Noncyclic Chronic Pelvic Pain Therapies for Women

Noncyclic Chronic Pelvic Pain Therapies for Women

Prepared for:

Agency for Healthcare Research and Quality (AHRQ)

www.ahrq.gov

Introduction to noncyclic chronic pelvic pain (CPP) and available surgical and non-surgical treatment options

Systematic review methods The clinical questions addressed by the CER Results of studies and evidence-based conclusions

about the relative effectiveness of various therapies for noncyclic CPP

Gaps in knowledge and future research needs What to discuss with patients and their caregivers

Outline of Material

Andrews J, Yunker A, Reynolds WS, et al. Comparative Effectiveness Review No. 41. Available at www.effectivehealthcare.ahrq.gov/pelvicpain.cfm.

For the purpose of this review, noncyclic CPP was defined as pain that:

■ Has persisted for more than 3 months

■ Is localized to the anatomic pelvis

■ Causes the patient to become functionally disabled or seek medical care

■ Always has a noncyclic component, and may have mixed cyclic and noncyclic components

■ Is not limited to dysmenorrhea, dyspareunia, dyschezia, or dysuria

This review focused on women over the age of 18 with CPP.

Prevalence estimates of noncyclic CPP vary and range from 4.0 to 43.4%.

Background: Definition of Noncyclic CPP and Its Prevalence


Latthe P, Latthe M, Say L, et al. BMC Public Health 2006;6:177. PMID: 16824213.

Gynecological causes for noncyclic CPP include: Endometriosis Pelvic inflammatory disease Adhesions Pelvic floor muscle spasm

Nongynecological causes of CPP include: Irritable bowel syndrome (IBS) Interstitial cystitis (IC)/painful bladder syndrome (PBS) Myofascial pain disorders Depression

In some cases, a definite underlying cause for CPP may not be identified.

Background: Etiology of Noncyclic CPP

Andrews J, Yunker A, Reynolds WS, et al. Comparative Effectiveness Review No. 41. Available at ww.effectivehealthcare.ahrq.gov/pelvicpain.cfm.

Ortiz DD. Am Fam Physician 2008;77:1535-42. PMID:18581833.

Noncyclic CPP can have significant impact on a woman’s Physical functioning Psychological well-being Social functioning Quality of life

A study conducted in the United States estimated that: $880 million were spent annually on outpatient

management of CPP. 15% of women with CPP reported time lost from work.

Background: Burden of Noncyclic CPP


Ortiz DD. Am Fam Physician.2008;77:1535-42. PMID: 18581833.

Mathias SD, Kupperman M, Liberman RF, et al. Obstet Gynecol. 1996;87:321. PMID: 8598948

Comorbidities and factors associated with noncyclic CPP include: IBS IC/PBS Endometriosis Psychological comorbidities (depression, anxiety, sleep disorders) General factors (history of physical or sexual abuse) Obstetric factors (history of miscarriage or cesarean birth)

Diagnosis and reporting of comorbidities in CPP is complex since: Uniform definitions and diagnostic criteria for comorbidities are

lacking. One or more conditions can co-occur with CPP or cause CPP.

Background: Comorbidities Associated With Noncyclic CPP


Zondervan KT, Yudkin PL, Vessey MP, et al. Am J Obstet Gynecol 2001;184:1149-55. PMID: 11349181.

Methods for evaluating and diagnosing noncyclic CPP include: Patient evaluation including pain history, pain mapping to

determine etiology, and initial therapeutic course Diagnostic laparoscopy to identify and treat pathologies such as

endometriosis and adhesions that cause CPP Assessment of physical, psychological, and social factors

associated with CPP for comprehensive management of the condition

Background: Evaluation of Noncyclic CPP


Ortiz DD. Am Fam Physician 2008;77:1535-42. PMID: 18581833.

For patients in whom the etiology of CPP is unknown or unclear, the condition is often managed based on clinician experience; a standard treatment algorithm is lacking.

The benefits and harms of the available therapeutic modalities have not been thoroughly investigated.

When an initial treatment approach fails, the rationale for selecting one intervention over another lacks guidance from evidence.

Background: Uncertainties Associated With Therapies for Noncyclic CPP


Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, members of the public, and others.

A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. The research questions and the results of the report are subject to expert input, peer review, and public comment.

The results of these reviews are summarized into Clinician Research Summaries and Consumer Research Summaries for use in decisionmaking and in discussions with patients. The Summaries and the full reports, with references for included and excluded studies, are available at www.effectivehealthcare.ahrq.gov/pelvicpain.cfm.

Agency for Healthcare Research and Quality (AHRQ) Comparative Effectiveness Review (CER) Development

Key Question (KQ) 1: Among women who have been diagnosed with noncyclic/mixed cyclic and noncyclic CPP, what is the prevalence of the following comorbidities: dysmenorrhea, major depressive disorder, anxiety disorder, temporomandibular joint pain disorder, fibromyalgia, IBS, IC/PBS, complex regional pain syndrome, vulvodynia, functional abdominal pain syndrome, low back pain, headache, and sexual dysfunction?

KQ 2: Among women with noncyclic/mixed cyclic and noncyclic CPP, what is the effect of surgical interventions on pain status, functional status, satisfaction with care, and quality of life?

Clinical Questions Addressed by the CER (1 of 2)

Andrews J, Yunker A, Reynolds WS, et al. Comparative Effectiveness Review No.41. Available at www.effectivehealthcare.ahrq.gov/pelvicpain.cfm.

Key Question (KQ) 3: What is the evidence that surgical outcomes differ if the etiology of noncyclic/mixed cyclic and noncyclic CPP is identified after surgery?

KQ 4: Among women with noncyclic/mixed cyclic and noncyclic CPP, what is the effect of non-surgical interventions on pain status, functional status, satisfaction with care, quality of life, and harms?

KQ 5: What is the evidence for choosing one intervention over another to treat persistent or recurrent noncyclic/mixed cyclic and noncyclic CPP after an initial intervention fails to achieve target outcome(s)?

Clinical Questions Addressed by the CER (2 of 2)


The strength of evidence was classified into four broad categories:

Rating the Strength of Evidence From the CER


Prevalence estimates for the most common comorbidities occurring in patients with CPP were:

Dyspareunia — 15–88%

Dysmenorrhea — 4–100%

IBS — 24–39%

Prevalence estimates for comorbidities varied widely due to lack of standardized definitions and complexity of their diagnosis.

Strength of evidence was not assessed for this Key Question since it did not focus on interventions.

Prevalence of Comorbidities in Women With Noncyclic CPP


Non-surgical interventions Pharmacologic interventions

D̶ Antineuropathics (gabapentin, amitriptyline)D̶ Neuromuscular blocking agents (botulinum toxin A)

Hormonal interventionsD̶ Estrogen/progesterone contraceptive agents (in oral, transdermal, or injection form)D̶ Gonadotropin releasing hormone analogs (depot leuprolide, goserelin, gestrinone)D̶ Selective estrogen receptor modulator (raloxifene)

Other interventionsD̶ Physical therapy (pelvic ultrasonography, pelvic floor muscle exercises)D̶ Counseling with or without photographic reinforcement*D̶ Integrated treatment approach†

Surgical interventionsD̶ Laparoscopic uterine nerve ablation (LUNA)D̶ Laparoscopic adhesiolysisD̶ Uterosacral ligament resection

Therapeutic Interventions for CPPAssessed in the CER

* Photographic enforcement = displaying operative photographs † Integrated treatment approach = equal attention devoted to organic, psychological, dietary, and environmental causes of pain; laparoscopy not routinely performed.


Evidence from one RCT suggested that there was an earlier return to pain with raloxifene than with placebo.Strength of evidence: low

Evidence from one RCT suggested that there was greater reduction in pain with depot leuprolide when compared with placebo.Strength of evidence: low

Comparative Effectiveness of Non-surgical Interventions for Noncyclic CPP: Pain Outcomes (1 of 2)


Evidence was insufficient to permit meaningful conclusions about the relative effectiveness of the following interventions in improving pain status: Hormonal therapies except raloxifene or depot leuprolide versus

placebo Gabapentin + amitriptyline versus amitriptyline alone Botulinum toxin versus placebo Pelvic ultrasonography plus counseling versus expectant

management Pelvic floor muscle therapy versus counseling Photographic reinforcement versus no reinforcement during post-

operative counseling Integrated treatment approach† versus standard treatment††

Strength of evidence: insufficient

Comparative Effectiveness of Non-surgical Interventions for Noncyclic CPP: Pain Outcomes (2 of 2)


† Integrated treatment approach = equal attention devoted to organic, psychological, dietary, and environmental causes of pain; laparoscopy not routinely performed.†† Standard treatment = exclusion of organic causes of pain and routine laparoscopy before attention is devoted to treating other causes.

There was no significant difference between laparoscopic uterine nerve ablation (LUNA) and diagnostic laparoscopy for improving pain status in CPP patients.

Evidence was based on 2 RCTs, including one with 5 years followup, in patients with endometriosis, adhesions or pelvic inflammatory disease.

Strength of evidence: low

Laparoscopic adhesiolysis and diagnostic laparoscopy were similarly effective in improving pain scores and quality of life.

Evidence was based on 1 RCT in patients with CPP associated with adhesions who were followed up for 12 months.

Strength of evidence: low

Comparative Effectiveness of Surgical Interventions for Noncyclic CPP: Pain and Quality-of-Life Outcomes (1 of 2)


Evidence was insufficient to permit meaningful conclusions about the relative effectiveness of the following interventions in improving pain status: LUNA versus uterosacral ligament resection Surgical versus non-surgical therapy


Comparative Effectiveness of Surgical Interventions for Noncyclic CPP: Pain and Quality-of-Life Outcomes (2 of 2)


Evidence was insufficient to permit meaningful conclusions about the relative effectiveness of hysterectomy versus non-surgical therapy in improving functional status.


Comparative Effectiveness of Surgical Interventions for Noncyclic CPP: Functional Outcomes


A thorough work-up may be required in patients with CPP given the various possible etiologies for this condition.

In patients with CPP where endometriosis is suspected, there may be benefit to hormonal therapy.

Among surgical approaches for CPP, both LUNA and laparoscopic adhesiolysis were not found to be superior to diagnostic laparoscopy.

Examination of current evidence is insufficient to change current approaches to care. Use of less-invasive therapeutic interventions may be warranted

before moving on to more invasive approaches, which could be associated with increased harms.

Conclusions (1 of 2)


The limited evidence suggests that current standard treatment practices are not well supported by existing research.

Improved characterization of the condition, intervention, and population in CPP research is necessary to inform treatment choices for this commonly reported entity.

There is an urgent need to address gaps in knowledge regarding decisionmaking for this condition.

Conclusions (2 of 2)


There are very few data on outcome measures such as quality of life, functional status, and patient satisfaction in studies of noncyclic CPP.

The evidence on hormonal therapies for noncyclic CPP that is not associated with endometriosis is limited.

There is a paucity of noncyclic CPP studies evaluating nonhormonal and nonpharmacological interventions, and comparing medical and surgical management.

Knowledge Gaps and Future Research Needs (1 of 2)


Prevalence estimates of noncyclic CPP-associated comorbidities (such as dyspareunia, dysmenorrhea, IBS, and major depressive disorder) are widely variable.

There is limited understanding of the role of a multidisciplinary approach in managing noncyclic CPP despite its complex, multifactorial etiology.

Knowledge Gaps and Future Research Needs (2 of 2)


The uncertainty about noncyclic CPP therapies The different types of interventions available for treating

noncyclic CPP The types of comorbidities and factors (including

psychosocial) that might be associated with noncyclic CPP and the importance of these in deciding treatment

The possibility that a definitive cause of the patient’s noncyclic CPP may not be identified, making the treatment process complex

Encouraging the patient to work with you to identify an optimal approach to manage the condition

What To Discuss With Your Patientsand Their Caregivers


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Noncyclic Chronic Pelvic Pain Therapies for Women