Abnormal Uterine Bleeding- Sorting It All Out Patricia Geraghty MSN, FNP-BC, WHNP Disclosures • Abbvie Inc. Speakers Bureau, Advisory Board • Therapeutics MD Speaker, Advisory Board • Sharecare Inc. Advisory Board • No commercial material is included in this presentation. All citations are from peer-reviewed academic sources. The speaker has not been paid by any outside entity for this presentation or any presentation on this topic. Objectives • Define the variation in normal uterine bleeding. • Distinguish the etiology of abnormal uterine bleeding according to the PALM-COEIN classification system. • Determine age appropriate approach to the diagnostic work- up of abnormal uterine bleeding. • Select the management strategies for specific abnormal bleeding etiology utilizing an understanding of structural and hormonal interventions. • Differentiate the interventions for acute heavy uterine bleeding. Defining Normal • Normal menses (95% of population)1 • Frequency every 24 to 38 days • Duration 4 to 6 days • Blood volume 20-80 cc; requires change of protection every 3 to 6 hours on heaviest day(s) • Tapers over following days • 50% volume loss is vaginal and cervical secretions • Regular -difference between longest and shortest interval < 20 days in 12 month period 1Fraser I, et al. Fertil Steril. 2007;87(3):466-476. ACOG Committee Practice Bulletin. Ob Gyn. 2012; 120(1):197-206. Sharp HT, Johnson JV et al. Obstet Gynecol. 2017 Apr;129(4):603-607 Updating Terminology Dimension < 5th Percentile 5th-95th Percentile >95th Percentile Regularity cycle- Absent Regular (variation Irregular (typical variation to-cycle over 12 Amenorrhea 2 ± 20d) >20d between mos longest/shortest interval) Intermenstrual Frequency Infrequent (>38d) Normal Frequent (<24d) Oligomenorrhea Polymenorrhea Duration Shortened (< 4.5d) Normal Prolonged (> 8d) Hypomenorrhea Hypermenorrhea Volume Light (< 5 cc) Normal Heavy (> 80 cc) Hypomenorrhea Menorrhagia Combination Irregular and Heavy Menometrorrhagia Sharp HT, Johnson JV et al. Obstet Gynecol. 2017 Apr;129(4):603-607 Abnormal Uterine Bleeding Etiology & Pattern: PALM-COEIN FIGO Classification System Abnormal Uterine Bleeding (AUB) Coagulopathy Polyp Systemic Ovulatory dysfunction Adenomyosis Endometrial eiomyoma Structural L Iatrogenic Malignancy & hyperplasia Not yet classified Munro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13. Definitions • Polyp- endometrial or endocervical • Typically asymptomatic but may contribute to AUB • Typically histology benign w/only small fraction malignant • Detected via ultrasound and hysteroscopic imaging • Adenomyosis- endometrial cells w/in the myometrium • Link to AUB unclear w/increasingly heavy bleeding and pain • Traditional dx histopathology s/p hysterectomy but now diagnostic criteria through ultrasound or MRI • Leiomyoma- benign fibromuscular tumor of myometrium • Location, number and size • Relationship to endometrium and serosa affects AUB • Malignancy and Hyperplasia Munro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13. • Coagulopathy- systemic disorders of hemostasis • Etiology of 13% of heavy menstrual bleeding (HMB) • Include anticoagulation therapy HMB here • Ovulatory dysfunction- unpredictable timing, variable flow of which some are HMB • Many r/t endocrinopathies (PCOS, hypothyroid, hyperprolactinemia, mental stress, obesity, anorexia, weight loss, extreme exercise) • Endometrial- HMB in presence of regular ovulatory cycles and no other identifiable etiology • Documented deficiencies vasoconstrictors (endothelin-1, prostaglandin F2α), accelerated endometrial clot lysis (excess plasminogen activator)or excess local production vasodilators. • No clinical tests available; dx of exclusion Munro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13. • Iatrogenic- caused by medical intervention or device • Direct impact on endometrium, blood coagulation or systemic control of ovulation • Unscheduled bleeding aka break through bleeding (BTB) while on gonadal steriods • Effect both the HPO axis and the endometrium directly • Missed/delayed doses • Drug effect: anticonvulsants, rifampin & griseofulvin, cigarettes • Dopamine metabolism effects (tricyclic antidepressants, phenothiazines) reduce serotonin uptake and inhibit prolactin release. • Any SSRI can cause ovulatory dysfunction w/amenorrhea or irregular • Not yet classified- connection unclear or not yet identified Cycle The Menstrual • Ovarian follicular phase- follicle develops in response to FSH from the pituitary and secretes estrogen. Estrogen stimulates growth, or proliferation of the endometrium. • Ovulation- High levels of estrogen trigger LH from the pituitary, which causes ovulation. The follicular structure becomes the corpus luteum, and secretes progesterone. • Ovarian luteal phase- Progesterone halts growth and causes maturation of the endometrium. The endometrium becomes secretory. The corpus luteum degenerates over 14 days. Estrogen and progesterone levels fall, triggering increase in FSH. Managment Acute Heavy Menstrual Bleeding • Estrogen/Progesterone Sequential • Conjugated estrogen 10 mg (2.5mg po q 6h) to cause rapid growth of endometrium over denuded basalis • Controls bleeding within 24 hours • May need antiemetic • Alternate IV estrogen 20-25 mg every 3-4 hours x 24 hours • After bleeding slows dramatically (12-24 hours), add progestin MPA 5-10 mg to stabilize endometrium • Continue both estrogen and progestin for 7 to 10 days • Close follow up Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott, Williams & Wilkins. 2011. Alternate Protocol Acute HMB • Estrogen/Progesterone Combined • High dose birth control pill (Norgestrel 0.5mg/EE 50 mcg; Ovral®) • 1 Tablet PO Q 12h x 5-7 days, then 1 tablet QD to finish pill pack. • May taper sooner if bleeding is controlled, and if patient complains of side effects • One study found this protocol less effective than sequential but compliance was better • Follow up 7-21 days • Continue Norgestrel 0.5 mg/EE 50 mcg or Conjugated estrogen 2.5mg PO with MPA 5-10 mg • Begin diagnostic work up Fritz MA, Speroff L. Clinical Gynecologic Endocrinology and Infertility. 8th ed. Lippincott, Williams & Wilkins. 2011. Management Acute Heavy Bleeding With Concerns About Estrogen Use High Dose Progestin Treatments for Acute Uterine Bleeding (n=40) MPA 20 mg 3 times Norethindrone 1 mg/EE daily x 7 days, then 35 mcg 3 times daily x 7 once daily x 3 weeks days, then once daily x 3 weeks No Surgery 100% 95% Cessation of Bleeding 76% 88% Days to Cessation 3 3 Patient Satisfaction 0-4 3 3 0 = unsatisfied Munro MG, et al. Obstet Gynecol. 2006; 108(4): 924-29. Acute Bleeding Tranexamic Acid • Anti-fibrinolytic • Data from CRASH-2 (trauma) and WOMAN (obstetrical hemorrhage) extrapolated to other acute bleeding OFF LABEL • 1 g (100 mg/ml) at 1 ml/min IV • Only effective if initiated within first 3 hours of bleeding in PP hemorrhage • Meets ACOG guidelines for therapy CRASH-2 Collaborators. Lancet. 2010;376:23–32. WOMAN Trial Collaborators. Lancet. 2017 May 27; 389(10084): 2105–2116. ACOG Committee Opinion 557. Obstet Gynecol. 2013 Apr;121(4):891-6. ACOG Committee Opinion 785. Obstet Gynecol. 2019; 134(3)e71-83. Approach to Work-up Abnormal Uterine Bleeding (AUB) Coagulopathy Systemic Polyp Ovulatory dysfunction Adenomyosis Endometrial Leiomyoma Structural Iatrogenic Malignancy & hyperplasia Not yet classified Munro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13. Parameters for Evaluation • Evaluate any woman with • Cycles < 24 days or > 38 days • Duration > 7 days • Volume > 80 ml • Evaluate any woman whose perception of her cycles is that of interfering with typical daily activities or of causing concern • Deviations from individual’s established pattern • AAP and ACOG call the menstrual cycle a “vital sign” in adolescents • Cycles established within 3 years of menarche; evaluate any change, evaluate any pattern of cycles > 90 days ACOG Committee on Adolescent Medicine Opinion No. 349. Obstet Gynecol. 2006:180(5):1323- 28. AAP Committee on Adolescence , et al. Pediatrics. 2006; 118(5): 2245050. 19 y with HMB and Irregularity • She reports irregular cycle length of 14 to 60 days • Both flow and duration vary from 5-10 days of light spotting to 4 days heavy bleeding followed by spotting. • The heavy flow days require changing protection every 2 hours • There are no temporal associations (post-coital, post-pill, weight gain or loss) • She has associated symptoms of cystic acne and complains it is harder for her to maintain her weight than for her friends • She is not on any medications and denies tobacco use. • She is not sexually active and STD screen is up to date. 19 y with HMB and Irregularity FIGO Classification System Abnormal Uterine Bleeding (AUB) Coagulopathy Systemic Polyp Ovulatory dysfunction Adenomyosis Endometrial Leiomyoma Structural Iatrogenic Malignancy & hyperplasia Not yet classified Munro MC, Critchley HOD, Broder MS, et al. Int J Gyn Ob. 2011;113:3-13. Ovulatory Dysfunction • Physiologic unopposed estrogen causes heavy but unstable endometrium • Irregular heavy bleeding w/o typical moliminal symptoms mixed with spotting d/t partial endometrial sloughing • Life stage is most common contributing factor • Menarche followed by 2 to 3 years of infrequent cycles • Early perimenopause (age 40-42) frequent and heavy cycles • Late perimenopause cycles infrequent, flow is variable Polycystic Ovarian Syndrome (PCOS) • Increased peripheral aromatization of