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Chronic Pelvic Pain / Endometriosis

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Title: Evidence-based management of endometriosis Author: Burke Last modified by: lectern Created Date: 9/22/2008 7:50:59 PM Document presentation format – PowerPoint PPT presentation

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Title: Chronic Pelvic Pain / Endometriosis


1
Chronic Pelvic Pain / Endometriosis
  • Dr Cathy Burke
  • MSc Programme
  • November 2009

2
Chronic Pelvic Pain
  • Definition
  • Various definitions
  • Intermittent or chronic pain in the lower
    abdomen or pelvis of at least six months
    duration, not occurring exclusively with
    menstruation or intercourse and not associated
    with pregnancy

3
CPP - Prevalence
  • Prevalence in primary care comparable to
    migraine, back pain and asthma
  • Yearly prevalence 38.3/1000 Zondervan 1999
  • Most common indication for referral to gynae
    outpatient clinics - 20 of referrals Howard 1993
  • 61 of women with pelvic pain did not have a
    clear diagnosis Mathias 1996

4
Dysmenorrhea - risk factors
  • INCREASED RISK
  • Age lt30
  • Being thin (BMI lt20)
  • Smoking (increased with no. of cigs)
  • Early menarche
  • Longer cycles
  • Heavy / irreg bleeding
  • Premenstrual sxs
  • Clinically suspected PID
  • Sterilisation
  • Hx of sexual assault
  • BMJ Feb 2006
  • DECREASED RISK
  • Oral contraceptive use
  • Fish intake
  • Physical exercise
  • Being married or in a stable relationship
  • Higher parity

5
Dyspareunia - risk factors
  • Hx of circumcision
  • Clinically suspected PID
  • Peri-postmenopausal
  • Anxiety / depression
  • Sexual assault
  • BMJ Feb 2006

6
Non-cyclical pain - risk factors
  • Previous miscarriage
  • Longer menstrual flow
  • Endometriosis
  • Clinically suspected PID
  • Caesarean section
  • Pelvic adhesions
  • Physical / sexual / other abuse
  • Anxiety / depression
  • Somatisation
  • BMJ Feb 2006

7
CPP - Causes
  • Pelvic inflammatory disease
  • Post-surgical adhesions
  • Irritable bowel syndrome
  • Constipation
  • Endometriosis
  • Interstitial cystitis / recurrent UTI
  • Psychological morbidity
  • History of childhood / adult sexual abuse
  • Pelvic congestion syndrome
  • Adenomyosis

8
CPP - History taking
  • Pain details
  • Location
  • Cyclicity
  • Timing
  • Character
  • Duration
  • Intensity (score out of 10)
  • Aggravating / relieving factors
  • What has / has not worked to date

9
CPP - History taking
  • Dysmenorrhea
  • Dyspareunia (superficial, deep)
  • Dyschezia (difficulty, pain), rectal bleeding
  • Urinary symptoms, haematuria
  • Non-cyclical pain
  • Periods
  • Associated features (bloating, nausea)
  • Vaginal discharge
  • Other pain syndromes
  • Family history

10
CPP - Examination
  • General - affect, weight
  • Abdominal
  • Speculum
  • Pelvic
  • Ultrasound

11
CPP - Investigations
  • Swabs
  • MSU
  • Pelvic ultrasound
  • Laparoscopy /- hysteroscopy
  • Cystoscopy (glomerulations, Hunners ulcers in
    PBS), biopsy

12
IBS - Treatment
  • Diet - food diary and exclusion, regular meals,
    hydration, caffeine elimination, limit fresh
    fruit
  • Exercise
  • Probiotics (not prebiotics) minimum 4 weeks
  • Stress reduction
  • Antispasmodics - mebevarine, peppermint oil
  • Bulk forming laxatives - increase fluid intake
  • Antimotility drugs - loperamide
  • Tricyclic antidepressants
  • Complementary therapies
  • Psychological interventions

13
PID - Treatment
  • Chlamydia - Azithromycin 1g stat PO and refer to
    STI clinic
  • PID, polymicrobial - Ofloxacin 400mg bd and
    Metronidazole 400mg bd x 14 days
  • Severely ill patients
  • Doxycycline 100mg bd
  • and
  • Ceftriaxone 1g iv stat
  • and
  • Metronidazole 400mg tds

14
Interstitial Cystitis (PBS) - Treatment
  • Bladder distention
  • Bladder instillation (dimethyl sulfoxide, DMSO)
  • Pentosan polysulfate (Elmiron) ?repairs defects
    in bladder epithelium
  • Aspirin, ibuprofen
  • TENS
  • Lifestyle - diet, smoking, exercise
  • Bladder training
  • Surgery - fulguration, resection, augmentation,
    cystectomy

15
Endometriosis
16
Introduction
  • Overview
  • Outline current treatment modalities
  • Explore evidence base for treatments
  • Present recommendations

17
Definition
  • The presence of endometrial glands and stroma
    outside the uterine cavity
  • endometrial glands
  • endometrial stroma
  • fibrosis
  • haemorrhage

18
Prevalence
  • Women with pelvic pain have a higher incidence
    of endometriosis (range 4080) than women with
    infertility without pain (2050) or control
    groups (520)
  • Koninckx et al, 1991
  • Prevalence increasing over the years
  • Guo et al Gynecol Obstet Invest 2006

19
Pathology
  • Peritoneal inflammation and fibrosis
  • Adhesions
  • Ovarian cysts
  • Deep nodules

20
Symptomatology
  • Dysmenorrhea
  • Dyspareunia
  • Dyschezia / bowel symptoms / rectal bleeding
  • Non-cyclical pelvic pain
  • Urinary symptoms / haematuria

21
Associations
  • Menorrhagia (adenomyosis)
  • Subfertility
  • IBS
  • PID Seaman et al BJOG 2008
  • Chronic pain syndromes
  • Depression - 86 vs 38
  • Lorencatto et al Acta Obsstet Gynecol Scand 2006

22
Pathogenesis
  • Retrograde menstruation / transplantation Sampson
  • Coelomic metaplasia Meyer
  • Metastasis (haematogenous / lymphatic) Javert
  • Genetic basis (Chr 7, 10, 20) Montgomery et al
    Hum Reprod 08
  • Immunologic basis

23
Susceptibility
  • Genetic predisposition
  • Increased exposure to menstrual debris
  • Abnormal eutopic endometrium
  • Altered peritoneal environment
  • Reduced immune surveillance
  • Increased angiogenic capacity
  • Healy et al 1998 Vinatier et al 2001 Treloar et
    al 2002 Varma et al 2004

24
Natural history
  • Largely unknown
  • Average sx duration 7 yrs prior to diagnosis
  • Remitting / recurring
  • Hormonally-driven

25
Lifetime experience
  • Symptom duration 16 years
  • Half tried three / more medical treatments
  • Half had surgical procedures performed at least 3
    times
  • One in five had hysterectomy / oophorectomy -
    most successful for sxs
  • Sinaii et al Fertil Steril 2007, 1998
    Endometriosis Association Survey

26
Symptom-to-diagnosis lag
  • Confusion with other conditions
  • Co-existence with other conditions
  • Lack of awareness of and enquiry into
    symptomatology
  • Un / Mis - diagnosed at laparoscopy

27
Mechanisms of pain
  • Inflammatory cytokines in the peritoneal cavity
  • Focal bleeding from implants
  • Irritation and direct infiltration of nerves
  • Hormonal modulation pain threshold

28
Mechanisms of subfertility
  • Distorted adnexal anatomy
  • Ovarian cysts
  • Adverse effects on folliculogenesis
  • Interference with oocyte/sperm survival,
    fertilization and embryogenesis

29
Endometriosis - diagnosis
30
VESICULAR LESIONS
31
PERITONEAL LESION WITH NEOVASCULARISATION AND
FIBROSIS
32
VESICULAR LESIONS
33
TUBAL ENDOMETRIOSIS
34
KISSING OVARIES
35
PERITONEAL SCARRING
36
SUBDIAPHRAGMATIC ENDOMETRIOSIS
37
SUBDIAPHRAGMATIC SCARRING
38
ADHESION-LIKE APPEARANCE
39
RECTUM ADHERENT TO POD
40
Endometriosis - location
Ovaries 60
Tubes 21
POD / pelvic sidewall 83
Ureter 13
Bowel 51
Bladder 13
41
Grading ofendometriosis
  • American Society for Reproductive Medicine
    (ASRM)
  • Peritoneal disease
  • Ovarian disease
  • POD disease
  • Adhesions
  • Stage I-IV

42
Endometriosis - Grade vs Symptoms
  • Grade not directly correlated with symptomatology
  • Advanced disease more frequently related to
    dysmenorrhea and dyspareunia compared to early
    disease
  • Milingos et al Gynaeol Obstet Invest 2006

43
Endometriosis - what is the impact?
  • Quality of life
  • (EuroQOL, Health score, EHPQ-30)
  • Social functioning
  • (SF36/12)
  • Sexual activity
  • (SAQ)

44
Medical treatment
45
Medical management
  • Non-steroidal anti-inflammatory drugs
  • Inhibition of ovulation
  • OCP
  • GnRH agonists
  • Depo-Provera
  • Atrophy of endometriotic lesions / local effect
  • Oral progestogens
  • Depo-provera
  • Mirena

46
Oral analgaesics
  • NSAIDS inconclusive evidence for use
  • Allen et al, Cochrane review 2005

47
Oral contraceptive pill
  • OCP effective for dysmenorrhea and reduced
    endometrioma size
  • Harada et al Fertil Steril 2007
  • OCP equivalent to GnRH
  • Cochrane Review 2007
  • Continuous OCP in women in whom recurrent
    dysmenorrhea not controlled by cyclical OCP
  • Vercellini et al Fertil Steril 2003

48
GnRH agonists
  • GnRH agonist use for endometriosis-related pain
    well-established
  • Dlugi et at Fertil Steril 1990, Waller et al
    Fertil Steil 1993, Henzl et al NEJM 1988
  • GnRH agonists with or without add-back E work
    better than OCP for post-surgical relapse.
    Add-back improves QOL scores
  • Zupi et al Fertil Steril 2004

49
Progestogens
  • Oral progestogens poorly tolerated due to
    side-effects
  • Depo-provera equivalent to GnRH for pain scores.
  • Less loss of bone mineral density with DMPA
  • Schlaff et al Fertil Steril 2006

50
Mirena
  • 70 symptomatic relief after 12 months
  • Vercellini et al 1999
  • Radiographic evidence of regression of
    rectovaginal lesions
  • Fedele et al 2001
  • Improvement in severity and frequency of pain
    and menstrual sxs, and staging of disease
  • Lockhat et al Hum Reprod 2004
  • Mirena equivalent to GnRH for pain
  • Petta et al Hum Reprod 2005

51
Surgical treatment
52
Surgery for endometriosis
  • Ablation / excision of superficial peritoneal
    deposits
  • Excision of deep peritoneal deposits
  • Stripping / drainage and ablation of
    endometriomata
  • Hysterectomy / Oophorectomy

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Extent of surgery - tertiary unit
Total laparoscopic hysterectomy 8
Resection endometriosis 81
Ureterolysis 51
Bowel dissection 57
Ablation of endometrioma(s) 10
Stripping of endometrioma(s) 30

Operative time (mins) med (IQR, R) (90-162) (20-270)
Blood loss (ml) med (IQR, R) (100-500) (50-2000)

Hospital stay (days) med, (IQR, R) (2-4) (1-8)
62
Evidence for surgical treatment
63
Ablation of endometriosis
  • Laser ablation superior to expectant mgt 62 vs
    25 clinical response at 6/12
  • Sutton et al Fertil Steril 1994
  • Helica thermal coagulation - 87 response at 6/12
  • Nardo et al Fertil Steril 2005
  • LUNA has no effect on endometriosis-related
    dysmenorrhea
  • Vercellini et al Fertil Steril 2003

64
Excision of deep endometriosis
  • Lap excision superior to placebo for pain and QOL
  • Abbott et al Fertil Steril 2004
  • Symptoms, QOL and sexual function improved after
    excisional surgery
  • Garry et al, Anaf et al, Redwine et al, Ford et
    al, Lyons et al, Dubernard et al, Wykes et al

65
Treatment of endometriomas
  • Stripping vs drainage and ablation of
    endometriomas reduces pain symptoms and
    recurrence
  • Hart et al Fertil Steril 2005, Cochrane Review

66
Hysterectomy / Oophorectomy
  • Hysterectomy associated with high rate of symptom
    resolution and low re-operation rate
  • Shakiba et al Obstet Gynecol 2008
  • Ovarian conservation associated with increased
    risk of recurrent pain (x 6) and re-operation
    rate (x 8)
  • Namnoun et al Fertil Steril 1995

67
Complications of surgery
  • Complications of laparoscopy
  • Organ injury
  • ureter
  • bowel
  • bladder
  • Bleeding

68
Adhesion prevention in endometriosis surgery
  • Suturing of ovary decreases adhesion formation
  • Pellicano et al Fertil Steril 2008
  • Adhesion prevention agents
  • Barrier Interceed reduces adhesions
  • Cochrane 2008
  • Fluid Limited evidence
  • Cochrane 2006
  • Icodextrin 4 (Adept) reduces adhesions
  • Brown et al Fertil Steril 2007

69
Surgery - outcomes
Mean pre-op VAS scores Mean post-op VAS scores (Med FU 6/12) Improvement in mean scores p-value
Period pain 8 4.5 2.5 lt0.001
Pelvis pain 5 2 3 lt0.001
Sexual intercourse pain 4 2 2 0.001
Pain opening bowels 5 1 4 lt0.001
Health scores 64 80 16 lt0.001
EUROQOL (Health state) 0.73 0.80 0.07 0.003
SF-12
Physical 46 52 6 0.074
Mental 41 49 7 lt0.001
70
Evidence for surgery Pain and QOL
  • Improvement in pain, SAQ and QOL scores up to 5
    years
  • Placebo response rate 30
  • Non-responsiveness to surgery 20
  • Ford et al 2004 Abbott et al 2003 2005
  • LUNA is not effective in this group
  • Johnson et al 2005

71
Evidence for surgery - Fertility
  • Laparoscopic ablation of minimal/mild endo
    improves fertility
  • Marcoux et al NEJM 1997, Cochrane Review 2002
  • Endometrioma excision
  • Ovulation rate in natural cycles reduced
    compared with pre-op
  • Horikawa et al, J Assist Reprod Genet 2008
  • Ovarian response in IVF-ET cycles reduced
  • Yazbeck et al, Gynecol Obstet Fertil 2006

72
Post-operative treatment
  • Post-op continuous OCP and POP useful
  • Razzi et al Eur J Obstet Gynaecol Rep Biol 2007
  • Postoperative GnRH improved pain when used for
    3/12 and 6/12
  • Parazzini et al Am J Obstet Gynecol 1994,
    Vercellini et al BJOG 1999
  • Post-op Mirena useful
  • Abbou Setta et al Cochrane Review 2006

73
Post-operative treatment
  • Post-operative hormonal suppression (COCP or
    GnRH) reduces dysmenorrhea vs placebo
  • Dietary supplementation improves non-menstrual
    pain post-operatively as much as OCP
  • Quality of life scores better with hormonal
    suppression
  • Sesti et al Fertil Steril 2007

74
Endometriosis recurrence
  • 30 recurrence of endometriomata 2 years after
    surgical excision
  • Koga et al Hum Reprod 2006
  • Re-operation rate 35 after 3 years
  • Abbott et al 2005

75
Multidisciplinary management of endometriosis
  • Associated with decrease in pain, anxiety,
    depression in CPP group
  • Kames et al Pain 1990
  • Integrated approach improved pain significantly
    more than standard approach with CPP
  • Peters et al Obstet Gynecol 1991

76
Complementary therapies and endometriosis
  • Acupuncture
  • Japanese-style acupuncture vs sham acupuncture
  • Wayne et at J Paed Adolesc Gynecol
  • Shu Mu vs standard vs danazol on clinical sxs and
    CA125
  • Sun et al, Zhongguo Zhen Jiu 2006
  • Traditional Chinese medicine
  • Neiyi pill / enema vs danazol x 3/12 on CA125
    levels
  • Lu et al Zhongguo Zhen Jiu, 2007

77
ESHRE guideline
  • Laparoscopy desirable for women presenting with
    sxs of endometriosis
  • Therapeutic trial of hormonal agents may be used
    first line
  • Laparoscopically-diagnosed endometriosis treated
    for 6/12 with ovarian suppression drug

78
ESHRE guideline
  • Inconclusive evidence that NSAIDS (Naproxen)
    efffective
  • Suppression of ovarian function for 6/12 reduces
    endometriosis-related pain. All hormonal drugs
    equally effective but side-effect and cost
    profiles differ
  • LNG-IUS reduces pain
  • GnRH treatment for up to 2 years with E/P addback
    acceptable

79
ESHRE guideline
  • Ideal practice is to diagnose and remove
    endometriosis at the same time provided consent
    has been obtained
  • Ablation of endometriosis reduces pain, less so
    with mild disease
  • No evidence that LUNA is effective
  • Excision of deeply-infiltrating lesions reduces
    pain
  • Severe / deeply infiltrating endometriosis should
    be referred to a centre with expertise

80
ESHRE guideline
  • Suppression of ovarian function not effective to
    enhance fertility
  • Insufficient evidence that excision of
    moderate-severe endometriosis enhances pregnancy
    rates

81
Future treatments for endometriosis
  • Presacral neurectomy
  • Mifepristone (anti-progesterone)
  • Aromatase inhibitors (anastrozole, letrozole)
  • TNF alpha inhibitors
  • Thalidomide

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THANK YOU
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