Dell Childrens Hospital

DELL CHILDREN’S MEDICAL CENTER EVIDENCE-BASED OUTCOMES CENTER

Abnormal Uterine Bleeding Heavy Menstrual Bleeding in Adolescents

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Definition: sexually active, including consensual and coerced sex7. An acute episode of heavy menstrual bleeding is one that, in Specific questions should be asked to determine possibility of the opinion of the clinician, is of sufficient quantity to require bleeding/coagulation disorder (see Table 2 in Addendum 1). immediate intervention to prevent future blood loss1. Chronic medical conditions and current medications should Normal menstrual cycles in adolescents typically last for 7 be reviewed3 to assess for other possible etiologies of days of fewer and occur 21-45 days apart. The average cycle bleeding. requires the use of 3-6 pads or tampons per day2,3. Physical Examination: Focus on detecting signs of conditions Incidence: known to cause abnormal bleeding such as obesity, It is thought that up to 20-30% women experiences abnormal hirsuitism, acne, acanthosis that might suggest androgen uterine bleeding during their menstrual life2,4. excess/PCOS; thyroid enlargement or nodules that may suggest thyroid derangement; and bruising or petechiae that Etiology/Differential Diagnosis: might suggest bleeding disorders2. An external genitourinary Anovulation is the most common etiology of abnormal and abdominal exam should be performed in all patients uterine bleeding during adolescence5. During the first 2-3 presenting with abnormal bleeding. If the patient is sexually years following menarche, many cycles are anovulatory due active a speculum exam and bimanual exam should also be to the immaturity of the hypothalamic-pituitary-ovarian axis2 included. If the patient is experiencing pain and an internal which can subsequently lead to abnormal bleeding. There GU exam cannot be performed (ie patient not sexually active) are other causes of anovulation that also occur in adolescents a transabdominal pelvic ultrasound should be considered. which can also lead to abnormal bleeding. Bleeding disorders are found in anywhere from 5-24% of women with heavy Guideline Inclusion Criteria: menstrual bleeding6 and up to 20% of adolescents who Post-menarchal adolescent female (up to age 18) present with heavy menstrual bleeding3. An expanded Patient/parent report of heavy menstrual bleeding differential diagnosis is in Addendum 1. Guideline Exclusion Criteria: Diagnostic Evaluation: Pregnancy History: Menstrual history should include onset of menarche, Contraindication to estrogen cycle length and variability over time, amount of menstrual Active malignancy blood loss. A confidential history should establish if patient is Inability to tolerate po medication

Practice Recommendations and Clinical Management (for full recommendations see attached pathway and addendums)

Principles of Clinical Management The initial management of heavy menstrual bleeding should be based on vital signs, symptoms, hemoglobin level and bleeding status. Patient’s ability to take estrogen based on CDC medical eligibility8 should be assessed prior to any management decisions. The most relevant absolute contraindications to estrogen in adolescent patients are listed below.

Sample of absolute contraindications to estrogen8 History of migraine headache with aura Personal history of DVT/PE/CVA or known clotting disorder Malignant HTN Last updated: 5/4/2015 1

DELL CHILDREN’S MEDICAL CENTER EVIDENCE-BASED OUTCOMES CENTER

All patients should have a prompt hemodynamic assessment upon presentation. Significant hemodynamic compromise should be treated per normal protocol with fluid resuscitation and stabilization. Treatment of bleeding should be done simultaneously and per treatment protocol. If patient not able to take po medication, should be excluded from treatment algorithm. Once hemoglobin level is available, use level and amount of current bleeding to determine appropriate therapy.

Laboratory Testing: Urine hCG5 CBC5 PT/PTT5 Type and Screen TSH +/- free T47 Von Willebrand panel if screen (Table 2) positive3 Free/Total Testosterone, DHEA-S, FSH, LH if irregular cycles7

Imaging: In the majority of adolescents presenting with abnormal uterine bleeding with heavy and prolonged cycles, routine imaging is not needed as the etiology is typically related to anovulation and not structural causes. However, if the patient is complaining of abdominal or pelvic pain imaging may be warranted.

Sexually active patients with abdominal/pelvic pain and bleeding can be considered for a transvaginal pelvic ultrasound to augment the speculum and bimanual exam.

Non-sexually active patients with abdominal/pelvic pain and bleeding can be considered for a transabdominal ultrasound.

For patients whose bleeding is not responding to appropriate hormonal management at 24 hours, consider an ultrasound.

Pharmacotherapy: All patients who present with heavy menstrual bleeding should be discharged on iron therapy.

Patients with mild anemia can be started on NSAIDs9 if no contraindication exists.

Patients with more significant anemia should be started on combination oral contraceptive pills with dosing frequency dependent on hemoglobin and amount of current bleeding2,5,7,10.

Oral contraceptive pills should be monophasic (dose of estrogen and progesterone should be equal in every pill) and should contain 30-35 mcg of ethinyl estradiol. Examples include: Nortrel 1/35 (on formulary at DCMC),Lo/Ovral, Necon 1/35, Sprintec, or Mononessa. A well-known side effect of estrogen-containing therapy is nausea, thus patients starting on oral contraceptive pills may benefit from an anti-emetic 2 hours prior to dosing of pills.

Inpatient Management: Administration of oral contraceptive pills should begin immediately, once decision is made to admit (should start in the emergency room).

A pad count should be started to gain an objective measure of bleeding.

Reassessment of bleeding should occur in 12-24 hours and if bleeding has not slowed or stopped, therapy may need to be altered which can include one of the following: • Increased OCP dosing frequency to every 4 hours • Increased estrogen amount in OCP to 50mcg (Ogestrel) • Starting IV estrogen (Premarin) for 2-3 doses (must be done concurrently with an OCP to prevent bleeding recurrence when stopped) • Starting tranexemic acid. • In over 90% of cases of heavy menstrual bleeding in adolescents, bleeding stops with oral OCP therapy without need for escalation of care or surgical intervention7.

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DELL CHILDREN’S MEDICAL CENTER EVIDENCE-BASED OUTCOMES CENTER

Consult/Referrals: Adolescent medicine and hematology consults can be considered based on individual patient and clinician comfort.

Adolescent Medicine Clinic direct line: 512-324-6534 Indicate whether the patient was seen in the Emergency Department only or admitted to the hospital.

Patient Disposition Admission Criteria: Discharge Instructions: A patient with a hemoglobin level of less than 8 and active Patients should follow-up with Adolescent Medicine in 3-5 bleeding should be considered for hospital admission. days following discharge for a bleeding assessment as well as repeat CBC. Patients with hemoglobin of greater than 8 but less than 10 should be considered for admission if there are concerns All patients and parents should understand the risk of DVT/PE about their adherence to therapy and they have continued that accompany all estrogen-containing products. Signs and heavy bleeding , unstable vital signs, or persistently symptoms should be reviewed and instructions on what to do symptomatic. should these occur.

Discharge Criteria: Clear dosing instructions and taper schedule should be Patients who are discharged from the hospital should have provided to patient with dates and times of medication normal vital signs for age and no orthostatic hypotension, administration. Prescriptions should be sent to the pharmacy tolerating PO intake, and have a good follow-up plan in place with clear dosing instructions and dispense 3 packages for and be able to obtain medication prior to or immediately ICD9: 626.2. after discharge. They should have a good understanding of the dosing of the medication, given that it is often complex.

Physician should order 3 packages of Nortrel 1/35 to have available for the patient at discharge from inpatient service. Discharge prescription from the ED should be based on provider preference.

Consider discharge prescription for Ortho-Cyclen or Sprintec for uninsured patients.

Outcome Measures Discharge Prescription for OCP Hospital Length of Stay Emergency Department Length of StayAverage Cost 15 & 30 Day Readmission Rate

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ABNORMAL UTERINE BLEEDING HEAVY MENSTRUAL BLEEDING IN ADOLESCENTS DIAGNOSTIC & EVALUATION PATHWAY Sample of absolute contraindications to estrogen History of migraine headache with aura EVIDENCE-BASED OUTCOMES CENTER Personal history of DVT/PE/CVA or known clotting disorder Malignant HTN INCLUSION CRITERIA EXCLUSION CRITERIA (Refer to CDC recommendations for additional Post-menarchal female with heavy bleeding Pregnancy contraindications) 1 Active malignancy Intolerance to PO medication

Transfer to Emergency Department Bleeding Disorder Screen Unstable vital YES OR signs? Positive with any one of the following: Continue on ED Treatment Pathway Heavy menstrual bleeding since menarche Post-partum hemorrhage Surgery or dental-related bleeding NO Clots > 10mm Patient description as “gushing”

Transfer to adult Emergency Positive with any two of the following: Urine HCG Positive Bruising 1-2 times a month Department for evaluation by OB Epistaxis 1-2 times a month Frequent gum bleeding Family history of bleeding symptoms 2 Negative

Internal & External GU External GU examination including YES Sexually Active? NO examination speculum

GC/CT Testing Consider internal GU exam Patient Patient AND/OR Complaining of YES Complaining of YES Consider Serum HCG Transabdominal pelvic pelvic pain? pelvic pain? Consider transvaginal pelvic US ultrasound

NO NO

GC/CT Testing Screen for Bleeding Disorder

Positive for Von Willebrand Panel YES Bleeding Disorder?

Consider: FSH Does patient have YES LH irregular cycles? DHEA-S Free & Total T

Abnormal CBC with diff Uterine Type & Screen Bleeding TSH reflex to T4 Treatment PT/PTT Algorithm

Assess for contraindication to estrogen based NO YES on CDC/WHO medical eligibility criteria

Iron Consult/Call Adolescent Medicine FeSO4 325mg BID Dosing for treatment recommendations.

High dose of NSAIDs (If no contraindication) Naproxen DISCHARGE HGB > 11 10-15 mg/kg/day BID dosing Reevaluate in 3 months OR if symptoms change May follow-up with Adolescent Medicine May offer OCP per pt/family preference OCP Daily starting immediately. Continue for normal pack dosing. YES Bleeding HGB 10 - 11 SLOWING NO OCP Therapy: STEP 1: q12h until bleeding stops STEP 2: Daily pills

OCP Therapy: Bleeding YES HGB 9 - 10 SLOWING STEP 1: q12h until bleeding stops STEP 2: Daily (without placebos) until HGB > 10

ADMIT CRITERIA DISCHARGE CRITERIA 1) Concerns about adherence/ Stable vital signs treatment/transportation Consider Consult/Call Adolescent Medicine Follow-up plan in place HGB 8 - 9 2) Continued heavy bleeding NO Document 2 reliable phone numbers for patient Patient able to obtain medication 3) Unstable vital signs Reevaluate by phone next day prior to or upon discharge OR 4) Persistently symptomatic YES YES OCP Therapy: STEP 1: q6h for 2 days STEP 2: q8h for 3 days DISCHARGE Start OCP Therapy: STEP 3: q12h for 14 days Follow-up with Adolescent Medicine in 5 to HGB < 8 As soon as possible in ED STEP 4: Daily (without placebos) until HGB > 10 7 days for CBC and Bleeding Assessment

Consider Ondanestron 2h prior to OCP Therapy.

Discharge Instructions: 1.Review risks of thrombosis with estrogen-containing Oral Contraceptive Pills (OCP) medication. Signs and symptoms of DVT/PE should be explained and Inpatient instructions given on what to do should patient experience. ADMIT Nortrel 2.Clear dosing instructions for OCPs with taper instructions written Outpatient with times and dates of pills until follow-up. Monophasic OCP with 30 or 35 mcg ethinyl 3.Perscription should be sent to pharmacy with instructions to estradiol dispense 3 packages of Nortrel for ICD9: 626.2 + prescription to Options: Nortrel, Lo Ovral, Necon 1/35, Sprintec outpatient pharmacy. Uninsured patients should have prescription for or Mononessa) 2 Ortho-Cyclen or Sprintec. 4.Review what to do should patient start bleeding on therapy. 3

For questions concerning this pathway, Click Here Last Updated May 4, 2015 ABNORMAL UTERINE BLEEDING Sample of absolute contraindications to estrogen HEAVY MENSTRUAL BLEEDING IN ADOLESCENTS History of migraine headache with aura Personal history of DVT/PE/CVA or known INPATIENT TREATMENT PATHWAY clotting disorder EVIDENCE-BASED OUTCOMES CENTER Malignant HTN (Refer to CDC recommendations for additional contraindications) 1 INCLUSION CRITERIA EXCLUSION CRITERIA Post-menarchal female with heavy bleeding Pregnancy Oral Contraceptive Pills (OCP) HGB < 8 Active malignancy Inpatient HGB < 9 - 10 with: Intolerance to PO medication Nortrel Outpatient 1) Concerns about adherence/treatment/transportation Monophasic OCP with 30 or 35 mcg ethinyl AND estradiol 2) Continued heavy bleeding OR Unstable vital signs Options: Nortrel, Lo Ovral, Necon 1/35, Sprintec or Mononessa) 2 Begin Treatment Immediately Start pad count for objective measure of bleeding Consider transfusion needs on individual basis Consider Adolescent Medicine consult Consider Hematology consult if bleeding screen positive or results of screening tests positive

Assess for contraindication to estrogen based Consult/Call Adolescent Medicine YES on CDC/WHO medical eligibility criteria for treatment recommendations.

OCP Therapy: STEP 1: q6h for 2 days STEP 2: q8h for 3 days STEP 3: q12h for 14 days STEP 4: Daily (without placebo) until HGB > 10

Bleeding Assessment in 12 - 24 hours

Consult Adolescent Medicine

Consider 1 of the following: ↑ OCP frequency to q4h Bleeding NO YES Continue OCP Therapy ↑ Dose of OCP to 50 mcg (Ogestrel) SLOWING Premarin 25 mg IV q6 x 2-3 doses Oral tranexamic acid with hematology consult for dosing DISCHARGE CRITERIA Stable vital signs Follow-up plan in place Patient able to obtain medication prior to or upon discharge Discharge Instructions: 1.Review risks of thrombosis with estrogen-containing medication. Signs and symptoms of DVT/PE should be explained and instructions given on what to do should patient experience. DISCHARGE 2.Clear dosing instructions for OCPs with taper instructions written Follow-up with Adolescent Medicine in 3 to 5 with times and dates of pills until follow-up. days for CBC and Bleeding Assessment 3.Perscription should be sent to pharmacy with instructions to dispense 3 packages of Nortrel for ICD9: 626.2 + prescription to outpatient pharmacy. Uninsured patients should have prescription for Ortho-Cyclen or Sprintec. 4.Review what to do should patient start bleeding on therapy. 3

For questions concerning this pathway, Click Here Last Updated May 4, 2015 DELL CHILDREN’S MEDICAL CENTER EVIDENCE-BASED OUTCOMES CENTER Addendum 1

Table 12: Differential Diagnosis of Causes of abnormal uterine bleeding in Adolescents Anovulatory Bleeding Uterine Problems • Immature HPO axis • Submucous myoma • Nutritional deficiency/malnutrition • Congenital anomalies • Chronic illness • Polyp • Carcinoma • Use of IUD • Ovulation bleeding Endocrine Disorders Ovarian Problems • Hypo- or hyperthyroid • Functional cyst • Adrenal disease • Tumor • Hyperprolactinemia • Polycystic ovary syndrome • Ovarian failure Pregnancy-related complications Endometriosis • Threatened ab • Spontaneous, incomplete, missed ab • Ectopic pregnancy • Gestational trophoblastic disease • Complications of termination procedures Infection Trauma • Cervicitis • Vaginal laceration • Vaginitis • Endometritis • PID Bleeding Disorders Foreign body (retained tampon) • Thrombocytopenia (ITP, TTP, leukemia, apastic anemia, hypersplenism, chemotherapy) • Clotting disorders (von Willebrand disease, disorders of platelet function, liver dysfunction) Vaginal abnormalities Systemic Diseases • Carcinoma or sarcoma • Diabetes mellitus • Renal disease • Systemic lupus erythematosus Cervical Problems Medications • Cervicitis • Hormonal contraceptives • Polyp • Anticoagulants • Hemangioma • Platelet inhibitors • Carcinoma or sarcoma • Androgens • Spironolactone • Antipsychotics

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Table 2: Bleeding Disorder Screening Positive screen is one or more of the following: • Heavy bleeding since menarche Kouides Questionnaire • One of the following o Post-partum hemorrhage o Surgery-related bleeding o Bleeding associated with dental work • Two or more of the following o Bruising 1 or 2 times per month o Epistaxis 1 or 2 times per month o Frequent gum bleeding o Family history of bleeding symptoms • Clots >10 mm Adolescent Screen • Description of “gushing”

Table 3: Sample of absolute contraindications to estrogen8 History of migraine headache with aura Personal history of DVT/PE/CVA or known clotting disorder Malignant HTN

Distorted uterine cavity Breast cancer Cirrhosis (severe) Diabetes mellitus w/ nephropathy/retinopathy/neuropathy Endometrial cancer Gestational trophoblastic disease Systolic > 160 or diastolic > 100 Vascular disease Liver tumors (malignant or hepatocellular adenoma) Peripartum cardiomyopathy (moderately or severely impaired cardiac function) Puerperal sepsis Immediately post-septic abortion Pregnant Current purulent cervicitis or chlamydial infection or gonorrhea Stroke Thrombogenic mutations Tuberculosis (pelvic) Unexplained vaginal bleeding Viral hepatitis (acute or flare)

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1. Munro MG, Critchley HOD, Broder MS, Fraser IS. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113(1):3-13. doi:10.1016/j.ijgo.2010.11.011.

2. Gray SH, Emans SJ. Abnormal vaginal bleeding in adolescents. Pediatr Rev. 2007;28(5):175-182. http://www.ncbi.nlm.nih.gov/pubmed/17473122. Accessed February 15, 2015.

3. Sokkary N, Dietrich JE. Management of heavy menstrual bleeding in adolescents. Curr Opin Obstet Gynecol. 2012;24(5):275- 280. doi:10.1097/GCO.0b013e3283562bcb.

4. Friberg B, Kristin Örnö A, Lindgren A, Lethagen S. Bleeding disorders among young women: A population-based prevalence study. Acta Obstet Gynecol Scand. 2006;85(2):200-206. doi:10.1080/00016340500342912.

5. Practice bulletin no. 136: management of abnormal uterine bleeding associated with ovulatory dysfunction. Obstet Gynecol. 2013;122(1):176-185. doi:10.1097/01.AOG.0000431815.52679.bb.

6. Shankar M, Lee CA, Sabin CA, Economides DL, Kadir RA. von Willebrand disease in women with menorrhagia: a systematic review. BJOG. 2004;111(7):734-740. doi:10.1111/j.1471-0528.2004.00176.x.

7. Bennett AR, Gray SH. What to do when she’s bleeding through: the recognition, evaluation, and management of abnormal uterine bleeding in adolescents. Curr Opin Pediatr. 2014;26(4):413-419. doi:10.1097/MOP.0000000000000121.

8. U S. Medical Eligibility Criteria for Contraceptive Use, 2010. MMWR Recomm Rep. 2010;59(RR-4):1-86. http://www.ncbi.nlm.nih.gov/pubmed/20559203. Accessed February 23, 2015.

9. Lethaby A, Duckitt K, Farquhar C. Non-steroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane database Syst Rev. 2013;1:CD000400. doi:10.1002/14651858.CD000400.pub3.

10. ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women. Obstet Gynecol. 2013;121(4):891-896. doi:10.1097/01.AOG.0000428646.67925.9a.

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EBOC Project Owner: Maria Monge, MD

Approved by the Abnormal Uterine Bleeding Evidence-Based Outcomes Center Team

Revision History Date Approved: May 4, 2015 Next Review Date: May, 2017

Abnormal Uterine Bleeding EBOC Team: EBOC Committee: Maria Monge, MD Sarmistha Hauger, MD Meena Iyer, MD Dana Danaher RN, MSN, CPHQ Winnie Whitaker, MD Mark Shen, MD Sujit Iyer, MD Deb Brown, RN Thanhhao Ngo, MD Robert Schlechter, MD Patrick Boswell Levy Moise, MD Sujit Iyer, MD Tory Meyer, MD Nilda Garcia, MD Meena Iyer, MD Michael Auth, DO

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