1. Abnormal Uterine Bleeding (AUB) /
Dysfunctional Uterine Bleeding (DUB)
Herbert L. Muncie, Jr., M.D.

2. How to control current bleeding?
The main issues!
How to control current bleeding?
How to prevent future abnormal bleeding?

3. 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?

4. 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 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 days

5. Normal general physical No bruising or petechia
Jeanie - More Data
Physical Exam
Tests ordered
Results
Ht - 64 in; Wt - 126
BMI
BP 106/68; P 70
Pregnancy test
Negative
Normal general physical
No bruising or petechia
CBC
Coagulation panel
TSH - reflex
Pending
Pelvic exam - normal
GC/Chlamydia probe
Interval between cycles – days
Proliferative (follicular) phase – days
Secretory (luteal) phase – 14 ± 2 days
Bleeding duration – days
Average blood volume lost - 45 ml

6. 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)

7. Normal Menstrual Cycle
Interval between cycles – days
Proliferative (follicular) phase – days
Secretory (luteal) phase – 14 ± 2 days
Bleeding duration – days
Average blood volume lost - 45 ml

8. Abnormal bleeding Heavy – Irregular intervals– Prolonged duration
> 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

9. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. Probable diagnosis – DUB
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

17. Fran What can reduce her current heavy bleeding?
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?

18. 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

19. 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

20. Terminology/Descriptions
Dimension
Categories
Regularity
Irregular
Regular
Absent
Frequency
Frequent
Normal frequency
Infrequent
Duration
Prolonged
Normal
Shortened
Volume
Heavy
Light

21. Terminology/Descriptions
Old terminology
Regularity
Frequency
Duration
Volume
Hypomenorrhea
Regular
Normal
Light
Oligomenorrhea
Irregular
Infrequent
Menorrhagia
Prolonged
Heavy
Metrorrhagia
Frequent
Menometrorrhagia

22. 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?

23. 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

24. Is It Ovulatory or Anovulatory?
Estrogen
FSH LH
Progesterone
Menstruation
Day 14
Follicular phase
Luteal phase

25. 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

26. Oligomenorrhea – Infrequent regular
Age
Adolescents
End of reproductive years
Etiology
Most often anovulatory
Rarely ovulatory

27. Oligomenorrhea – Infrequent regular
Anovulatory etiology
Adolescents
Failure of established cyclic estrogen pattern due to lack of maturity hypothalamic-pituitary-ovarian (H-P-O) axis

28. Oligomenorrhea – Infrequent regular
Etiology (continued)
End of reproductive years
Failure estrogen to increase or decrease in a regular manner
Estrogen is necessary for target tissue responsiveness
Without adequate estrogen, tissues fail to respond to progesterone therapy

29. Oligomenorrhea – Infrequent regular
Treatment
No treatment required
Medroxyprogesterone (Provera®) 10 mg for 5 days to induce menses
If no menses within 5-7 days after completing Provera®
Give estrogen prior to repeating progesterone
If patient wants regular periods
Combination oral contraceptive (OCP)
Use if also desires birth control

30. 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

31. 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

32. Indicative of Heavy bleeding
Soaking through pad or tampon < 1 hour
Soaking through bed clothes
Below normal ferritin
Anemia
[James 2009]

33. 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

34. 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

35. 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

36. 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

37. 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 doses or sooner if needed

38. 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

39. 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 doses or sooner if needed

40. 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

41. Fran After the acute bleeding is controlled.
What can she do to reduce her risk of future heavy bleeding?

42. 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

43. Menorrhagia - Treatment
NSAIDs
Inhibit prostaglandin which increases platelet aggregation
Increase uterine vasoconstriction
Mefenamic acid (Ponstel®) 500 mg tid had % decrease in flow
Naproxen 375 mg bid effective

44. 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

45. Menorrhagia - 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

46. 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]

47. Menorrhagia – treatment
Unlikely to be beneficial
Oral progesterone (longer cycle)
Likely to be ineffective or harmful
Oral progesterone (luteal phase)

48. 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

49. 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?

50. Pelvic – uterus 6 week size
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
General exam normal
Pelvic – uterus 6 week size
Tests ordered
CBC
TSH
Pelvic ultrasound
Pap smear

51. 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?

52. 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

53. 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

54. 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

55. 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

56. 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)

57. Summary of MedicalTherapies – Irregular Heavy Prolonged Bleeding
Drug
Mean reduction blood loss (%)
Women benefiting (%)
Levonorgestrel IUD 94
100
Oral PG (day 5-25) 87 86
Danazol 50 76
NSAIDs 29 51
OCP 43
Oral PG (day 12-26) -4 18

58. Joan Follow-up visit CBC Hgb – 11.1 g/dL Hct – 33.4% MCV – 88 fl TSH
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

59. 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

60. Joan Treatment Options
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

61. Key Points - DUB 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

62. Key Points - DUB
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

63. What Questions do you have?

64. References - Dysfunctional Uterine Bleeding
Claessens EA et al. Acute adolescent menorrhagia. Am J Obstet Gynecol 1981;139:
Hurskainen R et al. Clinical outcomes and costs with the levonorgestrel-releasing intrauterine system or hysterectomy for treatment of menorrhagia. JAMA 2004;291:
James A et al. Von Willebrand disease and other bleeding disorders in women: Consensus on diagnosis and management from an international expert panel. Am J Obstet Gynecol 2009;201:12.
Kaunitz AM et al. Levonorgestrel-releasing intrauterine system or medroxyprogesterone for heavy menstrual bleeding. Obstet Gynecol 2010;116: