HEAVY MENSTRUAL BLEEDING IN ADOLESCENTS · Bleeding history Menses >7 days, soaking through...

HEAVY MENSTRUAL BLEEDING IN ADOLESCENTS

Melina Dendrinos, MDSEMCME OB/GYN

March 13, 2019

Objectives

Review normal menstrual cycles for adolescents Discuss causes of heavy menstrual bleeding in

adolescents Identify treatment options for heavy menstrual

bleeding in adolescents

Disclosures

No conflicts of interest to disclose.

FIGO Terminology

Abnormal uterine bleeding “unpredictable timing and variable amount of flow”

Intermenstrual bleeding Metrorrhagia

Heavy menstrual bleeding Menorrhagia

Acute AUB Acute menorrhagia

What is the normal cycle interval in early menses?

A. 28-45 daysB. 21-35 daysC. 14-35 daysD. 21-45 days

Normal early menses

Average age of menarche 12.4 yo Cycle interval 21-45 days Duration 3-7 days 3-6 pads or tampons/day

ACOG Committee Opinion, 2015

At what age should you evaluate a patient for primary amenorrhea?

A. 14B. 15C. 16D. 17

Menarche

Age of menarche 12-13yo Well-nourished populations, developed countries At 15yo: 98% of girls will have had menarche

Within 2-3 years of thelarche At Tanner Stage IV breast development

ACOG Committee Opinion, 2015

Cycle length

Varies widely WHO study of 3,073 girls

Median length of 1st cycle after menarche was 34d 38% of cycle lengths exceeded 40d 10% of females had >60d between 1st and 2nd menses

7% had a first-cycle length of 20d

During early years, cycles may be somewhat long because of anovulation

World Health Organization, 1986

Cycle length

By 3rd yr after menarche 60–80% of menstrual cycles are 21–34d

Around the 6th yr Individual's normal cycle length established

ACOG Committee Opinion, 2015

Ovulation

Earlier menarche associated with earlier ovulatory cycles If <12yo at menarche, 50% girls have ovulatory cycles

in 2nd year If later-onset menarche, may take 8-12 years until

cycles fully ovulatory

ACOG Committee Opinion, 2009

Menstrual conditions that may require evaluation

Primary amenorrhea w/in 3yr of thelarche by 13yo with no signs of puberty by 14yo with signs of hirsutism by 14yo with concerns of obstruction or anomaly by 15yo

Cycle length more frequently than every 21d or less frequently than every 45d >90 days apart (even one cycle)

Last > 7d Require frequent pad/tampon changes (more than every 1-2h)

ACOG Committee Opinion, 2015

Heavy menstrual bleeding (HMB)

Regular bleeding that is heavy or prolonged Heavy

Blood loss/cycle >80ml Soaking through pad/tampon in 1 hr Soaking through bedclothes Clots >1 inch

Prolonged >7 days

Emans and Laufer 2012

Significance of HMB in adolescence

Anemia 9-16% prevalence of iron deficiency in girls 16-19 Highest prevalence

Decreased QOL Increased school absences Decreased participation in social activities,

sleepovers, travel, and sports

Underlying pathology

Pawar 2008

What is the most common cause of HMB in adolescents?

A. Bleeding disorderB. PregnancyC. TraumaD. Anovulation

Differential for HMB

Anovulatory Pregnancy-related PID/endometritis Bleeding disorder Endocrine Trauma Systemic diseases Medications

Vaginal Mass

Cervical Mass

Uterine Structural, mass

Ovarian

(PALM-COEIN)

Causes of HMB by age

James 2012

*

Anovulation

Most common cause of HMB in adolescents

Emans and Laufer 2012

Anovulation

Majority of cycles are anovulatory for 1st 2 years But many girls have “normal” cycles

Delayed maturation of negative feedback cycle Rise in E2 does not cause ↓ FSH Results in incomplete shedding of proliferative endometrium Bleeding heavy, prolonged, irregular

Sustained anovulation

Eating disorders Weight changes Athletic competition Chronic illness Stress Drug abuse Endocrine disorders PCOS

Severity of anovulatory bleeding

Mild Longer than normal menses or shortened cycles for ≥2 months Slightly or moderately increased menstrual flow Hgb usually normal, may be mildly decreased (10-12 g/dL)

Moderate Moderately prolonged (eg, >7 days) or frequent menses every

one to three weeks Moderate to heavy flow Hgb ≥10 g/dL

Severe Heavy bleeding that leads to decrease in hgb (to <10 g/dL) May cause hemodynamic instability

Emans and Laufer 2012

Patient #1

12yo girl with heavy menses Menarche 3 mo ago Menses every 30 days, last 7 days Soaking through >1 pad/hr during 1st 2 days, missing

2 days school/mo ED visit last month for bleeding, hgb 9.8 No medical issues

Approach to evaluation of teen with HMB

Can simply observe if recent menarche Further evaluation if:

Continuous spotting Cyclic bleeding with superimposed bleeding throughout

the cycle Anemia Persistent heavy bleeding

Emans and Laufer 2012

Evaluation - History

Menstrual history Medical and surgical history Medications

Anticoagulation Hormones

Sexual history Family history

Pictorial blood loss assessment chart (PBAC)

Patient chooses degree of saturation of pads or tampons from chart

Score >100 associated with menstrual blood loss >80ml

Validity uncertain Must be collected

prospectively

Higham 1990

Evaluation

There’s an app…

Quality free period tracking apps: “Most available menstrual cycle tracking apps are inaccurate,

contain misleading health information, or do not function” Moglia et al, Obstet Gynec 2016

Clue Glow Period Tracker

PBAC in app form Cross-over study of 25 adolescents Liked the app better than the paper chart No difference in compliance

Jacobson et al, 2017, JPAG

There’s an app…

Assessment of an Electronic Intervention in Young Women with Heavy Menstrual Bleeding

Adolescents in bleeding disorder clinic N=35 Given iPod touch with iPeriod

50% completed study If compliant Less missed medication Less readmission Less breakthrough bleeding

Dietrich et al JPAG 2017

Evaluation - ROS

Recent stress, weight changes, eating disorders Bleeding:

Mucosal bleeding Prolonged bleeding from minor wounds Bleeding after surgical procedures Epistaxis lasting >10min

Visual changes, headache GI symptoms Acne, hirsutism

Evaluation – Pelvic exam?

Individualize Can defer in many cases

External genitalia exam One-finger digital exam

Check for foreign bodies, masses or obstruction in vagina, palpate cervix

Speculum exam Bimanual exam

Rectoabdominal exam as alternative

Evaluation – Pelvic Ultrasound?

Individualize Often not needed

Transabdominal usually sufficient

The patient’s history and physical are unremarkable. Does she need additional evaluation?

A. YesB. No

Patient #2

16yo G0 girl with almost daily bleeding with occasional large clots Normal periods until 6 mo ago No medical issues, no sexual activity Normal pelvic ultrasound No improvement on COCs

What is the red flag in this presentation?

A. A. Age > 14yoB. B. No response to

COCsC. C. Daily bleedingD. D. All of the aboveE. E. B and C

Cyclic versus acyclic

Cyclic: Normal intervals but heavy bleeding during each cycle

Acyclic: Normal intervals but superimposed bleeding at any time throughout the cycleRed flag Foreign body, mass, malformation, infection

Patient #2

Single-digit exam: cervical polyp OR for EUA, vaginoscopy

5cm vascular endocervical polyp

Polypectomy Pathology:

rhabdomyosarcoma

Evaluation - Labs

CBC, TSH, hcg Consider

Gonorrhea and chlamydia Prolactin, FSH, LH, androgens

Testing for bleeding disorders?

When to test for bleeding disorders

ACOG vWD screening in adolescents with severe HMB

ACOG + AAP Hematologic disorders (especially vWD) should be considered in

subjects with HMB

Bleeding history Menses >7 days, soaking through pads/tampons, or impairment of daily

activities History of treatment for anemia Family history of bleeding disorder Excessive bleeding with surgery or delivery

Heavy cyclic bleeding since menarche Significant drop in hgb or hgb<10

Philipp 2008

When to test for bleeding disoders

Are we testing? n=673 (Medicaid claims data) HMB diagnosis x 2 21% screened for anemia

Severe HMB: n=107 Inpatient stay for HMB, iron-def anemia, or blood

transfusion 24% screened for vWD 3% of severe dx with bleeding disorder

Underestimate

Khamees, Journal of Pediatrics 2015

Bleeding disorders

Thrombocytopenia Platelet function

disorders Abnormal collagen Connective tissue

disorders Clotting factor

deficiency von Willebrand disease

James 2008

• 1-2% of general population

• 10-100% of women with HMB

• Depends on population and type and severity of disorder

von Willebrand disease

Most common inherited bleeding disorder von Willebrand factor

Pharmacafe.com

– Adheres platelets to subendothelium

– Protects clotting factor VIII from proteolysis in the circulation

Bleeding disorders in adolescents with HMB

James 2008

James 2008

Bleeding disorders in adolescents with HMB

James 2008

Bleeding disorders in adolescents with HMB

James 2008

Bleeding disorders in adolescents with HMB

James 2008

Bleeding disorders in adolescents with HMB

Menses in adolescents with bleeding disorders

46% with heavy bleeding at menarche Only 27% with treatment plan prior to menarche ½ failed initial treatment

66% of those successful with subsequent therapy Combination of hormonal and non hormonal

Dowlut-Mcelroy et al, JPAG 2015

Women with HMB and underlying bleeding disorders

Byams 2011

*Counsel (and possibly treat) premenarchal girls with

bleeding disorders*

What to test

CBC PT, aPTT Fibrinogen VWD panel

vWF Ag, ristocetin cofactor activity, Factor VIII activity Elevated on hormones (test either prior or 7 days after

stopping)

Referral to Hematology Testing for platelet defects

initial labs

Treatment of HMB in adolescents

Hormonal Hemostatic

Minimal data in adolescents

Hormonal treatment of HMB

Minimal data in adolescents First-line = combined oral

contraceptives (COCs) Cyclic, extended-cycle, or continuous Well-suited to short-term treatment

But…any hormonal contraception can be considered first line

Hormonal treatment of HMB

Progestin-only contraceptives Levonorgestrel IUD Case reports

Oral norethindroneDMPA injections Etonorgestrel implant?

GnRH agonists

Oral norethindrone

Retrospective review of norethindrone in adolescents N=176 prescribed norethindrone 0.35mg dailyMost common indication HMB (32.9%) Contraindication to estrogen

Discontinuation rate = 48.5% Irregular bleeding

Can increase dose!

Taper given to 20 patients with acute HMB 78.9% stopped bleeding <7 days

Santos JPAG 2014

Hemostatic treatment of HMB

• DDAVP– Stimulates release of vWF– Use for <48hr

• Antifibrinolytics– Aminocaproic acid– Tranexamic acid 1300mg tid x 5d– Use for <5 days

DDAVP versus tranexamic acid

Crossover prospective study N=116 (adults)

HMB + abnl coags/platelet function

Assigned to intranasal desmopressin (DDAVP) or tranexamic acid (TA) x 2 cycles Switched x 2 cycles

Both decreased PBAC scores but TA more effective DDAVP-64.1, TA-105.7

Both improved quality of life

Kouides et al, 2009

Oral tranexamic acid vesus COCs

Pilot study Randomized crossover N=17 (adolescents)Only 9 completed both arms

PBAC score significantly improved with TA and COC No difference

COC: Decreased length of cycle TA: Improved compliance, less side effects

Srivaths et al 2015 JPAG

Tranexamic acid

Prospective, non-blinded efficacy study of 25 girls <18yo with HMB 1300mg tid x 5 days for 4 cycles (first with no TA)

In all, improvement in PBAC and MIQ (Menorrhagia Impact Questionnaire) No serious adverse effects

O’Brien et al 2019 JPAG

Acute abnormal uterine bleeding

Episode of heavy bleeding requiring intervention to prevent further blood loss

Guidelines for management of acute AUB

2011 Case reports, small case series

Expert opinion

Management of acute AUB

Exclude pregnancy, trauma, malignancy Admission if

hgb < 8 Orthostatic Bleeding is heavy and hgb < 10

Stabilize Fluid resuscitation Blood transfusion

IV estrogen is contraindicated in adolescents?

A. TrueB. False

Treatment of acute AUB

OCPs Every 4 hours until bleeding slows Taper Continue 1 tab bid for at least 2 weeks

Conjugated estrogen IV 25mg q 4 hours for 24 hours or until bleeding slows

Must add progestin w/in 24-48hr

Treatment of acute AUB

Progestin taper Norethindrone 5-10mg q4h Medroxyprogesterone 10mg q4h

Tranexamic acid IV 10 mg/kg q8 h Oral 20–25 mg/kg q8h

Clotting factor concentrates Anticoagulation reversal

Treatment of acute AUB

Failed medical therapy at 24-36 hours EUA to exclude pelvic pathology D&C rarely indicated If suspect endometrial proliferation or intrauterine

pathologyMay worsen bleeding

Hysterectomy very rarely indicated

Treatment of acute AUB

Suction D&C and foley balloon tamponade 12yo w/ PAI deficiency during 2nd menses

Uterine artery embolization 12yo w/ PAI deficiency during 1st menses

Uterine packing 14yo w/ Glanzmann’s thrombasthenia during 2nd

menses

Rouhani 2003; Bowkley 2007, Markovitch 1998

How are we treating acute AUB in adolescents?

Retrospective chart review N=150 Presented to ED, treatment by mainly ED physicians

Single and multidose taper OCPs Norethindrone IV estrogen

CBC performed in only 50% Not related to vital signs

Huguelet et al 2016 JPAG

Huguelet et al 2016 JPAG

Acute AUB in adolescents requiring hospitalization

Retrospective N=37 (adolescents <20yr)

19 w/ significant medical disease Average age at admission 15.9yr

46 admissions Cause:

anovulation (21), hematologic disease (15), chemotherapy-related (5), and infections (5)

Treatment OCP or progestins (30), IV estrogen (8), antibiotics (4),

IgG (3), DDAVP (3), and prednisone (1) D&C (8), LSC (3), hysterectomy (1)

Smith 1998

Conclusions

Menstrual cycle as vital sign Know the normal ranges

Large differential for HMB in adolescents Often anovulatory

Initiate further workup if concerning aspects or warning signs

Treatments are hormonal or hemostatic Consider use of tranexamic acid

Questions?