ACTIVITY DISCLAIMER

Abnormal Uterine Bleeding and

Amenorrhea
Edward Mayeaux, MD, FAAFP

The material presented here is being made available by the American Academy of Family Physicians for
educational purposes only. This material is not intended to represent the only, nor necessarily best,
methods or procedures appropriate for the medical situations discussed. Rather, it is intended to present
an approach, view, statement, or opinion of the faculty, which may be helpful to others who face similar
situations.
The AAFP disclaims any and all liability for injury or other damages resulting to any individual using this
material and for all claims that might arise out of the use of the techniques demonstrated therein by such
individuals, whether these claims shall be asserted by a physician or any other person. Every effort has
been made to ensure the accuracy of the data presented here. Physicians may care to check specific
details such as drug doses and contraindications, etc., in standard sources prior to clinical application.
This material might contain recommendations/guidelines developed by other organizations. Please note
that although these guidelines might be included, this does not necessarily imply the endorsement by the
AAFP.

Edward Mayeaux, MD, FAAFP

DISCLOSURE
It is the policy of the AAFP that all individuals in a position to control content disclose any
relationships with commercial interests upon nomination/invitation of participation. Disclosure
documents are reviewed for potential conflict of interest (COI), and if identified, conflicts are
resolved prior to confirmation of participation. Only those participants who had no conflict of interest
or who agreed to an identified resolution process prior to their participation were involved in this
CME activity.
All individuals in a position to control content for this activity have indicated they have no relevant
financial relationships to disclose.

Professor and Chairman, Department of Family and Preventive Medicine, Professor of Obstetrics and
Gynecology, University of South Caroline School of Medicine in Columbia, SC.
Dr. Mayeaux lives and practices in Columbia, SC. He has received the American Society for Colposcopy and
Cervical Pathology Award of Merit three times and has also received numerous faculty teaching awards. Dr.
Mayeaux specializes in womens health and skin diseases, noting that the most important trends in his field
are the rise and fall of methicillin-resistant Staphylococcus aureus, changes in Pap test recommendations
and follow-up, and changes in human papillomavirus testing recommendations. He states that family
medicines most critical challenge is keeping up with the rapidly changing knowledge base in medicine.

The content of my material/presentation in this CME activity will include discussion of unapproved or
investigational uses of products or devices as indicated: Micronized progesterone for AUB treatment
2. Ibuprofen 600-1,200 mg/day Naproxen sodium 550-1,100 mg/day Mefenamic acid 1,500 mg/day
for AUB

Learning Objectives
1.

Implement current screening recommendations for endometrial cancer in

women who present with postmenopausal bleeding.

2.

Develop collaborative care plans for women with abnormal uterine

bleeding, emphasizing ways to increase quality of life and functional
activities.

3.

Formulate a treatment plan for women with abnormal uterine bleeding

including dysfunctional uterine bleeding, menorrhagia, and amenorrhea.

4.

Evaluate patients based on their treatment choice, tolerance, and clinical

risk profile when selecting a therapeutic intervention for the management
of heavy menstrual bleeding.

Audience Engagement System

Step1

Step2

Step3

Epidemiology

The Normal Menstrual Cycle

Abnormal uterine bleeding (AUB) 1

Occurs in 9-14% of women between menarche and
menopause
Significantly impacts quality of life
Imposes notable financial burden

Average age of menarche in U.S. = 12.3 years 2

Irregular and anovulatory cycles may persist for
1-5 years after onset of menstrual periods
1. Fraser IS. Expert Rev Obstet Gynecol. 2009;4(2):179-189.
2. Anderson SE. J Pediatr. Dec 2005;147(6):753-60.

The Normal Menstrual Cycle

Courtesy of Dr. E.J. Mayeaux, Jr.

The Normal Menstrual Cycle

Follicular Phase Day 5 to 14

Menstrual Phase Day 1 to 5

Involves the disintegration and sloughing of
the functionalis layer
Prostaglandin F2-alpha causes
contractions and vasoconstriction
Prostaglandin E2 causes vasodilatation
and muscle relaxation

Estrogen produced by developing follicles

Stimulated by FSH

Cellular proliferation and increase in convolution

of spiral arteries
Estrogen + feedback causes
FSH and LH surge and ovulation
Courtesy of Dr. E.J.
Mayeaux, Jr.

Courtesy of Dr. E.J. Mayeaux, Jr.

Fraser IS, et al. Expert Rev Obstet Gynecol. 2009;4(2):179-189.

Fraser IS, et al. Expert Rev Obstet Gynecol. 2009;4(2):179-189.

The Normal Menstrual Cycle

Luteal Phase Day 15 to 28

Menses

Corpus luteum produces progesterone and less

potent estrogens
The functionalis layer
increases in thickness
Glands become tortuous with
dilated lumens and stored
glycogen
Fraser IS, et al. Expert Rev Obstet Gynecol. 2009;4(2):179-189.

The Normal Menstrual Cycle

Courtesy of Dr. E.J. Mayeaux, Jr.

Estrogen and progesterone cause positive feedback

FSH and LH production falls
The spiral arteries become coiled and have
decreased blood flow
They alternately contract and relax, causing sloughing
of functionalis layer and menses
Fraser IS, et al. Expert Rev Obstet Gynecol. 2009;4(2):179-189.

Abnormal Uterine Bleeding (AUB)

Menstrual flow outside of normal volume,
duration, regularity, or frequency

Diagnosis of abnormal uterine bleeding in reproductive-aged

women. Practice Bulletin No. 128. American College of
Obstetricians and Gynecologists. Obstet Gynecol 2012;120:197206.

Abnormal Uterine Bleeding (AUB)

Amenorrhea
no bleeding

DUB
Anovulatory bleeding
irregular bleeding

Prepubertal Children
Neonates Some vaginal bleeding is normal in
the first few days
Beyond neonatal period
Abnormal in the absence of secondary sexual
characteristics

Most common causes are trauma, foreign body,

vulvovaginitis, and urologic factors

AUB Categories
Amenorrhea (no periods for more than 3 cycles)
Dysfunctional uterine bleeding (Anovulatory)
Oligomenorrhea (menses occurring at intervals of more than 35 days)
Metrorrhagia (menses at irregular intervals with excessive bleeding or
lasting more than 7 days)
Ovulatory dysfunction in which underlying etiologies have been ruled out

Menorrhagia
Ovulatory bleeding
heavy menstrual bleeding

Menorrhagia (Ovulatory)
Occurs at regular intervals (every 24 to 35 days), but with excessive
volume or duration of >7 days
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Amenorrhea Evaluation

Amenorrhea Evaluation (cont.)

3. TSH &
Prolactin

1. UPT/HCG
Evidence of
Androgen Excess

2. Physical
Examination

DHEA
Testosterone
Serum 17-hydroxyprogesterone

Abnormal
(17-HP <800 & +ACTH stimulation test)

Androgen secreting tumor

(DHEA-S > 7000 ng/dL)

21-hydroxylase deficiency

Abnormal
TSH
Hypothyroidism
Hyperthyroidism

EMB
Normal

Adrenal Hyperplasia

Evidence of
Estrogen Excess

Normal

3. TSH &
Prolactin

Abnormal

Endometrial
Hyperplasia or
Precancerous State

Withdrawal
bleeding
Chronic Anovulation:
Physiologic
PCOS

Both
normal

High
prolactin

4. Progesterone
Challenge Test

No withdrawal
bleeding
5. Estrogen &
Progesterone
Challenge

MRI

Abnormal
Intracranial pathology:
Pituitary tumor
Pituitary destruction
Hypothalamic Disease

(17-HP > 800 ng/dL)

HCA/PCOS

(DHEA =3300-7000 ng/dL or increased free

testosterone <200 ng/dL)

Amenorrhea Evaluation (cont.)

True statements about ovulatory AUB characteristics

include:

5. Estrogen &
Progesterone
Challenge

No withdrawal
bleeding
Tract Abnormality: Ashermans
Syndrome
Mullerian Agenesis

6. FSH, LH

Low

High
Karyotype

Gonadal
Failure

Intracranial pathology:
Pituitary tumor
Pituitary destruction
Hypothalamic Disease

A. Periods occur at irregular intervals

B. Periods are often scant and of
shorter than normal duration
C. <1% of women develop cancer or
hyperplasia if they have no more
than one risk factor for endometrial
cancer
D. It results from a estrogen- excess
state

Withdrawal
bleeding

7. MRI

Abnormal

Normal

Hypothalamic
Amenorrhea:
Drug Use
Eating Disorder
Excessive Exercise
Psychosocial Stress
Marijuana Use
Consider reevaluation for
chronic disease.

Ovulatory AUB Characteristics

DUB is caused by:

Regular intervals (every 24 to 35 days) with

excessive bleeding or duration greater than
7 days
<1% of women develop cancer or hyperplasia if
they have no more than 1 risk factor for
endometrial cancer

A. Pregnancy or pregnancyrelated disorders

B. Thyroid disease
C. Coagulation disorders
D. None of the above

Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Anovulatory DUB Characteristics

DUB Anovulatory Cycles

Most common cause in adolescents and adults
High estrogen with no progesterone
Continuous development of the functionalis
layer
Blood supply is outgrown and parts of the
endometrium slough
Estrogen promotes healing
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Irregular, infrequent periods

Progesterone-deficient/estrogen-dominant state
Flow ranges from absent or minimal to excessive
14% of women with recurrent anovulatory cycles
develop cancer or hyperplasia
Extremes of reproductive life and PCOS
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

DUB Anovulatory Cycles

Also from excessive estrogen from fatty tissue or
exogenous sources
Diminishing number and quality of ovarian follicles
No FSH trigger
Estrogen continues to be produced, which
usually results in late cycle estrogen
breakthrough bleeding
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

DUB Luteal Phase Deficiency

Shortened luteal phase insufficient
progesterone
Coexistent with high, low, or normal
estrogen
Similar to anovulatory cycles
May be especially prominent in
amenorrheic athletes and anorexia
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

DUB in Adolescence

Pregnancy related (inc. SAB, ectopic)

DUB Psychogenic Causes

Excessive Physical
Exercise
Stress
Anorexia
Alcohol and Drug Abuse
http://www.girlshealth.gov/

CDC. Youth risk behavior surveillance U.S. MMWR 2008:57(No.SS-4)

Infectious Causes

AUB Diagnosis
Obtain history and perform physical examination to rule
out systemic disease, medication effects, polycystic
ovary syndrome, and cervical or vaginal pathology

Can be initial sign in

STDs
Chlamydia cervicitis

Laboratory tests for pregnancy, TSH and prolactin levels

- Irregular or post-coital bleeding

Determine by pattern if

- Adolescents have highest

rates- screen

Ovulatory periods regular but heavy or >7 days

Anovulatory (DUB) irregular or infrequent periods

PID

Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Courtesy of Dr. E.J. Mayeaux, Jr.

Evaluation - Physical Exam

Mid-Point Q&A

Pelvic exam is
unnecessary in
oligomenorrheic patients
who are
not sexually active and
within 18 months of
menarche
Johnson CA. Am Fam Phys
1991; 44:149-57
Courtesy of Dr. E.J. Mayeaux, Jr.

Dx & Tx of Anovulatory Bleeding

Management Principles
Excluded pregnancy (including ectopic pregnancy)
and pelvic infections
All adolescents treated for DUB should maintain a
menstrual calendar to monitor response, subsequent
episodes of DUB 1
Monitor for iron deficiency anemia
Additional evaluation and consultation should be
obtained if bleeding not controlled with HRT 2

Obtain history and perform physical examination to rule out

systemic disease, medication effects, polycystic ovary syndrome,
and cervical or vaginal pathology
Laboratory tests for pregnancy, TSH and prolactin levels

Sweet MG, et al. Am Fam

Physician. 2012 1;85(1):35-43.

1. Adams PJ. Pediatr Clin North Am 2005; 52:179. 2. Rimsza ME. Pediatr Rev 2002; 23:227.

Dx &TxofAnovulatoryBleeding
Females <35 years with no
risks of endometrial cancer
Treat with combination OCP (ethinyl estradiol, 35 mcg)
or medroxyprogesterone acetate 10 mg per day for 10 to 14 days per month
or norethindrone 2.5-10 mg daily for 5-10 days per month
continued irregular or excessive bleeding

Endometrial biopsy
normal

Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Dx &TxofAnovulatoryBleeding
Treat with MPA 10
mg/day x
14 days/month or
Daily megesterol
40 mg or Insert
levonorgestrelreleasing IUS

normal

Females 35 years or <35 years with recurrent anovulation

and/or other risks of endometrial cancer
Hyperplasia (no atypia)

Refer
to Gyn

Refer
to Gyn

normal

Endometrial biopsy
normal

Treat with combination OCP (ethinyl estradiol, 35 mcg) or

or MPA10 mg per day for 10 to 14 days per month
or Norethindrone 2.5-10mg daily for 5-10 days per month

Atypia or
Adenocarcinoma

Adenocarcinoma
or atypia

Perform TUS or saline infusion sonohysterography

to rule out structural abnormality

Females 35 years
or <35 years with recurrent
anovulation and/or other risks of
endometrial cancer

Females <35 years with no

risks of endometrial
cancer

Continued irregular or
excessive bleeding

Endometrial biopsy
normal

Perform TUS or saline infusion sonohysterography

to rule out structural abnormality

Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Comparison of Imaging/Tissue Sampling for

Endometrial Pathology
Test

Endometrial Biopsy

Effectiveness

Endometrialbiopsy

91%sensitiveand98%specificfordetectingcancer
82.3%sensitiveand98%specificfordetectinghyperplasiawithatypia

Officehysteroscopy

94%sensitiveand89%specificfordetectingintracavitaryabnormality

Salineinfusion
sonohysterography

88to99%sensitiveand72to95%specificfordetectingintracavitary
abnormalityinpremenopausalwomen

Transvaginal
ultrasonography

Lesssensitiveandspecificthansalineinfusionsonohysterography6092%
sensitiveand6293%specificforintracavitaryabnormalityin
premenopausalwomen

Rarely required in adolescents

Should be reserved for adolescents
with unresponsive uterine bleeding
DUB histology = disordered
proliferative pattern without secretory
activity (no progesterone effect)
Courtesy of Dr. E.J.
Mayeaux, Jr.

ACOG PB 128. Obstet Gynecol 2012;120:197-206.

Dx & Tx of Ovulatory Bleeding

Dx&TxofOvulatoryBleeding
Imaging and endometrial biopsy

Obtain history and perform physical examination to rule out systemic

disease or enlarged uterus
Test for pregnancy, measure thyroid-stimulating hormone level perform
complete blood count
Adolescent or adult with possible bleeding disorder

Yes
Evaluate for bleeding disorder
and treat as indicated if
bleeding diathesis present
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

No
Perform imaging test for structural abnormality
with transvaginal ultrasonography or saline
infusion sonohysterography (if high risk of
endometrial cancer, consider adding endometrial
biopsy

Submucosal
fibroid

Refer for possible

fibroidectomy or
Uterine artery
embolization

Consider endometrial
biopsy, hysteroscopy,
endometrial ablation, or
hysterectomy

Endometrial
polyp

Refer for polypectomy

Unresponsive to
3-6-month trial of
therapy

Normal
imaging

Treat with 10 mg of MPA for 21

days/month for 3-6 mo
or
Norethindrone 2.5-10mg daily for 510 days
or
Insert levonorgestrel-releasing IUS
or
Trial of nonsteroidal antiinflammatory drug
or
Tranexamic acid 2 650-mg 3x/day
days 1-5 of cycle

Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Which of the following is not considered a risk factor for

bleeding disorders in AUB patients:
A. family history of bleeding disorder
B. A patient history of using lots of
pads
C. history of treatment for anemia
D. history of excessive bleeding with
tooth extraction, delivery or
miscarriage, or surgery

Ovulatory Bleeding Disorder?

Adolescents and women with 1 of the following risk factors:
family history of bleeding disorder
menses 7 days with flooding or impairment of activities
history of treatment for anemia
history of excessive bleeding with tooth extraction, delivery or
miscarriage, or surgery

von Willebrand disease (vWD), most common

13% of women with menorrhagia
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

ACOG: Ovulatory Bleeding Disorder?

Heavy menstrual bleeding since menarche
One of the following:
Postpartum or surgery-related hemorrhage
Bleeding associated with dental work

Two or more:

Bruising 1-2 times per month

Epistaxis 1-2 times per month
Frequent gum bleeding
Family history of bleeding symptoms

Patients with a positive screen should be

considered for further evaluation
Consultation with a hematologist
Testing for
von Willebrand factor antigen
factor VIII
vWF:RCo (von Willebrand factor ristocetin cofactor)
ACOG PB 128. Obstet Gynecol 2012;120:197-206.

ACOG PB 128. Obstet Gynecol 2012;120:197-206.

Observe vs Treat with HRT

Decision for adolescents depends

ACOG: Bleeding Disorder?

upon 1

Severity and chronicity of the DUB

Patient considerations
Guardian considerations

The primary purpose of hormonal treatment is to stabilize

endometrial proliferation and promote cyclic shedding
>90% of adolescents respond to hormonal treatment 2

AUB: Emergency Management

IV conjugated estrogen 25 mg q 4 hours until bleeding
slows or for 12 hours
75% will be controlled in 6 hours

Oral conjugated estrogen 1.25 mg or estradiol

2 mg for 7-10 days
Start OCPs or 10 days of monthly progestin after
bleeding stops to prevent recurrence
Can be given without placebos for 3 months (patients prefer)

1. Slap GB. Best Pract Res Clin Obstet Gynaecol 2003; 17:75. 2. Strickland JL. Obstet Gynecol Clin North Am 2003; 30:321.

Hospitalization

Hemodynamically unstable
Initial hemoglobin <7 g/dL or symptomatic
Orthostatic signs
Heavy active bleeding and hemoglobin <10 g/dL
Need for blood transfusion
Girls who require hospitalization for DUB should
undergo evaluation for a bleeding disorder

Anovulatory Treatment
Adolescent or <35 years with no Ca risks
Mild DUB consists of observation and reassurance
Combination OCP ethinyl estradiol, 30-35 mcg
Usually for 3-6 months
Treatment of choice in women with known von Willebrand
disease who also desire contraception

Progestin only treatment MPA 10 mg/day for

10-14 days/mo or similar
Consider Iron therapy
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Endometrial Hyperplasia
(Without Atypia) Treatment
Medroxyprogesterone acetate 10 mg per day for
14 days per month
Norethindrone 2.5-10 mg/day for 5-10 days
Levonorgestrel-releasing intrauterine device
releases 20 mcg per 24 hours
Micronized progesterone 200 mg/day for
12 days of each calendar month
NOT FDA indicated for this use or age group

Which of the following is not a treatment for ovulatory AUB:

A. Medroxyprogesterone acetate 10
mg daily for 3-6 months
B. Norethindrone 2.5-10mg daily for
5-10 days
C. Insert levonorgestrel-releasing IUS
D. Naproxen sodium 550-1,100
mg/day

Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Ovulatory AUB Treatment

Medroxyprogesterone acetate 10 mg/day for 21
days per month or norethindrone
2.5-10 mg daily for 5-10 days
Does not provide contraception
Effective short-term therapy
Not tolerated as well long-term as levonorgestrelreleasing IUD
Caution in patients with severe hepatic dysfunction
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Ovulatory AUB Treatment

Tranexamic acid 650 mg; two tablets 3x/day,
5 days/month begin day 1 of menses
FDA-approved for menorrhagia in 2009

Antifibrinolytic prevents plasminogen activation

Caution in patients with history or risk of thromboembolic or renal
disease
Contraindicated with active intravascular clotting or subarachnoid
hemorrhage

Desire fertility or have contraindications to OCPs

Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Ovulatory AUB Treatment

NSAIDs, 5 days/ month begin day 1 of menses

Ibuprofen 600-1,200 mg/day

Naproxen sodium 550-1,100 mg/day
Mefenamic acid 1,500 mg/day
Treats dysmenorrhea
Caution in patients with gastrointestinal risks

Levonorgestrel-releasing IUD
FDA-approved for menorrhagia in 2009
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Surgical Therapies
Available evidence suggests that hysteroscopic
polypectomy reduces AUB 75 to 100%
Menorrhagia with submucosal fibroids
Surgical resection may allow childbearing and
normalize menses
Uterine artery embolization
~20 percent of women subsequently undergo a
hysterectomy for recurrent AUB
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Surgical Therapies
If unresponsive to medical intervention, endometrial
ablation (the surgical destruction of the endometrium)
may be considered
Permanent - incompatible with continued fertility

Hysterectomy is definitive treatment

Women who no longer wish to conceive
Increased number of adverse effects, longer recovery time,
and higher initial health care costs
May be associated with earlier ovarian failure
Sweet MG, et al. Am Fam Physician. 2012 1;85(1):35-43.

Quality of Life
Young patients with irregular bleeding often only need
reassurance and observation prior to instituting a drug
regimen
Instruct patients to continue prescribed medications
although bleeding may still be occurring at first
Tell patients that medications will probably not be
necessary once cycles become regular
Discuss ways to maintain a normal BMI

Hysterectomy vs Medical Tx
Women with excessive uterine bleeding for
4 years, unresponsive to medical therapy
Randomized to hysterectomy or continued medical
therapy
Hysterectomy group: greater improvements in
mental health, sexual desire, overall satisfaction
53% of medical group eventually received
hysterectomy
Learman LA, et al. Obstet Gynecol. 2004 May;103(5 Pt 1):824-33.

Quality of Life
Health professionals can help support patients
self-esteem by providing reassurance and
information on physiology, treatments, and hygiene
Written educational materials are often helpful
Low-literacy and culturally sensitive and inclusive
materials often best

Communication with school or work may be

necessary
Dunn NF. Haemophilia. Jul 2011;17 Suppl 1:38-41.

Practice Recommendations
Abnormal uterine bleeding falls into 3 groups
Amenorrhea, Dysfunctional uterine bleeding
(Anovulatory,) and Menorrhagia (Ovulatory)
Workup and treatment depends upon which
group the patient falls into
Consider bleeding disorders in patients who
have heavy menstrual bleeding since menarche

10