GYNECOLOGY: Dysfunctional Uterine Bleeding

Darren Farley, M.D.

Department of Obstetrics and Gynecology
UKSM-Wichita

Introduction
• Dysfunctional uterine bleeding (DUB) is defined as ABNORMAL uterine
bleeding with no demonstrable organic cause, genital or extragenital.
• Diagnosis of EXCLUSION
• Patients present with “abnormal uterine bleeding”
• DUB occurs most often shortly after menarche and at the end of the reproductive
years.
o 20% of cases are adolescents
o 50% of cases in 40-50 year olds
Introduction

• DUB is most frequently associated with chronic anovulation.

• Heavy menses, prolonged menses, or frequent irregular bleeding are the most
common complaints.
• Up to 20% of women will experience irregular cycles in their lifetimes.
Goals
Define common terms
•
Briefly review normal menstruation
•
Discuss etiologies of DUB
•
Review the differential diagnosis for abnormal bleeding
•
Discuss the evaluation of abnormal uterine bleeding
•
Discuss the treatment of DUB
•
Definitions
• Menorrhagia (hypermenorrhea): prolonged (>7 days) and/or excessive (>80cc)
uterine bleeding occurring at REGULAR intervals.
• Metorrhagia: uterine bleeding occurring at completely irregular but frequent
intervals, the amount being variable.
• Menometorrhagia: uterine bleeding that is prolonged AND occurs at completely
irregular intervals.
• Polymenorrhea: uterine bleeding at regular intervals of less than 21 days.
• Intermenstrual bleeding: bleeding of variable amounts occurring between regular
menstrual periods.
Definitions
• Oligomenorrhea: uterine bleeding at regular intervals from 35 days to 6 months.
• Amenorrhea: absence of uterine bleeding for > 6 months.
• Postmenopausal bleeding: uterine bleeding that occurs more than 1 year after the
last menses in a woman with ovarian failure.
Normal Menstruation
• Life Cycle
o Menarche
o 5-7 years of relatively long cycles
o Increasing regularity of cycles
o In the 40’s cycles begin to increase in length with increasing episodes of
anovulation (2-8 years “perimenopause”)
o Menopause (average age = 52)
• Characteristics
o By age 25, 40% of women have cycles between 25-28 days
o Age 25-35, 60% of women have 25-28 day cycles.
o Overall 15% have 28 day cycles
o .5% have cycles < 21days
o .9% have cycles >35 days
Normal Menstruation
• Results from fluctuations in the circulating levels of estrogen and progesterone.
• Estrogen causes increased blood flow to the endometrium
 • A significant correlation exists between plasma Estradiol and endometrial blood
flow, with both increasing in the days preceding ovulation.
• These vasodilatory and vasoconstrictive effects are mediated by substances like:
o acetylcholine
o vasopressin
o endothelin
o histamine
Normal Menstruation
• Estradiol and progesterone levels decrease several days prior to the onset of
menses.
o Endometrial blood flow decreases
o Endometrial height decreases and vascular stasis occurs.
o Tissue ischemia occurs.
o Arterial relaxation
o Sloughing of the endometrium.
o Uterine bleeding occurs

• In women with DUB secondary to anovulation, endometrial blood flow is variable

and follows no orderly pattern
Cessation of Menses

• Two main mechanisms:

o Formation of the platelet plug
 important in the functional endometrium

o Prostaglandin dependent vasoconstriction

 important in the basalis layer
Menstrual Period Characteristics
Normal Abnormal
Duration 4-6 days <2d, >7d
Volume 30-35cc >80cc
Cycle length 21-35d <21d, >35
Average Iron loss: 16mg
Pathophysiology
• Two types: anovulatory and ovulatory

• Most women with DUB do not ovulate.

o In theses women, there is continuous E2 production without corpus luteum
formation and progesterone production.

• Ovulatory DUB occurs most commonly after the adolescent years and before the
perimenopausal years.
o Incidence in these patients may be as high as 10%
Causes of DUB
• The main cause of DUB is anovulation resulting from altered neuroendocrine
and/or ovarian hormonal events.
o In premenarchal girls, FSH > LH and hormonal patterns are anovulatory.
Causes of DUB
o The pathophysiology of DUB may also represent exaggerated FSH release
in response to normal levels of GnRH.
Causes of DUB

o After menarche, normal adult FSH and LH patterns eventually develop

with mid-cycle surges and E2 peaks.
Causes of DUB
 o In perimenopausal women, the mean length of the cycle is shorter
compared to younger women.
 Shortened follicular phase

 Diminished capacity of follicles to secrete Estradiol

o Other disorders commonly causing DUB

 Alterations in the life span of the corpus luteum.
 Prolonged (Halbans syndrome)
 Variable function or premature senescence in patients
WITH ovulatory cycles
 Luteal phase insufficiency
Differential Diagnosis of
Abnormal Uterine Bleeding
• Organic
o Reproductive tract disease
o Systemic Disease
o Iatrogenic causes
• Non-organic
o DUB
“You must exclude all organic causes first!”
Reproductive Tract Disease

• Complications of pregnancy
 Abortion
 Ectopic gestation
 Retained products
 Placental polyp
 Trophoblastic disease
Reproductive Tract Disease

• Benign pelvic lesions

o Leiomyomata
o Endometrial or endocervical polyps
o Adenomyosis and endometriosis
o Pelvic infections
o Trauma
o Foreign bodies (IUD, sanitary products)
Reproductive Tract Disease

• Malignant pelvic lesions

o Endometrial hyperplasia
o Endometrial cancer
o Cervical cancer
o Less frequently:
 vaginal,vulvar, fallopian tube cancers
 estrogen secreting ovarian tumors
 granulosa-theca cell tumors
Systemic Disease
• Coagulation disorders
o platelet deficiency
o platelet function defect
o prothrombin deficiency

• Hypothyroidism
 • Liver disease
o Cirrhosis
Iatrogenic Causes

• Medications
o Steroids
o Anticoagulants
o Tranquilizers
o Antidepressants
o Digitalis
o Dilantin
• Intrauterine Devices
Evaluation
• History
o Onset, frequency, duration, cyclic vs.acyclic, severity
o Pain, change from menstrual pattern (calendar)
o Age, parity, marital status, sexual hx, contraception
o medications, dates of pregnancies
o symptoms of pregnancy and reproductive tract disease
• Physical Exam
o pelvic exam
o pap smear
Evaluation
• Tests
o Choices are extensive
o Not practical or cost effective to do every test
o They are not used as general screening tests for all women with DUB.
o Selection should be tailored to suspected causes from the history and
physical
o Stepwise process should be considered

• Step One:
o Rapid assessment of vital signs
 Hemodynamically stable
 Hemodynamically unstable

• Step Two: (simultaneous with step 1)

o Baseline CBC, quantitative beta hCG

• Step Three (adolescents):

o Low risk for intracavitary or cancerous lesion
o High coagulopathy risk
 coagulation profile
 if abnormal, further testing and consultation is warranted
o If screen is normal, a diagnosis of anovulatory DUB is assumed and
appropriate therapy begun

• Step Four (Adults):

o Transvaginal ultrasound
 Lesion present
 biopsy
 hysteroscopy

 No lesion
  High risk for neoplasia
 endometrial biopsy
 Low risk for neoplasia
 can assume DUB and treat

• Step Five (Adults):

o Secretory endometrium
 >50% have polyp or submucosal fibroid
 next step is dx hysteroscopy
 lesion present
 biopsy/excision
 lesion absent
 consider systemic disease
 assume DUB and treat if disease absent

• Step Six (Adults):

o Proliferative endometrium or hyperplasia without atypia
 assume DUB
 manage according to desired fertility

o Hyperplasia with atypia or CA

 treat accordingly
Treatment of DUB

• Goals
o control bleeding
o prevent recurrence
o preserve fertility
o correct associated conditions
o induce ovulation in patients who want to conceive
Treatment of DUB

• Medical management before Surgical

o effective methods include:
 estrogens, progestins, or both
 NSAID’s
 antifibrinolytic agents
 danazol
 GnRH agonists
Treatment of DUB
• Acute bleeding
o Estrogen therapy
 Oral conjugated equine estrogens
 10mg a day in four divided doses
 treat for 21 to 25 days
 medroxyprogesterone acetate, 10 mg per day for the last 7
days of the treatment
 if bleeding not controlled, consider organic cause
OR
 25 mg IV every 4 to 12 hours for 24 hours, then switch to
oral treatment as above.
o Bleeding usually diminishes within 24 hours
Treatment of DUB

• Acute bleeding (continued)

 o High dose estrogen-progestin therapy
 use combination OCP’s containing 35 micrograms or less of
ethinylestradiol
 four tablets per day
 treat for one week after bleeding stops
 may not be as successful as high dose estrogen treatment
Treatment of DUB
• Recurrent bleeding episodes
o combination OCP’s
 one tablet per day for 21 days
o intermittent progestin therapy
 medroxyprogesterone acetate, 10mg per day, for the first 10 days
of each month
 higher doses and longer therapy my be tried if no initial response
 prolonged use of high doses is associated with fatigue, mood
swings, weight gain, lipid changes
Treatment of DUB
• Recurrent bleeding episodes (continued)
o Progesterone releasing IUD
 avoids side effects
 must be reinserted annually
 Levonorgestrel IUD
 80% reduction of blood loss at 3 months
 100% reduction at 1 year
 found to be superior to antifibrinolytic agents and
prostaglandin synthetase inhibitors
Treatment of DUB
• Immature hypothalamic-pituitary axis
o progestin therapy by itself for 10 days every month or every other month
until full maturity of the axis provides effective therapy.
• Older perimenopausal women
o cyclic progestin therapy
 prevents development of endometrial hyperplasia
o low dose OCP’s
 healthy non-smokers, free of vascular disease
Treatment of DUB
• Other options
o NSAID’s
 cyclooxygenase inhibitors
 inhibits prostacyclin formation
 administered throughout the duration of bleeding or for the first 3
days of menses.
 treatment results in a sustained reduction in blood loss so side
effects tend to be mild
 most effective in ovulatory DUB
Treatment of DUB
• Other options
o inhibitors of fibrinolysis
 EACA (epsilon-aminocaproic acid)
 AMCA (tranexamic acid)
 PABA (para-aminomethybenzoic acid)
o use limited by side effects
 nausea, dizziness
 diarrhea, headaches
 abdominal pain
 allergic manifestations
Treatment of DUB

• Danazol
o androgenic steroid
 200mg and 400 mg daily doses for 12 weeks studied
 200mg dose as effective as 400 mg
 androgenic side effects: weight gain, acne
 side effects minimized with 200mg dose
 100 mg not effective, expensive
Treatment of DUB

• GnRH agonists
o treatment results in medical menopause
o blood loss returns to pretreatment levels when discontinued
o treatment usually reserved for women with ovulatory DUB that fail other
medical therapy and desire future fertility
o use add back therapy to prevent bone loss secondary to marked
hypoestrogenism
Treatment of DUB

• Surgical Treatment
o Dilation and Curettage
 quickest way to stop bleeding in patients who are hypovolemic
 appropriate in older women (>35)to exclude malignancy but is
inferior to hysteroscopy
 follow with medroxyprogesterone acetate, OCP’s, or NSAID’s to
prevent recurrence
Treatment of DUB
• Surgical Treatment: (Ablation)

o Laser ablation

o Loop electrode resection

o Roller electrode ablation

Treatment of DUB
• Surgical Treatment: (Ablation)
o Thermal balloon ablation
o Microwave ablation
o Electromagnetic ablation
 poor follow up
o Intracavitary radiotherapy (case report)
 was common treatment in past
 used in a patient who failed medical treatment with multiple
contraindications for surgery
 chose radiation secondary to complications with a previous D&C
and the cost of long term GnRH agonist therapy
Treatment of DUB

• Surgical Treatment
o Hysterectomy