Dysfunctional Uterine Bleeding - September 2005

Dysfunctional Uterine
Bleeding
Jennifer Bergquist M.D.
September 6, 2005

Case #1
You are evaluating a 13yr old girl in your office.
She is c/o heavy menstrual bleeding. She
experienced menarche ~1yr ago and says her
periods never occur at the same time. They last
~10days. Her previous menses occurred ~2
months ago. She denies dysmenorrhea. dysmenorrhea.
Her
current period started 2 days ago and is
especially heavy. She denies sexual activity or
h/o STDs.
Physical exam findings are notable for mild
orthostatic hypotension and pallor; Exam is
otherwise normal

Case #2
You are evaluating a 13yr old girl in your office.
She is c/o heavy menstrual bleeding. She
experienced menarche ~1yr ago and says her
periods never occur at the same time. They last
~10days. Her previous menses occurred ~2
months ago. She denies dysmenorrhea. dysmenorrhea.
Her
current period started 2 days ago and is
especially heavy. She denies sexual activity or
h/o STDs.
Physical exam is notable for mild orthostatic
hypotension and pallor. She is mildly
overweight and is noted to have acne. Exam is
otherwise normal

Case #3
You are evaluating a 13yr old girl in your office.
She is c/o heavy menstrual bleeding. She
experienced menarche 6 months ago and says
her periods have always been heavy and last up
to 12 days. Although, she thinks they occur at
regular intervals. She frequently experiences
dysmenorrhea. dysmenorrhea.
She denies sexual activity or h/o
STDs.
Physical exam findings are notable for mild
orthostatic hypotension, pallor and a large
amount of menstrual blood at the vaginal
introitus. introitus.
Exam is otherwise normal.

Questions
1. What is the differential diagnosis?
2. What additional information would be helpful?
3. What laboratory evaluation would you pursue?
4. What initial therapy would help the patient’s patient s
symptoms?

Definition
Dysfunctional uterine bleeding (DUB) is defined
as abnormal uterine bleeding that is excessive or
occurs outside the normal cycle
In Adolescents, 95% is secondary to anovulation
anovulation
Patterns of abnormal bleeding:
– Menorrhagia Menorrhagia prolonged bleeding at regular intervals
– Metrorrhagia Metrorrhagia uterine bleeding at irregular intervals
– Menometrorrhagia Menometrorrhagia uterine bleeding that is
prolonged, excessive and occurring at irregular
intervals

Menarche
Mean age of menarche in the United
States:
– 12.88 years for Caucasian girls
– 12.16 years for African American girls
90% reach menarche by the time breast
and pubic hair development has reached
SMR stage 4.
On average, menarche occurs 2 years
after thelarche

Menstrual Cycle
Follicular Phase
– Pulsatile GnRH
– FSH and LH stimulate ovarian
follicle growth
– Predominant follicle secretes
estrogen
– Endometrium proliferates
Ovulation
– LH > FSH
– Occurs 12hrs after LH surge
Luteal Phase
– Corpus Luteum secretes
progesterone
– Secretory endometrium
– Corpus luteum regresses if no
implantation occurs
– Estrogen/progesterone fall;
endometrial lining sloughs

Anovulatory Menstrual Cycle
Endometrium experiences continued estrogen
stimulation that is unopposed by progesterone
Increased estrogen should cause a negative feedback on
the H-P H P axis; estrogen levels fall; endometrium sloughs
and mimics an ovulatory cycle
In DUB, impairments in the feedback system cause the
endometrium to be continuously stimulated, thickened
and unstable
Uterine bleeding occurs when endometrium outgrows its
blood supply
Uterine bleeding becomes asynchronous, prolonged and
sometimes profuse

Dysfunctional Uterine Bleeding
Pregnancy-related related
Pregnancy
– Ectopic pregnancy
– Abortion
Physiologic
– Post-menarchal
Post menarchal
(immature H-P-O H O Axis)
differential diagnosis
Physiologic Anovulation
Hormonal contraceptives
Hypothalamic-related
Hypothalamic related
– Systemic illness (DM, renal,
liver disease)
– Functional (diet, stress,
exercise)
– Eating disorders
– Hypothyroid
Pituatary-related
Pituatary related
– prolactinoma
Outflow tract-related
tract related
– Trauma
– Foreign body
– Polyps
– Uterine myomas
– Neoplasms
Androgen Excess
– PCOS
– Adrenal or ovarian tumor
– Adrenal hyperplasia (non-
classic type)
Coagulation defects
– Clotting factor deficiency
– Von Willebrand disease
Infectious
– PID, cervicitis, cervicitis,
vaginitis

Detailed menstrual
history
– Age of menarche
– Menstrual pattern
– Amount of blood loss
– Duration of menses
– +/- +/ menstrual cramps
– Recent changes in
cycles
symptoms of
hypovolemia
Genital trauma
Evaluation
Weight loss or gain
Non-menstrual Non menstrual bleeding
(easy bruising)
Emotional stress
Exercise patterns
Sexual history
Gestational events
Symptoms of chronic
illness
Family history of
menstrual or bleeding
disorders

Physical Exam
Vital signs (including orthostatics)
orthostatics
Gen: obesity, cachexia
HEENT: fundoscopic exam/visual field testing
Neck: thyroid
Breasts: SMR, evaluate for galactorrhea
Abdominal: uterine/ovarian mass
Skin: hirsutism, hirsutism,
acne, acanthosis nigrans
External genital exam: SMR, clitoral size
Internal genital exam (if sexually active or has painful
bleeding):uterine/adnexal
bleeding): uterine/adnexal masses, motion tenderness,
trauma, cervical os (size, color, discharge)

Urine B-HCG* B HCG*
Laboratory Assessment
– Even in adolescents who claim they are not sexually active!
Hematocrit*
Hematocrit
CBC, PT/PTT
– Should be performed in pts with + family history of bleeding d/o
and/or personal h/o excessive non-menstrual non menstrual bleeding
– Secondary evaluation includes a von Willebrand panel (vWF ( vWF
antigen; ristocetin cofactor activity)
Other tests (depending on history/physical)
– FSH, LH, prolactin, prolactin,
androgen panel (free/total testosterone,
DHEA), TSH, Cortisol
– Pelvic ultrasound- ultrasound always indicated in pts suspected of having
ectopic pregnancy, pts who have a palpable mass or if PCOS is
suspected
* Should be performed in all patients with irregular uterine
bleeding

Diagnostic Evaluation
Progesterone Challenge
– Evaluates uterine response to endogenous estrogen
– Progesterone is administered X 12 days to mimic
physiologic secretion
– Menstrual bleeding within 1 week after the challenge
suggests FSH/LH secretion is sufficient to maintain
normal estradiol secretion and endometrial
proliferation, but insufficient to cause ovulation
– Lack of menstrual bleeding suggests an endometrial
pathology or marked hypoestrogenemia

Physiologic Anovulation
Immaturity of the hypothalamic-pituitary
hypothalamic pituitary-
ovarian axis is the most common cause (in the
absence of pregnancy)
– Rising levels of estrogen do not cause suppression of
FSH; sustained estrogen secretion ensues
Most common during the first 2 years after
menarche when 55-80% 55 80% of cycles are
anovulatory
Regardless of cause, anovulation can present as
either amenorrhea or DUB
Laboratory evaluation may reveal elevated
FSH:LH ratio
It is a diagnosis of exclusion

Polycystic Ovarian Syndrome
Should be considered in any any adolescent girl with
hirsutism, hirsutism,
menstrual irregularity or obesity
2/3 have anovulatory symptoms
– Primary or secondary amenorrhea or DUB
Metabolic abnormalities
– Obesity (50%), insulin resistance, glucose intolerance and lipid
abnormalities
Diagnosis (clinical + biochemical criteria)
– Elevated LH:FSH ratio, elevated free testosterone
– Pelvic ultrasound finding of polycystic ovaries (“string ( string of
pearls”); pearls );
~45% of adolescents have normal-appearing normal appearing ovaries
Useful to exclude tumor from the differential
– Exclusion of other disorders that mimic PCOS
Virilizing tumors, hyperprolactinemia, hyperprolactinemia,
non-classical non classical CAH, Cushing

Coagulation Disorders
Often presents as menorrhagia at regular intervals
When to consider bleeding disorders:
– extremely heavy first menses, bleeding requiring blood
transfusion, refractory menorrhagia w/ anemia
All patients requiring hospitalization for uterine bleeding
requires an evaluation for a coagulation disorder
Approximately 20% of adolescents with menorrhagia
were found to have a coagulation defect
Von Willebrand disease was the most common defect
(Factor XI deficiency was second)
Blood for evaluation of bleeding disorders should be
obtained before before administration of blood products or
estrogen (may elevate vWF into the normal range)

Treatment: Treatment
Hormonal Therapy Therapy
Primary purpose is to stabilize endometrial
proliferation and promote shedding
>90% of adolescents with DUB respond to
hormonal therapy
– Alternative diagnosis should be considered for non-
responders
Estrogen “heals heals” sites of bleeding by causing
further proliferation and providing hemostasis
Progesterone stops proliferation and stabilizes
the endometrial lining

Treatment: Treatment
Mild Mild DUB DUB
Longer than normal menses or shortened
cycles for >2 months
Observation and Reassurance
– If anemia is not present/normal physical exam
Menstrual calendar recommended
Iron supplementation recommended
despite normal hemoglobin
Follow-up Follow up in 3-6 3 6 months

Treatment: Treatment
Moderate DUB DUB
Moderately prolonged or frequent menses every
1-3 3 weeks w/ moderate-heavy moderate heavy menstrual flow
Mild anemia is often present w/out signs of
hypovolemia
Outpatient management with hormonal therapy
– Active Active bleeding: bleeding:
combination oral contraceptives in
tapering doses (minimum 30mcg estradiol) estradiol
1 pill TID until bleeding ceases
1 pill BID X 5 days
1 pill QD X 21 days
– No No Active Active bleeding: bleeding:
Daily/Cyclic OCP
progestin-only progestin only regimens are an alternative option:
Medroxyprogesterone 10mg X first 12 days of the month

Treatment: Treatment
Severe Severe DUB DUB
Heavy menstrual bleeding causing a
decrease in Hgb

Combination OCPs
Treatment: Treatment
Severe Severe DUB DUB
OCPs (estradiol estradiol 50mcg)
– 1 pill Q4 until bleeding subsides (usually within 24 hrs)
– 1 pill QID X 4 days
– 1 pill TID X 3 days
– 1 pill BID X 2 weeks
Conjugated IV estrogen 25mg IV Q4-6 Q4 6 is required for
unstable patients
– No more than 6 doses
– Bleeding subsides 4-24 4 24 hrs
– Persistent bleeding > 24hrs requires hemostatic therapy (anti-
fibinolytic) fibinolytic)
or uterine curettage should be considered (rare)
– Combined OCPs should be initiated within 24-48 24 48 hrs of IV
estrogen
Anti-emetic Anti emetic therapy is recommended
Blood transfusion is indicated in symptomatic patients

Maintenance Therapy
Combination OCPs
– Without significant anemia (Hgb ( Hgb >10)
Cyclic therapy w/21 days + 7 days placebo
– With significant anemia (Hgb ( Hgb

Therapy: Therapy
Other Other Considerations
Iron therapy should be included in ALL
therapeutic regimens
NSAIDs
– Randomized control trials have shown
reduction in menstrual blood loss of 30-50% 30 50%
– Should be started at onset of menstruation
and continued until end of menses
– Helpful adjunct to hormonal therapy in pts
with DUB and menorrhagia

Prognosis
DUB should resolve with maturation of the
H-P-O O axis
Duration of time to maturity appears to be
related to the age of menarche
– 13 years: 50% at 4.5 years
(% of ovulatory cycles)
Prognosis depends upon underlying cause