Download Amenorrhea and Abnormal Uterine Bleeding

4/7/11
Amenorrhea and Abnormal Uterine Bleeding: You Will Never Be Confused Again
George F. Sawaya, MD
Professor
Department of Obstetrics, Gynecology and
Reproductive Sciences
Department of Epidemiology & Biostatistics
University of California, San Francisco
Objectives
To know how to evaluate secondary amenorrhea
To know how to define and evaluate “abnormal uterine
bleeding”
To know first steps in patient management and when to
refer
Day
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Normal, ordered endometrial
lining: bricks and mortar
Unstable, thick endometrial
lining: all bricks, no mortar
Unstable, thin endometrial lining:
all mortar, no bricks
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Endometrial lining on OCPs (containing estrogen and progestins): Lots of mortar with just a few stabilizing bricks
Definition: amenorrhea
Primary - the absence of menarche by age 16
years
Secondary - the absence of menstruation for 6 or
more months in women with past menses
Secondary amenorrhea:
differential diagnosis
1. 
2. 
3. 
4. 
5. 
6. 
7. 
8. 
Pregnancy
Menopause (premature ovarian failure if <age 40) Chronic anovulation / polycystic ovarian syndrome (PCOS)
Hyperprolactinemia (breastfeeding, prolactinoma)
Hypothyroidism Hypothalamic amenorrhea (weight loss / exercise)
Medications (e..g., neuroleptics)
Asherman's syndrome
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Work-up
• 
• 
• 
• 
History
Physical
Laboratory tests
Diagnostic in vivo tests
History
1. Pregnancy Exposure to pregnancy
2. Menopause
Hot flashes, night sweats
3. Chronic anovulation
(PCOS)
Prior irregular cycles
4. Hyperprolactinemia
Galactorrhea
5. Medications
OCPs, neuroleptics,
metaclopramide
6. Hypothalamic
Weight loss
7. Asherman's
syndrome
Recent uterine surgery
(D&C)
8. Hypothyroidism
Constipation, fatigue
Physical Examination
1. Pregnancy Uterine size
2. Menopause
Urogenital atrophy
3. Chronic anovulation
(PCOS)
Hirsutism
4. Hyperprolactinemia
Galactorrhea
5. Medications
-
6. Hypothalamic
Urogenital atrophy
7. Asherman's
syndrome
-
8. Hypothyroidism
-
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Laboratory
1. Pregnancy B HCG
2. Menopause
FSH
3. Chronic anovulation
(PCOS)
-
4. Hyperprolactinemia
Prolactin
5. Medications
-
6. Hypothalamic amen.
FSH/LH
7. Asherman's
syndrome
-
8. Hypothyroidism
TSH
At the end of the first visit…
•  3/8 diagnoses ruled out (pregnancy, Asherman’s, medications)
•  5 diagnoses still remain:
- 4 are hypoestrogenic states: menopause, hypothalamic
amenorrhea, hypothyroidism, hyperprolactinemia (lining thin:
no bricks, no mortar)
Order TSH, prolactin
- 1 is a hyperestrogenic state: chronic anovulation/PCOS;
(lining thick: many bricks, no mortar)
- Does the patient have “bricks”?
Progestin challenge test
•  Add mortar and take it away •  Mimics ovulation and the function of the corpus
luteum (you are providing progesterone instead)
•  Medroxyprogesterone acetate (Provera®) 10
mg po QD X 10 days
•  Return in 2 weeks
•  Did she have a withdrawal bleed?
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At second visit
•  Results of progestin challenge known (most
women will have a withdrawal bleed)
•  If no bleeding and prolactin, TSH are normal,
6/8 diagnoses are ruled out
•  Two diagnoses are left: hypothalamic
amenorrhea and menopause
•  Get an FSH (if high, menopause; if low,
hypothalmic amenorrhea)
Can we be even briefer?
•  Yes
•  First visit: rule out pregnancy, Asherman’s and
medications
•  Order a TSH, prolactin and FSH
•  Assume chronic anovulation and prescribe oral
contraceptive pills (OCPs)
•  If prolactin, FSH or TSH abnormal, treat
accordingly
Treatments
Contemporary practice focused on treatment of the
primary problem
• 
• 
• 
• 
Hyperprolactinemia
Hypothyroidism
Hypothalamic amenorrhea*
Medication-induced amenorrhea*
*estrogen supplementation may be warranted in some chronic
hypoestrogenic states to mitigate bone loss as per ACOG
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Treatments: chronic anovulation
•  If pregnancy not desired, OCPs, cyclic Provera,
progestin-containing IUS
•  If pregnancy desired, ovulation induction e.g.,
clomiphene citrate
Abnormal uterine bleeding
• 
• 
• 
• 
• 
Heavy, regular periods (menorrhagia)
Heavy, irregular periods (menometrorrhagia)
Spotting (intermenstrual bleeding)
Postmenopausal bleeding
Whatever the patient says is abnormal for her
Abnormal uterine bleeding
•  Heavy, regular periods (menorrhagia)
- think benign causes: fibroids, polyps, adenomyosis
- think medical treatments as a first line: OCPs, nonsteroidal anti-inflammatory medications (ibuprofen
800mg TID during menses)
- think diagnostic evaluation for medical treatment
failures: ultrasonography, hysteroscopy
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Abnormal uterine bleeding
•  Heavy, irregular periods (menometrorrhagia)
- think benign and malignant causes: chronic
anovulation/PCOS, fibroids, polyps, adenomyosis;
endometrial hyperplasia and cancer
- do endometrial biopsy in high-risk women
- think of medical treatments as a first line: OCPs,
NSAIDs, progestins
- think further diagnostic evaluation for medical
treatment failures: ultrasonography, hysteroscopy
Abnormal uterine bleeding
•  Spotting (intermenstrual bleeding)
- think benign and malignant causes: cervicitis,
cervical polyps, exogenous hormones (OCPs,
progestin-only medications); cervical and endometrial
cancer
- think diagnostic evaluation (cervical exam, cultures,
endometrial biopsy in high-risk women)
Abnormal uterine bleeding
•  Postmenopausal bleeding - think benign and malignant causes (atrophy,
endometrial cancer) 8
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Who is at high risk for
endometrial cancer? In whom is an EMB
indicated?
Endometrial Cancer: Facts
•  4th most common cancer in women
•  Average age 61 but 25% occur pre-menopausally
•  10% of post-menopausal women with bleeding have cancer
•  Presents at early stage with bleeding
•  Rare in the absence of bleeding
•  Major Risk Factors = obesity, increased estrogen,
anovulation (too many bricks)
•  Protective = smoking, OCPs
ACOG guideline
“…based on age alone, endometrial assessment to exclude cancer is
indicated in any woman older than 35 years who is suspected of
having anovulatory uterine bleeding.”
“Although endometrial carcinoma is rare in women younger than
35 years, patients between the ages of 19 and 35 years who do
not respond to medical therapy or have prolonged periods of
unopposed estrogen stimulation secondary to chronic
anovulation are candidates for endometrial assessment.”
ACOG Practice Bulletin 14, March 2000
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A Rational Approach to
Endometrial Biopsy
Postmenopausal women: EMB in all women with any
bleeding (except 4-6 months after starting HRT)
Pre-menopausal women aged 35+ years: EMB in all
women with recurrent episodic bleeding less than a
month apart
NOTE: Some Pap smear findings should prompt an EMB:
atypical glandular cells in women over 35 or any age
with risk factors for endometrial cancer; endometrial
cells noted in post-menopausal women
A Rational Approach to EMB (cont’d)
Further evaluation needed if:
1. Persistent abnormal bleeding after negative
endometrial biopsy or ultrasound
2. Persistent abnormal bleeding after 3-6 months of
medical therapy
Can I get an ultrasound instead?
Transvaginal Ultrasound •  Measure endometrial stripe
•  >5mm is abnormal •  Operator skill mandatory
•  May find things you do not want to find…
•  Not useful in pre-menopausal women (!) 10
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ARS: A 28 year old on oral contraceptive pills for one
year now has spotting for 2 months. She is not pregnant.
Cervix appears normal. Recent Pap test and cultures are
normal. What is the probable cause of her abnormal bleeding?
1)  Too much estrogen, too little progestin
2)  Too little estrogen, too much progestin Thin endometrial lining
Noted with OCPs, depo-progestins, progestincontaining IUS
Treatments: Lessen the progesterone effect: may discontinue
OCPs for one week (use back-up method of birth
control)
Add more estrogen: may prescribe oral estrogen
e.g., conjugated equine estrogens, 0.625 BID for
one week
Summary
•  Secondary amenorrhea: rule out the 8 major
causes systematically over 2 visits
•  Remember: always rule out pregnancy first
•  NSAID’s and hormonal treatments are the
mainstays of medical therapy for most abnormal
bleeding
•  Persistent abnormal bleeding requires continued
work-up even if EMB and/or ultrasound are
normal
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