Disclosures July 4, 2017. I have no disclosures. Management of abnormal uterine bleeding Jody Steinauer, MD, MAS Dept. Ob/Gyn & Reproductive Sciences University of California, San Francisco The Questions Case 1 • Too much – abnormal uterine bleeding A 46 year‐old woman reports her periods have – Differential and approach to work‐up become increasingly irregular and heavy over the • Too much – fibroids last 6‐8 months. Sometimes they come 2 times per • Too fast: She’s hemorrhaging—what do I do? month and sometimes there are 2 months between. • Side effect: due to hormonal contraception LMP 2 months ago. She bleeds 10 days with clots and frequently bleeds through pads to her clothes. She also has diabetes and is obese. 1: AUB and 2: fibroids 3: Acute hemorrhage 4: Contraceptive side effects 5: Bleeding in pregnancy Q1: Which is the first test should you order in this patient? Step 1: Pregnant? 1. FSH Pregnant Not Pregnant 2. Testosterone & DHEAS • Ectopic • Anovulation *** 3. Urine hcg • Spontaneous Abortion • Anatomic/structural ** 4. TSH • Threatened Abortion • Neoplastic * 5. Transvaginal Ultrasound (TVUS) • Molar Pregnancy • Infectious 6. Endometrial Biopsy (EMB) • Trauma • Iatrogenic • Other causes • Non‐gynecologic * = Most likely for this patient Terminology: What is abnormal? Pathophysiology: Anovulatory Bleeding • Normal: Cycle= 28 days (21‐35); Length=2‐7 days; Bricks & Mortar heaviness=self‐defined Estrogen=Bricks, build endometrium • Too little bleeding: amenorrhea or oligomenorrhea Progesterone (P) =Mortar, stabilizes, • Too much bleeding: Menorrhagia (regular timing but heavy only have P if ovulate (according to patient or >80cc) OR long flow (>7 days) Normal menses: Withdrawal of P • Irregular bleeding: Metrorrhagia, intermenstrual or post‐ causes wall to fall down, all at once coital bleeding (orderly bleed) Anovulation: No P so when wall • Irregular and Excessive: Menometrorrhagia grows too tall, it falls. It is heavy when wall is tall. Bricks can also fall intermittently & incompletely – • Preferred term for non‐pregnant heavy and/or irregularly, irregular irregular bleeding = Abnormal Uterine Bleeding (AUB) Bradley, AJOG, 2016 Abnormal Uterine Bleeding Reference: AUB Differential PALM-COEIN Uterus: Polyp, adenomyosis, leiomyoma, atrophy Not Pregnant Cervix: polyp, atrophy, trauma Vagina: atrophy, trauma Anovulation Uterus: Hyperplasia, malignancy Cervix: Dysplasia, malignancy Anatomic Ovary: hormone producing tumor Neoplastic Uterus: Endometritis, PID Cervix: Cervicitis Infectious Vagina: Vaginitis (eg Trich) Non‐Gynecologic Coagulopathy (vWD), severe renal or liver dz, GI or GU source History and Physical Examination Initial Work‐up: Menometrorrhagia • Hx: bleeding pattern, symptoms of anemia, sexual & • Always: Urine pregnancy reproductive history, chronic medical illness, medication • Usually: TSH • Acute v. chronic • Maybe: Hct, r/o coagulopathy • PE: signs of hypovolemia and anemia, thyroid • Maybe: EMB (Endometrial Biopsy) examination, gynecologic exam, abdominal examination, • Maybe but later: Transvaginal Ultrasound (screening for cervical dysplasia and STI) – Obesity: up to 60% of women who do not ovulate are obese – • Usually not necessary: FSH, LH, Testosterone, increased estradiol & testosterone; elevated insulin Estradiol disordered follicular development Do all women with AUB need an A Rational Approach to EMB ultrasound? Post‐Menopause: ALL women WITH ANY BLEEDING (except 4‐6 months Although TVUS is the best imaging choice for pelvic after HT) pathology (ie better than MRI, CT)…. Recent onset irregular bleeding: Consider treating first and if bleeding normalizes, no need for EMB • 80% with heavy menstrual bleeding have no >50: All women with recurrent, irregular bleeding (consider not doing if anatomic pathology periods light and spacing out) 45‐50: Recurrent irregular bleeding plus >1 risk factor OR > 6 mos • Incidental findings such as functional ovarian cysts menometrorrhagia (consider not doing if periods light and spacing out) and small fibroids (~50%) are often found leading <45: Long hx (>2 yr?) of untreated anovulatory bleeding or failed medical to anxiety and unnecessary treatments management EMB is not perfectly sensitive so further evaluation mandatory if: • SO….treat first, TVUS if treatment fails 1. Persistent AUB after negative EMB 2. Persistent AUB after 3‐6 months of medical therapy What about U/S instead of EMB for post‐ TVUS vs EMB to Detect Cancer menopausal bleeding? (in post‐menopausal women) Transvaginal Ultrasound TVUS EMB • Measure endometrial stripe 96% Sensitivity 94% • Abnormal= >4 mm (or 5) 61% Specificity 99% • Non‐specific: myomas, polyps also cause thick EM 99% NPV 99% • Operator skill mandatory 40‐50% Further w/u ? <5% necessary • NOT USEFUL PRE‐MENOPAUSE Can offer patient choice as long as either is quickly available and patient understands she may need EMB after U/S Q2: You decide to do a urine pregnancy test and check Q2: You decide to do a urine pregnancy test and check her TSH – which is the most appropriate next test? her TSH –which is the most appropriate next test? 1. FSH 1. FSH A 46 year‐old woman reports her periods have become 2. Testosterone & DHEAS 2. Testosterone & DHEAS increasingly irregular and 3. Serum beta‐HCG 3. Serum beta‐HCG heavy over the last 6‐8 months. Sometimes they come 4. Transvaginal Ultrasound 4. Transvaginal Ultrasound 2 times per month and 5. Endometrial Biopsy 5. Endometrial Biopsy sometimes there are 2 months between. LMP 2 months ago. She bleeds 10 days with clots and frequently bleeds through pads to her clothes. She also has diabetes and is obese. EMB=“Disordered Proliferative” How do I stop the bleeding? Treatment of AUB: NSAIDs Medical Surgical • Suppress prostaglandin synthesis, increase platelet NSAID’s Endometrial ablation aggregation, and reduce menstrual blood loss E+P pill, patch, ring D&C/Hysteroscopy • Reduces blood loss by 40% Oral Progestin Hysterectomy • Use alone or with other treatments Progestin IUD • Prescribe 5 days ATC IM Progestin – Ibuprofen, mefenamic acid, naproxen GnRH agonist Tranexamic Acid Disordered proliferative= Anovulation Treatment of AUB: CHC Treatment of AUB: Progestins • CHC – pill, patch, ring – improve cycle control, • Oral progestin – If ovulatory AUB = HMB: daily or days 5‐26 “extended use” decrease menstrual blood loss by 40% when used progestin decreases blood loss traditionally or continuously (MPA 2.5‐10mg qd, norethindrone 2.5‐5mg qd, NETA 5 TID) – Low satisfaction with extended use – One COC (with estradiol) approved by FDA for heavy – If anovulatory: cyclic progestin ‐12‐14 d/month improves menstrual bleeding menses in half of women – COCs often used to treat acute and chronic AUB • Injectable progestin – Few studies support up to 70% decreased EBL with COC – 50% amenorrhea after 1 year, irreg. bleeding in first few months and 50% at one year and one study with vaginal ring • Intrauterine progestin – Significant decrease in blood loss, superior to other progestins and CHCs Bradley, AJOG, 2016 Bradley, AJOG, 2016; Heikinheimo, Best Practice & Research Clin Ob Gyn, 2017. First Line Hormonal Treatments Where do you find the US MEC and SPR? • First choice: Levonorgestrel IUD – >80% reduction in blood loss, decreased cramping, prevents/treats hyperplasia, highly effective birth control – Blood loss and satisfaction comparable to ablation, satisfaction comparable to hysterectomy – Very few contraindications • 2nd choice: combined contraceptives (pill, patch, ring) or oral progestin (cyclic v. daily) or progestin injection – Decreases irregular perimenopausal bleeding – Any type ok, 20 mcg estrogen preferred for women >40 – Estrogen contraindications: smokers>35, HTN, complicated DM, multiple RF for CAD, h/o DVT, migraines with aura Birth Control Methods Treatment of AUB: Tranexamic Acid • Approved by FDA for treatment of ovulatory AUB • Prevents plasma formation, fibrin degradation, and clot degradation • In RCT’s, more effective than placebo, NSAID, cyclic progestin Medical • Dose: 1.0‐1.3 g every 6‐8 hours x 5 days Condition • Risks: Theoretic risk of VTE – contraindicated in history of or risk factors for VTE – not with CHC • Side effects: Minimal MEC Category Perimenopausal/Anovulatory Bleeding: Surgical Treatments Summary • D&C, Hysteroscopy: R/o pregnancy, thyroid dz – Not really a treatment EMB if meets criteria – Temporary reduction in bleeding – Curative if fibroid or polyp removed Treat first as if anovulatory bleeding: – NSAIDs + • Endometrial Ablation – Hormones (Levo IUD, CHC, DMPA) – Reduces but doesn’t eliminate menses If persists: – ~25% repeat ablation or hysterectomy in 5 years – U/S to check for anatomic causes (and – Must rule out cancer first EMB if not already done) – Can’t be done in >12 week uteri or for women who want fertility – Discuss surgical options for bleeding refractory to medical management. Heavy, irregular bleeding Case 2: Is it the fibroids? Fibroid Symptoms Same history as Case 1 except she has fibroids….On • Bleeding examination her uterus is 16 weeks’ size – Usually normal or menorrhagia (heavy but regular). Fibroids stretch • Very common 80% of hysterectomy specimens (done endometrium= more bleeding for any reason) and ~75% have on U/S at age 50 – Occasionally menometrorrhagia if • About 50% are asymptomatic submucous or intracavitary (Fibroids distort endometrium so it • Grow slowly until menopause and then decrease by can’t be stable) ~50% (can still cause bleeding post‐menopause) • Pressure (not pain) • Dysmenorrhea Heavy, regular bleeding