Update management of AUB

1. Salah Roshdy, MD
Prof. of Obstetrics & Gynecology
Sohag University, Egypt

2. Definitions & Diagnosis
The evidence base for recommended management
What tests are necessary & when
Treatment
Medical & Surgical
Indications & Options
Risks & Side Effects

3. starting at the age of Menarche (11-14years) till establishment
of Menopause (45-55 years).
It is regulated by hypothalmo-pituitary- ovarian hormones
secreted in pulsatile and cyclic pattern
Menstruation is a cyclic physiological phenomena

4. Normal Menstrual Cycle
1 14 28
PMS
Estrogen
Progesterone
Ovulatio
n
PG
+HA
IBU 400 q
8
Follicular Luteal

5. • Eliminated Misleading Terms
– Dysfunctional Uterine Bleeding (DUB)
– Menorrhagia
– Hypermenorrhea
– Hypomenorrhea
– Metrorrhagia
– Menometrorrhagia
– Polymenorrhagia
– Polymenorrhea
– Metrorrhagia
FIGO
International Federation of Gynecology and Obstetrics
Nomenclature System
Abnormal Uterine Bleeding
(AUB)

6. any variation from the normal menstrual
cycle, which includes:
changes in regularity and frequency of
menses,
in duration of flow,
or in amount of blood loss. •

7. Responsible for over one third of hysterectomies.
It is a common reason for gynecologic
consultation.
Abnormal uterine bleeding affects 10 to 30
percent of reproductive-aged women and up to
50 percent of perimenopausal women.

8. How often do you change your sanitary pad/tampon during peak flow days?
How many pads/tampons do you use over a single menstrual period?
Do you need to change the pad/tampon during the night?
How large are any clots that are passed?
Has a medical provider told you that you are anemic?

9. Women with a normal volume of menstrual blood loss tend to:
Change pads/tampons at ≥3 hour intervals
Seldom need to change the pad/tampon during the night
Have clots less than 1 inch in diameter
Not be anemic

10. In 2006, FIGO identified as the appropriate body to provide supervision &
international credibility to the ongoing evaluation of new terminology
In 2009, FIGO Menstrual Disorders Group was formed. FIGO World
Congress of Gynecology and Obstetrics , accepted the new terminology
In 2011, the PALM-COEIN Classification System created to:
In 2012, PALM-COEIN system was endorsed by ACOG:

14. Acute AUB
Is now defined as “an episode of bleeding in a woman
of reproductive age, who is not pregnant, that, is of
sufficient quantity to require immediate intervention to
prevent further blood loss.

15. Chronic AUB
is" bleeding from the uterine corpus that is
abnormal in duration, volume, and/or frequency
and has been present for the majority of the last 6
months..

16. When a woman experiences episodes of
bleeding that occur between normally timed
menstrual periods.
Such bleeding can be cyclic and predictable,
such as that often associated with ovulation.

17. The term HMB is used to describe the
woman’s perspective of increased
menstrual volume, regardless of
regularity, frequency, or duration

19. P – Polyps – scored as Present or Absent
A – Adenomyosis - scored as Present or Absent
L – Leiomyoma
Primary level – Present or Absent
Secondary level – Distinguish between submucosal (SM) &
others (O)
Tertiary level – Detail location/size of uterine fibroids
M – Malignancy & hyperplasia

20. Diagnosis: US, SIS, hysteroscopy
Further sub-classification: Dimensions, location & number
Pre-menopausal polyps:
64 – 88% have symptoms
Present with HMB, AUB, IMB, or post-coital bleeding
Symptoms do NOT correlate with number, diameter & site
Post-menopausal polyps:
Most are symptom free
Cause for 21-28% of PMP bleeding
Associated with cervical polyps in 24-27%
Incidence of carcinoma varies between 0–4.8%

21. E
Normal Tri-laminar Endometrium
Transvaginal Ultrasound
Endometrial Stripe (EMS)

23. Ectopic endometrial glands & stroma
within the myometrium
Hypertrophy & hyperplasia of
surrounding myometrium
Usual presentation: HMB, uterine
enlargement, & dysmenorrhea

24. TVUS with Adenomyosis
gland-in-the-muscle

26. 1ry level: AUB-L
2ry level:
- Submucosal – AUB-
LSM
- Other – AUB-LO
3ry level: Types 0-8

27. Courtesy
Polyp Coagulopathy
Adenomyosis Ovulatory Dysfunction
Leiomyoma Submucous Endometrial
Other Iatrogenic
Malignancy & Hyperplasia Not Classified
Leiomyoma
Subclassification
System
S - Submucous 0 Pedunculated Intracavitary
1 <50% Intramural
2 ≥ 50% Intramural
O - Other 3 Contacts endometrium; 100% Intramural
4 Intramural
5 Subserosal ≥50% Intramural
6 Subserosal < 50% Intramural
7 Subserosal Pedunculated
8 Other (specify eg. cervical, parasitic)
0
2
3
1
4
5
6
7
0
Hybrid
Leiomyomas
(impact both
endometrium and
serosa)
Two numbers are listed separated by a dash. By convention, the first
refers to the relationship with the endometrium while the second
refers to the relationship to the serosa. One example is below
2-5 Submucous and subserus, each with less
than half the diameter in the endometrial
and peritoneal cavities respectively.
2-
5
FIGO
AUB Classification
System
Courtesy of Malcolm Munro, MD

28. TVUS with Submucous Myoma

29. FIGO AUB Staged only as present or absent
Detected based upon results of office biopsy or curettage
Adenomatous hyperplasia (AH) atypical AH  endometrial
carcinoma
Post-menopausal bleeding
Recurrent perimenopausal metrorrhagia
Chronic anovulator (PCOS) with metrorrhagia
Leiomyosarcoma
Use existing WHO and FIGO categorization

30. Endometrial Adenocarcinoma
– Most common gyn CA of women in U.S.
– Increases with age: median age 61
• Risk factors
– Family history
• 1st degree relative
• Lynch (colorectal ca/endom ca)
– Exogenous estrogen
• Unopposed estrogen
• Tamoxifen (menopausal women)
– Annovulation
• Diabetes, obesity,
metabolic syndrome, PCOS
hyperestrogenism Hypertension
Adenocarcinoma
Age Related Risk
20 to 34 -- 1.5%
35 to 44 – 6.0%
45 to 54 – 19%
55 to 64 – 32.6%
65 to 74 – 22.6%
75 to 84 -- 13.5%
85 or older – 4.8%

32. C – Coagulopathy
O – Ovulatory Dysfunction
E – Endometrial
I – Iatrogenic
N – Not yet classified

33. Prevalence: 3% of women presenting
with HMB
Etiologies:
Von Willebrand’s disease (10%)
Platelet Dysfunction
Factor XI deficiency
Factor X deficiency
Idiopathic thrombocytopenic purpura
(ITP)
Aplastic anemia
Liver disease
Category includes patient’s taking anti-
coagulants

34. Screen for underlying disorder of hemostasis if any of
Heavy menstrual bleeding since menarche
One of the following
Post-partum hemorrhage
Bleeding associated with surgery
Bleeding associated with dental work
Two or more of the following
Bruising 1-2 times per month
Epistaxis 1-2 times per month
Frequent gum bleeding
Family history of bleeding symptoms
Munro M, Int J Gynecol Obstet (2011)

35. Etiology:
Polycystic Ovarian Syndrome (PCOS)
Hypothyroidism
Hyper-prolactinemia
Mental stress
Obesity
Anorexia
Weight loss
Extreme exercise
Adolescence
Menopausal transition

36. It is diagnosed by exclusion
Etiology:
Deficiencies of local production of
vasoconstrictors
Endothelin-1
Prostaglandin F2a
Excessive production of plasminogen
activators
Increased local production of vasodilators
Prostaglandin E2
Prostacyclin I2
Disorders of endometrial repair
(inflammation)

37. Idiopathic:
Unexplained menorrhagia
Endometritis
Post-partum
Post-abortive endometritis
Endometritis component of PID
In teenagers, PID commonly presents with
abnormal bleeding (menorrhagia, IMB),
not pelvic pain

38. Etiology:
Breakthrough bleeding (BTB) using gonadal
steroids is the major component of AUB-I :
Oral contraceptives
Continuous or cyclic
progesterone
Cigarette smoking : reduces the level of
steroids because of enhanced hepatic
metabolism
Systemic agents that interfere with dopamine
metabolism :
Serotonin uptake inhibitors

39. Disorders that would be identified or defined
only by biochemical or molecular biology
assays
Arterio-venous malformations
Endometrial pseudoanuersym
Myometrial hypertrophy
Uterine niche

41. History
Any known uterine disease, induced vaginal
bleeding
Any personal or family history of disorders of
hemostasis must be sought with specific
questions(Grade B)
Dyspareunia
Associated Vaginal Discharge
Recent Abortion / delivery / ectopic pregnancy
Post coital bleeding ?
Menstrual History—regularity, ,
frequency, duration of bleeding ,
Volume of blood loss.
Age at menarche
Age

42. When the history suggests nothing relevant, the
pictogram is normal, the clinical examination is
normal and no sign of anemia is present, no
diagnostic investigation is recommended (Grade
C).

45. (Grade A; Level 1)TVUS
Ultrasonography is mandatory in AUB
to evaluate uterus, adnexa and
endometrial thickness.
Endometrial Polyps
Adenomyosis
Leiomyomas
Uterine anomalies
Endometrial thickening associated with
hyperplasia and malignancy

46. If intracavitary lesion is suspected and
hysteroscopy is not available (Grade A;
Level 1)
Better discrimination of location and relationship
to the uterine cavity
May be useful prior to hysteroscopic or laparoscopic
procedure for
fibroids, polyps and uterine anomalies

47. Doppler ultrasonography: In
suspected arteriovenous
malformation, malignancy cases
and to differentiate between fibroid
and adenomyomas (Grade B; Level
3)
3D-USG:For evaluating intra
myometrial lesion in selected
patients for fibroid mapping
(Grade B; Level 4)

48. Sonohysterogram/Saline Infusion
Study (SIS)
3.12 x 2.91 cmType 2 Myoma

49. Hysteroscopy: For diagnosis and
characterization of intrauterine
abnormalities (Grade A;Level 1)

50. An endometrial biopsy must be performed in the case of
any risk factor for endometrial cancer and for all
patients older than 40 years (Grade A; Level 2).
A biopsy sample should be obtained with a
polypropylene endometrial suction curette (Pipelle de
Cormier)during the diagnostic hysteroscopy (Grade B)
Diagnostic curettage under general anesthesia is not
recommended as a first-line treatment (Grade A).

51. Systematic Review of TVS (10 studies), Saline I Son
ography (SIS, 11 studies) and Hysteroscopy (3 studi
es) for the identification of any pathology
TVS
Sensitivity 48 – 100% / Specificity 12 – 100%
SIS
Sensitivity 85 – 100% / Specificity 50– 100%
Hysteroscopy
Sensitivity 90 – 97% / Specificity 62 – 93%
Ultrasound better for the identification of fibroids

52. A patient may be found to have more than one
potential entity
Contributing to symptoms of AUB. A notation approach
has been designed to enable categorization.
For example, if a patient is found to have
endometrial hyperplasia and ovulation dysfunction
with no other abnormalities, she would be
categorized as follows:
May be abbreviated as : AUB – M,0

54. A- The primary etiology should be treated, if
possible
as
• Structural lesions should be resected via
hysteroscopy (endometrial polyp, submucosal
fibroid).

56. MANAGEMENT OF PATIENTS WITH AUB
AUB-P (Polyps)
• 1. Hysteroscopic polypectomy is recommended for
younger women who wish to preserve fertility.
(Grade A; Level 1).
• 2. In women multiple endometrial polyps and not
desirous of continued fertility, it is suggested to
perform hysteroscopic polypectomy followed by
LNG- IUS insertion after confirmation of benign
lesion on histopathology. (Grade A ; Level 2).
• 3. Polyp should be sent for histopathology. If
histopathology suggests malignancy, further
management should be as AUB-M.

58. B. Medical
Non-hormonal
Non-steroidal anti-inflammatory drugs
AntifibrinolyticsLevonorgestrel-releasing intrauterine system (Mirena)
Ethamsylate
Hormonal
Combined hormonal contraceptives
Oral progestins (long phase, days 5 to 26)
Depot-medroxyprogesterone acetate
Danazol------Estrogen
GnRH-agonists
Ormilexifene
Desmopressin

59. Rationale of Hormone Therapy
•Administration of exogenous
estrogen causes endometrial
proliferation, which heals the sites
of endometrial bleeding, and
provides haemostasis
• Administration of progestin
stabilizes the endometrial lining

60. C. Surgical
Endometrial ablation
Uterine artery embolization
Hysterectomy

61. Newer Options
Modified Release Tranexamic acid(3.9gm)
Quadriphasic COC- Estradiol valerate and
Dienogest
Vaginal Danazol
Lifestyle Intervention
Alternative Medicine

62. LNG-IUS
Cost- effective when
compared with other
hormonal and non
hormonal treatments
Vertical stem: release daily
doses of 20 micrograms of LNG
Reduction of MBL between
71-96%
Benefit seen after 6 months
Effects:
Prevent endometrial
proliferation
Thicken cervical
mucus
Suppress ovulation

63. LNG-IUS
1st line treatment of AUB
NICE Guidelines 2007, Magon et al April 2013
Midlife journal review article
LNG as effective as Surgery in improving QOL at 1 yr.
Marjori banks et al, Cochrane database syst review 2006
&Meta analysis of 6 RCTs, Obstet & Gynecol 2009
Progestin IUS system ,an alternative to Endoablation
SOGC May 2013
LNG IUS better than other Medical therapy. LNG
had better outcome 64%vs 38%
Gupta et al, N Eng J of Med, 2013 (571 women over 2yrs)

65. LNG-IUS
Side effects;
1. BTB in the first cycles
2. 20% develop amenorrhea within 1 yr
3. Functional ovarian cysts
Special indications:
1. Intractable bleeding associated with chronic
illness
2. Ovulatory heavy bleeding
Other Uses
1. Women on Tamoxifen for Breast cancer
2. Fibroids
3. Adenomyosis

66. Active viral hepatitis, severe
decompensated
cirrhosis, benign liver tumors or
malignant hepatomas
Ischaemic heart disease
Current deep vein thrombosis (DVT) or
pulmonary embolism(PE)
Marked immunosuppression
Pelvic inflammatory disease
Contraindication
Pregnancy
Recent sexually transmitted infection (STI)
Undiagnosed uterine or vaginal
bleeding
Distorted or small uterine cavity
Genital malignancy
Active trophoblastic disease.

67. COCs
Reduces MBL by 43 -50 %
- Greater than naproxen
- Less than danazol and
- tranexamic acid
Contain estrogen and
progestogen in combinations
Act on HPO axis to
suppress ovulation and fertility
Endometrial suppression
cause withdrawal bleeding

68. Combined oral contraceptives
• Acute bleeding
Contraceptives with ethinyl estradiol 30 mcg or
35 mcg 1 tablet every 8 hours, for 7 days,
followed by 1 tablet/day for 3 weeks.
• Chronic bleeding
Combined oral, combined transdermal
contraceptives or combined vaginal ring

69. COCs (Natazia)
Estradiol valerate (dose varies from 2 to 3 mg); this dose is equivalent to 1.5 to 2.25 mg of
micronized oral estradiol, which is equivalent to <20 mcg of ethinyl estradiol
FDA approved
Novel quadriphasic Estradiol Valerate (3-2-1mg) + Dienogest(2-3mg) 28 day pill
Better cycle control, strict
regimen, complex instructions
MBL decrease by 88% by 7th cycle
(comp to LNG-IUS)
Fraser et al 2011,-Pooled analysis of 2
RCTs
Reasonable choice to reduce and
control blood loss
(ACOG Practice Bulletin 2010)
More likely benefit for An ovulatory
bleeding
The estradiol valerate/dienogest OC formulation has 26 hormonally active tablets per each
28day pill pack
The progestin component is dienoge
st (dose varies from 2 to 3 mg).

71. Inhibit synthesis of
estrogen receptors
Promote conversion
of estradiol 
estrone
Inhibit LH
Organized slough to
basalis layer
Stimulate arachidonic
acid formation
Progestins: Mechanisms of Action
Inhibit endometrial
growth

72. • Acute bleeding
Medroxyprogesterone acetate 20 mg, every 8 hours,
for 7 days.
• Chronic bleeding
Oral medroxyprogesterone acetate (2.5–10 mg),
or norethisterone acetate (2.5–5 mg),
or megestrol acetate (20- 60 mg)
, or micronized progesterone(200–400 mg),
dydrogesterone (10 mg).

73. Progestational Agents
Depo-Provera® 150mg IM every 3 months
Side effects
weight gain, nausea, bloating, edema, headache, acne,
depression, exacerbation of epilepsy & migraine, loss of libido

74. Tranexamic acid
Dosage:
1g ( 2 tablets) 3-4x daily from onset of bleeding up
to 4 days
2nd line treatment for AUB
NICE guidelines 2007
Competitive inhibitor of
plasminogen activator
Anti-fibrinolytic agents
Menorrhagia
Reduced breakdown of fibrin preformed clot in spiral endometrium
arterioles  reduce MBL
Reduce MBL by 34-59%
However
Not reducing dysmenorrhea Not contraceptive Not regulating cycles

75. Adverse effects- Rare
Nausea, Vomiting & Diarrhea,
Allergy and
occasionally an Orthostatic reacti
on
Increased thrombotic tendency,
like deep vein thrombosis, during
prolonged treatment as with any
fibrinolysis inhibitors
Contraindications
Thrombo embolic disease
Active intravascular clotting
Severe renal insufficiency
Color vision disorders
Use with Caution:
Elderly
Children under 15 years of age

76. NSAIDs
Reduce prostaglandin
synthesis by inhibiting COX
Prostaglandin:
- Inflammatory response
- Pain pathways
- Uterine cramps
- Uterine bleeds
Treatment of
dysmenorrhea
However
Not contraception
Not to be used in bleeding
disorders

77. NSAIDs
Reduce blood loss by 20-30%
Reduce Dysmenorrhea by 70%
Start a day before menses and continue for
3-5days
NICE Guidelines 2007, SOGC
2013
Ibuprofen 600 mg once per day.
Naproxen 500 mg at onset and
three to five hours later, then 250
to 500 mg twice a day
Mefenamic acid 500 mg three times
per day

78. Ethamsylate
Mechanism of action:
maintain capillary integrity,
anti-hyalurunidase activity
& inhibitory effect on PG Dose:
500 mg qid, starting 5 days
before anticipated onset of
the cycle & continued for 10
days
Side effects:
headache, rash, nausea
Effect:
20% reduction in MBL.
There is no conclusive
evidence of the effectivness
of ethamsylate in reducing
menorrhgea (Grade A)

79. GnRH-analogues
Synthetic peptide that act like a natural GnRH but with longer
biological half life
Action
• Flare effect
Increase FSH and LH
• Profound
Hypo-gonadal effect
after 10 days downregulation
Reduces MBL but with high adverse
effects
Treatment
• Hormonal sensitive cancer
-breast cancer, prostate
cancer
• Estrogen dependant lesion
- leiomyoma, endometriosis

80. Vaginal Danazol
Does not effect HPO axis
Direct effect on the Endometrial cells-
DNA synthesis
High uterine and Ovarian
concentration Vaginal irritation, only adverse effect
Significant reduction in MBL,
Dysmenorrhea, Dyspaerunia
Results -90% had reduction in blood flow after 3 months, no change in Serum
chemistry, no adverse effects
Evaluation parameters- Serum chemistry, TVS , Hystersopy with biopsy
200mg /day vaginal Danazol for 6
months.

81. Desmopressin
Indicated in patients with
thromboembolic disorders
Has been used to treat abnormal uterine bleeding in
patients with coagulation defects
Transiently elevates factor VIII and von Willebrand factor
.3 MCg/kg IV.

82. Ormilexifene-SERM
Reduces blood loss and ET by 85-97.7 %. 60 mg tablet twice /d/3
month. One tab/week/3 month
Side effects
Headaches, GIT upsets, Ovarian cyst ,cx
erosion , Amenorrhea
Should be avoided in
Liver, Renal, PCOS, chronic
Cervicitis

83. Chinese Herbal Medicine for Dysfunctional Uterine
Bleeding: a Meta-analysis of trials compared Chinese
with Western Medicine
Poor quality trial, but showed
comparative efficacy, more RCTs needed
Alternative Medicine
Tu et al., 2009

84. Surgical treatment
Endometrial
ablation
Methods
I. Hysteroscopic:
1. Laser
2. Electrosurgical: a. Roller ball
b. Resection
II.Non-hysteroscopic:
1. Thermachoice
2. Microwave 3- Cryo
Indications:
1. Failure of medical treatment
2. Family is completed
3. Uterine cavity <10 cm
4. Submucos fibroid <5 cm
5. Endometrium is normal or low risk
hyperplasia.
Complications of
hysteroscopic methods
1. Uterine perforation
2. Bleeding
3. Infection.
4. Fluid overload
5. Gas embolismryo

85. Uterine artery embolization (UAE)
Indications
-Heavy bleeding
-Large fibroids
How it works?
-Small particles introduced into artery supply to
the uterus  fibroid shrinks
Adverse outcomes
-Persistent vaginal discharge
-Post-embolisation syndrome: pain, nausea, vomiting and fever
-Need additional surgery
-Premature ovarian failure
-hematoma
Fertility maintained!

86. Disadvantages:
1.Major operation
2.Hospital admission
3.Mortality & morbidity
Advantages:
1. Complete cure
2. Avoidance of long term medical
treatment
3. Removal of any missed pathology
Hysterectomy
Indications:
1. Failure of medical treatment
2. Family is completed
Routes:
1. Abdominal
2. Vaginal
3. Laparoscopic 4- Robotic

87. NICE Recommendations on Surgical
Options
Endometrial resection offered to all
women with HMB provided that
they have completed their family
If the uterus is <10w in size and or
fibroids < 3 cm diameter
A hysteroscopic technique is
used when there are
submucous fibroids
Hysterectomy, uterine artery embolization or myomectomy be
considered for fibroids >4 cm or uterus >10w size

88. EBM can avoid number of hysterectomies
For others COCP, norethisterone, Depo-provera can be
effective
For women wanting to conceive in short term – tranexamic
acid and mefenamic acid appropriate
Mirena is offered as first line treatment and has reduced
need for hysterectomies significantly
AUB is a common problem from menarche to
menopause
Take home message