Abnormal Uterine Bleeding
(AUB) /
Dysfunctional Uterine Bleeding
(DUB)
Herbert L. Muncie, Jr., M.D.
The main issues!
How to control current
bleeding?
How to prevent future abnormal
bleeding?
Jeanie
16 year old comes in complaining of
irregular heavy periods for 2 years
No medical problems and using condoms
for contraception since she became sexually
active 3 months ago
•
What can reduce current heavy bleeding?
• Not currently bleeding
•
What can reduce her risk of future irregular
heavy bleeding?
Jeanie - More History
Question
Answer
When did her last period start?
10 days ago
When was her PMP?
How irregular are her periods?
6 weeks ago, usually every 6 - 8 weeks
How heavy is the bleeding with most
periods?
Will sometimes have to change her
tampon every hour, has soaked her
clothes at times
Is this heavy bleeding unusual?
Has had heavier periods for almost 2
years, lasting 4 - 5 days
Jeanie - More Data
•
•
•
•
•
Interval
betweenTests
cycles
days
Physical Exam
ordered– 21 - 28 Results
Proliferative (follicular) phase – 7 - 21 days
Ht - 64 in; Wt - 126
Secretory
(luteal)
phase
days
BMI - 21.6
Pregnancy
test – 14 ± 2 Negative
BP 106/68; P 70
Bleeding duration – 2 - 6 days
Average
blood volume
Normal general
CBC lost - 45 ml
physical
No bruising or petechia
Coagulation panel
TSH - reflex
Pending
Pelvic exam - normal
GC/Chlamydia probe
Pending
Normal Menstrual Cycle
•
•
•
Maturation of endometrium relatively
uncomplicated
~ Dependent on estrogen and progesterone
First half of cycle is estrogen - dominant
~ Halts menstrual flow & promotes proliferation
(proliferative or follicular phase)
Second half is progesterone dominant
~ Stops endometrial growth, then promotes
differentiation (secretory or luteal phase)
Normal Menstrual Cycle
•
•
•
•
•
Interval between cycles – 21 - 28 days
Proliferative (follicular) phase – 7 - 21 days
Secretory (luteal) phase – 14 ± 2 days
Bleeding duration – 2 - 6 days
Average blood volume lost - 45 ml
Abnormal bleeding
•
Heavy –
» > 80 ml blood loss with period
•
•
•
Doubtful clinical utility or significance
» Changing pad > q 1 h at some point
» Soaking through to her clothes
Irregular intervals–
 > 35 days or < 21 days between periods
Prolonged duration
 Flow > 7 days
Jeanie - Follow-up Visit 3 days
later
Tests ordered
Results
CBC
Hgb – 10.6 g/dL
Hct – 31%
MCV – 76 fl
Platelet count 215,000
Coagulation panel
PT – 12 sec
INR – 1.1
aPTT – 22 sec
TSH
1.76 mU/L
GC/Chlamydia probe
Negative
Definitions
Dysfunctional uterine bleeding (DUB) abnormal bleeding with no organic cause
(neoplasm, inflammation, infection or
pregnancy) but which can co-exist with
organic pathology
Abnormal uterine bleeding (AUB) - includes
DUB and bleeding from structural or organic
causes
Assess for organic pathology
•
•
•
•
•
History
Physical exam including pelvic
Diagnostic tests ~
~
~
~
Pregnancy test
PAP smear if indicated
CBC, TSH, coagulation panel
Chlamydia, gonorrhea probe
Pelvic/transvaginal ultrasound
Endometrial biopsy in women over age 35
~ Only 2% of endometrial cancers occur in
women < 40 years old
DUB & Bleeding Disorders
•
Screening for von Willebrand (vWD)
disease with heavy menstrual bleeding?
~ ACOG recommends screening adolescents with
severe menorrhagia, women whom abnormal
bleeding etiology cannot be established & women
undergoing hysterectomy
» However, not sufficient evidence that it helps
~ 1% prevalence in general population
DUB & Bleeding Disorders
•
Case finding with heavy menstrual bleeding
~ Up to 16% have vWD [James 2009]
~ Consider if any of the following:
»
»
»
»
»
Menorrhagia since menarche
Minor wound bleeding > 5 minutes
Bleeding oral cavity/GI tract without anatomic lesion
Prolonged bleeding after dental extraction
Unexpected postsurgical bleeding
DUB & Bleeding Disorders
•
Case finding evaluation
~ Order CBC, PTT, PT & vWF level (ideally during
menses)
~ No single test will establish the diagnosis
~ Positive family history usually necessary
~ Ask about any bleeding with dental procedures, T&A, peripartum
bleeding
» OCPs can mask type 1 vWD but don’t stop them
» Patients with type O blood have 25 – 30% lower levels of
vWF
» In these patients with a lower level, a family history would be
needed to confirm or exclude the diagnosis
Menorrhagia – vWD treatment
•
If caused by vWD & not trying to get
pregnant
~ Oral contraceptive would be treatment of choice
~ Progestin IUD alternative
~ Desmopressin (DDAVP®) or antifibrinolytics if
pregnancy desired
~ Avoid NSAID with symptomatic vWD
Jeanie
Probable diagnosis – DUB



•
vWF ordered to be drawn during next menses
vWF results – 35 IU/dL (low but not diagnostic)
No family history or bleeding
What can reduce her risk of future irregular
heavy bleeding?
•
•
Because combination oral contraceptives (OCP) are
not contraindicated
She was started on a monophasic OCP to decrease
her flow and regulate her cycles
Fran
 A 23 year old woman complaining of heavy menstrual
bleeding. Her period started 2 days ago & today is very
heavy. She has to change her tampon at least every
hour.


•
•
She has no medical problems
Periods are usually regular
What can reduce her current heavy bleeding?
What can she do to reduce her risk of future
heavy bleeding?
Terminology/Descriptions
Does Fran Have
Definition
Hypomenorrhea
Abnormally reduced menstrual flow
Oligomenorrhea
Infrequent periods with normal flow
Menorrhagia
Regular periods with heavy flow
Metrorrhagia
Irregular periods with normal flow
Menometrorrhagia
Irregular heavy periods
Terminology/Descriptions
•
•
•
There has been a lack of uniformity in
definitions and descriptions of
menstrual bleeding abnormalities
February 2005, 35 international MDs
met in Washington DC to define terms
Settled on 4 key menstrual dimensions
for description
Terminology/Descriptions
Dimension
Regularity
Frequency
Duration
Volume
Categories
Irregular
Regular
Absent
Frequent
Normal frequency
Infrequent
Prolonged
Normal
Shortened
Heavy
Normal
Light
Terminology/Descriptions
Old terminology
Regularity
Frequency
Duration
Volume
Hypomenorrhea
Regular
Normal
Normal
Light
Oligomenorrhea
Irregular
Infrequent
Normal
Normal
Menorrhagia
Regular
Normal
Prolonged
Heavy
Metrorrhagia
Irregular
Frequent
Normal
Normal
Menometrorrhagia Irregular
Frequent
Prolonged
Heavy
Is It Ovulatory or Anovulatory?
•
With any abnormal bleeding it is helpful to
determine if it is ovulatory or anovulatory
• Most DUB is anovulatory
• In adolescents ovulatory cycles may take up to
3 years to be established
• How can you determine if it is ovulatory or
not?
Normal Ovulatory Cyclic Function
•
•
•
Depends on regular pulsatile release of
GnRH from hypothalamus
~ Which stimulates FSH & LH pulses from anterior
pituitary
Pulsatile FSH & LH leads to:
~ Folliculogenesis (proliferative or follicular phase)
~ Ovulation
~ Corpus luteum formation which sustains luteal phase
(luteal phase)
Atrophy of corpus luteum results in menses
Is It Ovulatory or Anovulatory?
Estrogen
FSH
LH
Progesterone
Menstruation
Follicular phase
Day 14
Luteal phase
Is It Ovulatory or Anovulatory?
•
Ovulatory Cycles
~ regular intervals
~ mittelschmerz
~ serum P4 > 3 ng/ml
~ 2nd half cycle
~ biphasic BBT
~ Serum LH > 25 mIU/ml
•
Anovulatory cycles
~ irregular intervals
~ no ovulatory pain
~ serum P4 < 3 ng/ml
~ 2nd half cycle
~ monophasic BBT
~ Serum LH < 25 mIU/ml
Fran – more information
Answer
Vital signs
Ht – 67”; Wt – 146 lbs; BMI 22.9
BP 124/76; P 88; T 98.8 (O)
Any other symptoms?
A little dizzy when standing
Contraception
Used OCP until 6 months ago
Using condoms past 4 weeks
Physical exam
Normal general exam
Pelvic – active bleeding from os
Uterus small nontender
No adenexal mass
Additional information
Tests ordered
Results
Stat CBC
Hgb – 11.6 g/dL
Hct – 34%
MCV – 76 fl
Pregnancy test
Negative
TSH
Results pending
GC/Chlamydia probe
Results pending
Indicative of Heavy bleeding
•
•
•
•
Soaking through pad or tampon < 1 hour
Soaking through bed clothes
Below normal ferritin
Anemia
~ [James 2009]
Regular heavy prolonged bleeding
(Menorrhagia)
•
•
Age
~ Any age
Etiologies
~ Anovulatory in younger & older women
» Immature hypothalamic-pituitary-ovarian axis
in adolescents
» Fluctuating estrogen levels each end of
reproductive age
~ Typically due to anatomic lesion (e.g. fibroid) in
women 30 – 50 years old
Regular heavy prolonged bleeding
•
Etiologies
~ Ovulatory – either:
» Corpus luteum insufficiency
» Inadequate progesterone from primary ovarian
failure or central/metabolic defect
» Corpus luteum prolonged activity
» Over stimulation of LH - irregular shedding
» Do not have 14 day luteal phase
Regular heavy bleeding
•
Etiologies
~ Up to 20% adolescents have bleeding
disorder as etiology [Claessens 1981]
~ Consider Von Willebrand disease
especially with family history of bleeding
~ If isolated prolonged PTT or normal PTT, PT,
platelet count & fibrinogen with bleeding then
specific test for VWD indicated
Acute Bleeding - Treatment
•
Outpatient treatment
~ Start monophasic OCP
~
~
~
~
1 pill QID for 4 days
1 pill TID for 3 days
1 pill BID for 2 days then
1 pill a day for 3 weeks
~ If OCP contraindicated cycle with Provera®
~ Give 10 mg daily for 14 days, then stop for 14 days
~ Continue this cycle for 3 months
Acute Bleeding –Treatment
•
Outpatient treatment
~ Oral conjugated estrogens (Premarin®) 2.5 mg
QID until bleeding is controlled
» Consider giving antiemetic with medication
~ D&C if no response after 2 - 4 doses or sooner
if needed
Fran – 23 year old
•
What can reduce her current heavy bleeding?
• Started on combination OCP 1 pill qid for 4 days
• Bleeding subsided significantly in 12 hours
Acute Bleeding – Treatment
•
Inpatient treatment
~ Conjugated Estrogens (Premarin®) 25 mg IV Q 4
H until bleeding is controlled
~ Give antiemetic prophylactically
~ D&C if no response after 2 - 4 doses or sooner
if needed
Acute Bleeding - Treatment
•
Inpatient treatment
~ Simultaneous with IV Conjugated Estrogens
(Premarin®) start monophasic OCP
~
~
~
~
1 pill QID for 4 days
1 pill TID for 3 days
1 pill BID for 2 days then
1 pill a day for 3 weeks
~ If OCP contraindicated cycle with Provera®
~ Give 10 mg daily for 14 days, then stop for 14 days
~ Continue this cycle for 3 months
Fran
 After the acute bleeding is controlled.
•
What can she do to reduce her risk of future
heavy bleeding?
Regular heavy bleeding
•
Evaluation
~ ACOG does not recommend routine CBC,
TSH or prolactin
~ Endometrial sampling rarely necessary
since regular bleeding is less concerning
for endometrial cancer
Menorrhagia - Treatment
•
•
•
NSAIDs
~ Inhibit prostaglandin which increases platelet
aggregation
~ Increase uterine vasoconstriction
Mefenamic acid (Ponstel®) 500 mg tid had
30-50% decrease in flow
Naproxen 375 mg bid effective
Menorrhagia - Treatment
•
Tranexamic acid (Lysteda®)
~ Two 650 mg tablets tid
~ Stabilizes a protein that helps blood clot
~ Concern about increased risk of clots has not
been confirmed in ongoing studies
~ Caution if combined with oral contraceptive
~ Contraindicated with history or increased risk of
thrombosis or VTE
Menorrhagia - Treatment
•
Treatment
~ Danazol 200 mg qd acceptable short-term
» Synthetic androgen, suppresses LH & FSH
which suppresses ovulation
» Can start low 100 mg/d & titrate up
» Rare side effects if < 600 mg/d
Menorrhagia
•
Treatment
~ Levonorgestrel-releasing IUD (Mirena®)
» Improved health quality of life
[Hurskainen 2004]
» Reduces blood loss more than NSAID,
Danazol, OCPs, oral progesterone [Kaunitz
2010]
Menorrhagia – treatment
•
•
Unlikely to be beneficial
~ Oral progesterone (longer cycle)
Likely to be ineffective or harmful
~ Oral progesterone (luteal phase)
Fran
•
•
•
•
What can she do to reduce her risk of future
heavy bleeding?
Because she did not want to become pregnant & had
no contraindications to OCP
She was started on a monophasic combination OCP
& will return in 3 months
She was given a prescription for mefenamic acid to
be used if her next period was heavy
Joan
•
47 year old female with hypertension &
type 2 diabetes
~ Complains of irregular heavier periods for the past 7
months
~ Married, non-smoker, BTL at age 32
~ Ht 63”; Wt 187 lbs; BMI 30.5; BP 146/92; P 74
•
•
What other information do you need?
What tests do you want to order?
More information
Results
LMP
PMP
Duration of flow
12 days ago
37 days before LMP
8 days
PMH:
Hypertension
Type 2 diabetes
Medications:
Lisinopril/HCTZ
Metformin, ASA
Physical exam
Tests ordered
General exam normal
Pelvic – uterus 6 week size
CBC
TSH
Pelvic ultrasound
Pap smear
Joan
•
•
•
•
Probable diagnosis is anovulatory DUB
Probably perimenopausal etiology
What can be done about the irregular
menses?
What can be done to decrease the duration
and excessive flow?
Irregular Heavy Menstrual Bleeding
(Menometorrhagia)
•
Etiology
~ Get decrease in estrogen & cannot initiate LH
surge, therefore anovulatory
~ FSH level > 40 IU/L suggest impending
ovarian failure
~ LH-FSH ratio > 2 compatible with chronic
anovulation
Irregular menstrual bleeding
•
Treatment
~ None medically required if that is only issue
~ OCPs will regulate menses if patient wants birth
control & no contraindications
~ If OCP contraindicated cycle with Provera®
~ Give 10 mg daily for 14 days, then stop for 14 days
~ Continue this cycle for 3 months
~ Postmenstrual bleeding – “endometritis”
~ Doxycycline 100 mg bid for 10 days
Irregular Heavy Menstrual
Bleeding
•
Treatment – for non-acute active bleeding
~ Therapy indicated for these patients:
» Bleeding > 7 days
» Anemia from blood loss
» Interferes with normal life activities
Irregular Heavy Menstrual
Bleeding
•
Treatment
~ Combination oral contraceptives
» To reduce bleeding slowly over several days
» Give standard OCP dosing
» To reduce bleeding quickly in 24 hours
» 1 pill qid for 5-7 days then
» 1 pill bid for three weeks
~ May need to pre-medicate with antiemetic
Treatment Menorrhagia – EBM
•
•
For women considering hysterectomy,
placement of levonorgestrel-releasing IUD
resulted in similar outcomes & was more
cost effective
InfoRetriever
~ Randomized controlled trial after 5 years found no
difference in outcomes (SOR 1b)
~
http://www.infopoems.com/irsearch/search_details.cfm?ID=60625&ResultKey=E&title=Prog
esterone%20IUD%20effective%20for%20menorrhagia
Summary of MedicalTherapies –
Irregular Heavy Prolonged Bleeding
Drug
Levonorgestrel IUD
Mean reduction Women
blood loss (%)
benefiting (%)
94
100
Oral PG (day 5-25)
87
86
Danazol
50
76
NSAIDs
29
51
OCP
43
50
Oral PG (day 12-26)
-4
18
Joan Follow-up visit
Tests ordered
Results
CBC
Hgb – 11.1 g/dL
Hct – 33.4%
MCV – 88 fl
TSH
2.6 mU/L (nl – 0.45 – 4.5)
Pelvic ultrasound
Diffuse uterine enlargement
Endometrial stripe < 4 mm
Ovaries normal appearance
Menometrorrhagia - EBM
•
•
Various types of surgery or IUD hormone device
are effective in reducing heavy bleeding & suit
most women better than oral medications
Cochrane Review
~ Controlled randomized trials
~ Surgery reduced bleeding better at 1 yr. than medical
therapy & IUD equally effective to surgery
~ Oral therapy suits minority of women
~ http://www.cochrane.org/reviews/en/ab003855.html
Joan Treatment Options
Treatment option
Oral contraceptive
Will control bleeding & make her regular
Not contraindicated
NSAIDS
Would reduce flow but not effect regularity
Progestine IUD
Would control flow & frequency
Would obviate the need for more invasive
procedure
Surgical options
Ablative therapies would be a reasonable
option
Key Points - DUB
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•
•
•
•
•
History determines the pattern & probable etiology
Four aspects: Regularity, frequency, duration & volume
Always assess for organic etiology
Pregnancy test, STDs, infection, etc
Assess desire for contraception
Oral contraceptive can frequently control the problem
Key Points - DUB
•
•
•
•
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Provide medical therapy that is effective and lowest
risk for patient
NSAIDs usually safe, OCPs, progesterone IUD, then surgery
Discuss progesterone IUD for significant bleeding in
older women who want to avoid surgery
Surgery is final therapeutic option
Multiple new modalities are effective
What Questions do you have?