertil Steril 2022;117(4):822–30. | |
Singh SS, Missmer SA, Tu FF. Endometriosis and Pelvic Pain for the Gastroenterologist. Gastroenterol Clin North Am 2022;51(1):195–211. | |
Ballard KD, Seaman HE, de Vries CS,, et al. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study–Part 1. BJOG 2008;115(11):1382–91. | |
Seaman HE, Ballard KD, Wright JT, et al. Endometriosis and its coexistence with irritable bowel syndrome and pelvic inflammatory disease: findings from a national case-control study–Part 2. BJOG 2008;115(11):1392–6. | |
Wu CY, Chang WP, Chang YH, et al. The risk of irritable bowel syndrome in patients with endometriosis during a 5-year follow-up: a nationwide population-based cohort study. Int J Colorectal Dis 2015;30(7):907–12. | |
DiVasta AD, Zimmerman LA, Vitonis AF, et al. Overlap Between Irritable Bowel Syndrome Diagnosis and Endometriosis in Adolescents. Clin Gastroenterol Hepatol 2021;19(3):528–37.e1. | |
Maroun P, Cooper MJ, Reid GD, et al. Relevance of gastrointestinal symptoms in endometriosis. Aust N Z J Obstet Gynaecol 2009;49(4):411–4. | |
Facchin F, Buggio L, Roncella E, et al. Sleep disturbances, fatigue and psychological health in women with endometriosis: a matched pair case-control study. Reprod Biomed Online 2021;43(6):1027–34. | |
Surrey ES, Soliman AM, Agarwal SK, et al. Impact of elagolix treatment on fatigue experienced by women with moderate to severe pain associated with endometriosis. Fertil Steril 2019;112(2):298–304.e3. | |
Soliman AM, Rahal Y, Robert C, et al. Impact of Endometriosis on Fatigue and Productivity Impairment in a Cross-Sectional Survey of Canadian Women. J Obstet Gynaecol Can 2021;43(1):10–8. | |
Ramin-Wright A, Schwartz ASK, Geraedts K, et al. Fatigue – a symptom in endometriosis. Hum Reprod 2018;33(8):1459–65. | |
DiBenedetti D, Soliman AM, Gupta C, et al. Patients' perspectives of endometriosis-related fatigue: qualitative interviews. J Patient Rep Outcomes 2020;4(1):33. | |
Bird CC, McElin TW, Manalo-Estrella P. The elusive adenomyosis of the uterus–revisited. Am J Obstet Gynecol 1972;112(5):583–93. | |
Vilasagar S, Bougie O, Singh SS. A Practical Guide to the Clinical Evaluation of Endometriosis-Associated Pelvic Pain. J Minim Invasive Gynecol 2020;27(2):270–9. | |
Matalliotakis M, Goulielmos GN, Kalogiannidis I, et al. Extra pelvic endometriosis: Retrospective analysis on 200 cases in two different countries. Eur J Obstet Gynecol Reprod Biol 2017;217:34–7. | |
Vercellini P, Sergenti G, Buggio L, et al. Advances in the medical management of bowel endometriosis. Best Pract Res Clin Obstet Gynaecol 2021;71:78–99. | |
Akpınar S, Yılmaz G, Çelebioğlu E. A rare cyclic recurrent hematuria case; bladder endometriosis. Quant Imaging Med Surg 2015;5(3):485–7. | |
Ghigna MR, Mercier O, Mussot S, et al. Thoracic endometriosis: clinicopathologic updates and issues about 18 cases from a tertiary referring center. Ann Diagn Pathol 2015;19(5):320–5. | |
Fluegen G, Jankowiak F, Zacarias Foehrding L, et al. Intrahepatic endometriosis as differential diagnosis: case report and literature review. World J Gastroenterol 2013;19(29):4818–22. | |
Victory R, Diamond MP, Johns DA. Villar's nodule: a case report and systematic literature review of endometriosis externa of the umbilicus. J Minim Invasive Gynecol 2007;14(1):23–32. | |
Bulun SE, Yildiz S, Adli M, et al. Adenomyosis pathogenesis: insights from next-generation sequencing. Hum Reprod Update 2021;27(6):1086–97. | |
Halvorson LM. New Perspectives on Adenomyosis. Semin Reprod Med 2020;38(2–03):87–8. | |
Upson K, Missmer SA. Epidemiology of Adenomyosis. Semin Reprod Med 2020;38(2–03):89–107. | |
Coccia ME, Rizzello F, Palagiano A, et al. Long-term follow-up after laparoscopic treatment for endometriosis: multivariate analysis of predictive factors for recurrence of endometriotic lesions and pain. Eur J Obstet Gynecol Reprod Biol 2011;157(1):78–83. | |
Isaacson K, Loring M. Symptoms of Adenomyosis and Overlapping Diseases. Semin Reprod Med 2020;38(2–03):144–50. | |
Chapron C, Vannuccini S, Santulli P, et al. Diagnosing adenomyosis: an integrated clinical and imaging approach. Hum Reprod Update 2020;26(3):392–411. | |
Missmer SA. Commentary: Endometriosis–epidemiologic considerations for a potentially 'high-risk' population. Int J Epidemiol 2009;38(4):1154–5. | |
Kvaskoff M, Mu F, Terry KL, et al. Endometriosis: a high-risk population for major chronic diseases? Hum Reprod Update 2015;21(4):500–16. | |
Vargas E, Aghajanova L, Gemzell-Danielsson K, et al. Cross-disorder analysis of endometriosis and its comorbid diseases reveals shared genes and molecular pathways and proposes putative biomarkers of endometriosis. Reprod Biomed Online 2020;40(2):305–18. | |
Breintoft K, Pinnerup R, Henriksen TB, et al. Endometriosis and Risk of Adverse Pregnancy Outcome: A Systematic Review and Meta-Analysis. J Clin Med 2021;10(4). | |
Shigesi N, Kvaskoff M, Kirtley S, et al. The association between endometriosis and autoimmune diseases: a systematic review and meta-analysis. Hum Reprod Update 2019;25(4):486–503. | |
Harris HR, Korkes KMN, Li T, et al. Endometriosis, Psoriasis, and Psoriatic Arthritis: A Prospective Cohort Study. Am J Epidemiol 2022;191(6):1050–60. | |
Harlow BL, Signorello LB, Hall JE, et al. Reproductive correlates of chronic fatigue syndrome. Am J Med 1998;105(3a):94s-9s. | |
Shafrir AL, Palmor MC, Fourquet J, et al. Co-occurrence of immune-mediated conditions and endometriosis among adolescents and adult women. Am J Reprod Immunol 2021;86(1):e13404. | |
Mu F, Rich-Edwards J, Rimm EB, et al. Endometriosis and Risk of Coronary Heart Disease. Circ Cardiovasc Qual Outcomes 2016;9(3):257–64. | |
Mu F, Rich-Edwards J, Rimm EB, et al. Association Between Endometriosis and Hypercholesterolemia or Hypertension. Hypertension 2017;70(1):59–65. | |
Farland LV, Degnan WJ, 3rd, Bell ML, et al. Laparoscopically Confirmed Endometriosis and Risk of Incident Stroke: A Prospective Cohort Study. Stroke 2022;53(10):3116–22. | |
Okoth K, Wang J, Zemedikun D, et al. Risk of cardiovascular outcomes among women with endometriosis in the United Kingdom: a retrospective matched cohort study. BJOG 2021;128(10):1598–609. | |
Rivera CM, Grossardt BR, Rhodes DJ, et al. Increased cardiovascular mortality after early bilateral oophorectomy. Menopause 2009;16(1):15–23. | |
Parker WH, Feskanich D, Broder MS, et al. Long-term mortality associated with oophorectomy compared with ovarian conservation in the nurses' health study. Obstet Gynecol 2013;121(4):709–16. | |
Stewart EA, Missmer SA, Rocca WA. Moving Beyond Reflexive and Prophylactic Gynecologic Surgery. Mayo Clin Proc 2021;96(2):291–4. | |
Cavaggioni G, Lia C, Resta S, et al. Are mood and anxiety disorders and alexithymia associated with endometriosis? A preliminary study. Biomed Res Int 2014;2014:786830. | |
González-Echevarría AM, Rosario E, Acevedo S, et al. Impact of coping strategies on quality of life of adolescents and young women with endometriosis. J Psychosom Obstet Gynaecol 2019;40(2):138–45. | |
Surrey ES, Soliman AM, Johnson SJ, et al. Risk of Developing Comorbidities Among Women with Endometriosis: A Retrospective Matched Cohort Study. J Womens Health (Larchmt) 2018;27(9):1114–23. | |
Estes SJ, Huisingh CE, Chiuve SE, et al. Depression, Anxiety, and Self-Directed Violence in Women With Endometriosis: A Retrospective Matched-Cohort Study. Am J Epidemiol 2021;190(5):843–52. | |
Agarwal SK, Chapron C, Giudice LC, et al. Clinical diagnosis of endometriosis: a call to action. Am J Obstet Gynecol 2019;220(4):354.e1–12. | |
Conroy I, Mooney SS, Kavanagh S, et al. Pelvic pain: What are the symptoms and predictors for surgery, endometriosis and endometriosis severity. Aust N Z J Obstet Gynaecol 2021;61(5):765–72. | |
Nnoaham KE, Hummelshoj L, Kennedy SH, et al. Developing symptom-based predictive models of endometriosis as a clinical screening tool: results from a multicenter study. Fertil Steril 2012;98(3):692–701.e5. | |
DiVasta AD, Vitonis AF, Laufer MR, et al. Spectrum of symptoms in women diagnosed with endometriosis during adolescence vs. adulthood. American Journal of Obstetrics and Gynecology 2018;218(3):324 e1- e11. | |
Tsonis O, Barmpalia Z, Gkrozou F, et al. Endometriosis in adolescence: Early manifestation of the traditional disease or a unique variant? Eur J Obstet Gynecol Reprod Biol 2020;247:238–43. | |
Shah DK, Missmer SA. Scientific investigation of endometriosis among adolescents. J Pediatr Adolesc Gynecol 2011;24(5 Suppl):S18–9. | |
Sasamoto N, Ngo L, Vitonis AF, et al. Circulating proteomic profiles associated with endometriosis in adolescents and young adults. Hum Reprod 2022;37(9):2042–53. | |
Ballard K, Lowton K, Wright J. What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis. Fertil Steril 2006;86(5):1296–301. | |
Nnoaham KE, Hummelshoj L, Webster P, et al. Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries. Fertil Steril 2011;96(2):366–73 e8. | |
Dunselman GAJ, Vermeulen N, Becker C, et al. ESHRE guideline: management of women with endometriosis †. Human Reproduction 2014;29(3):400–12. | |
Vercellini P, Crosignani PG, Abbiati A, et al. The effect of surgery for symptomatic endometriosis: the other side of the story. Hum Reprod Update 2009;15(2):177–88. | |
Bozdag G. Recurrence of endometriosis: risk factors, mechanisms and biomarkers. Womens Health (Lond) 2015;11(5):693–9. | |
Vignali M, Bianchi S, Candiani M, et al. Surgical treatment of deep endometriosis and risk of recurrence. J Minim Invasive Gynecol 2005;12(6):508–13. | |
Unger CA, Laufer MR. Progression of endometriosis in non-medically managed adolescents: a case series. J Pediatr Adolesc Gynecol 2011;24(2):e21–3. | |
Doyle JO, Missmer SA, Laufer MR. The effect of combined surgical-medical intervention on the progression of endometriosis in an adolescent and young adult population. J Pediatr Adolesc Gynecol 2009;22(4):257–63. | |
As-Sanie S, Laufer MR, Missmer SA, et al. Development of a visual, patient-reported tool for assessing the multi-dimensional burden of endometriosis. Curr Med Res Opin 2021;37(8):1443–9. |
Online Study Assessment Option
All readers who are qualified doctors or allied medical professionals can now automatically receive 2 Continuing Professional Development credits from FIGO plus a Study Completion Certificate from GLOWM for successfully answering 4 multiple choice questions (randomly selected) based on the study of this chapter.
Medical students can receive the Study Completion Certificate only.
(To find out more about FIGO’s Continuing Professional Development awards programme CLICK HERE)