Pelvic Pain – Dysmenorrhea and Endometriosis

1. Pelvic Pain – Dysmenorrhea and Endometriosis

2. Case 1 • A 20 y.o. woman presents to her gynecologist with a 4 year history of increasing lower abdominal pain with her menses. The pain begins on the first day of her menses and lasts 2-3 days. She also complains of lower back pain and nausea. Menarche occurred at the age of 13 and her menses occur every 28 days and last 5 days. Physical and pelvic exam are normal.

3. Case 1 • How is dysmenorrhea diagnosed? How is it distinguished from other types of pelvic pain? • What is the pathophysiology of dysmenorrhea? • What are reasonable approaches to treatment?

4. Dysmenorrhea • Dysmenorrhea – severe, painful cramping sensation in the lower abdomen often accompanied by other symptoms – sweating, tachycardia, headaches, n/v, diarrhea, tremulousness, all occurring just before or during menses - Primary: no obvious pathologic condition, onset < 20 years old - Secondary: associated with pelvic conditions or pathology

5. Primary Dysmenorrhea • Pathogenesis: elevated PG F2α in secretory endometrium (increased uterine contractility) • Treatment: NSAIDs – PG synthetase inhibitors – 1st line treatment of choice • Other treatment options: OCPs, other analgesics

6. Secondary Dysmenorrhea • Etiologies - Cervical Stenosis - Endometriosis and Adenomyosis - Pelvic Infection - Adhesions - Pelvic Congestion - Stress and Tension

7. Secondary Dysmenorrhea • Cervical Stenosis - Severe narrowing of cervical canal may impede menstrual outflow – congenital or iatrogenic - can cause an increase in intrauterine pressure during menses - can lead to endometriosis

8. Secondary Dysmenorrhea • Cervical Stenosis - Hx – scant menstrual flow, severe cramping throughout menses - Dx – inability to pass a thin probe through the internal os OR HSG demonstrates thin cx canal - Tx – cervical dilation via D&C or laminaria placement

9. Secondary Dysmenorrhea • Pelvic Congestion - Due to engorgement of pelvic vasculature - Hx – burning or throbbing pain, worse at night and after standing - Dx – Laparoscopic visualization of engorgement/varicosities of broad ligament and pelvic sidewall veins

10. Evaluation of Pelvic Pain • Detailed history, targeted physical exam, labs (UA, UCx, CBC, HCG, tumor markers), diagnostic imaging studies (US, MRI, CT) as appropriate • Consider age of patient • “OLDCAAR”: onset, location, duration, context, associated sx, aggravating/relieving factors • Temporal characteristics: cyclic (e.g. dysmenorrhea), intermittent (e.g. dyspareunia), non-cyclic • Risk factors • GYN and Non-GYN causes

11. DDx Pelvic Pain - GYN • GYN - Uterus - fibroids, adenomyosis, endometritis - Fallopian tubes - PID/salpingitis, hydrosalpinx, ectopic - Ovaries - cysts – functional, pathological, TOA, torsion; mittleschmerz - Other - endometriosis, adhesions, IUD/infection, severe prolapse

12. DDx Pelvic Pain – Non-GYN • Urologic - UTI/urethritis, interstitial cystitis (IC), OAB, urethral diverticulum, nephrolithiasis, malignancy • GI - constipation, IBS, IBD (Crohn’s, UC), bowel obstruction, diverticulitis, malignancy, appendicitis • Musculoskeletal - trigger points, fibromyalgia, hernias, neuralgia, low back pain • Other - psychiatric – depression, somatization; abdominal cutaneous nerve entrapment in surgical scar; celiac disease

13. Case 1 • At the age of 30, the patient presents with a 2 year history of infertility. Her menses are still regular but she has 2-3 days of spotting before her menses are due. She also complains of pain with intercourse and pelvic pain. In reviewing the patient’s history, the gynecologist notes that over the past year the patient was repeatedly treated by her internist with antibiotics for recurrent microscopic hematuria.

14. Case 1 • What is the most likely diagnosis? • What are the main theories regarding the pathogenesis in this case? • How would you evaluate and treat this patient?

15. Endometriosis - Symptoms • Variable and unpredictable - asymptomatic - dysmenorrhea - CPP - deep dyspareunia - sacral backache w/ menses - dysuria +/- hematuria (bladder involvement) - dyschezia/hematochezia (bowel involvement)

16. Endometriosis – Physical Exam • Uterosacral nodularity • Adnexal mass (endometrioma) • Normal exam

17. Endometriosis - Incidence • 7-10% of general population • 20-50% of infertile women • 70-85% in women w/ CPP • No racial predisposition • +Familial association with almost 10x increased risk of endometriosis if affected 1st degree relative

18. Endometriosis - Pathogenesis • Retrograde menstruation (Sampson) • Hematogenous or lymphatic spread (Halban) • Coelomic metaplasia (Meyer/Novack) • Iatrogenic dissemination • Immunologic defects (Dmowski) • Genetic predisposition

19. Endometriosis - Pathogenesis • Retrograde menstruation (Sampson’s theory) - Monkey experiments – sutured cervix closed to create outflow obstruction  caused development of endometriosis - Clinical observation of retrograde menstrual flow during laparoscopy in humans - Increased risk of endometriosis in women with cervical/vaginal atresia, other outflow obstruction - Increased risk with early menarche, longer and heavier flow - Decreased risk with decreased estrogen levels e.g. exercise-induced menstrual disorders, decreased body fat, + tobacco use

20. Endometriosis - Pathogenesis • Hematogenous or lymphatic spread - Endometriosis found in remote sites – lung, nose, spinal cord, pelvic lymph nodes.

21. Endometriosis - Pathogenesis • Coelomic metaplasia - Mullerian ducts are derived from coelomic epithelium during fetal development - Hypothesize that coelomic epithelium retains ability for multipotential development - Endometriosis seen in prepubertal girls, women w/ congenital absence of the uterus, and RARELY in men

22. Endometriosis - Pathogenesis • Iatrogenic dissemination - Endometriosis has been found in cesarean section scar • Immunologic defects • Genetic predisposition - polygenic, multi-factorial

23. Endometriosis - Diagnosis • Laparoscopy with biopsy proven histologic diagnosis – standard for dx of endometriosis • Empiric medical treatment with improvement in symptoms • CA 125 – NOT considered to be of clinical utility • Imaging – US, MRI, CT – only useful in the presence of pelvic or adnexal masses (endometriomas)

24. Endometriosis - Diagnosis • Laparoscopy with biopsy proven histologic diagnosis – standard for dx of endometriosis - Extent of visible lesions do not correlate with severity of sx, but depth of infiltration of lesions seems to correlate best with pain severity - classic powder-burn lesions, endometriomas - lesions can be red, clear or white – more commonly seen in adolescents

25. Endometriosis - Diagnosis

26. Endometriosis - Diagnosis 2 or more of the following histologic features are criteria for Dx: • Endometrial epithelium • Endometrial glands • Endometrial stroma • Hemosiderin-laden macrophages

27. Endometriosis - Diagnosis • Imaging – US, MRI, CT – only useful in the presence of pelvic or adnexal masses (endometriomas) - on US, endometriomas appear as cysts that contain low-level homogeneous internal echoes consistent with old blood (ddx includes hemorrhagic cysts)

28. Endometriosis - Diagnosis

29. Endometriosis - Treatment • Medications - Progestins - OCPs – continuous vs. cyclic – if no relief in 3 months, consider tx with Depo Provera or GnRH agonist - NSAIDs - GnRH agonists – most expensive - Danazol – appears to be as effective as GnRH agonist for pain relief but with increased side-effects

30. Endometriosis - Treatment • GnRH agonists – create a state of relative estrogen deficiency – vasomotor side effects and potential decrease in bone density - 12-month course of GnRH agonist therapy associated with 6% decrease in bone density - No data regarding extended treatment with GnRH agonists beyond 1 year

31. Endometriosis - Treatment • Add-back therapy is advocated for women undergoing long-term therapy (i.e. > 6 months) • Some evidence to suggest that immediate add-back therapy may result in even less bone loss - Add-back regimens: progestins alone, progestins + bisphosphonates, low-dose progestins + estrogens, pulsatile PTH

32. Endometriosis – Treatment Considerations in Adolescents • GnRH treatment is NOT recommended for patients < 18 years because the effects of these medications on bone formation and long-term bone density have not been adequately studied • Depo provera used for longer than 2 years has been shown to decrease bone density in adolescents – FDA warning against long-term use

33. Endometriosis – Treatment Considerations in Adolescents • If no improvement in symptoms after 3 months of empiric treatment with NSAIDs and OCPs, diagnostic laparoscopy should be offered

34. Endometriosis - Treatment • Surgery - Laparoscopic laser vaporization vs. cauterization vs. excision - Ovarian cystectomy for endometrioma - Hysterectomy +/- BSO

35. Endometriosis - Treatment • Medications vs. Surgery - Lack of data to support surgery vs. medical treatment for tx of pain symptoms due to endometriosis - Starting with empiric medical therapy is appropriate - Offer GnRH agonist therapy if initial medical treatment with OCPs and NSAIDs not helping - Cost of comparing empiric medical management with definitive surgical diagnosis is difficult to assess, but 3 months of empiric treatment is less than a laparoscopic procedure

36. Endometriosis - Treatment • Medications vs. Surgery - Surgery is associated with significant decrease in pain sx during the 1st 6 months following surgery - Approximately 40% experience recurrent symptoms within 1 yr post-op - Cumulative 5-yr recurrence rate of pain sx after d/c GnRH tx is ~50%

37. Endometriosis - Treatment • Medications vs. Surgery - No evidence exists regarding effectiveness of adjunctive tx w/ danazol, OCPs, or progestins post-op in comparison with surgical treatment alone in the management of endometriosis-related pain - However, 2 studies suuport the use of post-op GnRH agonists to extend the period of pain relief post-op

38. Case 2 • A 35 y.o. woman presents to your office with persistent RLQ pain. Her past medical history is unremarkable with the exception of a ruptured appendix 1 year ago requiring emergency surgery. Her abdominal and pelvic exams are also unremarkable with the exception of a well-healed appendectomy scar.

39. Case 2 • What questions would be important to ask in evaluating the patient? • What is the most likely diagnosis? • How would you treat this patient?

40. DDx Acute and Chronic Pelvic Pain • Acute - GYN or Non-GYN etiology - surgical emergency or not? • Chronic - GYN or Non-GYN etiology - conservative/medical management or surgery?

41. DDx Pelvic Pain - GYN • GYN - Uterus - fibroids, adenomyosis, endometritis - Fallopian tubes - PID/salpingitis, hydrosalpinx, ectopic - Ovaries - cysts – functional, pathological, TOA, torsion; mittleschmerz - Other - endometriosis, adhesions, IUD/infection, severe prolapse

42. DDx Pelvic Pain – Non-GYN • Urologic - UTI/urethritis, interstitial cystitis (IC), OAB, urethral diverticulum, nephrolithiasis, malignancy • GI - constipation, IBS, IBD (Crohn’s, UC), bowel obstruction, diverticulitis, malignancy, appendicitis • Musculoskeletal - trigger points, fibromyalgia, hernias, neuralgia, low back pain • Other - psychiatric – depression, somatization; abdominal cutaneous nerve entrapment in surgical scar; celiac disease

43. Pelvic Pain • Pain is always subjective • Chronic Pelvic Pain (CPP) – non-cyclic pain of 6 or more months duration that localizes to the anatomic pelvis, anterior abdominal wall at or below the umbilicus, the lumbosacral back, or the buttocks and is of sufficient severity to cause functional disability or lead to medical care

44. Pelvic Pain • Approximately 15-20% of women aged 18-50 years have CPP of greater than 1 year’s duration • 20-50% of women who receive care in primary care practices have > 1 diagnosis • Demographic profiles suggest no difference in woman w/ CPP compared to women w/o CPP in terms of age, race and ethnicity, education, socioeconomic status, or employment status

45. Populations at Increased Risk of CPP • Physical and sexual abuse • PID • Endometriosis • IC • IBS • OB history • Past surgery • Musculoskeletal disorders

46. Populations at Increased Risk of CPP • Physical and sexual abuse - 40-50% of women w/ CPP have a history of abuse - If a history of abuse is obtained, it is important to ensure that the woman is not currently being abused and in danger

47. Populations at Increased Risk of CPP • PID - Approximately 18-35% of all women with acute PID develop CPP - Whether acute PID is treated with outpatient or inpatient regimens does not appear to significantly alter the odds of developing subsequent CPP

48. Populations at Increased Risk of CPP • Endometriosis - Diagnosed laparoscopically in approximately 33% of women w/ CPP (other dx – adhesions, no visible pathology) - Abnormal exam findings correlate in 70-90% of cases w/ abnormal laparoscopic findings - More than half of those w/ abnormal laparoscopic findings have normal pelvic exams

49. Populations at Increased Risk of CPP • IC - Chronic inflammatory condition of the bladder characterized by voiding sx of urgency and frequency in the absence of another cause (such as infection) - As many as 38-85% of women presenting to gynecologists w/ CPP may have IC

50. Populations at Increased Risk of CPP • IBS - One of the most common disorders associated w/ CPP - Chronic relapsing pattern of abdomino-pelvic pain and bowel dysfunction with constipation or diarrhea