There is no more noteworthy clinical dilemma in outpatient gynecology than the evaluation and management of chronic pelvic pain (CPP), a benign pain disorder with measurable impacts on health-related quality of life and health care utilization.1 Prevalence of CPP is estimated between 14% and 24% of reproductive-aged women.2 The American College of Obstetricians and Gynecologists defines CPP as “noncyclical pain of at least 6 months’ duration that appears in locations such as the pelvis, anterior abdominal wall, lower back, or buttocks, and that is serious enough to cause disability or lead to medical care.”3 A catch-all phrase, CPP is a nonspecific term that includes a wide range of diagnoses from pudendal neuralgia to painful bladder syndrome.
Despite the known economic and health care effect, CPP is often neglected by health care professionals due to lack of clear understanding of the condition and limited treatment options.4 The etiology of CPP is not fully understood but considered a complex network of physical and psychological symptoms without an agreed-upon algorithm in the diagnosis, evaluation or management.4 To further complicate the clinical presentation, CPP may be a symptom of underlying pathology of various organ systems, may coexist with other pathology, or may present alone. This review describes the currently available knowledge of CPP in women, important clinical features to improve management of symptoms, and identifies areas for further research.
CHRONIC OVERLAPPING PAIN CONDITIONS (COPC)
Underlying etiology of CPP can be one of, or a manifestation of urological, gastrointestinal, gynecologic, neurological, musculoskeletal and psychosocial conditions, but often has >1 contributory factor (Table 1). Sometimes only one of these system disorders is present and focused treatment is curative of the pain presentation. More often, the pain is believed to be caused by a single condition but it is secondary to a combination of disorders with overlapping symptoms. This clinical presentation clouds the diagnosis and may make it difficult to identify a specific cause in many cases.
There is increased recognition that many of the common pain conditions are intersecting disorders. Commonly referred to as COPC, they include temporomandibular disorder, fibromyalgia, irritable bowel syndrome (IBS), vulvodynia, chronic fatigue syndrome, interstitial cystitis/painful bladder syndrome, endometriosis, chronic tension-type headaches, migraine headaches, and chronic lower back pain. The prevalence of individual COPCs vary from 4 million (chronic fatigue syndrome) to 44 million (IBS).5 Peters et al6 evaluated 87 women who presented for care for interstitial cystitis/painful bladder syndrome. During the comprehensive evaluation, these women reported multiple comorbid pain conditions, 93% with pelvic pain, 70% with dyspareunia, 60% with vulvodynia, 49% with IBS, and 17% reported a diagnosis of fibromyalgia.6
COPCs vary significantly in clinical presentation making prevalence estimates of individuals who suffer from multiple conditions difficult, though COPCs are generally thought to be more prevalent in women.7 The strongest predictor of developing a new COPC is the presence of another chronic pain condition and this risk increases as the number of pain conditions a person has increases.7
VISCEROVISCERAL AND VISCEROSOMATIC CONVERGENCE
An in-depth understanding of the pelvic anatomy and unique innervation may explain some of the complexities of CPP. Close proximity of visceral organs within the pelvic cavity alone obscures the exact source of CPP clinically. While a single organ system may be the initial culprit, the overlap of noxious stimuli (inflammation, nerve injury, hormonal status, endometriosis) via the neural pathways over time can transmit pain signals to an innocuous organ system.8 Noxious afferent information travels from pelvic viscera (colon, rectum, bladder, and uterus) to the dorsal root ganglion via the hypogastric, splanchnic, pelvic, and pudendal nerves.9
Traditionally, providers have believed visceral organ systems to be the primary cause of CPP, however, dysfunction of the musculoskeletal system often coexists.10 The visceral pain and sympathetic nerve fibers of the pelvic region often travel with somatic fibers. In the same manner, viscerovisceral convergence occurs, noxious stimuli from the viscera connect with somatic afferents in the spinal cord and result in viscerosomatic convergence. Clinically this presents as muscle spasm and hypertonicity of the pelvic floor seen in pain response of the pelvic organs.11 This has also been described in the hyperalgesia of the rectus abdominis in patients with endometriosis and dysmenorrhea.12
The investigation of risk factors for CPP is difficult due to the complexity and length of time required for a CPP diagnosis, as well as the heterogeneous and overlapping conditions with which it coexists. Furthermore, differences in associations observed are likely to vary depending on the study setting (community vs. primary care settings).13 It is unsurprising then, that there are few clear patterns of associations between CPP and demographic factors.1,14–18
CPP has been strongly, and consistently, linked to adverse childhood experiences such as sexual abuse, neglect, and family upheaval. An early meta-analysis16 found significant, increased odds among those who reported childhood physical or childhood sexual abuse (odds ratio=2.18, 95% confidence interval: 1.55-3.06, odds ratio=1.51, 95% confidence interval: 1.16-1.97, respectively). Adult or lifetime sexual abuse, psychological abuse, and disturbed puberty or painful early memories as also significantly associated with an increased odds of CPP.16 More recently, Schrepf et al19 found that adverse childhood experience severity was associated with more complex chronic pain including more diffuse pain, comorbid functional symptoms or syndromes, and worse perceived physical wellbeing.
Patient medical and surgical histories are important in identifying and treating patients with CPP. History of infertility, ectopic pregnancy, and miscarriage are all associated with CPP.17 Positive associations have also been found for pelvic adhesions, previous pelvic inflammatory disease, and endometriosis.16 Surgery can serve as both a risk factor and a modifier of CPP. Multiple studies have shown that prior abdominal surgery is associated with a later diagnosis of CPP.16,20 To avoid exacerbating symptoms, the standard of care for CPP patients undergoing surgery should be a minimally invasive approach as it causes the least amount of surgical injury. Additional efforts, such as enhanced recovery after surgery pathways, should also be implemented to significantly improve the surgical experience of patients.21
MANEUVERING THROUGH A CLINIC VISIT
A detailed clinical history is a powerful tool for all providers, particularly in the evaluation of multisystem complaints. Most gynecologists are familiar with a pain history, however, in an effort to decrease the intake burden while optimizing information, a pelvic pain questionnaire can facilitate the history portion of the visit. The International Pelvic Pain Society created a free and accessible form that may be used for patients with CPP.22
Unique to pain intake forms, the presence of a body map can be useful in directing additional questions and focusing the physical examination (Fig. 1). The pain map may reveal that the patient has other areas of pain. In addition, the map may show a distribution of pain suggesting a dermatomal pattern or pain limited to the low back or vulva.
A directed physical examination guided by the history intake should include the low back, abdomen, and pelvis. Moving through the examination in this order allows for the patient to prepare for the pelvic component and the clinician to identify extrapelvic sites of pain that may contribute to the symptom profile. If pain is elicited during the examination, inquiring about the pain and how it contributes to their pain profile is helpful in the assessment and designing a treatment plan.
The first part of the low back examination begins with the inspection while the patient is sitting up, evaluating the contour of the spine, specifically for kyphosis or lordosis. Palpation of the back, specifically the vertebral spine, paraspinal muscles, facet joints, posterior superior iliac spines, and sacroiliac joints can identify areas of pain. The patient then should then lay supine and the provider passively elevates a fully extended leg of the affected side to 30 to 60 degrees. A positive test will elicit pain in the low back, often radiating down the leg, if low back pain is the main generator of pain.
Visual inspection of the abdomen is followed by light and deep palpation. If suspicious for neuropathy, a neurosensory evaluation to assess for allodynia or hyperalgesia can be performed with a Q-Tip.
The pelvic examination should begin with a visual inspection for abnormalities (redness, discharge, lesions, fissures). A moistened cotton swab is used to evaluate the vulva and vestibule for tenderness. The manual portion of the pelvic examination should begin with a lubricated single-digit bypassing the vestibule, noting introital tenderness or spasm. Here the patient can be asked to engage the pelvic muscles and squeeze around the digit and then relax, assessing the patient’s ability to control the muscles as well as general muscle tone. The levator ani muscles should be directly palpated for tone and tenderness at the 5 and 7 o’clock position. The obturator internus muscles can also be readily palpated by hooking the index finger around the pubic rami, asking the patient to abduct the knee, engaging the muscle. The bladder and urethra should also be evaluated for tenderness with the single-digit examination. A bimanual examination assessing the uterine size, tenderness, uterosacral nodularity, or a fixed, immobile uterus should be conducted followed by a rectovaginal examination if endometriosis or rectovaginal disease is suspected.
As CPP is a diagnosis of exclusion, appropriate evaluation of bowel and bladder symptoms should be completed to rule out organ system pathology. Pelvic ultrasound is the first-line imaging modality in women with pelvic pain to rule out uterine and adnexal pathology. Magnetic resonance imaging can be considered for the evaluation of female pelvic pain, particularly if advanced endometriosis or hernia is suspected on physical examination or if there was a finding on ultrasound that requires further evaluation. Computed tomography is often used in emergency settings, particularly in patients in whom ultrasound is inadequate for diagnosis, but should be limited due to radiation exposure. Women who receive imaging as a component of their evaluation for CPP (in addition to the reassurance and counseling from a negative imaging study) are more likely to report improved pain outcomes.23
Multimodal Approach to Treatment
There are a variety of treatment options for patients suffering from CPP, however, with the complexity of the conditions, it is unlikely that any 1 approach will work alone. Instead, physicians should seek a multimodal approach with their patients involving lifestyle modifications, medications, physical therapy, and surgical management based individually on patients’ disease stage and goals for improvement.
Lifestyle modifications are considered the foundation of interventional treatment for the management of all chronic pain disorders, though limited studies have focused on specific interventions or measured outcomes in women with CPP. Despite this, sleep difficulties are significantly associated with increased pain sensitivity24 and women with CPP are at risk of reporting poor sleep quality.25 Sleep hygiene is recommended as first-line treatment for patients and includes limiting daytime naps, avoiding stimulants and troublesome foods before bed, regular exercise and sun exposure, establishing a bedtime routine and ensuring a comfortable sleep environment.
Specific dietary changes have suggested improvement in pain reports, with the theory that by addressing diet-a known modifier of many disease states—can reduce systematic inflammation and oxidative stress. In endometriosis, several diets have been trialed with results supportive of pain improvement, including gluten-free26 and the anti-inflammatory diet.27 One of the largest studies evaluating existing dietary patterns in women with suspected endometriosis led by Harris et al28 suggests that higher predicted plasma 25-hydroxyvitamin D levels and increased intake of dairy foods is associated with a decreased risk of endometriosis at diagnostic laparoscopy. A recent systematic review and meta-analysis29 evaluating patients with multiple pain complaints suggests supplementation with polyunsaturated fatty acids shows modest improvement of chronic pain, particularly in patients with dysmenorrhea.
Current recommendations for exercise among healthy adults is at least 150 minutes a week of moderate or 75 minutes a week of vigorous physical activity.30 A recent overview of Cochrane Reviews evaluated the evidence for physical activity and adults with a variety of chronic pain conditions. Although many studies were small and underpowered, there is some support that exercise is a low-risk intervention with favorable outcomes in several studies, including a reduction in pain and improved physical function and quality of life.31
Medical treatments for CPP can be an effective component in the multimodal approach to pain management. Because of the number of disease-specific treatments for CPP, we will not be able to address all of them in this brief article. An extensive systematic review evaluating treatments of noncyclic pelvic pain in women did not identify any nonhormonal treatments that provided significant pain relief.32 In this section, we will highlight promising novel treatments and areas of future research as we continue to identify therapeutics directed toward prevention and treatment.
The vast majority of published data and significant efficacy is in women with endometriosis-associated pelvic pain. In 2014, an overview of Cochrane Reviews evaluated treatment for endometriosis specific to pain and infertility. Suppression of menstrual cycles with gonadotrophin-releasing hormone analogs, the levonorgestrel-releasing intrauterine system, and danazol were identified as favorable treatments for women with endometriosis-associated pain.33 Although there is evidence that combined hormonal contraceptives are effective in the treatment of pain, dysmenorrhea, and dyspareunia in women with endometriosis,34 there is increasing evidence that progestin-only treatments may have greater efficacy in pain management.35 The levonorgestrel-releasing intrauterine system has also shown effectiveness in women with adenomyosis, CPP and dysmenorrhea with minimal adverse events.36 Systemic progestin therapy has moderate evidence in pain improvement in CPP not specific to endometriosis and should be considered as a therapeutic option.23
Acetaminophen and nonsteroidal anti-inflammatory drugs may provide temporary pain relief, although there is limited efficacy in the treatment of CPP. Opioid therapy should be considered when other therapies have failed, with the caveat that opioids have significant risks across organ systems and these may be heightened with prolonged use for chronic disorders.37 Consultation with a pain medicine specialist is a reasonable option when deciding to offer long-term opioid therapy.
Although there is limited data on the strong efficacy of neuropathic medications alone in the treatment of CPP, modest pain improvements have been identified.38 Tricyclic antidepressants increase circulating levels of norepinephrine, can decrease pain and improve depression symptoms and sleep.39 A small randomized controlled trial deemed gabapentin alone or with amitriptyline more effective in CPP pain management than amitriptyline alone.40 Duloxetine and venlafaxine have not been studied in women with CPP, though there is evidence that duloxetine is an effective treatment for chronic pain, neuropathy, and fibromyalgia at ≥60 mg doses.41 Though general pain guidelines report amitriptyline and gabapentin as first-line agents and nortriptyline and pregabalin as alternatives,42 there is a need for additional research focused specifically on antidepressants and CPP management.
MYOFASCIAL PAIN TREATMENT
Pelvic floor muscle spasm is a common finding in women with CPP and symptoms of dysfunction may overlap with CPP symptom presentation. Once painful pelvic floor muscles or increased pelvic floor muscle tone have been identified on the examination, treatment is indicated. Like CPP, the treatment of pelvic floor muscle spasm involves a multimodal approach, beginning with targeted pelvic floor physical therapy. In women who continue to have CPP with myofascial pain refractory to physical therapy, the addition of muscle relaxants, anesthetic trigger point injections, or botulinum toxin may be appropriate next steps.43 Although a frequent finding in women with CPP, additional research regarding effective treatment options are warranted in this patient population.
Surgical treatment can be effective in disease-specific causes of CPP, particularly with identifiable gynecologic causes. The fulguration and excision of endometriosis are both associated with improvement in pain, though at 12 months postoperatively excision of disease appears to provide a greater reduction of CPP, dysmenorrhea, and dyschezia than fulguration alone.44 A recent systematic review and meta-analysis evaluated pain relief for the surgical treatment of adhesion-related abdominal and pelvic pain following gynecologic and general surgery. In patients who develop new chronic pain following surgery and adhesion formation is suspected, adhesiolysis may be an effective treatment option, with up to 70% of patients reports short-term relief of pain.45 Long-term efficacy has not been determined and should be further investigated.
In addition to the established treatments outlined above, there are a number of emerging therapies which have shown promise in CPP patients. Many of these therapies are being studied for their ability to modulate the nervous system dysfunction that is thought to underlie CPP. There have been promising results in studies utilizing neuromodulation, which is thought to attenuate pain signals to the brain, though there is no universally accepted mechanism of action. Tam et al46 recently published a review of the different types of neuromodulation and the efficacy of each modality in CPP patients.
Another promising area of research is the use of photobiomodulation therapy (PBMt) for the treatment of neuropathic pain. PBMt uses direct light exposure to painful or injured areas, on trigger points, acupuncture points, nerve roots, or lymph nodes.47 A study of patients undergoing total hip anthroplasty has shown that PBMt is effective in decreasing acute pain from surgery,48 but most of the work on chronic pain is limited to animal studies. There are currently 2 ongoing clinical trials (NCT03089424 and NCT03437967) evaluating this therapy in chronic pain patients.
In 2015, Hill et al49 reviewed the literature for the use of medical marijuana for the treatment of chronic pain. There were 5 placebo-controlled studies and 1 case cross-over study, each of which showed a significant improvement in pain measures. Benefits of cannabis use has also been seen in patients with IBS, though questions still remain about whether use provides symptom control or actually treats inflammation. If cannabis therapy becomes more mainstream, physicians must take an active role. The first population-based study50 using the National Health and Nutrition Examination Survey (NHANES) in 2015, showed that patients infrequently reported cannabis use to their physicians. In addition, improved symptom control resulted in patients not presenting to physicians for routine care.51
Psychology of CPP
On its own, CPP is a difficult condition to diagnose and treat, however, it has also been further complicated by patients with no identifiable physical causes. These findings have led to a considerable amount of research on the psychological factors of CPP. The prevalence of anxiety and depression in CPP patients is high, with 1 study reporting anxiety in 73% of patients and depression in 40% of patients. Like other chronic illnesses, CPP may be the cause of anxiety and depression, however, there is evidence that these psychosocial factors may predict the onset of various pain symptoms.52,53 That said, even after improvement of pain after surgery, some CPP patients don’t report improvements in depression scores,54 suggesting that pain and depression may not be as tightly linked as previously thought. This also underscores the importance that patients may still need treatment after surgery.
Understandably, the chronicity of persistent pain is associated with poor coping behaviors over time. Pain catastrophizing, a negative coping response among individuals who tend to focus on, and potentially exaggerate, an actual or impending pain experience,55 has been associated with a decreased probability of symptom improvement.56 It has been linked to increased behavioral expressions of pain in patients and may account for variance in postsurgical pain ratings (patients who catastrophize report higher levels), narcotic use and depression.55 This suggests that the practice of catastrophizing may be a target for interventions to decrease pain and improve quality of life in CPP.
Cognitive behavior therapy (CBT) is a guided, goal-focused form of psychological therapy designed to assist in identifying maladaptive behaviors and change behaviors with directed training. Behavior modifications can result in long-lasting positive effects on pain coping. A small cohort of women 60 women with vulvodynia evaluated the CBT intervention, where there was a significant improvement in anxiety and sexual function in CBT. More importantly, these results were maintained at the 6-month follow-up.57 Although evidence of use and efficacy in pelvic pain patients is limited, a large meta-analysis58 of 23 randomized clinical trials evaluated CBT in fibromyalgia patients. A significant benefit was identified over the control interventions across multiple arenas including pain reduction as well as improved mood and less disability. These benefits were not only identified at the end of treatment but were sustained when measured at long-term follow-up.
Patients with long-standing chronic pain may benefit most from CBT, however preparing patients to undergo treatment should be prefaced that treatment is focused on behavioral changes related to their current response to their pain. With all treatment modalities in pain management, goal setting and managing patient expectations is an important part of the provider’s counseling. As goal-directed therapy is at the core of CBT, these practices often go hand in hand.
CPP is an incapacitating condition for reproductive-aged women, further limited by the inability to identify a single identifiable cause in many cases. Heterogeneity in the population and variance in the definition has been a challenge in guiding research efforts. Clinically, a detailed history and focused physical examination can guide treatment options. Although many drug therapies would benefit from randomized controlled trials to evaluate the efficacy, the true clinical value is identifying multimodal therapy regimens effective in pain management. Establishing patient goals for the visit and expectations for pain outcomes are important to highlight in the clinical setting and can improve satisfaction for both the patient and provider. Understanding the psychology of pain allows the provider to validate the patient’s pain while recommending treatment directed at actively changing negative behaviors which propagate pain perception.
1. Mathias S, Kuppermann M, Liberman R, et al. Chronic pelvic pain
: prevalence, health-related quality of life, and economic correlates. Obstet Gynecol. 1996;87:321–327.
2. Gorayeb R, Roma GS, Reis FJC, et al. High levels of anxiety and depression have a negative effect on quality of life of women with chronic pelvic pain
. Int J Clin Pract. 2009;63:707–711.
3. Andrews J, Yunker A, Reynolds WS. Noncyclic Chronic Pelvic Pain
Therapies for Women. Rockville, MD: Agency for Healthcare Research and Quality (US); 2012.
4. Baranowski AP, Lee J, Price C, et al. Pelvic pain: a pathway for care developed for both men and women by the British Pain Society. Br J Anaesth. 2014;112:452–459.
5. Veasley C, Clare D, Clauw D, et al. Impact of chronic overlapping pain conditions on public health and the urgent need for safe and effective treatment. Chronic Pain Research Alliance; 2015.
6. Peters KM, Carrico DJ, Ibrahim IA, et al. Characterization of a clinical cohort of 87 women with interstitial cystitis/painful bladder syndrome. Urology. 2019;71:634–640.
7. Maixner W, Fillingim RB, Williams DA, et al. Overlapping chronic pain conditions: implications for diagnosis and classification. J Pain. 2016;17(suppl):T93–T107.
8. Malykhina AP. Neural mechanisms of pelvic organ cross-sensitization. Neuroscience. 2007;149:660–672.
9. Berkley KJ. A life of pelvic pain. Physiol Behav. 2005;86:272–280.
10. Tu FF, Holt J, Gonzales J, et al. Physical therapy evaluation of patients with chronic pelvic pain
: a controlled study. Am J Obstet Gynecol. 2008;198:272.e1–272.e7.
11. Howard FM, Perry P, Carter J, et al. Pelvic Pain Diagnosis
. Philadelphia, PA: Lippincott Williams & Wilkins; 2000.
12. Giamberardino MA, Berkley KJ, Iezzi S, et al. Pain threshold variations in somatic wall tissues as a function of menstrual cycle, segmental site and tissue depth in non-dysmenorrheic women, dysmenorrheic women and men. Pain. 1997;71:187–197.
13. Zondervan K, Barlow D. Epidemiology of chronic pelvic pain
. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000;14:403–414.
14. Blikkendaal MD, Schepers EM, van Zwet EW, et al. Hysterectomy in very obese and morbidly obese patients: a systematic review with cumulative analysis of comparative studies. Arch Gynecol Obstet. 2015;292:723–738.
15. Zondervan K, Yudkin P, Vessey M. The community prevalence of chronic pelvic pain
in women and associated illness behaviour. Br J Gen Pract. 2001;51:541–547.
16. Latthe P, Mignini L, Gray R, et al. Factors predisposing women to chronic pelvic pain
: systemic review. BMJ. 2006;332:749–755.
17. Ayorinde AA, Bhattacharya S, Druce KL, et al. Chronic pelvic pain
in women of reproductive and post-reproductive age: a population-based study. Eur J Pain. 2017;21:445–455.
18. Grace V, Zondervan K. Chronic pelvic pain
in New Zealand: prevalence, pain severity, diagnoses and use of the health services. Aust N Z J Public Health. 2004;28:369–375.
19. Schrepf A, Naliboff B, Williams DA, et al. Adverse childhood experiences and symptoms of urologic chronic pelvic pain
syndrome: a multidisciplinary approach to the study of chronic pelvic pain
research network study. Ann Behav Med. 2018;52:865–877.
20. Silva G, Nascimento A, Michelazzo D, et al. High prevalence of chronic pelvic pain
in women in Ribeirao Preta, Brazil and direct association with abdominal surgery. Clinics (Sao Paulo). 2011;66:1307–1312.
21. Moulder JK, Johnson KP. Enhanced recovery after surgery for the patient with chronic pain. BG Manag. 2018:30.
23. Cheong Y, Smotra G, Williams A. Non-surgical interventions for the management of chronic pelvic pain
(review). Cochrane Database Syst Rev. 2014;3:CD008797.
24. Sivertsen B, Lallukka T, Petrie KJ, et al. Sleep and pain sensitivity in adults. Pain. 2015;156:1433–1439.
25. Cosar E, Gungor AC, Gencer M, et al. Sleep disturbance among women with chronic pelvic pain
. Int J Gynaecol Obstet. 2014;126:232–234.
26. Marziali M, Venza M, Lazzaro S, et al. Gluten-free diet: a new strategy for management of painful endometriosis related symptoms? Minerva Chir. 2012;67:499–504.
27. De Leo V, Cagnacci A, Cappelli V, et al. Role of a natural integrator based on lipoic acid, palmitoiletanolamide and myrrh in the treatment of chronic pelvic pain
and endometriosis. Minerva Ginecol. 2019;1:191–195.
28. Harris HR, Chavarro JE, Malspeis S, et al. Dairy-food, calcium, magnesium, and vitamin d intake and endometriosis: a prospective cohort study. Am J Epidemiol. 2013;177:420–430.
29. Prego-Dominguez J, Hadrya F, Takkouche B. Polyunsaturated fatty acids and chronic pain: a systematic review and meta-analysis. Pain Physician. 2016;19:521–535.
30. US Department of Health and Human Services. Physical Activity Guidelines for Americans, 2nd ed. Washington, DC: US Department of Health and Human Services; 2018.
31. Geneen L, Moore R, Clarke C, et al. Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews (Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;1:CD011279.
32. Yunker A, Sathe N, Reynolds W, et al. Systematic review of therapies for noncyclic chronic pelvic pain
in women. Obstet Gynecol Surv. 2012;67:417–425.
33. Mira TAA, Buen MM, Borges MG, et al. Systematic review and meta-analysis of complementary treatments for women with symptomatic endometriosis. Int J Gynecol Obstet. 2018;143:2–9.
34. Jensen JT, Schlaff W, Gordon K. Use of combined hormonal contraceptives for the treatment of endometriosis-related pain: a systematic review of the evidence. Fertil Steril. 2018;110:137.e1–152.e1.
35. Casper RF. Progestin-only pills may be a better fi rst-line treatment for endometriosis than combined estrogen-progestin contraceptive pills. Fertil Steril. 2017;107:533–536.
36. Bahamondes L, Petta CA, Fernandes A, et al. Use of the levonorgestrel-releasing intrauterine system in women with endometriosis, chronic pelvic pain
and dysmenorrhea. Contraception. 2007;75:134–139.
37. Tyan P, Carey ET. Physiological response to opioids. Clin Obstet Gynecol. 2019;62:11–21.
38. Roy H, Offiah I, Dua A. Neuromodulation for pelvic and urogenital pain. Brain Sci. 2018;8:533–536.
39. Khouzam HR. Psychopharmacology of chronic pain: a focus on antidepressants and atypical antipsychotics. Postgrad Med. 2016;128:323–330.
40. Sator-Katzenschlager S, Scharbert G, Kress H, et al. Chronic pelvic pain
treated with gabapentin and amitriptyline: a randomized controlled pilot study. Wien Klin Wochenschr. 2005;117:761–768.
41. Lunn M, Hughes R, Wiffen P. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database Syst Rev. 2014;1:CD007115.
42. Fall M, Baranowski AP, Elneil S, et al. EAU guidelines on chronic pelvic pain
. Eur Urol. 2010;57:35–48.
43. Kotarinos R. Myofascial pelvic pain. Curr Pain Headache Rep. 2012;16:433–438.
44. Pundir J, Omanwa K, Kovoor E, et al. Laparoscopic excision versus ablation for endometriosis-associated pain: an updated systematic review and meta-analysis.. J Minim Invasive Gynecol. 2017;24:747–756.
45. Hunter C, Yang A. Dorsal root ganglion stimulation for chronic pelvic pain
: a case series and technical report on a novel lead configuration. Neuromodulation. 2019;22:87–95.
46. Tam J, Loeb C, Grajower D, et al. Neuromodulation for chronic pelvic pain
. Curr Urol Rep. 2018;19:5.
47. Lizarelli R, Paolillo F, Jorge A, et al. Photobiomodulation for pain relief—a comparative in vivo study abstract. J Oral Med. 2017;1:1–5.
48. Langella LG, Casalechi HL, Tomazoni SS, et al. Photobiomodulation therapy (PBMT) on acute pain and inflammation in patients who underwent total hip arthroplasty—a randomized, triple-blind, placebo-controlled clinical trial. Lasers Med Sci. 2018;33:1933–1940.
49. Hill KP. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems a clinical review. JAMA. 2015;313:2474–2483.
50. Weiss A, Friedenberg F. Patterns of cannabis use in patients with inflammatory bowel disease: a population based analysis. Drug Alcohol Depend. 2015;156:84–89.
51. Storr M, Devlin S, Kaplan GG, et al. Cannabis use provides symptom relief in patients with inflammatory bowel disease but is associated with worse disease prognosis in patients with Crohn’s disease. Inflamm Bowel Dis. 2014;20:472–480.
52. Aggarwal VR, Macfarlane GJ, Farragher TM, et al. Rish factors for onset of chronic oro-facial pain—results of the North Cheshire oro-facial pain prospective population study. Pain. 2010;149:354–359.
53. Chung S, Lin H. Association between chronic prostatitis/chronic pelvic pain
syndrome and anxiety disorder: a population-based study. PLoS One. 2013;8:1–5.
54. Cagnacci A, Della Vecchia E, Xholli A. Chronic pelvic pain
improvement: impact on quality of life and mood. Gynecol Endocrinol. 2019;35:502–505.
55. Quartana PJ, Campbell CM, Edwards RR. Pain catastrophizing: a critical review. Expert Rev Neurother. 2009;9:745–758.
56. Weijenborg PTM, ter Kuile MM, Gopie JP, et al. Predictors of outcome in a cohort of women with chronic pelvic pain
—a follow-up study. Eur J Pain. 2009;13:769–775.
57. Lindström S, Kvist LJ. Treatment of provoked vulvodynia in a swedish cohort using desensitization exercises and cognitive behavioral therapy. BMC Womens Health. 2015;15:108.
58. Bernardy K, Klose P, Busch A, et al. Cognitive behavioural therapies for fibromyalgia. Cochrane Database Syst Rev. 2013;9:CD009796.