Dysfunctional Uterine Bleeding

1
Dysfunctional Uterine Bleeding

• Darren Farley, M.D.
• Department of Obstetrics and Gynecology
• UKSM-Wichita

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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.
• 20 of cases are adolescents
• 50 of cases in 40-50 year olds

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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.

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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

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Definitions

• Menorrhagia (hypermenorrhea) prolonged (gt7
  days) and/or excessive (gt80cc) 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.

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Definitions

• Oligomenorrhea uterine bleeding at regular
  intervals from 35 days to 6 months.
• Amenorrhea absence of uterine bleeding for gt 6
  months.
• Postmenopausal bleeding uterine bleeding that
  occurs more than 1 year after the last menses in
  a woman with ovarian failure.

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Normal Menstruation

• Life Cycle
• Menarche
• 5-7 years of relatively long cycles
• Increasing regularity of cycles
• In the 40s cycles begin to increase in length
  with increasing episodes of anovulation (2-8
  years perimenopause)
• Menopause (average age 52)
• Characteristics
• By age 25, 40 of women have cycles between 25-28
  days
• Age 25-35, 60 of women have 25-28 day cycles.
• Overall 15 have 28 day cycles
• .5 have cycles lt 21days
• .9 have cycles gt35 days

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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
• acetylcholine
• vasopressin
• endothelin
• histamine

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Normal Menstruation

• Estradiol and progesterone levels decrease
  several days prior to the onset of menses.
• Endometrial blood flow decreases
• Endometrial height decreases and vascular stasis
  occurs.
• Tissue ischemia occurs.
• Arterial relaxation
• Sloughing of the endometrium.
• Uterine bleeding occurs
• In women with DUB secondary to anovulation,
  endometrial blood flow is variable and follows no
  orderly pattern

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Cessation of Menses

• Two main mechanisms
• Formation of the platelet plug
• important in the functional endometrium
• Prostaglandin dependent vasoconstriction
• important in the basalis layer

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Menstrual Period Characteristics

• Normal Abnormal
• Duration 4-6 days lt2d, gt7d
• Volume 30-35cc gt80cc
• Cycle length 21-35d lt21d, gt35
• Average Iron loss 16mg

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Pathophysiology

• Two types anovulatory and ovulatory
• Most women with DUB do not ovulate.
• 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.
• Incidence in these patients may be as high as 10

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Causes of DUB

• The main cause of DUB is anovulation resulting
  from altered neuroendocrine and/or ovarian
  hormonal events.
• In premenarchal girls, FSH gt LH and hormonal
  patterns are anovulatory.

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Causes of DUB

• The pathophysiology of DUB may also represent
  exaggerated FSH release in response to normal
  levels of GnRH.

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Causes of DUB

• After menarche, normal adult FSH and LH patterns
  eventually develop with mid-cycle surges and E2
  peaks.

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Causes of DUB

• 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
• 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

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Differential Diagnosis of Abnormal Uterine
Bleeding

• Organic
• Reproductive tract disease
• Systemic Disease
• Iatrogenic causes
• Non-organic
• DUB
• You must exclude all organic causes first!

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Reproductive Tract Disease

• Complications of pregnancy
• Abortion
• Ectopic gestation
• Retained products
• Placental polyp
• Trophoblastic disease

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Reproductive Tract Disease

• Benign pelvic lesions
• Leiomyomata
• Endometrial or endocervical polyps
• Adenomyosis and endometriosis
• Pelvic infections
• Trauma
• Foreign bodies (IUD, sanitary products)

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Reproductive Tract Disease

• Malignant pelvic lesions
• Endometrial hyperplasia
• Endometrial cancer
• Cervical cancer
• Less frequently
• vaginal,vulvar, fallopian tube cancers
• estrogen secreting ovarian tumors
• granulosa-theca cell tumors

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Systemic Disease

• Coagulation disorders
• platelet deficiency
• platelet function defect
• prothrombin deficiency
• Hypothyroidism
• Liver disease
• Cirrhosis

22
Iatrogenic Causes

• Medications
• Steroids
• Anticoagulants
• Tranquilizers
• Antidepressants
• Digitalis
• Dilantin
• Intrauterine Devices

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Evaluation

• History
• Onset, frequency, duration, cyclic vs.acyclic,
  severity
• Pain, change from menstrual pattern (calendar)
• Age, parity, marital status, sexual hx,
  contraception
• medications, dates of pregnancies
• symptoms of pregnancy and reproductive tract
  disease
• Physical Exam
• pelvic exam
• pap smear

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Evaluation

• Tests
• Choices are extensive
• Not practical or cost effective to do every test
• They are not used as general screening tests for
  all women with DUB.
• Selection should be tailored to suspected causes
  from the history and physical
• Stepwise process should be considered

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• Step One
• Rapid assessment of vital signs
• Hemodynamically stable
• Hemodynamically unstable
• Step Two (simultaneous with step 1)
• Baseline CBC, quantitative beta hCG

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

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• Step Four (Adults)
• Transvaginal ultrasound
• Lesion present
• biopsy
• hysteroscopy
• No lesion
• High risk for neoplasia
• endometrial biopsy
• Low risk for neoplasia
• can assume DUB and treat

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• Step Five (Adults)
• Secretory endometrium
• gt50 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

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• Step Six (Adults)
• Proliferative endometrium or hyperplasia without
  atypia
• assume DUB
• manage according to desired fertility
• Hyperplasia with atypia or CA
• treat accordingly

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Treatment of DUB

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

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Treatment of DUB

• Medical management before Surgical
• effective methods include
• estrogens, progestins, or both
• NSAIDs
• antifibrinolytic agents
• danazol
• GnRH agonists

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Treatment of DUB

• Acute bleeding
• 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.
• Bleeding usually diminishes within 24 hours

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Treatment of DUB

• Acute bleeding (continued)
• High dose estrogen-progestin therapy
• use combination OCPs 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

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Treatment of DUB

• Recurrent bleeding episodes
• combination OCPs
• one tablet per day for 21 days
• 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

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Treatment of DUB

• Recurrent bleeding episodes (continued)
• 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

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Treatment of DUB

• Immature hypothalamic-pituitary axis
• 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
• cyclic progestin therapy
• prevents development of endometrial hyperplasia
• low dose OCPs
• healthy non-smokers, free of vascular disease

37
Treatment of DUB

• Other options
• NSAIDs
• 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

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Treatment of DUB

• Other options
• inhibitors of fibrinolysis
• EACA (epsilon-aminocaproic acid)
• AMCA (tranexamic acid)
• PABA (para-aminomethybenzoic acid)
• use limited by side effects
• nausea, dizziness
• diarrhea, headaches
• abdominal pain
• allergic manifestations

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Treatment of DUB

• Danazol
• 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

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Treatment of DUB

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

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Treatment of DUB

• Surgical Treatment
• Dilation and Curettage
• quickest way to stop bleeding in patients who are
  hypovolemic
• appropriate in older women (gt35)to exclude
  malignancy but is inferior to hysteroscopy
• follow with medroxyprogesterone acetate, OCPs,
  or NSAIDs to prevent recurrence

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Treatment of DUB

• Surgical Treatment (Ablation)
• Laser ablation
• Loop electrode resection
• Roller electrode ablation

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Treatment of DUB

• Surgical Treatment (Ablation)
• Thermal balloon ablation
• Microwave ablation
• Electromagnetic ablation
• poor follow up
• 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 DC and the cost of long term GnRH
  agonist therapy

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Treatment of DUB

• Surgical Treatment
• Hysterectomy