Abnormal Uterine

Bleeding
Mitra A. Razzaghi, MD
Womens Integrated Services in Health

WISH

Why WISH?

Objectives

Quick review terminology and etiology of AUB

Work up for AUB - most important steps
New trend in treatment of most common causes
of AUB
New non-invasive and minimally invasive
technology
Organize the madness
Quick practical summary on how to diagnose and
treat AUB

Case

56 y/o AA lady, presents for follow up on hospital

admission for asthma exacerbation in Las Vegas.
Asthma is now controlled. By the way she also had
5 days of moderate vaginal bleed which has
stopped
She is G2P2, postmenopause for past 4 years, no
significant gyn history. She was on combination
HRT for severe hot flashes which stopped 2 yrs ago
Patient reluctant to have any studies done
What to do?

AUB - Overview

Common problem in ambulatory medicine

30% of outpatient gyn visits
Broad differential diagnosis
Much of the evaluation and treatment can
be done by internists

AUB: Is uterus the origin?

Rectal
Urethral
Vulvar
Vaginal wall
Cervix
Uterus
Fallopian tube or ovary

Non-Uterine Genital
Sources

Vaginal trauma- external/internal

Vaginitis
Vaginal atrophy
Cervical polyps
Cervicitis

Terminology

Menorrhagia

Metrorrhagia

Intervals >35 days

Menometrorrhagia

absence of periods x 3 usual cycle lengths

Oligomenorrhea

light bleed, irregular intervals

Amenorrhea

bleeding >80cc/cycle

Heavy bleed >80 ml, irregular intervals

Abnormal Uterine Bleeding

(AUB)

Structural

Dysfunctional (DUB)

Leiomyoma
Polyps
Carcinoma
Pregnancy complications
Ovulatory
Anovulatory

Diagnostic tools

History and physical including pelvic exam

Beta-HCG
Pap test
Screening for STIs if indicated
Blood tests as indicated
Endometrial sampling
Pelvic ultrasound (transabdominal and transvaginal
(TVUS)
Saline Infused Sonohystogram (SIS)
Hysteroscopy
10

Endometrial sampling

11

Fast and easy to do -may be tricky in

postmenopausal women
Minimal discomfort for patient
Should be done in almost all AUB patients over
age 35
Provides important information
Comparable results with diagnostic D&C
Best time at or beyond day 18 of cycle

12

Treatment based on Biopsy

Results

Polyp

Endometritis
Hyperplasia without atypia

Cyclic or continuous progestin

Repeat EMBX in 3-6 months
Refer to Gyn if hyperplasia persists

Atypia or carcinoma
Disordered endometrium, stromal collapse,
proliferative or secretory

13

Hysteroscopy or D&C
Observation sometimes acceptable

Treat based on bleeding pattern

Saline Infused
Sonohystogram (SIS)

Indication

How it is done

14

Suspect intra-cavity lesion (polyp, fibroid)

Endometrial thickness eval with Tamoxifen
Vaginal Ultrasound first
4 mm catheter guided into uterus through cervical os
Small balloon or plug keeps the catheter in place
20 cc saline infused with vaginal transducer in place
Distension of the uterine allows visualization

Hysteroscopy

15

Endometrial polyp

16

Systemic Diseases causing

AUB

17

Thyroid disease
Chronic liver disease
Cushing syndrome
Renal disease
Emotional or physical stress
Excessive exercise
smoking

Common medications
causing AUB

18

Hormones (including Tamoxifen)

Anticoagulants
Phenytoin
Antipsychotics (Olanzapine, Risperidone)
Tricyclic antidepressants
Corticosteroids
Antibiotics (toxic epidermal necrolysis or
Stevens-Johnson Syndrome)

Polycystic Ovarian
Syndrome
Affects 10% of women in the US

Definition by NIH Consensus, 1990:

Oligo- or anovulation
Hyperandrogenism
Exclusion of other causes of hypergonadism and menstrual
irregularity

Rotterdam Criteria, 2003:

Exclusion of other causes of hypergonadism and menstrual

irregularity
and 2 of following 3 criteria

19

Anovulation
Hyperandrogenism
Polycystic ovaries by ultrasound

PCOS - Pathophysiology

20

Elevated LH and insulin levels

Combination enhances ovarian androgen
production
High androgen levels lead to abnormal
follicular development and function

PCOS

Clinical manifestations

Medical complications

21

Irregular menses
Androgen excess
Obesity
Acanthosis nigricans
Endometrial cancer
Insulin resistance/Diabetes
Infertility
Coronary artery disease (CAD)
Obstructive sleep apnea (OSA)
Non-Alcoholic steatohepatitis (NASH)

PCOS - Diagnosis

Clinical diagnosis based on NIH criteria

Ultrasound results using Rotterdam criteria
Rule out other causes

Menstrual irregularities

Androgen excess

22

Pregnancy
Hyperprolactinemia
hypothyroidism
Hyperprolactinemia
Nonclassical adrenal hyperplasia
Androgen secreting tumors

PCOS - Work up

Rule out other etiologies

Supportive data

23

TSH, Prolactin, B-HCG, FSH

17-OH Progesterone
Testosterone level (<200)
Dehydroepiandrosterone sulfate, DHEA-S (<800)
LH:FSH ratio of 2:1
Elevated testosterone and DHEAS levels
Pelvic US not necessary

PCOS - Treatment

Concentrate on metabolic syndrome and

risk reduction
Treatment of unopposed estrogen

24

Need at least 3-4 endometrial shedding a year

if not on any other treatment
Androgen excess treated with OCP,
spironolactone, or Eflomithine

Adenomyosis:

25

Benign histological finding of endometrial

glands into myometrial wall
Causes pain, menorrhagia and large
uterus during reproductive years

Uterine Leiomyoma

26

Uterine Leiomyoma
(Fibroids)
Most common gynecological tumor

20-40% of reproductive age women

Cause unknown
Symptoms

27

Menorrhagia
Pelvic pressure/pain
Decreased fertility

Improvement after menopause or other

hypoestrogenic states

Uterine Fibroids

Increased risk

Reduced risk

28

Nulliparity
Obesity
ETOH use
Black-American ethnicity
Genetic/Familial predisposition

Pregnancy
Combination OCP
Depo-Provera
Tobacco use

Uterine Fibroids

Asymptomatic

Expectant management

Mildly symptomatic

OCP
NSAIDs
Useful in idiopathic menorrhagia
Do not reduce blood loss caused by fibroids
May alleviate cramping

29

Uterine Sparing Treatment

for Fibroids

Hormonal
Uterine artery embolization
MR directed ultrasound (ExAblate)
Myomectomy

30

Hysteroscopic resection
Laparoscopic myomectomy

GnRH Agonists

31

Most effective medical therapy

Down regulates pituitary GnRH receptors
Profound decline in ovarian steroid
production
35-65% size reduction, mostly within first
3 months
Return to pretreatment size after
discontinuation
Ideal treatment before surgical excision
Induces menopause

Raloxifene

Selective estrogen receptor modulator

Postmenopausal: reduces fibroid volume
Premenopausal: conflicting data
Combination with GnRH agonist

Side effects

32

70% vs. 40% reduction in size with GnRH

agonist alone
Venous thromboembolism
Vasomotor symptoms

Other Therapies

Danazole

Mifepristone (RU-486)

Antiprogestin
Side effects: vasomotor symptoms, 25%
hyperplasia

Levonorgestrel-releasing IUD

33

Androgenic steroid
Inhibits pituitary gonadotropin secretion
Side effects: weight gain, acne, oily skin

Contraindications: uterine distortion,

submucosal intracavitary fibroids

Uterine Artery Embolization

UAE

34

Uterine Artery
Embolization-UAE

35

Disadvantages of UAE

36

Painful!!!
Reduces bleeding more than bulk
Pedunculated fibroids cannot be embolized
Not definitive
Can induce menopause
Not recommended for women who desire
fertility
IR data skewed- minimal long term follow
up

MR Guided Ultrasound
(ExAblate)

37

MRI maps the fibroids

High frequency ultrasound heats the
fibroid
Size decreases by 13%
80% decreased symptoms
Contraindicated if pregnancy is desired
Lower complication compared to UAE

Uterine Leiomyoma

38

ExAblate

39

Limitations of MR-US
Ablation

40

Few sites in the US - available in Denver

Cannot go through scars, bladder, bowel
Limited to smaller fibroids
No fertility data
Limited long term data (8 years)

Abdominal Myomectomy

41

Major surgery
Complications significantly higher than
hysterectomy
Long recovery
Recurrence rate 50%
Small chance of uterine perforation in
subsequent pregnancy

Laparoscopic Myomectomy

42

Only for pedunculated or subserosal

fibroids
Advanced laparoscopic techniques required
Very limited availability

Hysteroscopic myomectomy

43

Suitable for submucous or intracavitary

fibroids
Limited by size and location of the tumor
High recurrence rate
Requires advanced hysteroscopic skills

Hysterectomy

44

Laparoscopic Hysterectomy

45

Laparoscopic assisted vaginal

hysterectomy
Laparoscopic sub-total hysterectomy
Total laparoscopic hysterectomy

Treatment of
Dysfunctional
Uterine Bleeding

OCP- New Formulations

Chewable tablet

24/4 day regimen

Shorter hormone-free interval

FDA indication for PMDD

84/7 day regimen

47

35 ug Ethinyl Estradiol+ 0.4 mg Norethindrone

75 mg Ferrous Fumarate in placebo

12 weeks active pill + 7 days placebo

Four menstrual periods per year
Menstrual migraine, dysmenorrhea
12 weeks active pill + 7 days 10 ug Ethinyl Estradiol

Contraindication to OCP

48

Previous thromboembolic event or stroke

History of estrogen-dependent tumor
Active liver disease
Pregnancy
Uncontrolled hyperlipidemia
Older than 35 and smokes >15 cigarettes per day
Older than 40 not contraindicated but progestin
preferred
Avoid Desogestrel-containing OCP if risk factors for
VTE

Progestins

Commonly used oral forms:

Cyclic progestin (e.g. Provera 14 days on 14

days off)
Continuous progestin:

49

Medroxy progesterone (Provera) cheaper but has

PMS-like side effect
Micornized progesterone (Prometrium)
Norethindrone (Aygestin)
Megestrol (Megace)

Norethindrone Minipill 0.35 daily

Depo-Provera (new SC form) or progesterone Implant
(Implanton)
Levonorgestrel IUD (Mirena)

Levonorgestrel IUD
(Mirena)
T-shaped polyethylene with a collar

containing 52 mg of levonorgestrel
Visible on X-Ray
Effective up to 7 years, approved for 5
As effective as endometrial ablation for
treatment of menorrhagia
May also decrease the risk
of PID

50

Implanon (contraceptive
implant)

51

Serum level of etonogestrel detectable within

hours of insertion
Relatively rapid return of fertility - 3 months
Continuous protection for 3 years
Appropriate for women after 4th postpartum
week
Easy insertion and removal by physician
Does not protect against STI

Balloon Ablation

52

Uses hot liquid is balloon to treat uterine

lining
Minimally invasive, inserted through cervix
Procedure is quick, uterine lining is treated
for 8 minutes
Uterine lining will slough off like a period
in 7-10 days

Advantages of Ablation

53

Many patients report decreased bleeding

and are satisfied
Minimal recovery time
Low complication rate
Easy to perform

Disadvantage of Ablation

54

No long term studies

May not be definitive
Patient selection is the key!
Works best with normal shaped cavity
Often inappropriately performed
High failure rate with adenomyosis and
fibroids

55

Postmenopausal bleeding

56

Atrophy 59%
Polyp 12%
Endometrial cancer 10%
Endometrial hyperplasia 9.8%
Hormonal effect 7%
Cervical cancer <1%
Other 2%

Endometrial Hyperplasia

57

Adenocarcinoma

58

Postmenopausal bleeding

History and physical to direct clinician towards 4

groups

Cervical cytology very important

59

Neoplasm
Atrophy
Medications
Foreign body
Mean age for cervical cancer 52.2
Visible lesion needs biopsy even if pap is normal

Postmenopausal bleeding

Evaluation to include

60

Pap test
Transvaginal Ultrasound
Endometrial biopsy if endometrial thickness
5mm or higher
EMBx <5 mm if risk factors like obesity, chronic
anovulation, breast cancer, Tamoxifen use, FHx
of endometrial, ovarian, breast or colon cancer
May need SIS or hysteroscopy for focal lesions
MRI if US not definitive for fibroids or
adenomyosis

Special considerations

Intrauterine infection

Post Radiation Therapy

Can be late effect

Obliterative endarteritis, tissue necrosis
Hemorrhagic cystitis or proctitis

Disease of adjacent organs

61

Rare in this age group

Think malignancy
Occasionally due to cervical stenosis

Diverticulitis can fistulize into uterine

Quick Practical
Summary

AUB Initial approach

63

History and physical - pelvic exam

Rule out pregnancy
Determine bleeding pattern

Bleeding patterns

Normal

Irregular
Menorrhagia

64

Interval 21-35 days

Duration 2-7 days
Amount <80cc (<1pad/tampon change every 3hrs)

Heavy but regular cyclic

> 7days, clots or iron deficiency anemia
If >12 days consider irregular regardless of cyclic
pattern

Acute Severe Bleeding

Contraceptive related

Irregular bleeding Perimenarche

Up to 2 years after menarche

65

Immature hypothalamic-pituitary-ovarian axis

Reassurance
If not enough: OCP or progestin

Irregular bleeding nonpregnant

TSH, Prolactin if oligomenorrhea

>35 or unopposed estrogen: EMBX, consider TVUS

Consider cause

If no desire for pregnancy

66

Endometritis
Medications
Advanced systemic disease
PCOS
OCP low -> high
Progestins: oral, injection, implant, IUD

If persists TVUS, EMBx

Have to scratch your head more? Refer to our Gyn
friends

Menorrhagia

Blood loss of >80 ml per cycle

Poor correlation of actual loss with pts perception of
excessive bleed
May try hormonal therapy

If inadequate response TVUS or SIS

OCP if not contraindicated

Progestins including Levonorgestrel IUD or Provera 10 mg 14
days on 14 days off
NSAIDs- 400mg Ibuprofen TID x 4 days start the day before
menses
EMBX if endometrial thickness >10mm
Surgical options if Polyp or submucosal myoma
MRI if possible adenomyosis

Screen for Von Willebrand disease early if suspected

67

Severe Acute Bleeding

Orthostatic hypotension or Hgb<10 or

profuse active bleed

68

Hospital admission
Studies: Coags, CBC, TSH, Platelet function, TVUS
IV Conj Estrogen (Premarin) 25 mg Q4h + antiemetic
and OCP
D&C if no response after 2 doses

Severe Acute Bleeding

Hemodynamically stable

Oral Premarin 2.5 mg qid +antiemetic

Studies: TVUS, TSH, CBC, Coags
D&C if no response after 4 doses or bleed >1 pad per
hour
After bleeding stopped:

69

OCP(monophasic) QID x4 days

TID x 3 days
BID x 2 days
QD x 3 weeks
One week off
then cycle on OCP for at least 3 months
Dont forget oral Iron!

Peri-menstrual Spotting

Pre and post menstrual (<8 days total) maybe

normal variant
Postmenstrual spotting and pain/tenderness could
be endometritis (test for GC/CT, empirical Doxy
100 mg BID x 10 days)
Midcycle spotting

70

If brief may be normal due to dip in serum estrogen

level
> 35 years of age : Endometrial biopsy warranted

OCP Associated Bleeding

Breakthrough Bleeding

common with low dose OCP

If persistent for 3 months, switch to high dose
Screen for GC/CT (common in young females)
If persistent rule out structural cause (TVUS/SIS or
hysteroscopy)

Amenorrhea

71

Rule out pregnancy

May continue same pill (no risk of hyperplasia)
May switch to higher estrogen OCP

Bleeding Associated with

IUD
Rule out endometritis

Empiric therapy acceptable

Common for first 4-6 months of use
Copper IUD

72

One cycle of OCP or

10 mg Medroxyprogesterone x 7 days
Trial of NSAIDs

Progesterone-releasing IUD

One cycle of OCP

If bleeding persists consider removal of IUD

Depo-Provera Associated
Bleeding

Spotting common, no treatment necessary

If persistent irregular bleed

7-day course of estrogen:

1.25 mg Premarin daily or
Estradiol 1mg daily or
Estrogen patch e.g. Climara 0.1mg

73

Maybe repeated if bleeding recurs

Back to our case

74

Pelvic exam normal

All labs normal - not pregnant!
Pap smear HGSIL
TVUS normal, Endometrial thickening 5 mm
Colposcopy normal
ECC and EMBx normal
Good news from cytology review!!!
Conclusion

Womens issues named in

honor of MEN

MENtal illness

MENstrual cramps

MENtal breakdown

MENopause

G(U)Ynecologist

H(I)Sterectomy
75

The men of WISH

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