Abnormal Uterine Bleeding (AUB) / Dysfunctional Uterine Bleeding (DUB) Herbert L. Muncie, Jr., M.D. The main issues! How to control current bleeding? How to prevent future abnormal bleeding? Jeanie 16 year old comes in complaining of irregular heavy periods for 2 years No medical problems and using condoms for contraception since she became sexually active 3 months ago • What can reduce current heavy bleeding? • Not currently bleeding • What can reduce her risk of future irregular heavy bleeding? Jeanie - More History Question Answer When did her last period start? 10 days ago When was her PMP? How irregular are her periods? 6 weeks ago, usually every 6 - 8 weeks How heavy is the bleeding with most periods? Will sometimes have to change her tampon every hour, has soaked her clothes at times Is this heavy bleeding unusual? Has had heavier periods for almost 2 years, lasting 4 - 5 days Jeanie - More Data • • • • • Interval betweenTests cycles days Physical Exam ordered– 21 - 28 Results Proliferative (follicular) phase – 7 - 21 days Ht - 64 in; Wt - 126 Secretory (luteal) phase days BMI - 21.6 Pregnancy test – 14 ± 2 Negative BP 106/68; P 70 Bleeding duration – 2 - 6 days Average blood volume Normal general CBC lost - 45 ml physical No bruising or petechia Coagulation panel TSH - reflex Pending Pelvic exam - normal GC/Chlamydia probe Pending Normal Menstrual Cycle • • • Maturation of endometrium relatively uncomplicated ~ Dependent on estrogen and progesterone First half of cycle is estrogen - dominant ~ Halts menstrual flow & promotes proliferation (proliferative or follicular phase) Second half is progesterone dominant ~ Stops endometrial growth, then promotes differentiation (secretory or luteal phase) Normal Menstrual Cycle • • • • • Interval between cycles – 21 - 28 days Proliferative (follicular) phase – 7 - 21 days Secretory (luteal) phase – 14 ± 2 days Bleeding duration – 2 - 6 days Average blood volume lost - 45 ml Abnormal bleeding • Heavy – » > 80 ml blood loss with period • • • Doubtful clinical utility or significance » Changing pad > q 1 h at some point » Soaking through to her clothes Irregular intervals– > 35 days or < 21 days between periods Prolonged duration Flow > 7 days Jeanie - Follow-up Visit 3 days later Tests ordered Results CBC Hgb – 10.6 g/dL Hct – 31% MCV – 76 fl Platelet count 215,000 Coagulation panel PT – 12 sec INR – 1.1 aPTT – 22 sec TSH 1.76 mU/L GC/Chlamydia probe Negative Definitions Dysfunctional uterine bleeding (DUB) abnormal bleeding with no organic cause (neoplasm, inflammation, infection or pregnancy) but which can co-exist with organic pathology Abnormal uterine bleeding (AUB) - includes DUB and bleeding from structural or organic causes Assess for organic pathology • • • • • History Physical exam including pelvic Diagnostic tests ~ ~ ~ ~ Pregnancy test PAP smear if indicated CBC, TSH, coagulation panel Chlamydia, gonorrhea probe Pelvic/transvaginal ultrasound Endometrial biopsy in women over age 35 ~ Only 2% of endometrial cancers occur in women < 40 years old DUB & Bleeding Disorders • Screening for von Willebrand (vWD) disease with heavy menstrual bleeding? ~ ACOG recommends screening adolescents with severe menorrhagia, women whom abnormal bleeding etiology cannot be established & women undergoing hysterectomy » However, not sufficient evidence that it helps ~ 1% prevalence in general population DUB & Bleeding Disorders • Case finding with heavy menstrual bleeding ~ Up to 16% have vWD [James 2009] ~ Consider if any of the following: » » » » » Menorrhagia since menarche Minor wound bleeding > 5 minutes Bleeding oral cavity/GI tract without anatomic lesion Prolonged bleeding after dental extraction Unexpected postsurgical bleeding DUB & Bleeding Disorders • Case finding evaluation ~ Order CBC, PTT, PT & vWF level (ideally during menses) ~ No single test will establish the diagnosis ~ Positive family history usually necessary ~ Ask about any bleeding with dental procedures, T&A, peripartum bleeding » OCPs can mask type 1 vWD but don’t stop them » Patients with type O blood have 25 – 30% lower levels of vWF » In these patients with a lower level, a family history would be needed to confirm or exclude the diagnosis Menorrhagia – vWD treatment • If caused by vWD & not trying to get pregnant ~ Oral contraceptive would be treatment of choice ~ Progestin IUD alternative ~ Desmopressin (DDAVP®) or antifibrinolytics if pregnancy desired ~ Avoid NSAID with symptomatic vWD Jeanie Probable diagnosis – DUB • vWF ordered to be drawn during next menses vWF results – 35 IU/dL (low but not diagnostic) No family history or bleeding What can reduce her risk of future irregular heavy bleeding? • • Because combination oral contraceptives (OCP) are not contraindicated She was started on a monophasic OCP to decrease her flow and regulate her cycles Fran A 23 year old woman complaining of heavy menstrual bleeding. Her period started 2 days ago & today is very heavy. She has to change her tampon at least every hour. • • She has no medical problems Periods are usually regular What can reduce her current heavy bleeding? What can she do to reduce her risk of future heavy bleeding? Terminology/Descriptions Does Fran Have Definition Hypomenorrhea Abnormally reduced menstrual flow Oligomenorrhea Infrequent periods with normal flow Menorrhagia Regular periods with heavy flow Metrorrhagia Irregular periods with normal flow Menometrorrhagia Irregular heavy periods Terminology/Descriptions • • • There has been a lack of uniformity in definitions and descriptions of menstrual bleeding abnormalities February 2005, 35 international MDs met in Washington DC to define terms Settled on 4 key menstrual dimensions for description Terminology/Descriptions Dimension Regularity Frequency Duration Volume Categories Irregular Regular Absent Frequent Normal frequency Infrequent Prolonged Normal Shortened Heavy Normal Light Terminology/Descriptions Old terminology Regularity Frequency Duration Volume Hypomenorrhea Regular Normal Normal Light Oligomenorrhea Irregular Infrequent Normal Normal Menorrhagia Regular Normal Prolonged Heavy Metrorrhagia Irregular Frequent Normal Normal Menometrorrhagia Irregular Frequent Prolonged Heavy Is It Ovulatory or Anovulatory? • With any abnormal bleeding it is helpful to determine if it is ovulatory or anovulatory • Most DUB is anovulatory • In adolescents ovulatory cycles may take up to 3 years to be established • How can you determine if it is ovulatory or not? Normal Ovulatory Cyclic Function • • • Depends on regular pulsatile release of GnRH from hypothalamus ~ Which stimulates FSH & LH pulses from anterior pituitary Pulsatile FSH & LH leads to: ~ Folliculogenesis (proliferative or follicular phase) ~ Ovulation ~ Corpus luteum formation which sustains luteal phase (luteal phase) Atrophy of corpus luteum results in menses Is It Ovulatory or Anovulatory? Estrogen FSH LH Progesterone Menstruation Follicular phase Day 14 Luteal phase Is It Ovulatory or Anovulatory? • Ovulatory Cycles ~ regular intervals ~ mittelschmerz ~ serum P4 > 3 ng/ml ~ 2nd half cycle ~ biphasic BBT ~ Serum LH > 25 mIU/ml • Anovulatory cycles ~ irregular intervals ~ no ovulatory pain ~ serum P4 < 3 ng/ml ~ 2nd half cycle ~ monophasic BBT ~ Serum LH < 25 mIU/ml Fran – more information Answer Vital signs Ht – 67”; Wt – 146 lbs; BMI 22.9 BP 124/76; P 88; T 98.8 (O) Any other symptoms? A little dizzy when standing Contraception Used OCP until 6 months ago Using condoms past 4 weeks Physical exam Normal general exam Pelvic – active bleeding from os Uterus small nontender No adenexal mass Additional information Tests ordered Results Stat CBC Hgb – 11.6 g/dL Hct – 34% MCV – 76 fl Pregnancy test Negative TSH Results pending GC/Chlamydia probe Results pending Indicative of Heavy bleeding • • • • Soaking through pad or tampon < 1 hour Soaking through bed clothes Below normal ferritin Anemia ~ [James 2009] Regular heavy prolonged bleeding (Menorrhagia) • • Age ~ Any age Etiologies ~ Anovulatory in younger & older women » Immature hypothalamic-pituitary-ovarian axis in adolescents » Fluctuating estrogen levels each end of reproductive age ~ Typically due to anatomic lesion (e.g. fibroid) in women 30 – 50 years old Regular heavy prolonged bleeding • Etiologies ~ Ovulatory – either: » Corpus luteum insufficiency » Inadequate progesterone from primary ovarian failure or central/metabolic defect » Corpus luteum prolonged activity » Over stimulation of LH - irregular shedding » Do not have 14 day luteal phase Regular heavy bleeding • Etiologies ~ Up to 20% adolescents have bleeding disorder as etiology [Claessens 1981] ~ Consider Von Willebrand disease especially with family history of bleeding ~ If isolated prolonged PTT or normal PTT, PT, platelet count & fibrinogen with bleeding then specific test for VWD indicated Acute Bleeding - Treatment • Outpatient treatment ~ Start monophasic OCP ~ ~ ~ ~ 1 pill QID for 4 days 1 pill TID for 3 days 1 pill BID for 2 days then 1 pill a day for 3 weeks ~ If OCP contraindicated cycle with Provera® ~ Give 10 mg daily for 14 days, then stop for 14 days ~ Continue this cycle for 3 months Acute Bleeding –Treatment • Outpatient treatment ~ Oral conjugated estrogens (Premarin®) 2.5 mg QID until bleeding is controlled » Consider giving antiemetic with medication ~ D&C if no response after 2 - 4 doses or sooner if needed Fran – 23 year old • What can reduce her current heavy bleeding? • Started on combination OCP 1 pill qid for 4 days • Bleeding subsided significantly in 12 hours Acute Bleeding – Treatment • Inpatient treatment ~ Conjugated Estrogens (Premarin®) 25 mg IV Q 4 H until bleeding is controlled ~ Give antiemetic prophylactically ~ D&C if no response after 2 - 4 doses or sooner if needed Acute Bleeding - Treatment • Inpatient treatment ~ Simultaneous with IV Conjugated Estrogens (Premarin®) start monophasic OCP ~ ~ ~ ~ 1 pill QID for 4 days 1 pill TID for 3 days 1 pill BID for 2 days then 1 pill a day for 3 weeks ~ If OCP contraindicated cycle with Provera® ~ Give 10 mg daily for 14 days, then stop for 14 days ~ Continue this cycle for 3 months Fran After the acute bleeding is controlled. • What can she do to reduce her risk of future heavy bleeding? Regular heavy bleeding • Evaluation ~ ACOG does not recommend routine CBC, TSH or prolactin ~ Endometrial sampling rarely necessary since regular bleeding is less concerning for endometrial cancer Menorrhagia - Treatment • • • NSAIDs ~ Inhibit prostaglandin which increases platelet aggregation ~ Increase uterine vasoconstriction Mefenamic acid (Ponstel®) 500 mg tid had 30-50% decrease in flow Naproxen 375 mg bid effective Menorrhagia - Treatment • Tranexamic acid (Lysteda®) ~ Two 650 mg tablets tid ~ Stabilizes a protein that helps blood clot ~ Concern about increased risk of clots has not been confirmed in ongoing studies ~ Caution if combined with oral contraceptive ~ Contraindicated with history or increased risk of thrombosis or VTE Menorrhagia - Treatment • Treatment ~ Danazol 200 mg qd acceptable short-term » Synthetic androgen, suppresses LH & FSH which suppresses ovulation » Can start low 100 mg/d & titrate up » Rare side effects if < 600 mg/d Menorrhagia • Treatment ~ Levonorgestrel-releasing IUD (Mirena®) » Improved health quality of life [Hurskainen 2004] » Reduces blood loss more than NSAID, Danazol, OCPs, oral progesterone [Kaunitz 2010] Menorrhagia – treatment • • Unlikely to be beneficial ~ Oral progesterone (longer cycle) Likely to be ineffective or harmful ~ Oral progesterone (luteal phase) Fran • • • • What can she do to reduce her risk of future heavy bleeding? Because she did not want to become pregnant & had no contraindications to OCP She was started on a monophasic combination OCP & will return in 3 months She was given a prescription for mefenamic acid to be used if her next period was heavy Joan • 47 year old female with hypertension & type 2 diabetes ~ Complains of irregular heavier periods for the past 7 months ~ Married, non-smoker, BTL at age 32 ~ Ht 63”; Wt 187 lbs; BMI 30.5; BP 146/92; P 74 • • What other information do you need? What tests do you want to order? More information Results LMP PMP Duration of flow 12 days ago 37 days before LMP 8 days PMH: Hypertension Type 2 diabetes Medications: Lisinopril/HCTZ Metformin, ASA Physical exam Tests ordered General exam normal Pelvic – uterus 6 week size CBC TSH Pelvic ultrasound Pap smear Joan • • • • Probable diagnosis is anovulatory DUB Probably perimenopausal etiology What can be done about the irregular menses? What can be done to decrease the duration and excessive flow? Irregular Heavy Menstrual Bleeding (Menometorrhagia) • Etiology ~ Get decrease in estrogen & cannot initiate LH surge, therefore anovulatory ~ FSH level > 40 IU/L suggest impending ovarian failure ~ LH-FSH ratio > 2 compatible with chronic anovulation Irregular menstrual bleeding • Treatment ~ None medically required if that is only issue ~ OCPs will regulate menses if patient wants birth control & no contraindications ~ If OCP contraindicated cycle with Provera® ~ Give 10 mg daily for 14 days, then stop for 14 days ~ Continue this cycle for 3 months ~ Postmenstrual bleeding – “endometritis” ~ Doxycycline 100 mg bid for 10 days Irregular Heavy Menstrual Bleeding • Treatment – for non-acute active bleeding ~ Therapy indicated for these patients: » Bleeding > 7 days » Anemia from blood loss » Interferes with normal life activities Irregular Heavy Menstrual Bleeding • Treatment ~ Combination oral contraceptives » To reduce bleeding slowly over several days » Give standard OCP dosing » To reduce bleeding quickly in 24 hours » 1 pill qid for 5-7 days then » 1 pill bid for three weeks ~ May need to pre-medicate with antiemetic Treatment Menorrhagia – EBM • • For women considering hysterectomy, placement of levonorgestrel-releasing IUD resulted in similar outcomes & was more cost effective InfoRetriever ~ Randomized controlled trial after 5 years found no difference in outcomes (SOR 1b) ~ http://www.infopoems.com/irsearch/search_details.cfm?ID=60625&ResultKey=E&title=Prog esterone%20IUD%20effective%20for%20menorrhagia Summary of MedicalTherapies – Irregular Heavy Prolonged Bleeding Drug Levonorgestrel IUD Mean reduction Women blood loss (%) benefiting (%) 94 100 Oral PG (day 5-25) 87 86 Danazol 50 76 NSAIDs 29 51 OCP 43 50 Oral PG (day 12-26) -4 18 Joan Follow-up visit Tests ordered Results CBC Hgb – 11.1 g/dL Hct – 33.4% MCV – 88 fl TSH 2.6 mU/L (nl – 0.45 – 4.5) Pelvic ultrasound Diffuse uterine enlargement Endometrial stripe < 4 mm Ovaries normal appearance Menometrorrhagia - EBM • • Various types of surgery or IUD hormone device are effective in reducing heavy bleeding & suit most women better than oral medications Cochrane Review ~ Controlled randomized trials ~ Surgery reduced bleeding better at 1 yr. than medical therapy & IUD equally effective to surgery ~ Oral therapy suits minority of women ~ http://www.cochrane.org/reviews/en/ab003855.html Joan Treatment Options Treatment option Oral contraceptive Will control bleeding & make her regular Not contraindicated NSAIDS Would reduce flow but not effect regularity Progestine IUD Would control flow & frequency Would obviate the need for more invasive procedure Surgical options Ablative therapies would be a reasonable option Key Points - DUB • • • • • • History determines the pattern & probable etiology Four aspects: Regularity, frequency, duration & volume Always assess for organic etiology Pregnancy test, STDs, infection, etc Assess desire for contraception Oral contraceptive can frequently control the problem Key Points - DUB • • • • • Provide medical therapy that is effective and lowest risk for patient NSAIDs usually safe, OCPs, progesterone IUD, then surgery Discuss progesterone IUD for significant bleeding in older women who want to avoid surgery Surgery is final therapeutic option Multiple new modalities are effective What Questions do you have?