Dysfunctional Uterine Bleeding in the Adolescent

Dysfunctional Uterine Bleeding in the Adolescent

Jennifer E. Dietrich MD, MScDivision of Pediatric and Adolescent Gynecology

Department of Obstetrics and Gynecology

Baylor College of Medicine

Disclosures

• I the following financial relationships with a commercial interest:

• CSL Behring

• Merck

• Duramed

• Bayer

Basic Terminology can be Confusing

• Polymenorrhea

• Oligomenorrhea

• Amenorrhea

• Metrorrhagia

• Menometrorrhagia

Polymenorrhea

• Frequent regular or irregular bleeding at <21 day intervals

Oligomenorrhea

• Infrequent irregular bleeding at >35 day intervals

Irregular Menses

• Bleeding at varying intervals >21 days but <45 days

Metrorrhagia

• Intermenstrual irregular bleeding between regular periods

Menorrhagia

• Excessive amount and increased duration of uterine bleeding >7 days, occurring regularly

Menometrorrhagia

• Frequent irregular, excessive prolonged episodes of uterine bleeding >7 days in duration

Pubertal Effects

• Menses should occur ~2 years after thelarche

• Expect menses to gradually become more regular

• Most adolescents should have regular cycles within 2-3 years of menarche

What is a normal menstrual cycle for an adolescent just beginning menarche?

• Average age of first menses is 12.5 years of age

• Menstrual cycles can be irregular for up to three years after onset of the first cycle

• Bleeding should occur between every 21-35 days– <21 days between cycles Needs evaluation!– >35 days between cycles Needs evaluation!– With each menstrual cycle, bleeding that lasts for more

than 7 days Needs evaluation!

General Features of Menses by Gynecologic Year

• First Gynecologic Year– 5 % = 23 days– 95 % = 90 days

• Fourth Gynecologic Year– 95 % = 50 days

• Seventh Gynecologic Year– 5 % = 27 days– 95 % = 38 days

• Cycle length more VARIABLE for teens than women 20-40 years of age

Treloar AE et al. Variations in the human menstrual cycle through reproductive life. Int J Fertil, 1967. 12: 77-126. 275,947 cycles in 2702 women over 27 years.

Menstruation: Additional Practical Points

• Educate Moms and Daughters about what is normal in the first year:

– 21-45 days (how to count)– </= 7 days of flow– 3-6 pads/day is typical

• Variation in pad/tampon capacity – WRITE IT DOWN!

Menstrual calendar

The most common causes of DUB in an adolescent

• Annovulation

• Infections

• Do not forget to check a pregnancy test!

Importance of History

• Timing• Menstrual history• Pad/tampon count and size• Presence of vaginal discharge• Presence of abdominal pain• Past medical history• Medication exposures• Personal and/or family history of easy bruising,

gingival bleeding or epistaxis

Physical Exam

• Assess stability—check vitals

• General- presence of noticeable factors (ie., hirsute features)

• Thyroid

• Breast

• Abdomen

• Pelvic

Differential Diagnosis

• Annovulation (most common)– Due to immaturity of the hypothalamus– Hypothalamic dysfunction– Polycystic ovarian syndrome

Strickland J, Gibson EJ, Levine SB. ”Dysfunctional uterine bleeding in adolescents,” J Pediatr Adolesc Gynecol. 2006; 19(1):49-51.


• Pregnancy-related– Miscarriage– Ectopic pregnancy– Retained products after elective termination



• Chronic Diseases– Renal– Liver

– Thyroid– Diabetes



• Infections– Chlamydia– PID

– Shigella



• Neoplasms– Vaginal/cervical tumors– Polyps– Hemangiomas– Leiomyomas– Granulosa cell tumor

– Sertoli-Leydig cell tumor



• Other– Endocrine Disorders (thyroid is most common)– Anorexia Nervosa– Medications



• Hematologic– Von Willebrand’s– Platelet function defects– Idiopathic thrombocytopenic purpura– Other rare bleeding disorders


In the U.S.

• Over 2-3 million U.S. women have an underlying bleeding disorder.

• >300,000 hysterectomies/year occur for menorrhagia alone

James A. More than menorrhagia, a review of the obstetric and gynecological manifestations of bleeding disorders. Haemophilia. 2005; 11:295.

Bleeding Disorders

• In the general population 1% of individuals worldwide are diagnosed with von Willebrand’s Disease.

• Bleeding disorders are common in women with menorrhagia with prevalence ranging from 10-50%

• Von Willebrand’s is the most common of all bleeding disorders with a prevalence of 5-15% among those with bleeding conditions.


Give me the stats!

• Average time to diagnosis for a woman with menorrhagia is 8 years!

• Distribution 70:30 (female:male)

• Overall prevalence higher in Northern European countries (18%)

• Prevalence of severe vWD highest in Sweden (1/200,000)


American College of Obstetricians and Gynecologists (ACOG) Recommendations

• The first adolescent female health care visit should occur between the ages of 13 and 15

• Adolescents presenting with menorrhagia should be screened for bleeding disorders

How to AVOID missing a bleeding disorder

Of patients with a history of menorrhagia, 20% will have an underlying bleeding disorder.

Patients with a diagnosis of von Willebrand’s disease report menorrhagia at the onset of menarche ~50% of the time and 93% of the time by the time they reach adulthood.

Key elements from history

• Easy bruising

• Epistaxis

• Frequent gum bleeds

• Family history of menometrorrhagia, post partum hemorrhage, easy bruising, epistaxis, frequent gum bleeds, menorrhagia

Family history and menorrhagia probably most important!

What types of bleeding disorders are most common?

• Von Willebrand’s Disease (Prevalence=1%)– 3 types

• Type 1• Type 2—many subtypes• Type 3

• Platelet function defects

Bleeding symptoms in women with vWD

Symptom Number Reporting

Mean Age Onset

%Reporting %Transfused

Bruising 36 7 48 0

Nosebleeds 33 7 44 0

Bleeding after injury

25 11 33 11

Dental bleeding 38 16 51 36

Menorrhagia 63 13 84 18

Postoperative bleeding 36 17 48 12

Postpartum Hemorrhage 24 24 32 25

James A, Ragni MV, Picozzi V. “Bleeding disorders in post menopausal women (another) public health crisis for hematology?” Hematology 2006.

NHLBI Testing Recommendations 2008

• Primary– CBC, PT, PTT, fibrinogen– VWF Ag, Ristocetin Cofactor, Factor VIII

• Values <30 are convincing• Values 30-50 may be VWD or simply “low VWF”

• Secondary– Multimers, genetic testing– Specialized platelet testing, RIPA, ratios

The difficulty…

• Spectrum of disorders– Autosomal Dominant, Autosomal Recessive– Variable penetrance– Acquired forms

• No one test is “the best”• Repeating tests may be necessary

– Stress– Exercise– Pregnancy– Hormone use– Inflammatory states

Correlates of >80ml blood loss…

• Bleeding heavier than one pad/hour

• Low serum ferritin

• Passing clots greater than 1 inch diameter

• PBAC score >100

NHLBI Guidelines 2008

Morbidity

• Loss of time from work

• Psychological effects

• Loss of time from school

• Peer interactions

• Lifestyle modification

• Focussing ONLY on the bleeding condition

Barr RD, et. Al. “Health status and health-related quality of life associated with von Willebrand disease.” Amer J of Hematol. 2003; 73:108-114.

The Acute Bleed

• History and exam are critical!

• Recommended work-up– CBC, TSH, von Willebrand’s panel (vWD Ag,

Ristocetin cofactor, Factor VIII), Type and screen, PT, PTT, INR, fibrinogen, PFA 100

– Draw labs BEFORE administering hormones

• Imaging– Ultrasound– MRI in some cases

The Acute Bleed and Treatment

• Starting Hormones– IV Estrogen: recommended for the acute bleeding

episode in which patient is unable to tolerate po intake. May be given 25mg IV q6 hours until vaginal bleeding stops.

– Combination oral contraceptives• A 50 mcg pill with ethinyl estradiol has the SAME

bioavailability as conjugated equine estrogens administered IV.

• Pills should be administered every 6 hours until vaginal bleeding stops

• Tapers are useful-a variety of protocols exist

How do hormones work?

FSH and LH

Estrogen and Progesterone

OCPs, Contraceptive Ring, Contraceptive patch,

Injection

ResultsSuppression of hormonal

activity

Negative feedback loop

Hormones Come in Many Shapes and Sizes

Differences in Progestins

• Some are more androgenic than others

• Low, Medium and High dose Progestins

• Less breakthrough bleeding reported with levonorgestrel, norgestimate and desogestrel (all are MORE androgenic)

Treatment of mild, moderate and severe episodes with known negative pregnancy test

Amount of Bleeding Hb Management/Treatment

Mild>11

Reassurance, education. Offer iron and low dose OCP. Reevaluate 3 months

Moderate9-11

Education. Rule out STD and coagulopathy. Offer iron and low dose OCP taper. Reevaluate 2 months.

Severe7-9

Rule out coagulopathy. Offer iron and high dose OCP taper. Reevaluate in 4 weeks.

Hypovolemic Shock

<5-6

Stabilize, rule out coagulopathy. Offer transfusion. Admit for high dose hormones until VB stops (IV or po route). D&C or balloon tamponade in extreme cases.

Other tips for the acute bleed…

• May need to premedicate some patients with Phenergan or Odansetron during high dose hormone administration

• If labs return normal, but you remain clinically suspicious during follow up visits—recheck blood work.

Managing the Chronic DUB patient

• The bleeding may not be quite as heavy, or have lasted quite as long—rest assured it has been just as much of a nuisiance to the patient.

• MANY options for hormonal management.

Summary

• Dysfunctional uterine bleeding (DUB) is multifaceted in the adolescent patient

• The most common condition resulting in DUB for the adolescent is annovulation

• Bleeding is often easily controlled with hormonal manipulation

• Adolescents have a number of options these days to fit their needs

• Good evidence for guiding management in women with diagnosed bleeding disorders thus far, but more research is needed.

Dysfunctional Uterine Bleeding in the Adolescent

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