Persistent Pelvic Pain in Patients With Endometriosis : Clinical Obstetrics and Gynecology

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Controversies in Gynecology

Persistent Pelvic Pain in Patients With Endometriosis

Green, Isabel C. MD, MEHP; Burnett, Tatnai MD; Famuyide, Abimbola MBBS

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Clinical Obstetrics and Gynecology: December 2022 - Volume 65 - Issue 4 - p 775-785
doi: 10.1097/GRF.0000000000000712
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Abstract

Introduction

Endometriosis is a benign disease characterized by the proliferation and vascularization of ectopic endometrial-like tissue, in association with a neuroinflammatory response. It impacts 7% to 10% of reproductive age women, an estimated 200 million women and teens worldwide.1,2 Endometriosis can lead to symptoms of dysmenorrhea, dyspareunia, dysuria or dyschezia, and chronic pelvic pain. The prevalence of endometriosis in women with chronic pelvic pain has been reported as high as 71% to 87%.2

While laparoscopic visualization and excision with pathologic diagnosis of endometriosis is the only definitive method of diagnosing endometriosis, it may no longer be required for diagnosis.3 Clinical suspicion alone is sufficient to initiate medical therapy, and surgery can be reserved for those women in whom imaging studies are normal and/or empiric medical treatment has failed or not indicated, or for therapeutic and not solely diagnostic purposes.3

Many women face significant delays between the onset of their symptoms and a diagnosis of endometriosis, on average, 7 to 12 years.2 Younger women face extended delays compared with older women and represent the higher range, closer to 12 years of symptoms before the diagnosis.2 On average, women make 7 visits to a primary health care provider before referral to a specialist for evaluation of endometriosis.2

Delays in treatment and access to specialist care is one challenge facing patients with endometriosis. Unfortunately, the recurrence of endometriosis-associated pain and persistent pelvic pain, despite medical and surgical therapy, are also common and represent an additional significant challenge to patients living with endometriosis.

OUTCOMES OF SURGICAL THERAPY

Surgical approaches to the management of endometriosis depend on the type of lesions and include conservative surgical approaches or more radical surgery including hysterectomy with or without removal of the ovaries. Surgical management as a compliment or in lieu of medical management is a mainstay in the treatment of endometriosis and is commonly performed. In a 2007 study examining rates of surgery in commercially insured women diagnosed with endometriosis (n=15,891), >65% underwent an endometriosis surgical treatment in the 12 months following diagnosis.4 Endometriosis is the second most common indication for hysterectomy and accounts for 17.7% of hysterectomies performed.2 It is the leading cause of hysterectomy in younger women (age 30 to 34 y old).2

Surgical excision or ablation of endometriosis is recommended for superficial lesions.3,5 Full excision is recommended for deep endometriosis, and ovarian cystectomy over drainage is recommended in the management of endometriomas.3,5 Hysterectomy with or without removal of the ovaries is reserved for women that have refractory endometriosis-related symptoms which have failed to improve despite conservative surgery or medical therapy after a process of shared decision-making.3 Conservative therapy with retention of the uterus and at least 1 ovary is recommended in women desiring future fertility.5

Historically, diagnostic laparoscopic was the gold standard for diagnoses of endometriosis, commonly resulting in incomplete treatment, with most patients undergoing a subsequent surgical treatment.5–7 Diagnostic laparoscopy can be hindered by the possible unexpected finding of severe endometriosis, and in turn, contribute to possible suboptimal treatment outcomes.6

Planning for surgical management of endometriosis, especially complex endometriosis, therefore, requires preoperative planning with cooperation between gynecologic surgeon and radiologist.6,8 Targeted endometriosis transvaginal ultrasound protocols specifically assessing for adhesions in the posterior cul de sac and magnetic resonance imaging remain the most used modalities, and both demonstrate high sensitivity and specificity for endometriomas and deep endometriosis.6,9 Preoperative preparation allows for the patient to be counseled on disease severity, expectations, possible risks, and outcomes, as well as assembly of appropriate multidisciplinary teams including colorectal and urologic surgeons.

Recurrence of endometriosis and endometriosis-related pain can be reduced using postsurgical hormonal suppression.10,11 Hormonal treatment should be considered and individualized for patients not seeking immediate fertility postsurgical management.3,10

Research in the surgical management of endometriosis is hindered by a lack of standardization of reported outcomes, which subsequently limits efforts to develop evidence-based treatment plans and expected improvements postsurgery to inform patients during shared decision-making. A 2020 systematic review by Singh et al5 identified 38 studies assessing outcomes for surgical management of endometriosis, and notably, most studies failed to describe pain outcomes. Fewer than a third of the studies reported persistence of pain, recurrence of pain, or need for further surgery as an outcome of the study.5 Diagnostic laparoscopy was associated with 77.4% of patients noting no improvement in pain and underwent repeat surgery at a mean follow-up of 18 months.5 Excision of endometriosis, and excision of deep endometriosis were associated with no improvement in pain in the range of 3.6% to 22% and 0% to 4.4%, respectively.5 Based on the studies reviewed, on average, 25% of patients undergoing excision of endometriosis experience persistent pain, 15.8% of patients undergoing excision of endometriosis experience recurrence of pain, and 22.6% of patients underwent repeat surgery with mean follow-up of 24 months.5

Most notably, even after hysterectomy, patients are at risk for persistent pain, with 20% of patients undergoing a repeat surgery within 7 years.5 Although endometriosis is the second leading indication for hysterectomy, hysterectomy may not be a cure for all women with endometriosis.2 Oophorectomy decreases the rate of repeat by surgery by half, but this difference is impacted by patient age, with the differences between pain outcomes after ovarian preservation or removal decreasing in younger women.2 Decisions to proceed with hysterectomy and oophorectomy should be weighed against long-term risks of these surgeries.2,12,13

A thorough evaluation for other contributing factors to pain recurrence can limit unnecessary repeat surgical intervention in patients with endometriosis and will be the focus of the remainder of our review (Table 1).

TABLE 1 - Considerations for Evaluation of Persistent Pelvic Pain Associated With Endometriosis
Questions Possible Interventions
Has medical management been optimized for therapeutic amenorrhea? Hormonal therapies for suppression (eg, combination oral contraceptive pill and norethindrone) GnRH analogues as second-line therapy Aromatase inhibitors as second-line line therapy
Has surgical management been optimized? Assess prior operative notes for evidence of complete treatment of disease Evaluate for deep disease with targeted imaging
Has central sensitization been considered? Central acting medications Mindfulness-based interventions or cognitive-behavioral therapy Pain rehabilitation
Have chronic overlapping pain conditions (COPCs) been assessed and optimized? Multidisciplinary care Central acting medications Address sleep disturbances Treat coexisting affective disorders Improve functional status
Has myofascial pain been assessed? Physical therapy and behavioral modifications Trigger point injections
Have coping responses been assessed for catastrophizing and dysfunctional pain management? Mindfulness-based interventions Cognitive-behavioral therapy Functional goal setting
GnRH indicates gonadotropin-releasing hormone.

CONTRIBUTORS TO PERSISTENT PAIN—BEYOND THE ENDOMETRIOSIS

Inadequate surgical or medical therapy, underrecognized and undertreated comorbid conditions, and central sensitization are likely causes of persistent or recurrent pelvic pain in patients with endometriosis.2,5 Comorbidities are common, with most women with endometriosis (95%) reporting 1 or more comorbid disorder (adenomyosis, fibroids, migraines, fibromyalgia, ovarian cysts, irritable bowel syndrome, interstitial cystitis, or depression).1 Some patients with endometriosis will develop chronic pelvic pain. Chronic pain is a complex condition characterized by a transition from acute to chronic pain, neuroplasticity, and pain amplification. The experience of chronic pain is also influenced by biopsychosocial factors.

Central Sensitization—From Acute to Chronic Pain

When acute pain becomes chronic, a chronic stress phenotype can develop, characterized by a dysfunctional cycle of psychological and physical consequences.14 Endometriosis is commonly associated with chronic pelvic pain, whether the pain is cyclic or acyclic. Chronic pelvic pain, defined as pain perceived to originate from the pelvis, is often associated with negative cognitive, behavioral, and emotional consequences and symptoms.14,15 Fear of pain, fear-avoidance behaviors, anxiety, and distress, can lead to deterioration of mood and social isolation, while activity restrictions can lead to physical deconditioning.14 Symptoms are suggestive of lower urinary tract, sexual, bowel, myofascial or gynecologic dysfunction, and can be related to menstruation (dysmenorrhea) and intercourse (dyspareunia) and typically occur for >6 months.14,15

The following hypotheses explain how ectopic endometrial-like tissue, characteristic of endometriosis, activates the nervous system to generate symptoms of chronic pain, central sensitization, and pain amplification.14 They include: (1) peripheral sensitization of new sensory fibers within endometriosis lesions; (2) central sensitization which can become independent of the original peripheral signaling; (3) branching within the sacral spine to propagate sensitization to distant spinal cord segments and remote central sensitization; and (4) central integration of visceral input and development of viscerosomatic reflexes—producing increased muscle tone and spasm in the area of pain referral.14,16

Patients with a central component to pain are less likely to improve with conventional therapies targeting peripheral endometriosis lesions.17 An important question, therefore, is how do clinicians identify those patients likely to have a central component to provide them with individualized care beyond conventional therapies? The Central Sensitization Inventory (CSI) has been validated to differentiate between patients with and without central sensitization. In 2022, Orr et al17 applied the CSI to 355 patients with endometriosis and determined that patients who scored >40 (range: 0 to 100) were more likely to have 3 or more central sensitization syndromes or pain-related conditions in addition to their diagnosis of endometriosis, as well as higher pain scores. The CSI was similarly applied to gynecologic patients seeking outpatient care with similar findings.18

Whether utilizing a validated questionnaire or by recognizing those patients during history taking and physical examination, suspected central sensitization should be identified during endometriosis treatment and especially in the evaluation of recurrence of endometriosis-related pain. Features during the history and examination may include pain described as daily, multifocal, or diffuse pain and tenderness on examination, patients experiencing >1 pain condition (dysmenorrhea, dyspareunia, dysuria, etc.), and significant distress and burden secondary to pain. Patients are likely to report that prior medical therapies and interventions have failed to adequately treat their symptoms.17,19

Treatment of chronic pain is best achieved by allowing for additional time for visits and employing multidisciplinary care teams to address both peripheral and central components of a patient’s pain and their comorbid conditions. Targeted treatments at central sensitization include both pharmacologic and nonpharmacologic therapies and are well outlined in a recent review by Lamvu et al.15 A combination of mind-body and interdisciplinary interventions are recommended over surgery or single-agent pharmacotherapy.15 Pharmacologic options including gabapentinoids (gabapentin, pregabalin), serotonin-norepinephrine reuptake inhibitors, and tricyclic antidepressants.20 Nonpharmacologic therapies include physical therapy, exercise, pain management strategies including cognitive therapies, functional goal setting, patient education and treatment of affective disorders, optimizing sleep and environmental factors contributing to the pain cycle.14,15,20 Trauma history should be assessed, and trauma-informed care employed. A sensitive and psychologically safe environment is paramount.

Chronic Overlapping Pain Conditions (COPCs)

Individual treatments that specifically target endometriosis-related pain in isolation, such as surgical and hormonal therapies, are likely to overlook other comorbid pain conditions which contribute to the multifactorial nature of chronic pain. Numerous overlapping etiologies, termed chronic overlapping pain conditions (COPCs), share common central mechanisms (Table 2).21 These conditions can also exist in isolation and contribute to abdominal and pelvic symptoms that can mimic endometriosis. The degree of overlap or coprevalence of these conditions can correlate with increased symptom severity and worse treatment outcomes.22,23

TABLE 2 - Common Chronic Overlapping Pain Conditions
Chronic fatigue syndrome
Chronic low back pain
Chronic migraine
Chronic tension-type headache
Endometriosis
Fibromyalgia
Interstitial cystitis
Irritable bowel syndrome
Temporomandibular disorders
Vulvodynia

The presence of a chronic pain condition characterized by a state of pain amplification, or enhanced perception of pain, is a risk factor for the development of a different COPC.23 In addition, there appears to be a component of psychosocial vulnerability which can also contribute to the onset and maintenance of COPCs.23 While COPCs vary in their clinical presentation, they can share common symptoms including fatigue, impaired sleep, physical dysfunction, problems with cognition and disturbances in affect (anxiety, depression, etc.), in addition to the cardinal symptom of pain.23 These coexisting pain conditions are more common in women compared with men. Some patients develop multiple conditions simultaneously, while others develop them in succession over time.21 Almost half of women with bladder pain syndrome have endometriosis, and up to 75% of patients with bladder pain syndrome also have irritable bowel syndrome.15,24,25

Diagnosing COPCs within the same patient is made difficult by a lack of standardized diagnostic criteria, the multidisciplinary etiologies, and the time available in the clinical setting during the evaluation of a chronic pelvic pain patient. Our health care system is structured by specialists in each body system, leading each specialist to conduct diagnostic examinations for each of the COPCs, and not necessarily a comprehensive evaluation for multiple COPCs.21

Despite these challenges, identifying the presence of COPCs can help target therapies and possibly enlist more intensive treatments.17,23 Within and across COPCs, subgroups of patients respond to treatments targeted to their common underlying disease mechanisms.21,26 Widespread pain may respond better to central acting therapies, nonpharmacologic therapies and treatments targeted at affect, pain coping strategies or resilience and functional status. A comprehensive treatment plan should consider each coexisting condition and factor playing a role in the individual’s health.21 For example, while treatment for endometriosis is optimized, therapies for irritable bowel syndrome and underlying depression and sleep disturbances should be addressed simultaneously. Due to our specialized health care system, this typically will require a multidisciplinary team and should include a patient’s primary care provider.

Myofascial Pain

Myofascial pain can be a source of initiation, amplification, and perpetuation of pain in patients with endometriosis and can propagate pain-related symptoms even after optimal surgical and medical/hormonal treatments.16 Myofascial pain syndrome is a muscle condition that has local and referred pain, typically generated from a myofascial trigger point (MTrP).27 MTrPs are palpable nodules, commonly found in taut muscle fibers or bands, and refer pain beyond the local tissue, spontaneously or when stimulated.16,27,28 MTrPs can be a result of a primary injury, such as trauma, overuse, or altered mechanics, or secondary to viscerosomatic pain.27 The hallmark of secondary MTrPs is that they may persist despite improvement or reversal of the visceral tissue injury.27

Initial reports of an interconnection between visceral diseases and myofascial pain were made in relation to the finding of specific and reproducible sensitized areas of the skin, corresponding to a visceral etiology.27 Examples include referred pain and allodynia of the abdominal wall after cholecystitis, chest wall pain after angina related to myocardial ischemia, and in the case of pelvic pain, myofascial pain of the abdominal wall and pelvic muscles secondary to endometriosis. As described above, sensitization and the activation of the nervous system can occur with endometriosis. Those processes, including the development of viscerosomatic reflexes, increase the risk of development of MTrPs, and in the case of endometriosis can sustain pain and dysfunction despite hormonal therapies or lesion removal.15,16

The evaluation of pelvic pain should include assessments for abdominal wall MTrPs as well as the pelvic floor musculature, specifically the levator ani muscles and the obturator internus. Patients may describe exacerbation of pain with movement or contraction.15 In addition to MTrPs, examination may identify overall hypertonicity of muscles or an inability to voluntarily relax muscles.15 Abdominal examination includes assessment of pain as diffuse versus local, assessing for allodynia of the skin and MTrPs of the abdominal wall.16 Carnett’s can be useful in identifying a myofascial component to abdominal and pelvic pain29 (Fig. 1). The pelvic musculature is examined through a unidigital transvaginal examination, applying gentle pressure at clock face positions for each muscle group.30 The superficial layers are palpated first, comprised of the bulbospongiousus, ischiocavernosus, and the superficial transverse perineii.30 Next the deeper pelvic floor muscles are palpated (Fig. 2). Palpation of the obturator internus can be facilitated by requesting the patient to rotate the leg externally while palpating the contraction of the muscle. The pelvic musculature examination is performed distinctly and separately from the portion of the examination assessing the pelvic viscera, and typically performed before the bimanual examination and speculum examination.

F1
FIGURE 1:
Carnett’s sign—Abdominal examination to differentiate possible abdominal wall pain versus visceral pain. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved. Originally published in Kamboj et al.29 Copyright [Mayo Clinic], [Rochester, MN]. All permission requests for this image should be made to the copyright holder.
F2
FIGURE 2:
Illustration of single digit examination of the pelvic floor muscles. Used with permission of Mayo Foundation for Medical Education and Research, all rights reserved. Copyright [Mayo Clinic], [Rochester, MN]. All permission requests for this image should be made to the copyright holder.

The primary therapy for myofascial pain is physical therapy and myofascial release techniques.15,16,28 Physical therapy may include a combination of manual techniques combined with exercises with stretching, biofeedback and electrical stimulation, dilator usage and dry needling.28 Pain management strategies such as breathing and relaxation techniques are often included. Trigger point injections and Botulinum Toxin A (Botox) injection have also been employed for the treatment of MTrPs.16,31 Pelvic floor trigger point injection with Botox is currently an off label use and not Food and Drug Administration (FDA) approved for this purpose.

Myofascial pain is often overlooked as a component of chronic pelvic pain.16 Early consideration of this diagnosis can inform treatment plans and aid in avoiding additional surgical interventions for endometriosis, and instead allow for targeting of the myofascial component of pain specifically.15,28 Patient education is also paramount to address the high probability that a patient relates the sensation of and persistence of the pain to the underlying viscera (uterus, ovary, etc.). Patient’s may frequently refer to their pain as “ovary pain,” or “endometriosis pain,” supporting a need for education during the examination process and treatment planning.

Pain Catastrophizing

Patients with endometriosis experience pain that does not necessarily correlate with the severity of the disease and cannot be explained by a purely physiological or tissue-damage approach to pain generation.32 Instead, the experience of chronic pain is influenced by an interplay of physical, psychological, social, and environmental factors.20,32

Catastrophizing describes a negative cognitive and emotional coping response to anticipated or actual pain and is an important determinant of short-term and long-term pain-related outcomes.20,33,34 It is characterized by feelings of helplessness and pessimism, with a tendency to amplify and focus on pain symptoms.33,35

Endometriosis patients with a catastrophizing coping response have higher baseline self-reported pain levels and higher rates of recurrence of pain, persistence of pain and reintervention.32,33,36–38 Higher pain catastrophizing is also associated with reduced health-related quality of life in patients with endometriosis, irrespective of pain severity.32,39 These patients avoid activities that may cause pain, leading to disengagement from social activities.32

Pain catastrophizing, rumination, an inability to engage attention away from pain and deal with the pain experience negatively influences the effects of therapies targeting endometriosis and chronic pelvic pain.32 Negative pain management and cognition is a risk factor for postoperative pain, opioid use in the perioperative period, and persistent pain despite surgery.32,40 Given the potential impact of this psychosocial trait on treatment outcomes, there may be an important role for assessing a patient’s coping responses, and specifically pain catastrophizing as part of their endometriosis treatment plan. Reducing catastrophizing may mediate positive treatment outcomes.34,41,42

The Pain Catastrophizing Scale (PCS) is a 13-item scale assessing elements of pain catastrophizing in 3 subgroups; rumination, helplessness, and magnification.37 The maximum score is 52, and a high score (30/52) on the PCS reflects a high degree of pain catastrophizing.32 To facilitate more efficient screening and assessment, shorter forms of the PCS have been developed and tested in different clinical settings with results showing retained discrimination between high and low scores.34,43,44

Identifying patients with high or moderate scores could inform an individualized treatment plan in endometriosis, a treatment plan that includes targeted therapies for addressing catastrophizing and pain cognition.45 Both mindfulness-based interventions and cognitive-behavioral therapy have been shown to decrease pain catastrophizing and improve patient self-efficacy in pain management.20,46–48 Encouraging patients to develop positive strategies can help them cope with pain and decrease their disability.32

Conclusions

As our understanding of chronic pain conditions, including endometriosis-related pain and chronic pelvic pain evolves, the evaluation and management of patients should reflect our increasing appreciation of the role of central sensitization, comorbid conditions and biopsychosocial factors on the pain experience and treatment outcomes. Due to the complexity and possible span of symptoms and etiologies, endometriosis care has evolved to include multidisciplinary care teams. Endometriosis centers of excellence include experts in surgical and medical management, pain education, physical therapy and psychology, and their interdisciplinary approach can be successful in lessening pain, reducing emergency room visits, and improving functional quality of life.2,49 Because patients may have 7 clinical visits on average before diagnosis of endometriosis, collaborative teams should span to include primary care providers and gynecologists that serve as the entry point for patients with endometriosis in the health care system. Expanding the evaluation and treatment of endometriosis-related pain by all health care providers could limit unnecessary surgical interventions and best meet our patient’s needs.

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Keywords:

endometriosis; chronic pelvic pain; central sensitization; chronic overlapping pain conditions

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