Karen C. Wang, MDDepartment of Obstetrics and Gynecology

Director of Minimally Invasive SurgeryBeth Israel Medical Center

April 22, 2010

Define and review the impact of chronic pelvic pain (CPP)

Discuss the potential etiologies of CPP

Review current treatment modalities for common gynecologic causes of CPP

Emphasize the importance of a multidisciplinary approach to the management of CPP

Non-cyclic pain Duration > 6 months Localized to: anatomic pelvis,

anterior abdominal wall, lumbrosacral back or buttocks

Sufficient severity to cause functional disability or lead to medical care

American College of Obstetricians and Gynecologists Practice Bulletin No. 51, March 2004

15-20% of women between the ages of 18-50 years have pelvic pain lasting more than one year during their lifetime

Primary indication for: 10% outpatient gynecology visits 12% hysterectomy 40% diagnostic laparoscopy

Howard FM, Ob Gyn Surv 1993, Lee NC et al AJOG 1984, Zondervan K, et al Br J Gen Prac 2001, Tu FF, AJOG 2006

Among women with CPP Use 3x more medications Have 4x more GYN surgeries Are 5x more likely to have a hysterectomy

58% reduce normal activity >1 day/month 26% stay in bed >1 day/month 15% report lost time from work 48% report reduced work productivity

Mathias SD et al Obstet Gynecol 1996, Reiter R et al. Obstet Gynecol 1990

$300-500 million/year in laparoscopic evaluations

$881 million/year in direct costs

$2 billion/year in indirect costs

Tu FF & Beaumont, JL AJOG 2006, Mathias SD et al Ob/Gyn 1996

Pain is subjective A normal physical

examination does not preclude the presence of pathology

Never expect only one diagnosis or etiology

Simultaneously evaluate and treat all contributing factors (collaboration)

Treatment is challenging due to the lack of effective durable treatments

Economic pressures often hinder extensive workup

GYN

GU

PM&R

GI

Neurology/pain med

Gynecologic Urologic GastrointestinalMusculoskeletal/

Neurologic

• Endometriosis• Adenomyosis• Adhesions• Chronic PID• Uterine fibroids• Pelvic congestion• Ovarian remnant•Residual ovarian

syndrome•Vaginal apex pain•Vestibulodynia

• Interstitial Cystitis• Urethral syndrome• Chronic UTI• Bladder stones

• IBS• Functional Bowel

disorders• Chronic appendicitis• Inflammatory bowel

disease• Hernias• Diverticular disease• Intermittent bowel

Obstruction

• Pelvic floor myalgia• Trigger points• Idiopathic low back

pain• Disc disease• SI joint disease• Coccydynia

• Nerve entrapmentsyndromes

*excludes carcinomas

Gynecologic Urologic Gastrointestinal Musculoskeletal/Neurologic

• Endometriosis• Adenomyosis• Adhesions• Chronic PID• Uterine fibroids• Pelvic congestion• Ovarian remnant• Residual ovarian

syndrome• Vaginal apex pain

• Interstitial Cystitis• Urethral syndrome• Chronic UTI• Bladder stones

• IBS• Functional Bowel

disorders• Chronic appendicitis• Inflammatory bowel

disease• Hernias• Diverticular disease• Intermittent bowel

Obstruction

• Pelvic floor myalgia• Trigger points• Idiopathic low back

pain• Disc disease• SI joint disease• Coccydynia

• Nerve entrapmentsyndromes

*excludes carcinomas

26 year-old G0 presents with complaints of crampy intermittent shooting pelvic pain for the past four years. +dysmenorrhea since menarche, previously controlled with NSAIDs. Now with daily pelvic pain worse shortly before and during menses. +deep dyspareunia and +dyschezia. Never been on oral contraceptives.

Examination Abdomen diffusely tender Cervix deviated to the left on speculum examination Uterus retroverted and minimally mobile Thickening and tenderness of the left uterosacral

ligament Fullness and tenderness of the right adnexa

Pelvic ultrasound shows a complex 5 cm right adnexal mass that is persistent on serial ultrasounds over 4 months.

Uterus

Ovary

endometriosisadhesions

Defined by the presence of endometrial glands and stroma outside of the uterus

Histological diagnosis that requires surgical evaluation

Implantation Theory Retrograde menstruation

Direct transplantation Theory Post-surgical (cesarean section, myomectomy, episiotomy)

Lymphatic or vascular dissemination

Coelomic metaplasia Peritoneal cavity has cells that can de-differentiate into

endometrial tissue

-None-None-Chronic non-menstrual -Chronic non-menstrual

pelvic painpelvic pain-Dysmenorrhea-Dysmenorrhea-Dyspareunia -Dyspareunia

-Pelvic mass-Pelvic mass-Dyschezia-Dyschezia-Decreased quality of life-Decreased quality of life-Infertility-Infertility

• Severity of symptoms do not correlate with severity of anatomic disease except for depth of infiltration

• Co-occurrence with: interstitial cystitis, irritable bowel syndrome, temperomandibular disorder, migraine, fibromyalgia, vulvodynia.

Histological confirmation after surgical exploration Ultrasound

Adnexal mass MRI

Adnexal mass Adenomyosis Infiltrating endometriosis of uterosacrals or cul de sac

CA-125 Nonspecific. May be elevated with benign or malignant

disease

10%

30%

60%

0%0% 100%100%

reproductive aged women

subfertile

chronic pelvic pain

50% adolescent with chronic pelvic pain

ACOG practice bulletin 2000

asymptomatic2%

Prevalence of EndometriosisPrevalence of Endometriosis

1999 Joan Beck

Posterior cul-de-sac 69%Ovaries 33%Fossa ovarica 45%Anterior cul-de-sac 24%Bowel/appendix 5%

SurgicalMedical

MEDICAL NSAIDs Combination OCP Progestins

Oral Depo-Provera Mirena IUD

GnRH agonist (> 18 y.o.) Danazol Aromatase inhibitor

Treatment Route Cost/ 6 mo. Adverse Effects

Estrogen & progesterone

Pills, patch, ring

$240 Breast tenderness, spotting, headaches

Progesterone Oral, injectable

$60-400 Weight gain, mood swings, breast tenderness, edema

Danazol Oral $350 Hirsutism, acne, voice change, vaginal atrophy

GnRH agonists IM, nasal spray

$1900-3200 Hot flushes, vaginal atrophy, bone loss

Advantage – low maintenance, minimal side effects 5 year lifespan

Systemic and local effects RCT LNG-IUD vs. Lupron

6 month follow-up Significant improvement from baseline in

both groups No difference between groups

3 year follow-up data in observational series (n=34) 56% continuation rate at end VAS dropped from 7.7 -> 2.7

(average pain, previous month)

Petta, Hum Rep 2005; Lockhat F et al, Hum Rep 2005

Decrease lesion size and pain symptoms in rectovaginal nodules

Equivalent to GnRH agonist (Lupron) in randomized controlled trial

Decrease in recurrence of pain after surgery for endometriosis

Over 50% of women choose to retain IUD after 3 years

Petta, Hum Rep 2005; Lockhat F et al, Hum Rep 2005

Most treatment decrease symptoms in 70-85% of users

Choose treatment based on patient preference, cost, and side-effects

Recurrence is common after discontinuation of medical therapy

SURGICAL Conservative

Laparoscopy* Excision/ablation LUNA/presacral neurectomy Adnexal mass

Oophorectomy Hysterectomy + BSO Resection of lesions (rectovaginal, small bowel,

extrapelvic)*Sutton CJ et al, Fertil Steril 1997

To establish a diagnosis To improve or relieve symptoms To normalize anatomy for sub-fertility To investigate a mass To evaluate pain that is refractory to other

treatments

Recurrence rate is correlated with disease severity 37% mild disease 74% severe disease 67% within two years of surgery

Use of GnRH agonist for 3 months delays recurrence

Sutton et al. 1994 Study design

RCT, double blinded N=63 stage I-III ♀

endometriosis [Laparoscopic laser ablation +

LUNA] vs. expectant management

Results No difference at 3 months

(48% of expectant group with improved pain)

Significant improvement with laser ablation at 6 months (63% vs. 23%, p<0.01)

Sutton et al. Fertil Steril 1994; 62(4):696-700. * p=0.01, laser vs. expectant

0

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10

Before 3 mo 6 mo

Expectant

LaserVA

S pa

in s

core

(0-1

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8.5

4.5

*

Touted as “definitive treatment”

No RCTs to evaluate efficacy

Endometriosis &/or pelvic pain may recur, even if BSO performed Incidence unknown,

estimates vary widely ~2-60%

Namnoun et al. Fertil Steril 1995; Matorras et al. Fertil Steril 2002.

Recurrent pain Reoperation for recurrent pain

Namnoun 1995

Hysterectomy 62% 31% Hysterectomy +BSO 10% 3.7%

Matorras 2002

Hysterectomy +BSO 0%

Hysterectomy +BSO +HRT 2.5% 3.7%

Chronic pelvic pain with significant reduction in quality of life

Does not desire fertility Unresponsive to medical therapy and prior conservative

surgical therapy If undergoing BSO, understands and accepts negative

impact of castration on other health parameters Osteoporosis, cardiovascular disease, sexual

dysfunction, menopausal symptoms, long-term risk/benefits of HRT, etc.

AND….

Other sources of pain have been excluded and/or maximally treated!!!

Interstitial cystitis Fibromyalgia

Urerthral syndrome Irritable bowel syndrome

Pudendal neuralgia Levator ani myalgia

Piriformis syndrome

Little, if any, correlation between extent of disease and severity of pain.

Medical and surgical therapies are non-specific.ex. Lupron is an effective therapy for cyclic-IBS.

Medical and surgical therapies are inadequate for many patients.

ex. Hysterectomy/BSO is not curative for all patients, 5-10% report persistent/recurrent pain.

Frequency of recurrent pain is high following medical and surgical therapies.

Pain recurs often in the absence of recurrent endometriotic disease.

High co-prevalence with other central pain disorders

Nerve fiber proliferation in endometriosis lesions

Nerve fiber proliferation in endometrial lining and myometrium in women with endometriosis and women with chronic pelvic pain

Increased generalized pain sensitivity in women with endometriosis

55-100% incidence at second look laparoscopy (average 85%)

>90% incidence following major abdominal surgery

Following myomectomy, adnexal adhesions occur: 94% with posterior uterine incisions 56% with anterior/fundal uterine incisions

Lau, Tulandi in Peritoneal Surgery 1999; Diamond, Fertil Steril 1987; Tulandi, et al. Obstet Gynecol 1993

~ 25% prevalence among CPP patients

80% of patients undergoing pain mapping reported pain when adhesions palpated

Nerves, sensory neuron markers found in adhesions of both pain & pain-free patients

Howard F, Ob Gyn Surv 1993; Sulaiman et al. Ann Surg 2002

Infertility (40%) Chronic pelvic pain (50%) Small bowel obstruction (49-74%)

20% within 1 month 40% within 1 year

Reoperation

Liakakos Dig Surg, 2001; Monk et al.AmJ Obstet Gynecol 1994El-Mowafi Prog Obstet Gynecol 2000

RCT of laparoscopic lysis of adhesions vs. diagnostic laparoscopy

100 participants with chronic abdominal pain (> 6 months) Participants, assessors masked Outcome: overall improvement

in pain, function No difference in groups at one

year

Swank D et al. Lancet 2003

Pain scores

hrQOL scores

Sensory nerve fibers are present in human peritoneal adhesions

Nerve fibers were present in all the peritoneal adhesions examined

Nerve fibers expressing substance P were present in all adhesions irrespective of chronic pelvic pain

Nerves were often associated with blood vessels

Sulaiman H, Annals of Surgery, 2001

0

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60

70

80

90

Chan '85 Daniell '89 Sutton '90 Steege '91

42 42

6520

One Year Follow-up

Several observational studies suggest adhesiolysis may be of some benefit for women with CPP

Patients most likely to benefit: Severe, stage IV adhesions No endometriosis Patients with limited psychological distress and/or

comorbidities

Steege 1991, Malik 2000

Involuntary spasm of the pelvic floor muscles

Etiology Inflammation Childbirth Pelvic surgery Trauma

History “heavy aching pelvic pressure,

falling-out sensation,” often later in the day after prolonged sitting

dyspareunia Diagnostic tests (unvalidated)

Contracted, painful muscles on intravaginal exam

EMG or vaginal manometry– elevated baseline tone, muscle instability, and decreased endurance contractile capacity

Hetrick DC et al Neurourol Urodyn 2006

Identified in over 20% of women in CPP referral clinics

Associations with IC, vulvodynia, endometriosis

Treatment includes pelvic floor physical therapy and other adjuvant therapies

Weiss JM et al J Urol 2001, Glazer HI et al JRM 1998,Tu FF et al. JRM 2006, Tu et al OGS 2005

Only 2 RCTs identified in systematic review extremely limited focus (pregnancy-related pelvic

pain and botulinum toxin for myofascial pain) Small n (44, 30 respectively) Methodological issues: no power analysis and

mixture of myofascial pain conditions in botulinum toxin study

For now: individualized therapeutic approach – goal is desensitization

Tu FF et al Ob Gyn Surv 2005

Manual therapy muscle core

strengthening (pelvic/lumbar stabilization)

muscle re-education joint mobilization myofascial release

Modalities Biofeedback electrical stimulation

(TENS)

Orthotic devices pelvic stability belt gait assistance vaginal cones

Must refer to physical therapist with expertise in pelvic pain and intravaginal pelvic floor modalities!

Medications analgesics/NSAIDs tricyclic antidepressants and antiepileptic agents muscle relaxants topical analgesics (camphor, menthol, xylocaine,

lidoderm patch) trigger point injections (botulinum toxin, local

anesthetics, steroids) Psychotherapy, education, work evaluation

Chronic pelvic pain: 89% of 122 women treated had significant symptom

improvement (> 3 months follow-up)

Interstitial cystitis: 70% of 10 patients treated with both injections and

manual therapy had >50% improvement on global symptom severity (mean follow-up 20 months)

Slocumb JC AJOG 1984 Weiss J, J Urol, 2001

Design Double-blinded, RCT of botulinum toxin A 80U vs.

placebo (30 per arm) bilateral injections into puborectalis, pubococcygeus

Outcomes 26 month follow-up no group differences in nonmenstrual pelvic pain (VAS

40 vs. 22) Improvements from pretreatment in both groups

Botox (VAS 51 v. 22 p <0.01), placebo (VAS 47 v. 40, p > 0.05)

Abbott JA et al Ob Gyn 2006

Diagnose endometriosis and/or pelvic adhesions Evaluate an adnexal mass Keep in mind that:

30-50% of diagnostic laparoscopies for pelvic pain are negative

Initial multi-disciplinary therapy is superior to diagnostic laparoscopy and unidimensional therapy

Adhesion removal is no better than sham surgery

Chronic pelvic pain is generally multifactorial, often with multiple organ systems involved

expand differential diagnosis to include GI, GU, musculoskeletal, and central nervous system causes of pain

Begin with “gold-standard” therapies for contributing factors Ex. Hormonal suppression for cyclic pain or chronic pain

with cyclic exacerbation Ex. Physical therapy for abdominal wall and pelvic floor

myofascial pain Ex. Laparoscopy for excision/ablation of endometriosis

When standard treatments fail, then reconsider the diagnosis, re-evaluate comorbid psychosocial variables

Hysterectomy should be considered last resort for treatment of chronic pelvic pain Depending on population surveyed and whether BSO

performed, 3-62% of women will report persistent or recurrent pain

Women with pelvic pain and depression are more likely to report persistent pain and decreased QOL following hysterectomy than women with either condition alone

Patients & physicians should have reasonable expectations

Anecdotally, women with chronic daily pain, diffuse abdominal &/or pelvic floor pain are more likely to report recurrent or persistent pain following surgery

Namnoun et al. Fertil Steril 1995. Matorras et al. Fertil Steril 2002. Hartmann et al. Obstet Gynecol 2004.

Abnormalities in pain processing are a common mechanism in many chronic pain disorders (IBS, IC, fibromyalgia, etc.) It is likely to be an underlying mechanism in at least some

women with CPP Consider adding centrally-acting medication when

standard “gynecology” treatments fail Antidepressants for pain Antiepileptics for pain

Consider using centrally-acting medication as part of first-line therapy Chronic pelvic pain with negative laparoscopy Chronic pelvic pain with diffuse abdominal and pelvic floor

tenderness with no or minimal endometriosis Pelvic nerve entrapment syndromes (ex. Pudendal nueralgia)