Abnormal Uterine Bleeding

E. Hengstebeck, D.O.

2
Disclosures

None

3
Objectives
Discuss the etiology of abnormal uterine bleeding (AUB) in
non-pregnant reproductive age and postmenopausal
women.
Describe the PALM-COIEN classification for causes of
abnormal uterine bleeding.
Discuss the diagnostic approach to AUB in the non-
pregnant reproductive age and postmenopausal women.
Describe the World Health Organization classification for
endometrial hyperplasia.
Discuss the management of AUB in the non-pregnant
reproductive age and postmenopausal women.
Describe the clinical presentation and management of
women with uterine cancer.

4
Case #1
A 28-year-old female presents to your office complaining of heavy menstrual
periods. Her periods occur every 3-4 months and have been irregular for several
years. She has not been sexually active for the past 6 months. She has had two
lifetime partners and has only used condoms for contraception in the past. She
denies any fever, galactorrhea, abdominal or pelvic pain, or vaginal discharge. She
was recently diagnosed with Type 2 diabetes and prescribed metformin.

PE: BMI 40
Skin: moderate facial acne, increased facial hair, acanthosis nigricans
Pelvic exam: no active bleeding, no vaginal discharge, vagina and cervix grossly
unremarkable, uterus non-tender and not enlarged
The remainder of the exam is unremarkable.

Urine HCG- negative

What is the most likely etiology of her abnormal uterine bleeding?

What would be the initial step in the management of this patient?

5
Case #2
A 45-year-old female presents to your office complaining of increasingly heavy,
painful menstrual periods. Her periods occur every 28 days and last 5-6 days. She
states that she has to frequently change tampons and pads for the first 3-4 days
due to the heavy flow. She has been taking OTC ibuprofen with minimal relief. She
denies any fever, galactorrhea, abdominal or pelvic pain, or vaginal discharge. Her
last annual exam was two years ago and everything was normal. She is married
and monogamous with her husband of 20 years. He has had a vasectomy. She has
a history of depression and takes sertraline.

PE: BMI 26
Pelvic exam: no active bleeding, no vaginal discharge, vagina and cervix grossly
unremarkable, uterus is non-tender and is asymmetrically enlarged on the right
The remainder of the exam is unremarkable.

Urine HCG- negative

What is the most likely etiology of her abnormal uterine bleeding?

What would be the initial step in the management of this patient?

6
Case #3
A 65-year-old female presents to the office complaining of 3 days of dark
red spotting that has now resolved. Her last menstrual period was 15
years ago. She is widowed and is not sexually active. She has a history of
HTN and takes lisinopril. She is otherwise healthy and has no complaints.

PE: BMI 26
Pelvic exam: no active bleeding, no vaginal discharge, vagina and cervix
grossly unremarkable, uterus is non-tender and is asymmetrically
enlarged on the right
The remainder of the exam is unremarkable.

What is the most likely etiology of her abnormal uterine

bleeding?

What would be the initial step in the management of this

patient?

7
What is the origin of the bleeding?

Abnormal vaginal bleeding

Sources
Vulva
Vagina
Cervix
Uterus
Other
Urinary
GI
8
Incidence of AUB
Premenopausal women
10-30% of women
Estimated that only 10% seek care
Postmenopausal women
4-11% of women
Impact
Quality of life
Interference with daily activities
Productivity
Absenteeism from work, school
Utilization of healthcare services
Direct costs
Medical treatment
Surgical treatment
Indirect costs
Loss of productivity

9
 The Hypothalamic-Pituitary-
Ovarian Axis
From: Reproductive Endocrinology
Williams Gynecology, 3e, 2016

Legend:
Positive and negative feedback loops seen with the hypothalamic-pituitary-ovarian axis. Pulsatile release of gonadotropin-releasing hormone (GnRH) leads to
release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. Effects of LH and FSH result in follicle maturation,
ovulation, and production of the sex steroid hormones (estrogen, progesterone, and testosterone). Rising serum levels of these hormones exert negative
feedback inhibition on GnRH and gonadotropin release. Sex-steroid hormones vary in their effects on the endometrium and myometrium as discussed in the
text. Inhibin, produced in the ovary, has a negative effect on gonadotropin release. Copyright 2016 McGraw-Hill Education. All rights reserved.
 The Menstrual Cycle
From: Disorders of the Female Reproductive System
Harrison's Principles of Internal Medicine, 19e, 2015

Legend:
Relationship between gonadotropins, follicle development, gonadal secretion, and endometrial changes during the normal
menstrual cycle. E2, estradiol; Endo, endometrium; FSH, follicle-stimulating hormone; LH, luteinizing hormone; Prog, progesterone.
Copyright 2016 McGraw-Hill Education. All rights reserved.
Normal Menstrual Cycle

Length of cycle
24-35 days
Duration
Normal range: 4-6 days
Abnormal: <2 days or >7 days
Volume of flow
Normal: 30 ml
Abnormal: >80 m

12
Patterns of Abnormal Uterine Bleeding
Menorrhagia (hypermenorrhea, heavy menstrual bleeding)
Heavy, prolonged menstrual flow
Hypomenorrhea (cryptomenorrhea)
Unusually light flow or spotting
Metrorrhagia (intermenstrual bleeding)
Occurs between cyclic menses
Polymenorrhea
Periods that occur too frequently
Menometrorrhagia
Heavy, irregular bleeding
Oligomenorrhea
Menstrual periods that occur more then 35 days apart
Postcoital bleeding
Occurs after intercourse
Post-menopausal bleeding
Any uterine bleeding after menopause

13
Acute versus Chronic AUB
Acute
Episode of severe heavy bleeding
Urgent or emergent situation requiring
immediate intervention to prevent
further blood loss
May co-exist with chronic AUB
Chronic
Uterine bleeding that is abnormal in
volume, regularity, and/or timing present
for the previous 6 months
14
Estimating Blood Loss in HMB

Subjective
Patients perceptions
# and types of pads or tampons used
Presence of large clots
Positive correlation between passing clots > 1 inch in
diameter and changing pads more frequently than
every 3 hours
Pictorial blood assessment chart
Score of >100 correlate with > 80 ml blood loss

Objective
Hemoglobin and hematocrit
A normal level does not exclude significant bleeding

15
Pictorial Blood Assessment Char
From: Abnormal Uterine Bleeding
Williams Gynecology, 3e, 2016

Legend:
Scoring for the pictorial bleeding assessment chart. Patients are counseled to evaluate the degree of saturation for each sanitary
product used during menstruation. The total number of points are tallied for each menses. Point totals greater than 100 indicate
menorrhagia. Copyright 2016 McGraw-Hill Education. All rights reserved.
AUB in Non-pregnant Reproductive Age
Women: Ovulatory Bleeding
Heavy menstrual bleeding (HMB) or menorrhagia
FIGO classification
PALM (polyp, adenomyosis, leiomyoma, malignancy)
COEIN (coagulopathy, ovulatory disorders, endometrium, iatrogenic, not
classified)
Most common
Leiomyoma
Adenomyosis
Cesarean scar defect
Bleeding disorder
von Willebrand disease
Most common inherited bleeding disorder (1/800-1/1000)
Idiopathic thrombocytopenia (ITP)
Leukemia
Hypersplenism

Approximately 50% of women with menorrhagia

have no discernable cause
17
PALM-COEIN Classification

18
Iatrogenic and Not Yet Classified
Etiologies
Exogenous
IUD, foreign bodies, trauma
Medications
Sex steroids
Combined oral contraceptives (COC)
Progesterone-releasing IUD
Anticoagulants
Hyperprolactinemia-inducing
Infection
STD, TB, chronic endometritis, postabortal or postpartum
Systemic abnormalities
Thyroid
Liver
Decreased ability to metabolize estrogen
Inability to normally synthesize clotting factors
Chronic kidney disease
Obesity

19
AUB in Non-pregnant Reproductive Age
Women: Anovulatory Bleeding
Unopposed estrogen levels causes chronic
stimulation of endometrium (no progesterone=no
withdrawal bleed)
Irregular or infrequent periods
HMB
Causes
Pituitary or hypothalamic disorder
Hypothyroidism
Androgen excess
Polycystic ovary syndrome
Congenital adrenal hyperplasia
Androgen producing tumors
Ovarian failure
Iatrogenic
Medications

20
Diagnostic Approach: The History
Menstrual
LMP
Presence of absence of typical premenstrual symptoms
Obstetrical
History of C-sections
Medications
Drugs that affect coagulation or platelet function
Anticoagulants
Antiplatelet drugs
Sex steroids
Contraceptives
Oral
IUD
Hormone replacement therapy
Selective estrogen receptor modulators (SERMs)
Stimulates endometrial proliferation
Raloxifene, tamoxifene
Medications that increase prolactin
Metoclopramide
Antipsychotics
Tricyclic antidepressants (TCAs)
Associated symptoms
Lower abdominal pain, fever, vaginal discharge
Dysmenorrhea, dyspareunia, infertility
Galactorrhea, heat or cold intolerance, hirsutism, hot flushes
Recent illness, stress, excessive exercise, possible eating disorder

21
Diagnostic Approach: The Physical Exam
Vital signs
BMI
Skin/hair growth patterns
Acne
Hirsutism
Acanthosis nigricans
Thyroid
Breasts
Galactorrhea
Abdomen
Pelvic
Verify source of bleeding
Size and contour of uterus
Adnexal masses or tenderness

22
Diagnostic Approach: Laboratory Tests

Initial labs
Pregnancy test
Urine versus serum
Urine Hcg
Detects pregnancy two weeks after conception
Serum Hcg
Detects pregnancy one week after conception
CBC (evaluation of HMB)
Hemoglobin and hematocrit
Platelets
Other labs based on history and
physical exam
23
Additional Tests: Endocrine Evaluation
Thyroid function tests
Presence of amenorrhea or oligomenorrhea
Thyroid disease uncommon cause of HMB
Prolactin level
Presence of anovulatory bleeding, amenorrhea, or galactorrhea
Hyperprolactinemia-inducing medications
Androgen levels (testosterone, DHEA-S)
Presence of anovulatory bleeding and signs of virilization i.e. hirsutism
Polycystic ovary syndrome
FSH or LH
Suspected premature ovarian failure or hypothalamic dysfunction
Estrogen levels
Presence of adnexal mass and consideration for estrogen-secreting
ovarian tumor

24
Additional Tests: Coagulation Studies
Heavy or prolonged menses at menarche
Chronic systemic disease
Liver
Inability to normally synthesize clotting factors
Kidney
Medications
Anticoagulants
Warfarin
Newer agents
Antiplatelet
Aspirin
Clopidogrel (Plavix)
Cilostazol (Pletal)
Labs
PT, PTT, INR, bleeding time
Fibrinogen level
von Willebrand factor

25
Endometrial Sampling
Preferred evaluation in the evaluation of AUB in non-
pregnant, reproductive age women
10-20% of endometrial cancers are diagnosed in premenopausal women
Options
Endometrial biopsy
Advantages
Readily available
Low complication rate
D&C
Stratification based on risk factors for endometrial cancer
< 45 years-old
Majority of AUB is due to benign etiologies
Reserve endometrial sampling for:
Persistent AUB
History of unopposed estrogen
Failed medical management
High risk for endometrial cancer
Age 45 years to menopause
Proceed with endometrial sampling for
All ovulatory AUB
Any bleeding that is frequent, heavy, or prolonged

26
 Imaging
Transvaginal ultrasonography (TVS)
Detects uterine tumors, polyps, endometrial and myometrial
abnormalities
Limitations in premenopausal women for evaluation of endometrial wall
Variation in endometrium during menstrual cycle
Saline sonohysterography (SIS)
Performed with intrauterine saline infusion
Superior to TVS in the detection of intracavitary lesions
More expensive than TVS
Limited availability
MRI
More sensitive than TVS and SIS for detecting adenomyosis and
leiomyomas
Less reliable in the diagnosis of endometrial abnormalities such as
polyps

27
From: BENIGN GENERAL GYNECOLOGY
Williams Gynecology, 3e, 2016

Legend:
A. Saline infusion sonography catheter. B. Saline infusion sonography.

Copyright 2016 McGraw-Hill Education. All rights reserved.

Hysteroscopy
Direct visualization of the endometrial cavity
Proliferative phase of menstrual cycle allows for best visualization
Indicated for evaluation and treatment of the endometrial cavity, endocervical
canal, or tubal ostia
Minimally invasive
May be both diagnostic and therapeutic
Combine evaluation and treatment
Removal of polyps
Resection of submucosal fibroids
Outpatient or operative procedure
Cannot adequately assess for myometrial disease
(adenomyosis), tubal abnormalities, or external uterine
structures
Common reasons for failure
Pain
Cervical stenosis
Poor visualization

29
From: Minimally Invasive Surgery Fundamentals
Williams Gynecology, 3e, 2016

Legend:
Differences between a 0-degree hysteroscope (left) and 30-degree hysteroscope (right). A. Intracavitary views B. A 30-degree
endoscope has an angled tip. C. Views of the endocervical canal (black dot) during hysteroscope insertion.
Copyright 2016 McGraw-Hill Education. All rights reserved.
Medical Management: Hormonal Therapies
Goals of treatment
Regular shedding of endometrium
Conversion of proliferative to secretory endometrium
Cyclical progestins
Oral
Medroxyprogesterone (Provera) 5-10 mg daily x 5-10 days
Begin on day 16 or 21 of cycle
Progesterone-releasing intrauterine systems (LNG-IUS)
Combination oral contraceptives
Danazol
Suppresses estrogen and progesterone
Leads to endometrial atrophy and reduced menstrual loss
Weak androgenic properties
Side effects
Development of male characteristics
Acne
Weight gain
Menopause-like symptoms

31
Medical Management: Nonhormonal
Therapies
NSAIDs
Reduce menstrual bleeding by decreasing
prostaglandins
No evidence that one NSAID is more effective than
another
Transexamic acid
Antifibrinolytic
Prevents platelet activation of plasminogen
Two 650 mg tabs TID for the first 5 days of the cycle
decreased bleeding significantly more than NSAIDs
Expensive compared with NSAIDs
Risk of thromboembolism

32
 Surgical Management
Generally reserved for medical management failures
Endometrial resection and ablation
Surgical destruction of the endometrium
Level of the basalis (4-6 mm)
Indications
Ovulatory HMB in premenopausal women
Types
Non-resectoscopic ablation
May be performed in the office
Resectoscopic ablation
Requires regional or general anesthesia
Complications
Uterine perforation
Hemorrhage
Hematometra
Pelvic infection

33
From: Abnormal Uterine Bleeding
Williams Gynecology, 3e, 2016

Legend:
Drawing of endometrial anatomy as it varies through the menstrual cycle.

Copyright 2016 McGraw-Hill Education. All rights reserved.

Surgical Management contd
Hysteroscopy
D&C
Not preferred for long-term management of AUB
Effects are temporary
Symptomatic leiomyomas
Uterine artery embolization
Medical management failure
Complications
Pain requiring hospital admission
Post-embolization syndrome
Need for re-intervention
Myomectomy
Best suited for subserosal and intramural leiomyomas
Complications
Bleeding requiring transfusion

Hysterectomy
Most common surgical treatment for AUB
Multiple techniques available
Abdominal and vaginal approaches
Laparoscopic-assisted
Decreased morbidity with laparoscopic-assisted vaginal techniques
35
Surgery versus Medical Therapy for HMB
Cochrane systematic review
Compared the effectiveness, safety, and acceptability of surgery
versus medical therapy
Selection criteria
15 RCTs comparing conservative surgery (endometrial ablation or resection) or
hysterectomy versus medical therapy (oral or IUD)
Results
Hysterectomy, endometrial surgery, and levonorgesterol-releasing intrauterine
system (LNG-IUS) were all effective in reducing HMB
Surgery most effective over the short term
Possible serious complications
All were preferred over oral medications
Both conservative surgery and LNG-IUS appear to be safe, acceptable,
and effective
Limitations
Lack of blinding, attrition of patients, and imprecision of study designs
Difficult to interpret data for long-term follow-up
Large number of women randomized to medical therapy subsequently underwent surgery
36
Postmenopausal Bleeding
Main objective in the evaluation is to
exclude cancer
Endometrial cancer is the cause of
bleeding in 10% of women with AUB
Most common cause of AUB is
endometrial atrophy

37
Differential Diagnosis
Uterine cancer
Endometrial atrophy
Endometrial polyps
Postmenopausal hormone therapy
Endometrial hyperplasia
Leiomyomas
Higher incidence of uterine sarcoma
Adenomyosis
Identified in the presence of hormone replacement therapy (HRT)
Disease in adjacent organs
Urinary
GI
Post-radiation therapy
Medications
OTC herbal and dietary supplements

38
Diagnostic Approach: The History
Associated symptoms
Pain, fever, changes in bowel or bladder function
Medications
HRT
Drugs that affect coagulation or platelet function
Anticoagulants
Antiplatelets
Selective estrogen receptor modulators (SERMs)
Stimulates endometrial proliferation
Raloxifene, tamoxifene
Medications that increase prolactin
Metoclopramide
Antipsychotics
TCAs
OTC
Soy-containing herbal or dietary supplements
One randomized trial of 376 postmenopausal women who received soy versus placebo
showed a significant increase in endometrial hyperplasia over 5 years
Family history of breast, colon, or endometrial cancer
Lynch syndrome

39
Diagnostic Approach: The Physical Exam

Vital signs
BMI
Obesity is a risk factor for endometrial
cancer
Abdomen
Pelvic
Verify source of bleeding
Size and contour of uterus
Adnexal masses or tenderness

40
Diagnostic Studies
Endometrial biopsy
High sensitivity
Low complication rate
Low cost
Sample may be insufficient for diagnosis common
TVS
Acceptable as an initial test
Endometrial cancer can be excluded if the endometrium is homogenous and <
4 mm
Potential limiting factors to adequate assessment
Obesity
Coexisting myomas
Previous uterine surgery
Failure to identify a thin, distinct endometrial lining should trigger some
alternative method of evaluation
Further evaluation indicated for postmenopausal women with an endometrial
thickness of > 4mm

41
Endometrial Hyperplasia
Histologic diagnosis
Requires tissue sample
World Health Organization
Classification
Simple hyperplasia
Complex hyperplasia
Simple atypical hyperplasia
Complex atypical hyperplasia
Atypical hyperplasia
Nuclear atypia of endometrial cells
Associated with higher rates of cancer
42
 Risk of Progression to Cancer
Health Organization Classification of Endometrial Hyp

Types Progressing to cancer

(%)
Simple hyperplasia 1

Complex hyperplasia 3
Simple atypical hyperplasia 8

Complex atypical hyperplasia 29

43
Management of Nonatypical Hyperplasia
Premenopausal
May spontaneously regress without treatment
Cause is usually chronic anovulation and estrogen excess
Commonly used therapies
Low-dose progestin therapy
Cyclic or continuous medroxyprogesterone (Provera)
Combined oral contraceptives
LNG-IUS
Follow-up endometrial biopsy indicated
Postmenopausal
Ensure adequate sample obtained to exclude atypia
Consider D&C if sample inadequate
Commonly used therapies
Low-dose progestin therapy
Cyclic or continuous medroxyprogesterone (Provera)

Risk of progression to cancer is low (1-3%)

44
Management of Atypical Hyperplasia
Hysterectomy is the preferred treatment for
both pre and postmenopausal women
Risk of progression to cancer may be as high as 29%
High rate of coexistent malignancy found at the time of
surgery
Postmenopausal
Hysterectomy with removal of both fallopian tubes and
ovaries (BSO)
Premenopausal
Hysterectomy with removal of fallopian tubes recommended
Removal of ovaries is optional
If preservation of fertility is desired:
High dose progestin therapy or LNG-IUS
Serial endometrial biopsies every 3 months
45
Endometrial Cancer
Statistics
Most common gynecologic cancer in the
United States (4th leading cancer overall)
7th leading cause of cancer death
Estimated 54,870 new cases (2015)
Estimated 10,170 deaths (2015)
Approximately 80 percent of these cancers are
diagnosed in postmenopausal women older
than 55 years of age
Most patients are diagnosed early and
subsequently cured
46
Risk Factors
Demographics
Older age
White race
North America or northern Europe residence
Higher education or income level
Exposure to estrogen
Obesity
Polycystic ovarian syndrome
Early age of menarche
Late age of natural menopause
Reproductive factors
Menstrual irregularities
Nulliparity
Infertility
Medications
Tamoxifen, high cumulative doses
Long-term COC use
Chronic disease
DM, HTN, or gallbladder disease

47
Types of Cancers

Type I
Occurs more frequently in white women
Most common type
Endometrioid adenocarcinoma histology
Estrogen-dependent
Low grade
Derived from atypical endometrial hyperplasia
Type II
Occurs more frequently in black women
Serous or clear cell histology
No precursor lesion
More aggressive clinical course
48
Clinical Presentation
Signs and symptoms
Premenopausal
High index of suspicion
Prolonged, heavy menstruation
Intermenstrual spotting
Does not respond to medical therapy as expected
Postmenopausal
Any uterine bleeding
Abnormal vaginal discharge
Pap test
Benign endometrial cells
Premenopausal
Limited clinical significance especially if sample obtained following menses
Postmenopausal
3-5% risk of endometrial cancer
Atypical glandular cells
Higher risk for underlying cervical or endometrial neoplasia
Colposcopy and endocervical curettage required for further evaluation

49
Management
Surgical patients
TAH-BSO
Nonsurgical patients/fertility-
sparing management
Continuous progestin treatment or LNG-
IUS
Adjuvent therapy
Chemotherapy
Radiation

50
 Case #1
A 28-year-old G0P0 female presents to your office complaining of heavy menstrual periods. Her
periods occur every 3-4 months and have been irregular for several years. She has not been
sexually active for the past 6 months. She has had two lifetime partners and has only used
condoms for contraception in the past. She denies any fever, galactorrhea, abdominal or pelvic
pain, or vaginal discharge. She was recently diagnosed with Type 2 diabetes and prescribed
metformin.

PE: BMI 40
Skin: moderate facial acne, increased facial hair, acanthosis nigricans
Pelvic exam: no active bleeding, no vaginal discharge, vagina and cervix grossly unremarkable,
uterus non-tender and not enlarged
The remainder of the exam is unremarkable.

Urine HCG- negative

What is the most likely etiology of her abnormal uterine bleeding?

Anovulation due to obesity, ?PCOS.

What would be the initial step in the management of this patient?

Consider labs i.e. TSH, prolactin. Begin oral progestins or COC.

51
 Case #2
A 45-year-old G2P2 female presents to your office complaining of increasingly heavy, painful
menstrual periods. Her periods occur every 28 days and last 5-6 days. She states that she
has to frequently change tampons and pads for the first 3-4 days due to the heavy flow. She
has been taking OTC ibuprofen with minimal relief. She denies any fever, galactorrhea,
abdominal or pelvic pain, or vaginal discharge. Her last annual exam was two years ago and
everything was normal. She is married and monogamous with her husband of 20 years. He
has had a vasectomy. She has a history of depression and takes sertraline.

PE: BMI 26
Pelvic exam: no active bleeding, no vaginal discharge, vagina and cervix grossly
unremarkable, uterus is non-tender and is asymmetrically enlarged on the right
The remainder of the exam is unremarkable.

Urine HCG- negative

What is the most likely etiology of her abnormal uterine bleeding?

Ovulatory bleeding due to uterine abnormality (?fibroids).

What would be the initial step in the management of this patient?

TVUS or SIS. Consider endometrial biopsy. Treatment based on underlying cause.

52
Case #3
A 65-year-old G4P4 female presents to the office complaining of 3 days of
dark red spotting that has now resolved. Her last menstrual period was 15
years ago. She is widowed and is not sexually active. She has a history of
HTN and takes lisinopril. She is otherwise healthy and has no complaints.

PE: BMI 26
Pelvic exam: no active bleeding, no vaginal discharge, vagina and cervix
grossly unremarkable, uterus is non-tender and is asymmetrically enlarged
on the right
The remainder of the exam is unremarkable.

What is the most likely etiology of her abnormal uterine bleeding?

Could be endometrial atrophy. Need to rule out cancer.

What would be the initial step in the management of this patient?

TVUS. Perform endometrial biopsy based on results.

53
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Goodman A. Postmenopausal uterine bleeding. UpToDate. May 3, 2016.
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Hoffman, Barbara L., et al.Endometrial Cancer. In: Hoffman BL, Schorge JO, Bradshaw
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