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. INCREASED RISK Age <30 Being thin (BMI <20) 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 Dysmenorrhea - risk factors

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, Hunner’s 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: 40–80%) than women with infertility without pain (20–50%) or control groups (5–20%) 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. SUBDIAPHRAGMATICSCARRING

38. ADHESION-LIKE APPEARANCE

39. RECTUM ADHERENT TO POD

40. Endometriosis - location

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