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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?
