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Abnormal Uterine Bleeding1,2,3 1,2,3 ABNORMAL UTERINE BLEEDING Kellie Towriss BSP www.RxFiles.ca Jun 2015 Abnormal Uterine Bleeding (AUB)4 Goals of Treatment:10 FIGO & SOGC Classification of AUB6,16 Premenopausal: Any variation from the normal menstrual cycle, & includes changes 1. Manage underlying medical condition contributing to AUB. Causes (& some tx) of AUB in non-pregnant, reproductive aged women in regularity & frequency of menses, in duration of flow, or amount of blood loss 2. If anemia present- start iron supplementation (see below). Abnormal Uterine Bleeding during or between regular menstrual periods. 3. Manage AUB- restore predictability of menses or stop it entirely. Postmenopausal: spontaneous or unexpected uterine bleeding that occurs >1 year 4. Encourage patient to achieve & maintain healthy active lifestyle. Structural (PALM) Non-Structural (COEIN) after the last menstrual period. Important to rule out endometrial carcinoma! 5. Ensure activities of daily living (e.g. work, social) are achievable Often Surgical 4,5,6,7,8,9 Coagulopathy (AUB-C) Precipitating Causes: Treatment Considerations: Desire for fertility is often the Anatomic Causes (see examples under FIGO classification at upper right) determinant for medical vs. surgical approach. Tailor therapy to Polyps (AUB-P) Ovulatory Dysfunction (AUB-O) Systemic Causes: PCOS, obesity, uncontrolled DM, thyroid dysfunction, individual’s therapeutic goals, patient preference, patient age, Tx: LNG-IUS, DMPA, OCs, cyclic Adenomyosis (AUB-A) hyperprolactinemia, liver dx, kidney failure, leukemia, inherited bleeding contraception, underlying medical conditions or CI, presence of progestin disorders (e.g. Von willebrand’s, deficiencies in Factor XI, VII, or XIII, carrier for dysmenorrhoea, severity of bleeding & tolerance of AEs. hemophilia A or B, platelet function abnormalities), endometrial dysfunction Leiomyomas (AUB-L) Treatment Options: Surgery vs. Drug Therapy Factors to Consider6,11, 12 Endometrial (AUB-E) Drug-Related Causes: anticoagulants, antiepileptics (e.g. phenytoin, valproic acid), Medical tx: should be first line once malignancy & pelvic pathology antipsychotics (1st gen & risperidone), corticosteroids, herbal products (e.g. Malignancy/Hyperplasia have been ruled out due to invasiveness & risk unless: (AUB-M) Iatrogenic (AUB-I) chasteberry,danshen, ginseng, gingko, motherwort, & soy), hormonal Failure to respond to, or inability to utilize medical therapy (due to Tx. Hysterectomy contraceptives, levothyroxine, long-term estrogen therapy, NSAIDs, SSRIs, AE/CI); significant anemia Not Yet Specified (AUB-N) tamoxifen, TCAs; recent hx of epidural steroid injection (<2 months). Surgical options: endometrial ablation, hysteroscopic polypectomy, 4 Initial Assessment: myomectomy, & hysterectomy (only definitive/curative treatment) * Inherited Bleeding Disorders: if typical treatments fail, consider desmopressin or History: sexual & reproductive history, impact on social functioning & QOL, thyroid Note: approx. 50% of women who receive drug therapy eventually choose 6 factor replacement (consult hematologist) 13,14 dysfunction, coagulation disorders, family history of cancer, coagulation surgical treatment due to refractory bleeding or desire for definitive treatment Acute Bleeding Treatment:6,10,17,18 disorders, & co-morbid conditions, medication Anemia Treatment Considerations (see RxFiles pg. 138 & 164)15 IV estrogen, IV tranexamic acid, or OCs/progestins at high doses or in Physical: symptoms suggestive of anemia; abnormal vaginal discharge; pelvic pain Elemental iron (Fe++) 180-200mg/day e.g. Ferrous sulphate 900mg or pressure; weight; hirsutism (=180mg Fe++) po HS(~3 months to replenish stores) ± Folate multi-dose regimens (up to 3x/daily) Dilatation & curettage or ablation considered in urgent situations Lab: pregnancy test, CBC, TSH, prolactin, ferritin, Pap smear, STI eg. chlamydia, FSH/LH, Best to take on empty stomach (or HS) but GI AE; therefore can take Select Investigations: endometrial biopsy, transvaginal ultrasound, dilatation & with food but absorption 50% Reserve hysterectomy as last resort due to morbidity with acute curettage, hysteroscopy, saline infusion sonohysterography, bleeding disorders Ferrous gluconate tolerability but Fe++ (300mg=35mg Fe++) anemia & resulting impaired healing, further bleeding, & infection Post Menopausal: endometrial sampling ± ultrasound to rule out Recommend with Vit C >200-1000mg to absorption If patient presents with stroke (due to anemia), consider leuprolide hyperplasia/carcinoma SR and enteric coated forms GI AE, but absorption & $ acetate to manage bleeding until therapeutic plan determined TREATMENT OVERVIEW19,20,21,22,23 After Specialist/Gynecology consult: 2nd line agents include GnRH agonists, danazol & ulipristal Evidence suggests LNG-IUS superior to non-surgical treatment methods Adolescents: all else being equal, patient preference toward OCs and NSAIDs *Contraindications to combined OCs: see next page for drug comparison table; can be used until menopause if Pre-Menopausal Adult: higher suspicion for disease-related causes of AUB; patient preference toward LNG-IUS. non-smokers & no additional cardiovascular risk factors (e.g. Hypertension, obesity, DM). 123 ABNORMAL UTERINE BLEEDING: Drug Comparison Charts Kellie Towriss BSP www.RxFiles.ca Jun 2015 Form/strength Dosing $/yr Adverse Effects/ Contraindications Place in Therapy/ Evidence 24,25,26 HORMONAL OPTIONS- regulate menstrual cycle, likelihood of unscheduled/prolonged & heavy bleeding episodes (see RxFiles pg.125-127)27 Protect endometrium from unopposed estrogen & risk of Levonorgestrel AE: Minimal amount absorbed systemically - hormonal AE hyperplasia/carcinoma with addition of progestin Initial $360/5yr 31 Intrauterine System Most common : irregular bleeding/spotting (esp.in first 3-6months), women with AUB who desire reliable contraception (LNG-IUS) cramping, risk of expulsion & hormonal (breast tenderness, mood LNG-IUS28,29: Releases 20mcg daily for 5 years $70 3mos 12 mos 1yr MIRENA 52mg changes, acne) Rare: perforation, PID (low risk; more likely within ~20 days Menstrual blood loss: by 86% &97% , 20-80% ammenorrhic (less S OGC ‘14 after insertion); consider screen for STI risk via hx & physical exam before insertion effective than surgery for bleeding, similar QOL) [New USA: ”Mini-Mirena” [Releases 6mcg daily for 3 years ?? CI: large intracavitary pathology, breast CA, recurrent/recent PID Dysmenorrhea improves SKYLA 13.5mg] (Not yet available in Canada)] Note: caution with patients who are severely immunocompromised Other: most reliable in obese & overweight women30; may be used in or at high risk for sexually transmitted infections leiomyoma, adenomyosis, & bleeding dx; pelvic pain; efficacy for 3-5 Monophasic combined 1 tab TID until bleeding ceases (usually $235 AE: breast tenderness, mood change, fluid retention, breakthrough years but greatest seen in first 3 months oral contraceptives (OCs), <7 days), then taper to once daily bleeding, nausea, headache (Rare: VTE, stroke, MI) If difficult to insert in nulliparous : misoprostol 400mcg x1 inserted vaginally (30mcg Ethinyl Estradiol) taken continuously x 3 mos OR CI: history of stroke or VTE, uncontrolled HTN, migraine with 4hr prior to procedure (ensure pregnancy test negative!); insert during menses e.g. MIN-OVRAL Daily pill for 21d each month OR neurological sx, CAD, active liver dx, hx of breast CA, smoker >35yrs Combined OCs: {many opt for continuous use, without a pill-free interval} [Alternately, NUVARING or EVRA patch & 15 cigarettes/day {Triphasics NOT suitable!} Initial dosing varies in practice (e.g. initial 1 tab BID-QID) & duration (2-14d) cyclic or continuous, are options] Menstrual blood loss: by 40-50% In regard to ovarian cysts: Depot 150mg IM q12weeks $110 AE: irregular BTB or spotting, breast tenderness, nausea, weight Dysmenorrhea improves Medroxyprogesterone o OCs thought not to formation gain, mood disturbance, small in BMD reversible upon cessation DMPA: acetate DEPO-PROVERA o Progestin-only pills, LNG-IUS & CI: Pregnancy, breast CA, active liver disease, liver tumours Menstrual blood loss: ~60-70% hysterectomy formation slightly Progestin-only pills: Cyclic dosing AE: breast tenderness, bloating, weight gain, headaches, acne, mood changes, amenorrheic after 1st year Medroxyprogesterone irregular bleeding/spotting o Most cysts asymptomatic, small 5-10mg po from days 14- 28 Other: no published trials for AUB PROVERA,g 2.5, 5, 10mg tab 5mg po TID from day 5-26 (long-phase) $300 CI: pregnancy, breast CA, liver disease in size and resolve spontaneously Micronized Progesterone Prometrium contains peanut oil; should not be used if peanut allergy Progestin-only: PROMETRIUM 100mg cap 100-200mg po HS from days 14-28 Note: long-cycle (21 days) high dose progestin shown to heavy menstrual Menstrual blood loss: 50% achieve menstrual regularity; cyclic luteal-phase bleeding, but AE limits practicality is less effective than NSAIDs, tranexamic acid or danazol; luteal-phase [Norethindrone acetate NORLUTATE] [2.5-10mg po daily day 5-25 of cycle] [Norethindrone acetate (5mg) not commonly available in Canada] progestin alone not effective for heavy menstrual bleeding NON-STEROIDAL Anti-inflammatory Agents (NSAIDs) - total prostaglandin production to promote uterine vasoconstriction & bleeding in AUB Non-hormonal option 17 Naproxen NAPROSYN, Initial 1000mg x 1, then 500mg BID $130 AE: GI, gastritis, dypepsia, peptic ulcers, edema, phototoxic reaction,
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