Clinical Expert Series

Chronic Pelvic Pain John F. Steege,

MD,

and Matthew T. Siedhoff,

MD, MSCR

As opposed to the satisfying solutions found in the management of acute pain, chronic pelvic pain can be a vexing problem for the patient and physician. Seldom is a single source or cause found, and nearly always the condition is influenced by the broader social and psychological context of the patient. In this article, we discuss the evaluation of chronic pelvic pain, often considering pain as the disease itself, and identify peripheral generators, which gynecologists can address to help reduce their contributions to symptoms. (Obstet Gynecol 2014;124:616–29) DOI: 10.1097/AOG.0000000000000417

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he American College of Obstetricians and Gynecologists proposed the following definition of chronic pelvic pain: noncyclic pain of 6 or more months’ duration that localizes to the anatomic pelvis, anterior abdominal wall at or below the umbilicus, the lumbosacral back or the buttocks, and is of sufficient severity to cause functional disability or lead to medical care.1 The problem costs the economy of the United States well in excess of $3 billion2 and costs women greatly in the areas of work, family responsibilities, and relationships. The practicing gynecologist finds the problem time-consuming, challenging, and less rewarding than the usually successful obstetric and gynecologic endeavors. Traditional thinking about chronic pelvic pain has emphasized observable organic pathology (eg, endometriosis, adhesions), but the connection between these problems and pain symptoms is actually more tenuous than previously thought. For example, even the most optimistic clinical reports note pain relief in only 60– 70% of women undergoing laparoscopic surgery for endometriosis,3,4 suggesting that in many women, there

From the Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Continuing medical education for this article is available at http://links.lww. com/AOG/A541. Corresponding author: John F. Steege, MD, Department of Obstetrics and Gynecology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; e-mail: [email protected]. Financial Disclosure The authors did not report any potential conflicts of interest. © 2014 by The American College of Obstetricians and Gynecologists. Published by Lippincott Williams & Wilkins. ISSN: 0029-7844/14

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is more to the story than just the implants. More and more data confirming the coexistence of one or more other chronic pain disorders in patients—conditions such as interstitial cystitis (also known as painful bladder syndrome), irritable bowel syndrome, temporomandibular joint disorder, migraine headaches, vulvodynia, and fibromyalgia—suggest that perhaps we should be treating pelvic pain itself as the disease rather than as just a manifestation of a specific pathologic change.5 In this review, we describe chronic pelvic pain and point out common peripheral pain generators—nociceptive stimuli—that can be modulated by gynecologic interventions.

HISTORY OF PELVIC PAIN CONCEPTS Over the past 60 years, the study of chronic pelvic pain has gone through significant changes in approach. Before the advent of laparoscopy and based in a Cartesian framework in which pain perception should be proportional to the degree of tissue damage, gynecologists were understandably reluctant to operate on any pathology not large enough to palpate. In addition, much of clinical medicine was practiced from the perspective of the mind–body split: causation of symptoms was distinctly divided between physical and psychological sources. Although this model was sufficient to address most causes of acute pain, it fails to interpret the majority of chronic pain disorders in gynecology as well as other areas of medicine. The gate-control theory, an alternative proposed by Melzack and Wall in 1965, suggests that pain information flows in two directions: 1) nociceptive signals from peripheral tissue ascend through the spinal cord to higher centers; and 2) central centers can modulate, using descending signals altering spinal

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cord neurotransmitter and interneuron activity, the transmission of these nociceptive signals from the periphery. Deterioration of these regulatory processes were thought to potentially account for development of chronic pain states by allowing too many peripheral signals to pass through the spinal cord “gates.” Variation in patients’ relative degree of gate opening could thus explain why similar amounts of physical tissue damage result in different degrees of pain perception.6 While these theory changes were stimulating the field of pain research, gynecologists were busy developing laparoscopy and with it the hope that treating visible pathology could fix chronic pelvic pain. A focus on “laparoscopy-negative” patients in chronic pelvic pain clinics emerged, implying that if some pathology were found, it must be a “real” cause for pain. Subsequent experience has shown that although treatment of laparoscopically diagnosed pathology can be helpful, the clinical reality is more complex: 1) in many instances, visible pathology found at laparoscopy may be incidental and not related to the pain; 2) in those with pathology that does contribute to nociception, the pain experienced by the patient may differ from another patient with anatomically similar pathology; and 3) pain from a laparoscopic finding is often best understood in the larger context of a centralized pain disorder. Research of the 1980s added the observation of distressingly high rates of physical and sexual abuse, especially in the chronic pelvic pain population. These observations led to the speculation that the experience of abuse may make a person more vulnerable to the development of chronic pelvic pain or perhaps be a specific cause for pain. In relation to pain, abuse, particularly that which occurs in formative years, may serve to alter the response to nociception and central pain processing. That said, not all abused patients go on to have chronic pain nor do all patients with pain have a history of abuse, so it might be the response to trauma that plays a key role in development of chronic pain. Health care providers need to take into account the presence of abuse in a patient’s history when detected but be careful to avoid necessarily concluding a causal relationship in that patient’s pain. Melzack’s neuromatrix theory7 added the pivotal notion of neuroplasticity, which suggests that experience can change the neurophysiologic behavior of the central nervous system in a manner that influences the subsequent processing of nociceptive stimuli. It may explain the apparent development of pain responses to stimuli usually thought of as nonpainful (allodynia) as well as exaggerated responses to painful stimuli (hyperalgesia). Every practicing gynecologist has seen

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patients whose pain responses seem out of proportion to the pathology found. This may reflect the emotional meaning of the problem for the patient as well as past or present trauma, but it may also be the result of sensitization of spinal cord interneurons that have become pain amplifiers as a result of being on the receiving end of peripheral nociceptive stimuli for prolonged periods. On the positive side, neuroplasticity suggests that given enough time and the right treatment, even seemingly intractable chronic pain problems can improve substantially. The concept of central sensitization adds the most recent layer to theoretical understanding of chronic pain: the notion that multiple repetitions of lower-level stimuli may over time result in a more severe central perception of pain. This centralized pain hypersensitivity helps us understand how multiple organ systems can be recruited into the syndrome, incorporating genetic and social factors in pain amplification. Whatever the nociceptive stimulus (bowel, bladder, muscle, uterus), it can register as pain at a lower threshold in the patient with a centralized pain disorder (Box 1). Box 1. Definitions of Pain Terms Allodynia—pain resulting from a nonnoxious stimulus Hyperalgesia—painful sensation of abnormal severity after noxious stimulation Neuropathic pain—pain persisting after healing of disease or trauma-induced tissue damage Neuroplasticity—the malleability of central pain perception mechanisms in response to chronic pain states Nociceptor—a nerve receptor for pain

This understanding contributes to the framework a clinician needs when taking a clinic history of pelvic pain and performing the physical examination. The inquiry should set out in pursuit of all the factors relevant to a person’s pain, not simply trying to identify one factor with an acceptably plausible relationship to her complaints. Once the patient is aware that the clinician is keeping an open mind about multiple contributing factors, she may become less defensive about any inquiries in emotional areas.

EVALUATION OF PATIENTS WITH CHRONIC PELVIC PAIN History-Taking The site, duration, pattern during activities, relation to position changes, and association with bodily functions are all important elements of pain. For example, pain that is absent in the morning but worsens

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progressively during the day may be associated with pelvic floor muscle dysfunction, whereas a tender “spot” of dyspareunia might be related to nodular cul de sac endometriosis. A previous review supplies a very detailed description of both history-taking and physical examination techniques that are useful in the evaluation of chronic pelvic pain.8 We focus here on the most frequently useful elements of this process. The chronology of a patient’s pain is critical. As a pain syndrome develops, pain can be present over a progressively larger area despite stable detectable pathology. Interpreting this as the breakdown or wearing out of physiologic systems that deal with pain signals has some biologic validity and may make sense to the patient. The clinician may need to counter the idea patients sometimes have that endometriosis “flares” like rheumatoid disease or spreads like a malignancy. From a cognitive perspective, it is invaluable to discern the patient’s and her family’s ideas about the causes of and future for her pain. Fears of cancer can be discovered even if this diagnosis was never even remotely considered by the clinician. Less dramatic but equally powerful attributions of cause can emerge such as pelvic infection that is the result of sexual acts remote in time, arguments with a spouse, divine retribution, and so forth. When a patient has been under that care of previous health care providers, it is important to review the effects of previous treatments and the evolution of how the patient has thought about her own disease. For example, when a prior treatment for mild endometriosis was only briefly successful, did she (and her health care provider?) see this as evidence for increasing severity of disease or did it make them question the diagnosis in the first place? In a referral-based practice, it is a frequent event to deal with a patient with mild disease who has not responded to any of four or five medical or surgical measures that would ordinarily improve symptoms. She then sees herself as having increasing and invasive disease, prompting even more aggressive treatment, rather than wondering if something else is contributing to her pain.

Physical Examination The physical examination begins with observing the patient’s gait, comfort with sitting, ease of going from sitting to standing, and from sitting on the table to lying down. Dysfunctions of the pelvic floor and hip muscles may be manifested by discomfort with these motions. For example, if the patient sits up on one buttock during the interview, one might suspect pelvic floor muscle pain.

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With the patient sitting on the examination table, it can be helpful to begin the examination with the back, evaluating for tenderness of the spine, paraspinous muscles, and sacroiliac joints. This may identify pain generators and sites for therapeutic intervention, but it also allows for touch to begin in a very nonthreatening way. Gynecologic assessment is uncomfortable to some degree for almost all women, but the patient with chronic pelvic pain is particularly vulnerable. Moving from back to abdomen to pelvis can establish trust and reduce fear. The patient is then asked to recline on the table, observing how comfortably she can do this. The abdominal wall is examined with and without flexed rectus muscles. A positive Carnett sign (increased tenderness when palpation is done in the presence of abdominal wall flexion) implies at least a contribution to the pain from abdominal wall myofascial sources. Decreased pain during this maneuver implies a higher contribution from visceral sources. On occasion, gentle fingertip palpation of the abdominal wall can detect such trigger points in the musculature. Rarely, a subcutaneous abdominal wall endometrioma is discovered, a diagnosis supported by a history of predictable, cyclic, focal tenderness. An abdominal wall endometrioma, or a hernia, is often more readily appreciated by examining the patient in the standing position. Pelvic examination then begins with external review of the vulva and vestibule. Gentle palpation with a cotton swab can detect areas of sensitivity consistent with vulvar vestibular syndrome in the introitus or trigger points higher in the vagina. Intrinsic cervical allodynia (from cervical conization or after obstetric cervical laceration) may be detected in the same manner with gentle cotton-tipped applicator palpation. Guiding a patient through contraction–relaxation sequences of the abdominal, thigh, and vaginal introital muscles can reduce the discomfort of the examination and can indicate the patient’s degree of control over muscle tension. Single-digit palpation of the levator plate, piriformis, and obturator muscles can elicit the tenderness of pelvic floor tension myalgia. This condition can present as a sequel to some other pelvic pain or a problem in itself. Discomfort is usually felt as pelvic pressure and radiation pain to the sacrum, near the insertions of the levator plate muscles. The exact sequence of the examination should be adjusted in view of the information obtained during the history: examine the areas less likely to be tender first, saving the more tender areas for the end. Palpating the most tender areas first can elevate anxiety and distort pain responses from subsequent areas.

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Single-digit palpation should also be used to discover areas of tenderness in the cervix, uterus, adnexa, bladder, and urethra. Premature addition of the abdominal hand to the examination adds in nociceptive signals from abdominal wall myofascial components that may lead the examiner to overattribute pain to the viscera. Finally, the abdominal hand is added to assess size, shape, and mobility of pelvic structures. Adnexal thickening and mobility, pelvic relaxation, coccygeal tenderness, and foci of pain that reproduce dyspareunia should be noted. A rectovaginal examination is important when deep infiltrating endometriosis is suspected. During all components of the physical examination, it is important to not only ask the question “Does this hurt?,” but also “Do you feel pain where I am pressing or somewhere else?” and “Is this the pain you were describing earlier—is this your pain?” If a patient answers affirmatively to the final question, it can be helpful to point out what structure you are palpating (eg, pelvic floor muscle compared with ovary). As you are going along through the examination, it can be useful to mention the items you are adding to the list of possible contributing factors to her pain, thus reinforcing what you discussed during the history in terms of pain being multifactorial. Having concluded the most important part of the evaluation, the history and physical, you are now prepared to discuss diagnostic possibilities and a treatment plan. What follows is a review of the commonly described contributors to pelvic pain, which might be part of that discussion.

CONTRIBUTIONS OF PERIPHERAL PAIN GENERATORS This section deserves an important caveat. Although we believe that types of tissue damage or other nociceptive input can generate pain, they cannot be viewed in isolation of the patient’s individual central pain processing. Management strategies are discussed in more detail, but, in general, the goal of the treating health care provider involves trying to dampen overall pain signaling sensitivity—“turning down the master volume”—and looking for areas in the periphery that can be “tuned up” toward better functioning. This effort is more likely to be successful in the patient who takes an active role in her own improvement and avoids seeing herself as helpless in the face of her discomforts.9 The following peripheral generators represent areas where we can intervene but should not be described to patients with chronic pelvic pain as the only cause of their pain. Because these conditions can be completely asymptomatic in many patients, their importance needs

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interpretation in the context of her overall health, taking into account her other pain disorders and general capacity for dealing with life’s challenges.

Endometriosis Evidence that endometriosis causes pain results from observations that the disease is more commonly encountered in women undergoing laparoscopy for pain than for other reasons10 and that laparoscopic treatment results in better pain reduction than diagnostic surgery alone.11–13 However, amount of disease does not correlate with symptom severity14,15; endometriosis is a frequently encountered incidental finding, and peritoneal implants do not localize to symptom location.16 A variety of proposed mechanisms explaining pain associated with endometriosis exist, including inflammatory, nociceptive, and neuropathic.17 There is no pathognomonic symptom associated with endometriosis, however. Many of the symptoms often attributed to endometriosis (eg, dyspareunia, dysmenorrhea, abnormal bowel or bladder function) are commonly found in functional disorders such as irritable bowel syndrome or interstitial cystitis, making it difficult to understand the relevant contribution of endometriosis to chronic pelvic pain. Deeply infiltrating endometriosis—fibrotic, vascular, desmoplastic tissue destruction— is a biologically different disease, in which detectable physical examination or imaging findings relate to specific symptoms such as tender rectovaginal nodularity or ovarian endometrioma with dyspareunia or dyschezia with intrinsic rectal involvement.18–20 The relationship of a related condition, adenomyosis, to pelvic pain is less established, but the disease should be considered, especially when symptoms include dysmenorrhea or heavy bleeding.21

Pelvic Adhesions Early reviews supported the role of adhesions as a significant contributor in chronic pelvic pain.10,22 More recent investigations23 demonstrate a relatively weak correlation between adhesions and chronic pelvic pain, much less than other factors such as psychosomatic symptoms and substance abuse. Few, if any, well-designed studies demonstrate effective treatment of chronic pelvic pain with adhesiolysis. Unfortunately, in an effort to provide some explanation for complex pain disorders, health care providers often still posit adhesions as an etiology, even when a patient’s surgical history includes only laparoscopy with findings of minimal or no endometriosis, pelvic inflammatory disease, or other conditions associated with meaningful adhesions. This explanation can happen even when the patient’s pain escalation is remote from her last surgery.

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Adhesions may play some role in pain conditions in some women, but the relative contribution is probably small. Also, the putative treatment—repeat surgical intervention—can add new contributions to pain syndromes such as the effect of surgical trauma, disappointment from lack of pain relief, feeding the psychological need of being “ill” with more surgery, and, in the worst case, generating a complication such as enterotomy.

Pain from the ovary can be increased by confinement within postoperative adhesions, rupture or leakage of a cyst prompting additional adhesion formation, or attachment of the ovary to the sigmoid colon or vaginal apex by postoperative adhesions. In the case of attachment to the vaginal apex, deep dyspareunia can result when the area is struck.

Pelvic Support

A more difficult situation can develop if a small fragment of ovarian tissue is left behind during attempted oophorectomy.35 In most instances, this happens when challenging dissection is required, such as cases of extensive pelvic adhesions or deeply infiltrating endometriosis. Within 1–3 years of the attempted oophorectomy, continued follicle-stimulating hormone stimulation will result in growth of the ovarian fragment, often producing an intermittently symptomatic pelvic mass located along the course of the ovarian vascular supply. A postulated mechanism for pain generation includes the cystic enlargement of the mass confined within fibrotic adhesions. If the remnant developed because endometriosis made for difficult oophorectomy, that disease is often found in the remnant and probably also serves as a pain generator. Classic remnant symptoms include absence of vasomotor symptoms after ostensible bilateral oophorectomy and the presence of cyclic unilateral pain. Like in the case of the residual ovary, the remnant can produce dyspareunia if it is located close to the vaginal apex. When performing oophorectomy, it is best to open the pararectal space and completely skeletonize the infundibulopelvic ligament not only to avoid complications such as ureteral injury, but also to prevent ovarian remnant syndrome. In difficult cases, dividing the pedicle at or above the pelvic brim, like in riskreduction prophylactic oophorectomy, is prudent.

Most women in pain clinics are in their third or fourth decade of life, whereas pelvic organ prolapse affects significantly older women, suggesting a very minimal role for support problems in chronic pelvic pain. Pelvic relaxation usually leads to reports of heaviness, pressure, dropping sensations, or aching. In attempting to hold in prolapsing organs, the patient may tense the levator plate, leading to tenderness during daily activities and intercourse. Fear of (or actual) loss of urinary control during coitus can add to the discomfort by impairing physiologic sexual response. The retroverted uterus is another potential contributor to chronic pelvic pain, particularly in the form of deep dyspareunia. Clearly for many women, retroversion is an innocent anatomic variant, but for those with pain, uncontrolled clinical series of uterine suspension procedures suggest changing the position of the uterus to an axial or anteverted position can improve dyspareunia by elevating the fundus out of the posterior cul de sac24–26 and allowing for better vaginal expansion as a natural part of the sexual response cycle.27

Pelvic Congestion Overfilling (congestion) of the pelvic venous system has been implicated as a cause of dull chronic aching pain that usually is bilateral, worse at the end of the day after prolonged standing, premenstrually, and postcoitally. Some studies suggest the condition is present in nearly one-third of women with chronic pelvic pain,28 but there is no agreed-on reference standard for diagnosis despite individual technical regimens involving venography, magnetic resonance, and ultrasonography.29 Hormonal suppression,30,31 percutaneous embolotherapy, and surgery (vein ligation, hysterectomy and salpingo-oophorectomy) represent available treatments,32 but study protocols involving these interventions are diverse and few have been investigated in controlled trials.33

Residual Ovary When the uterus has been removed, with or without removal of one ovary, the remaining ovary or ovaries become symptomatic in a small percentage of women.34

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Ovarian Remnant

Vaginal Apex Pain After hysterectomy, pain may persist or recur because of intrinsic sensitivity of the vaginal apex. Although the cuff may appear to have healed perfectly well, gentle examination with a cotton-tipped applicator may reveal focal sensitivity of a moderate to severe degree, many times located in one lateral fornix or the other and often replicating the reported pain of dyspareunia. When the cotton applicator examination is not done, the unaware examiner may then, noting pain on traditional bimanual examination, mistakenly conclude that the source of nociception lies cephalad, for example, in a remaining ovary, pelvic scarring, or bowel adhesions. The diagnosis may be confirmed by noting elimination of the pain after injection of a local

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anesthetic. The condition is generally considered neuropathic by virtue of the character of the pain (burning, stinging, sharp) and that neuropathic treatments (overnight application of lidocaine, oral medications such as nortriptyline, amitriptyline, gabapentin, etc) seem to benefit some patients. Laparoscopic revision of the vaginal cuff may give good initial relief in approximately two-thirds of patients, but pain tends to recur to a degree over the subsequent 2–3 years, although perhaps at a less intense level.36,37

Musculoskeletal Problems Musculoskeletal changes can become involved with chronic pelvic pain, either as the primary problem or as a secondary reaction to the pelvic pain. The muscular problem that most often produces pelvic pain is pelvic floor tension myalgia (also called levator spasm or levator ani syndrome).38 The clinical symptom profile commonly includes pain with sitting flat on a chair, worsening pelvic pressure over the course of the day, and midvaginal dyspareunia. Intermittent or constant painful contraction of the levator plate can be present as a primary problem or a reaction to some other source of pain. The patient with levator pain will often sit up on one buttock during the interview and will report that pelvic floor soreness persisted for 1–2 days after palpation of the muscles during pelvic examination. The piriformis and obturator muscles warrant further emphasis because they are seldom appreciated as possible sources of pain. These muscles are external rotators of the leg, and rotation against resistance can allow detection of tender spasm of the muscles during the pelvic examination. The sciatic nerve can traverse the belly of the piriformis as a normal anatomic variant, producing symptoms similar to sciatica when the muscle is in spasm. Pain caused by the iliopsoas complex can manifest as anterior hip or groin pain and is diagnosed with passive or active extension at the hip. The mainstay of treatment of muscular components of pelvic pain is physical therapy, most commonly performed by a therapist with specialized training in the treatment of female pelvic pain. This subspecialty of the field has grown enormously over the past 15 years in obvious response to growing recognition of muscular elements to pelvic pain and in recognition that it works.39 Most physical therapists specializing in women’s care will address pelvic floor and hip muscles issues with transvaginal muscle treatments as well as other treatment measures. Other measures that are sometimes helpful are self-directed pelvic floor contraction and relaxation exercises, muscle relaxants, vaginal valium, and Botox injections. When the problem is severe enough to require these

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measures, it is generally advised that they be used along with simultaneous physical therapy.

Medical Comorbidity Peripheral pain generation in chronic pelvic pain often involves nongynecologic systems.40,41 A careful history and close physical examination of gastrointestinal, urologic, musculoskeletal, and neurologic systems are needed to evaluate these additional contributions to chronic pelvic pain. Most of the available literature examines these problems independently of each other and without reference to their relevance to chronic pelvic pain or to the overall prevalence of these disorders in chronic pelvic pain. The gastrointestinal system is the most common nongynecologic contributor to chronic pelvic pain, typically manifesting as irritable bowel syndrome. Perhaps second in terms of prevalence, functional urinary problems (ie, interstitial cystitis) are another common comorbid contributor in chronic pelvic pain. These as well as others such as migraine, temporomandibular joint disorder, and fibromyalgia should be viewed in the context of a larger centralized pain problem and treatment should be symptom-specific. Psychological comorbidity also travels with chronic pelvic pain. Depression, anxiety, anger–hostility, somatization, and catastrophization9 (the belief that things are as bad as they can be and are not likely to improve) are all more common among women with chronic pain than in women in a control group.42,43 Whether mood disorder is a predisposing factor to, or a result of, chronic pain is not clear and may differ from patient to patient, but the situation is symbiotic at a minimum. Many women with chronic pelvic pain fear physicians’ recognition of mood disorder leads to the conclusion that their pain problem is not “real” or “in her head.” Thus, from a treatment perspective, it makes sense to attend to each disorder to the degree it manifests, but not necessarily attempt to discern causality in a gynecologic visit. Studies vary in describing the prevalence of sexual abuse,44,45 but regardless, it is difficult to judge whether these events are directly relevant to present pain and hence demand attention or whether they contribute to a psychologically vulnerable substrate influenced by subsequent physical and emotional events. In these circumstances, it may be worthwhile to suggest further mental health evaluation as an exploratory measure, being careful not to imply that the patient is being referred because the physician is certain that the abuse is related to the development of the pain. Lastly, marital distress and sexual dysfunction, particularly dyspareunia, are common further

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burdens for patients with pain. Although some women report satisfactory sexual functioning before the onset of pain symptoms, others appear to have long-standing impairments in sexual response. In our experience, sexual difficulties are often the problem that makes a person seek (or is encouraged by her partner to seek) help for her pain.

DIAGNOSTIC STRATEGIES Recognizing a Chronic Pain Syndrome Many women can experience pain for longer than 6 months without becoming debilitated. Although their pain is chronic, such women are not described as having a chronic pain syndrome. The following are the common clinical hallmarks of this syndrome46: 1) duration of 6 months or longer, 2) incomplete relief by most previous treatments, 3) significantly impaired physical function at home or at work, 4) signs of depression (sleep disturbance, weight loss, loss of appetite), 5) hypersensitive response to nociceptive stimuli, and 6) altered family roles. Of the signs of depression, sleep disturbance is usually the first to appear. Careful questioning is needed to distinguish awakening caused by pain from awakening that just happens. In the true vegetative sign, the person usually cannot get back to sleep even if pain is relieved (by medication or other means). The alteration of family roles is perhaps the most important of those mentioned. This includes changed responsibilities for household, children, finances, and so forth. Initially intended as helpful, such changes may eventually diminish the patient’s self-esteem and progressively reduce her family’s interactions with her to little more than checking on her pain. Over time, this covertly reinforces the symptom of pain and imparts to it unintended value as a major means of maintaining communication within the family.

Imaging Studies If the physical examination is relatively benign and is not severely limited by body habitus, extensive imaging usually adds little to the database needed before laparoscopy is performed. This is especially true in the case of organ-specific studies (intravenous pyelography, barium enema, colonoscopy) in the absence of symptoms or signs pointing to an explicit organ problem (eg, blood in the stools). Intervening for chronic pelvic pain on the basis of an imaging study finding alone is unlikely to be fruitful. On the other hand, with a specific question in mind—for example, pelvic ultrasonography to confirm ovarian endometrioma, magnetic resonance imaging when adenomyosis is suspected, or lower endoscopic ultrasonography to rule

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out invasive rectal endometriosis—imaging can be quite helpful.

Laboratory Studies Relatively few hematologic or chemical measures are useful in diagnosing chronic pelvic pain. An elevated leukocyte count and erythrocyte sedimentation rate may make the clinician suspect chronic pelvic inflammatory disease even when cervical probes are negative for the most common sexually transmitted infections. Serum CA-125 can confirm suspicions of deeply infiltrating endometriosis in those without prior surgical evaluation but is not sufficiently sensitive to detect early-stage disease. In those with advanced endometriosis, the anti-Müllerian hormone level, a measure of ovarian reserve, can help fertility counseling in a woman considering extirpative surgical treatment for her disease. In those status postbilateral oophorectomy with remnant ovarian tissue, folliclestimulating hormone and estradiol levels remain in premenopausal ranges. Women using replacement estrogen therapy should stop 3 weeks before these levels are measured.

Anesthetic Blocks Injection of small volumes of a local anesthetic, 1–5 mL of 1% lidocaine or 0.25–0.5% bupivacaine, blocks pain from either an entrapped segmental nerve (eg, ilioinguinal) or an abdominal wall trigger point. Such blocks can be therapeutic as well as diagnostic. Many anesthesia pain clinics administer epidural or spinal anesthetics to distinguish pain arising from peripheral organs from pain that has become completely central in origin. In some instances, it is useful to attempt diagnostic and therapeutic transvaginal blocks with the same local anesthetics for vaginal apex pain, as discussed previously. A series of three or four blocks administered 1–2 weeks apart may provide durable relief in some instances.

Psychologic Tests and Interviews In the attempt to distinguish physical from psychological contributions to pain, many studies of chronic pelvic pain have used traditional psychological instruments that were developed to measure general psychopathology or personality factors. These psychometric instruments generally have uncertain face value for patients with chronic pain, and their use can support the patient’s fears that the health care provider thinks her pain is imagined. Psychometric tests are most useful when they are interpreted by a psychologist who has interviewed the patient, and they

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serve best as a means to better understand the patient’s strengths and weaknesses rather than as a means to decide who has “organic” compared with “psychological” pathology or who needs surgery. The newer specialty of pain psychology holds promise in assisting women dealing with chronic pelvic pain to better focus on the positives in their lives and encourages them to take an active role in dealing with their pain.

Laparoscopy Great strides have been made in operative laparoscopy in the past three decades. Laparoscopy can be useful diagnostically and therapeutically (even in the face of negative findings), but when a chronic pain syndrome is clinically evident, results of laparoscopic treatment alone, despite comparable pathology, are much less impressive. For a patient with the clinical markers of chronic pain syndrome listed earlier, a complete workup should be performed before laparoscopy. In some puzzling cases, laparoscopy under local anesthesia can be used to “pain map” the pelvis.47 A 2mm laparoscope and a small suprapubic probe are placed with the use of short-acting, reversible intravenous analgesia (eg, remifentanil) and local anesthetic. Having been oriented to the procedure beforehand, as each organ is touched, the patient is asked if the site is painful, to rate it on an ordinal scale from 1 to 10, and if the discomfort represents her pain. It is possible in some cases to block the superior hypogastric plexus during pain mapping to better predict benefit from presacral neurectomy.48 In this approach, mapping is done before and after injecting 10 mL of 1% lidocaine just underneath the peritoneum over the sacrum using a 7-inch, 22-gauge spinal needle. Limiting patient characteristics for using pain mapping include high states of anxiety and obesity, in which the torque required to move an instrument against a thick abdominal wall can provide a distracting nociceptive stimulus. Once thought to be the “holy grail” of chronic pelvic pain diagnostics, better understanding of the central mechanisms of chronic pain and the relationship among various named pain disorders has led to diminished use of laparoscopic pain mapping in routine practice. The enthusiasm for laparoscopy has its negative aspects as well. When pain recurs after the first laparoscopic treatment of endometriosis, for example, many patients and their gynecologists will automatically assume that this is the result of a return of their disease. The surgeon must also consider the possibility that the improvement seen after the first laparoscopy was a nonspecific effect of the surgery and that, in fact, the “disease” seen and treated was not actually

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relevant to the pain. The second laparoscopy, in perhaps the majority of circumstances, reveals less disease than was present at the first surgery.49 This would suggest that the pain is multifactorial and that over time, in many cases, the relative importance of the endometriosis may diminish. Ironically, in most practices, medical and surgical treatment is nevertheless escalated in such situations. We would recommend instead starting all over again, making no assumption ahead of time that the endometriosis is playing a role at all.

MANAGEMENT Relatively straightforward pain problems are not challenging to manage such as treating isolated dysmenorrhea with hormonal suppression or a chronic tubo-ovarian abscess with adnexectomy. More often, however, chronic pelvic pain represents a complex and nuanced syndrome in which treatment may vary considerably depending on the patient. When pain itself is the disease, the goal of treatment is not necessarily complete eradication of pain, but rather finding strategies that afford more functional living. Neuromodulatory medications (eg, tricyclic antidepressants, neurotransmitter reuptake inhibitors, neuroleptics), psychological adjuncts (eg, cognitive–behavioral therapy, pain psychotherapy, sexual counseling), and complementary strategies (eg, mindfulness-based medication, yoga, acupuncture) can be useful to dampen central hypersensitivity. For the peripheral elements, physical therapy, diet modification, peripheral nerve blocks, and surgery can be helpful depending on the target pain generator. In all cases, good sleep hygiene, exercise, smoking cessation, healthy eating, and social support are important foundational elements that improve the effectiveness of chronic pelvic pain treatment.

Medication Use Analgesics Analgesics such as nonsteroidal anti-inflammatory drugs and opioid narcotics can be quite effective for acute conditions, but their use in chronic pain is marred by a host of adverse outcomes and limited efficacy associated with long-term use. Dose-related effects of medications such as acetaminophen (liver toxicity) and cyclooxygenase inhibitors (gastric and renal damage) are well known, but they are not major offenders in the realm of tolerance and withdrawal. Opioid narcotics, on the other hand, are notoriously dangerous in regard to these consequences in addition to problems such as narcotic bowel syndrome and opioid-induced hyperalgesia. Some patients benefit from structured narcotic therapy, but, if they are to be

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used for chronic pelvic pain, clinicians should screen carefully for factors associated with high risk for misuse50,51 and set nonnegotiable ground rules such as limiting prescriptions to one health care provider, not entertaining requests for early refills, mandating scheduled urine drug screens, and refraining from uncontrolled dose escalation. Newer opioid medications such as oxymorphone and tapentadol are considered less euphoria-generating than the more

commonly used narcotics such as hydrocodone, oxycodone, and hydromorphone (Table 1). Antidepressants and Neuroleptics These classes of drugs are commonly used in the treatment of chronic pain, including chronic pelvic pain, although few controlled trials have been carried out specifically in this population. Although no longer first line for mood disorders, tricyclic

Table 1. Narcotics Used in Pain Management Drug

Dosing

Hydrocodone bitartrate with acetaminophen

5–10 mg hydrocodone either every 6 or every 8 h

Lortab 2.5/500, 5/500, or 7.5/500 Vicodin 5/750 Lorcet 10/650 Lorcet Plus 7.5/650 Oxycodone hydrochloride Percocet 5/325

1 tablet every 6 or every 8 h Additional acetaminophen between doses 10–40 mg every 12 h 2.5 mg every 8 h to 10 mg every 6 h

Dolphine 5 or 10 mg scored tablets Acetaminophen with codeine

Ultram Tapentadol

Common effects

Common effects Common effects, lower extremity edema or joint swelling may occur and require discontinuation, concurrent use of desipramine may increase methadone blood level, cautious use in patients on monoamine oxidase inhibitors

Commonly 15–20 mg per day total 1–2 tablets every 6–8 h

Tylenol #3: 300 mg acetaminophen with 30 mg codeine Morphine sulfate 15–60 mg every 12 h (controlledrelease tablets) MS Contin Oramorph Avinza Fentanyl transdermal system 25-microgram patch, 1 every 72 h

Actiq Fentora Tramadol

Lightheadedness, dizziness, sedation, nausea and vomiting, constipation (these are common side effects of all narcotics)

Can use additional acetaminophen between doses

Oxycodone controlled release Oxycontin Methadone hydrochloride

Duragesic

Side Effects

Common effects, constipation very likely, nausea and vomiting more common than with other narcotics, more common allergy—rash

Common effects, higher doses increase risk of respiratory depression

Common effects, patch must be kept from heat sources or dose may be increased, extreme caution in patients on other central nervous system medications, respiratory depression can result

Also available in 50 or 75 micrograms Always start with lowest dose 50 mg every 6–8 h

Common adverse effects, less gastrointestinal, less euphoric effects

50 mg every 6–8 h; 50–100 mg daily for extended release

Nucynta, Nucynta ER

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antidepressants such as amitriptyline, nortriptyline, and desipramine have a long record of being effective in treating chronic pain.52 Newer-generation neurotransmitter reuptake inhibitors such as duloxetine and desvenlafaxine can also be useful. Neuroleptics such as gabapentin, pregabalin, and lamotrigine are generally used when symptoms are more specifically neuropathic in nature. It is important to discuss with patients that, although they tend to diminish with continued use, all of these medications have central side effects, some of which are predictable and others quite idiosyncratic. When higher doses or multiple agents are used, it can be helpful to consult with a psychiatrist or psychopharmacologist to avoid complications such as severe mood dysregulation or serotonin syndrome (Table 2). Anxiolytics Anxiolytic drugs are certainly widely prescribed by gynecologists, although it is uncertain how often they are given for pain. In one study, alprazolam had a surprising degree of analgesic effect in moderate-tohigh doses in patients with chronic pain of malignant origin and concomitant mood changes or anxiety.53 These patients were already receiving narcotics, which may suggest that alprazolam potentiates the analgesic effect of narcotics. Their role in conjunction

with nonnarcotic analgesics is uncertain, and the addiction potential is obvious. Hormonal Medications Combined oral contraceptives are effective in reducing dysmenorrhea and cyclic symptoms associated with endometriosis. It is not uncommon, however, to meet resistance to using these medications in women with chronic pelvic pain—either because they were previously used and did not cure the entirety of the pain syndrome and were thus deemed ineffective or because of sensitivity to side effects such as nausea, an understandable consequence in a viscerally hypersensitive group. Avoiding ultralow-dose 20-microgram ethinyl estradiol formulations can help reduce unscheduled bleeding, important for women who may closely associate bleeding with pain. Outside of deeply infiltrating endometriosis, progestin-only formulations, by enteral or parenteral route, run the risk of exacerbating depressive symptoms in a vulnerable population. A notable exception includes the levonorgestrel intrauterine system, which has little systemic absorption and can control dysmenorrhea and pain from endometriosis in a low-risk, reversible, long-acting manner. The use of gonadotropin-releasing hormone agonists deserves special mention. They have been recommended to distinguish gynecologic from

Table 2. Antidepressants and Neuroleptics Used in Pain Management Medication Class

Dosing

Tricyclic antidepressants

Amitriptyline Nortriptyline Desipramine

Tricyclics commonly cause sedation, dry mouth, weight gain, constipation; this can be exploited for urinary frequency problems; nortriptyline or desipramine used more frequently when patients have constipation, generally administer at night Start 10–25 mg nightly, titrate to 75–150 mg Start 25 mg nightly, titrate to 50–150 mg Start 25 mg nightly, titrate to 50–150 mg

Serotonin–norepinephrine reuptake inhibitors

Duloxetine Desvenlafaxine Gamma-aminobutyric acid analogues Gabapentin Pregabalin

Consideration, Side Effects

Most common side effects are nausea and central nervous effects such as lethargy and dizziness, provide warning signs of serotonin syndrome for patients on other serotonergic drugs and do not stop abruptly Start 30 mg daily, titrate to 60, occasionally 90 mg 50–100 mg daily No major drug interactions, reduce central nervous effects by slow titration (for example, over 4 wk); do not stop abruptly 100–300 mg divided 3 times daily 75 mg twice daily

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nongynecologic sources of pain based on interpretation of some data,54 but pain relief after gonadotropinreleasing hormone treatment does not make a gynecologic (including endometriosis) diagnosis. In that study, patients without endometriosis improved with the same the frequency as those with the disease, and these agents also relieve symptoms of other functional conditions such as irritable bowel syndrome. Furthermore, pain thresholds have been shown to be lower premenstrually, even in women without chronic pelvic pain. The effect of the menstrual cycle itself in patients with chronic pain has not been well-explored, but it seems likely that it may impart some cyclicity even to conditions unrelated to the reproductive tract. Cyclicity of symptoms must therefore be interpreted with caution, and the disappearance of symptoms or of their cyclicity by pharmacologically obliterating the menstrual cycle does not demonstrate a gynecologic cause. Gonadotropin-releasing hormone agonists can be useful when differential diagnosis includes ovarian remnant syndrome or residual ovary syndrome or in the treatment of deeply infiltrating endometriosis, but its use in treating general chronic pelvic pain is limited by cost and morbidity. Contrary to popular belief, gonadotropin-releasing hormone agonists are not more effective than other more benign hormonal manipulations directed at pelvic pain.55–57 For deeply infiltrating endometriosis, aromatase inhibitors with norethindrone may work similarly without as significant hypoestrogenic effects.58,59

Surgery Two basic surgical approaches have been used to treat chronic pelvic pain: removing pelvic organs and treating visible disease while leaving the pelvic organs in place. The use of both approaches is guided by clinical experience, because high-quality scientific data regarding the role of surgery in pelvic pain are sparse. Expansion of literature on the topic, including stratification for characteristics that lead to strong or poor response, would be most welcome. In the United States, approximately 12% of hysterectomies are performed with pelvic pain as the primary indication.60,61 Although hysterectomy should not be viewed as a final curative step in an algorithm for treating chronic pelvic pain in general, it can be quite helpful for central uterine pain, dyspareunia associated with fundal tenderness, dysmenorrhea, abnormal bleeding, and cyclic symptoms. Quality of life, with particular attention to the effect of pain and depression on outcomes, was studied using data from the Maryland Women’s Health Study, in which 1,249 women were evaluated at several-month intervals up to

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2 years after hysterectomy. Not surprisingly, women without pain or depression had the highest functional levels, but even among women with pain and depression, pelvic pain decreased from 97% to 19%, and there was a reduction by half in limited physical and social function. Women with depression only had improvement in impaired mental health (85% down to 33%) and dyspareunia decreased in all groups.62 Another study suggests hysterectomy done for various conditions, including pelvic pain, outperforms medical or uterus-preserving surgical treatment on quality-of-life measures.63 Furthermore, the majority of hysterectomies in these studies were performed using laparotomy. Newer randomized controlled trial data suggest improved quality of life laparoscopic over abdominal hysterectomy durable to 4 years out from surgery.64 When considering hysterectomy in the treatment of chronic pelvic pain, it is essential to discuss with patients which pain symptoms are likely to improve after surgery and that some may remain. Just because hysterectomy does not fix every problem does not exclude it from being a helpful aspect of treatment provided attention is still provided to centralized pain disorders and symptoms linked to other organ systems. Although many patients and health care providers still consider endometriosis nearly synonymous with pelvic pain, as discussed previously, the relationship is probably more tenuous than previously thought. Laparoscopic treatment, even of mild disease, however, does provide pain relief.10–13 Some studies suggest superiority of excision to ablation of endometriosis implants, and this approach probably makes good clinical sense, but there is insufficient evidence to conclude one is definitively superior to the other in pain reduction.65,66 Specific symptom improvement after deeply infiltrating endometriosis (gastrointestinal, urologic, cul de sac) resection is best documented in the literature.67,68 Given the complexity of these operations and the potential for harm to adjacent vital structures, advanced endometriosis resection should be performed by experienced surgeons. The benefits of surgical excision may be prolonged by subsequent medical therapy. Numerous studies have been done of postsurgical treatment with hormonal medications. Oral contraceptive pills, danazol, progestins, aromatase inhibitors, and gonadotropin-releasing hormone agonists (with and without add-back estrogen and progestin) have all been shown to be effective.69–74 Although gonadotropinreleasing hormone agonists have become perhaps the most widely used of these, definitive evidence for their superiority is lacking. The more economical and less physiologically intrusive approach would seem to favor sex steroids over gonadotropin-releasing hormone

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agonists. Most troublesome in reviewing all of these studies is the observation that dyspareunia is the symptom that is most refractory to treatment, testifying to its multifactorial nature. Presacral neurectomy through surgical interruption of the superior hypogastric plexus has been described in clinical series as effective at treating central uterine pain, dysmenorrhea, and endometriosis.75,76 In the most rigorous study, Zullo et al4 investigated the question with a double-masked randomized trial and demonstrated a 20% difference in pain improvement when presacral neurectomy was added to endometriosis excision in women with a midline component to their pain. When considering presacral neurectomy, patients must be counseled about risks of postoperative bowel and bladder dysfunction and should also be offered more conservative (eg, levonorgestrel intrauterine systemic) as well as more definitive (ie, hysterectomy) treatments. An ovarian remnant should be removed if it is persistently symptomatic despite attempts at medical suppression and if menopause cannot be expected in the patient’s near future. The dissection should be detailed and should include all the peritoneum surrounding the mass. The pararectal space, and paravesical space if needed, should be opened systematically and the ureter and pelvic sidewall vessels exposed and carefully freed from the specimen. Usually there is a vascular supply along the tract of the infundibulopelvic ligament, and it is prudent to divide the pedicle well above the pelvic brim. When a gonadotropin-releasing hormone agonist has been used preoperatively for symptom control or to distinguish the relative contributions made by the remnant and other pelvic pathology, the remnant tissue may become so small as to make it difficult to identify. Hence, if a palpable (or visible by imaging) mass disappears after gonadotropin-releasing hormone agonist treatment, it may be wise to allow time for it to regrow before pursuing surgical excision. When the remnant is small, some surgeons have stimulated the remnant with clomiphene citrate to make it easier to find.77

Alternative Treatments Psychological disorders should be treated in chronic pelvic pain, whether independently present or the result of a long-standing pain disorder. Some practitioners may find cognitive–behavioral or biofeedback therapy useful in reducing automatic responses to painful stimuli. Sexual counseling, couples counseling, and psychotherapy can be helpful adjuncts. Alternative strategies such as mindfulness-based meditation, yoga, and acupuncture may have roles in individual cases, but none is

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so clearly applicable or effective that its automatic use is supported in cases of chronic pelvic pain.

Management Overview The most effective clinical approach requires simultaneous treatment of as many factors as possible: anatomic, musculoskeletal, functional bowel and bladder, psychological, and so forth. The patient and physician must contract for the long term and work from a rehabilitation perspective rather than hope that the latest single addition to the treatment will prove to be the answer. The physician, to prevent frustration and feelings of defeat, must often play the role of helping to manage and relieve the pain while helping to maximize function, even when pain persists. To the surgically trained gynecologist who prefers a clear-cut single answer to a clinical problem, this can be the most difficult part of dealing with the problem of chronic pelvic pain. It is important to free oneself from the responsibility of needing to “fix” a patient’s chronic pelvic pain. Although the compassionate health care provider can be an invaluable aide, much of the work in improving from pelvic pain is the burden of the patient herself. REFERENCES 1. Chronic pelvic pain. ACOG Practice Bulletin No. 51. American College of Obstetricians and Gynecologists. Obstet Gynecol 2004;103:589–605. 2. Mathias SD, Kuppermann M, Liberman RF, Lipschutz RC, Steege JF. Chronic pelvic pain: prevalence, health-related quality of life, and economic correlates. Obstet Gynecol 1996;87:321–7. 3. Deguara CS, Pepas L, Davis C. Does minimally invasive surgery for endometriosis improve pelvic symptoms and quality of life? Curr Opin Obstet Gynecol 2012;24:241–4. 4. Zullo F, Palomba S, Zupi E, Russo T, Morelli M, Cappiello F, et al. Effectiveness of presacral neurectomy in women with severe dysmenorrhea caused by endometriosis who were treated with laparoscopic conservative surgery: a 1-year prospective randomized double-blind controlled trial. Am J Obstet Gynecol 2003;189:5–10. 5. Warren JW, Morozov V, Howard FM. Could chronic pelvic pain be a functional somatic syndrome? Am J Obstet Gynecol 2011;205:199.e1–5. 6. Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971–9. 7. Melzack R. Pain and the neuromatrix in the brain. J Dent Educ 2001;65:1378–82. 8. Howard FM. Chronic pelvic pain. Obstet Gynecol 2003;101: 594–611. 9. Martin CE, Johnson E, Wechter ME, Leserman J, Zolnoun DA. Catastrophizing: a predictor of persistent pain among women with endometriosis at 1 year. Hum Reprod 2011;26:3078–84. 10. Howard FM. The role of laparoscopy in chronic pelvic pain: promise and pitfalls. Obstet Gynecol Surv 1993;48:357–87. 11. Sutton CJ, Ewen SP, Whitelaw N, Haines P. Prospective, randomized, double-blind, controlled trial of laser laparoscopy in

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