Abnormal Uterine Bleeding

1. Abnormal Uterine Bleeding • John Bettler • UNM DFCM Resident School • February 1, 2017

2. Audience texts JOHNBETTLER830 to 22333 to join the session, then they text a response.PollEv.com/johnbettler830

3. Objectives 3 • Discuss the classification of abnormal uterine bleeding • Understand the evaluation of abnormal uterine bleeding in reproductive aged women • List the non surgical treatment options of abnormal uterine bleeding • Discuss the indications for surgical management for abnormal uterine bleeding

4. Many terms 4 Menorrhagia Hypermenorrhea Menometorrhagia Metrorrhagia Oligomenorrhea Polymenorrhea Amenorrhea

5. Nomenclature 5 Acute AUB “an episode of bleeding in a woman of reproductive age, who is not pregnant, that, in the opinion of the provider, is of sufficient quantity to require immediate intervention to prevent further blood loss.” Chronic AUB “bleeding from the uterine corpus that is abnormal in duration, volume, and/or frequency and has been present for the majority of the last 6 months.”

6. What’s normal bleeding?

7. What volume of blood is in a soaked, regular-sized tampon or pad? 7 • 5 L • 10 mL • 5 mL • I don’t know, I’m a dude! • 1 mL

8. What’s normal? 8 1 normally soaked “regular” product is approximately 5mL of blood, a “super” or “maxi” size holds 10mL

9. Etiology of AUB

10. We need a mneumonic! 10 • HELPERR • CHADSVASc • SIGECAPS • O BATMAN! • I GET SMASHED • ABCDEFGH • PPPPPPP

11. If I had a coin in my palm for every women with AUB… 11

12. Classification: PALM-COEIN 12 Causes of AUB in nonpregnant reproductive-aged women International Federation of Gynecology and Obstetrics, 2011

13. Structural causes (PALM) 13 • Polyps – AUB-P ◦ endocervical or endometrial • Detected by ultrasound or sonohysterography • Often irregular, light bleeding

14. Structural causes (PALM) 14 • Adenomyosis –AUB-A • Controversial as a cause of bleeding • Diagnosed with ultrasound, MRI, pathology

15. Structural causes (PALM) 15 • Leiomyoma – AUB-L ◦ Submucous ◦ Intramural ◦ Subserosal • Diagnosed with exam, ultrasound, MRI, CT • Heavy, regular bleeding

16. Structural causes (PALM) 16 • Malignancy and hyperplasia – AUB-M • Diagnosed by biopsy • Irregular bleeding

17. Non-structural causes COEIN 17 Coagulopathies or bleeding disorders Ovulatory dysfunction Endometrial Iatrogenic sources (medications, smoking) Not yet classified

18. Causes of AUB - Anovulatory 18 • Most common cause of AUB • Many reasons for anovulation • Physiologic • PCOS • Stress, weight change, exercise • Endocrine ◦ Thyroid, PRL ◦ Secreting tumors

19. So She’s bleeding, now what?!?

20. Diagnosis: H&P 20 • History • Acute vs Chronic • Characterize bleeding pattern • Menstrual bleeding hx (incl. severity and assoc pain) • FamHx: AUB/ bleeding disorders • Meds: warfarin, heparin, NSAID, OCP, ginkgo, ginseng, motherwort • Physical • PCOS: obesity, hirsutism, acne • Thyroid dysfunction: cold/heat intolerance, dry skin, lethargy, proptosis • DM: acanthosis nigricans • Bleeding disorder: petechiae, pallor, signs of hypovolemia • Pelvic exam ◦ Is it from the uterus?!

21. Diagnosis: Labs and Imaging 21 • Labs • Pregnancy test (Strong recommendation) • CBC (Strong recommendation) • Targeted screening for bleeding disorder (when indicated) • TSH • Gonorrhea/Chlamydia in high risk patients • Imaging: • TVUS • Sonohysterography • Hysteroscopy • MRI • Endometrial biopsy

22. Uterine Evaluation 22 Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012 Jul;120(1):197-206. doi: 10.1097/AOG.0b013e318262e320.

23. Who should get an EMB? 23 • Women aged > 45 years as first-line test • Women aged > 35 years as first-line test • Women aged < 45 years with risk factors for endometrial cancer • Women aged < 35 years with risk factors for endometrial cancer • Women with persistent bleeding refractory to medication, regardless of age

24. Who should be offered EMB? 24 ◦women aged > 45 years as first-line test ◦ women with persistent bleeding refractory to medication, regardless of age ◦ women aged < 45 years with risk factors for endometrial cancer, such as ◦ obesity (body mass index > 30 kg/m2) ◦ nulliparity ◦ hypertension ◦ irregular menstruation ◦ polycystic ovary syndrome ◦ diabetes ◦ hereditary nonpolyposis colorectal cancer ◦ family history of endometrial cancer Practice bulletin no. 128: diagnosis of abnormal uterine bleeding in reproductive-aged women. Obstet Gynecol. 2012 Jul;120(1):197-206. doi: 10.1097/AOG.0b013e318262e320.

25. Endometrial biopsy 25

26. EMB Considerations 26 • Consent • Cramping is common • vaginal bleeding for several days • vasovagal • pelvic infection • uterine perforation (1 to 2 per 1000 procedures - vs 3 to 26 per 1000 D&C) • Contraindications • Active vaginal/pelvic infection • bleeding diathesis • pregnancy • Preprocedure prep • Anesthesia not required, consider NSAID 30-60 min prior • Difficult passage - consider 200 to 400 µg misoprostol night before (PV>PO) • Don’t need prophylactic abx Comparison of endometrial aspiration biopsy techniques: specimen adequacy. Sierecki AR, Gudipudi DK, Montemarano N, Del Priore G Reprod Med. 2008;53(10):760. 

27. EMB procedure 27 Am Fam Physician. 2001 Mar 15;63(6):1131-5, 1137-41. Endometrial biopsy. Zuber TJ • Bimanual • Speculum then clean cervix • +/- tenaculum (if not axial) • Insert pipelle - stop @ resistance (avg 6-8cm) • Pincer grasp, Pull out piston for suction • Corkscrew combined w/ cephalic-caudal motion to sample entire endometrial surface • Don’t remove until sampling completed • Expel the specimen into a formalin container (replace piston) • Consider second pass if insufficient tissue ◦ If the biopsy material looks like a dark red earthworm and does not disintegrate in the formalin, it is likely that appropriate biopsy material has been obtained. • Remove tenaculum, hold pressure w/ Texas swab PRN

28. How reliable is the EMB result? 28 For diagnosis of endometrial cancer, outpatient endometrial biopsy had ◦ likelihood ratio 66.48 (95% CI 30.04-147.13) for a positive test result ◦ likelihood ratio 0.14 (95% CI, 0.08-0.27) for a negative test result In cases of abnormal uterine bleeding in which symptoms persist despite a negative biopsy, further evaluation and input from individual patients is recommended. BJOG 2002 Mar;109(3):313 only 34% of patients had an adequate sample Saso S, et al. Endometrial cancer. BMJ.2011;343:d3954.

29. Hysteroscopy 29 MRI U/S Sonohysterogram

30. Management

31. Management 31 • Medical management should be initial treatment for most patients • Need for surgery is based on various factors (stability of patient, severity of bleed, contraindications to med management, underlying cause) ◦ Type of surgery dependent on above + desire for future fertility • Long term maintenance therapy after acute bleed is controlled

32. Treatment - Acute 32 • Unstable? • High dose hormones vs D&C ◦ IV estrogen – 25 mg IV q 4-6 hours x 24 hrs • Endometrial balloon tamponade • Stable • Oral meds ◦ Monophasic OCPs – One TID for seven days, then daily for at least one cycle ◦ Medroxyprogesterone (Provera) – 20 mg TID for seven days, then daily for at least three weeks ◦ Tranexamic acid (Lysteda) – 1.3 mg TID on days 1-5 of cycle

33. Chronic Treatment Considerations 33 • Etiology and severity of bleeding (eg, anemia, interference with daily activities) • Associated symptoms (eg, pelvic pain, infertility) • Contraceptive needs or plans for future pregnancy • Contraindications to hormonal or other medications • Medical comorbidities • Patient preferences regarding medical versus surgical and short-term versus long-term therapy

34. Non-surgical treatment Options 34 • Expectant management • NSAIDs • Antifibrinolytic agents - Tranexemic acid (Lysteda) • Hormonal methods • Combination methods • Levonorgestrel IUD • Cyclic progestin • GnRH agonists (leuprolide) • Metformin and other insulin-sensitizing drugs for irregular bleeding in women with polycystic ovary syndrome

35. Surgical Management Options 35 • D&C • Endometrial Ablation • Uterine Artery Embolization • Hysterectomy

36. Ready to test your knowledge?!

37. Case 1 37 A 35 year old female is evaluated for a 5 month history of heavy menstrual bleeding. She has been menstruating for the last 8 days and is still going through 10 maxi pads or more daily with frequent clots. She has fatigue but no dizziness. She and her husband would like to conceive a 2nd child next year. She does not smoke. PMHx: DM2 Vitals: Afebrile, BP 138/71, HR 80. Neg orthostasis. BMI 40.2 Pelvic exam: moderate amount of blood in vaginal vault. What do you want to do next?

38. Case 1(continued) 38 urine hcg is negative. Hct 30 EMB is negative. Pelvic u/s shows a large submucosal fibroid. You consult ob/gyn for a myomectomy, scheduled in 2 weeks. Which of the following is the most appropriate next step in management? • Levonorgestrel IUD (Mirena) • IV estrogen • Estrogen-progesterin oral contraceptive • Re-evaluate in 2 weeks

39. Case 1: Correct Answer = C 39 Estrogen-progestin OCPand IUD are effective treatments for heavy menstrual bleeding. Estrogen/progestin OCP is the better choice as pt is planning to conceive in the near future. Pt also does not have any contraindications to estrogen. IV Estrogen (B) would be appropriate if pt was orthostatic or dizzy from blood loss. PE and DVT are complications of IV estrogen. Monitoring (D) is not appropriate given her significant, ongoing blood loss.

40. Case 2 40 49 year old women presents to your primary care clinic with a 3 day history of heavy menstrual bleeding. She denies dysmenorrhea but reports that her menstruation cycle have been increasingly irregular over the past couple years, including bleeding between periods. She is not sexually active and had a bilateral tubal ligation 10 years ago.Her physical exam demonstrated normal vital signs, no signs of hypovolemia, no bruises. Pelvic exam was unremarkable for tenderness, nodularities, or abnormal size uterus. Cervix was normal with blood in the os. What do you want to do next?

41. Case 2 (continued) 41 Pregnancy test is negative and pap smear was performed and was wnl. Which of the following is the most appropriate next step in management of this patient? • Endometrial biopsy • Measure serum LH and FSH • Pelvic U/S • Oral contraceptives

42. Case 2: Correct Answer = A 42 • Endometrial biopsy—Need to rule out endometrial cancer in patients older than 45 with AUB • Measuring LH and FSH can confirm menopause, but does not rule out endometrial cancer. • Pelvic ultrasound– good with uncertain findings on pelvic exams • Oral contraceptives are appropriate for patients with anovulatory bleedings. But endometrial carcinoma needs to be ruled out first

43. Case 3 43 26 year old female presents with 4 days of history of light vaginal bleeding after intercourse. Prior to this incident, she reports regular menstruation cycle and no vaginal discharge. She is in a monogamous relationship with her husband. Her physical exam was unremarkable. Her pelvic exam was unremarkable except small amount of blood in the cervical os. What is the next best step in management? • Perform endometrial biopsy • Start oral contraceptive • Perform pelvic ultrasound • Urine HCG

44. Case 3: Correct Answer = D 44 • Endometrial biopsy is important to rule of endometrial cancer. In this younger patient, need to rule out more common causes initially • Oral contraceptives are appropriate in anovulatory women. However, need to rule out endocrine and pregnancy first • Pelvic ultrasound important for the identification of anatomical abnormalities or staging of pregnancy. However, pelvic exam was unremarkable and screening of pregnancy with serum markers has not been performed yet • Urine HCG– Pregnancy is a common cause of abnormal uterine bleeding and needs to be ruled out in all women who have not gone through menopause

45. Case 4 45 A 46 year old woman presents to your office with a complaint of intermenstrual bleeding. Her last menstrual period ended 10 days ago, however for the past 3 days she noticed bleeding requiring 3-4 pads/daily. She reports that prior to this her periods were regular, lasting 5 days with occasional light intermenstrual bleeding over the last 6 months. She is sexually active only with her husband and uses barrier contraception. On physical exam she was afebrile, BP 134/86, HR 74, negative orthostasis. Pelvic exam demonstrated slightly enlarged, globular uterus, with blood noted in cervical os. Pregnancy test is negative. Which of the following is the most appropriate next step in the evaluation of this patient? • Magnetic resonance imaging • Transvaginal ultrasound • Hysteroscopy • Reassurance and monitoring

46. Case 4: Correct Answer = B 46 • MRI is not the primary imaging modality to evaluate AUB, however may be used as a follow-up test after ultrasonography • Transvaginal ultrasound is important in this patient with AUB and exam findings suggestive of structural abnormality. Would consider EMB as >45 yo. • Hysteroscopy/SIS should be done in patients with concerning uterine cavity findings on TVUS • Monitoring would not be appropriate in the setting of abnormal bleeding and concerning physical exam findings

47. Case 5 47 A 29 year old woman presents to your office with a complaint of heavy menstrual bleeding. She has been menstruating for the last week with persistent heavy bleeding and passage of clots. She denies being sexually active. She is a current smoker (1-2 pack/day) and her only medications are metformin and lisinopril. On physical exam she was afebrile, BP 154/102, HR 62, negative orthostasis. BMI 31. Pelvic exam demonstrated moderate amount of blood in vault. What do you want to do?

48. Case 5 (continued) 48 Pregnancy test negative. Endometrial biopsy was performed and results are negative for malignant or hyperplastic disease. Which of the following is the most appropriate next step in the management of this patient? • Estrogen-progestin oral contraceptive • Endometrial ablation • Levonorgestrel (Mirena) IUD • Hysterectomy

49. Case 5: Correct Answer = C 49 • Estrogen-progestin OCPs are effective in the treatment of heavy menstrual bleeding, however this patient has several risk factors for thrombosis • Endometrial ablation is a minimally invasive option in patients in which medical therapy has failed. Medical therapy should be initiated, also it is unknown whether the patient wants to maintain fertility • Levonorgestrel IUDs are effective in the treatment of heavy menstrual bleeding and would be an appropriate choice in this patient with contraindications to estrogen use • Hysterectomy is curative in the treatment of uterine bleeding, however medical therapy and less invasive treatments are preferred initially

50. Thank you!Now let’s go play with Pipelles!