Abnormal Uterine Bleeding

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Abnormal Uterine Bleeding

• District 1 ACOG Medical Student Education Module
  2008

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Disorders of the Menstrual Cycle

• Amenorrhea
• Dysmenorrhea
• Premenstrual Syndrome
• Abnormal Uterine Bleeding

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Abnormal Uterine Bleeding Definitions

• Menorrhagia heavy or prolonged uterine bleeding
  that occurs at regular intervals. Some sources
  define further as the loss of 80 mL blood per
  cycle or bleeding 7 days.
• Hypomenorrhea periods with unusually light flow,
  often associated with hypogonadotropic
  hypogonadism (athletes, anorexia). Also may be
  associated with Ashermans syndrome
• Metrorrhagia irregular menstrual bleeding or
  bleeding between periods
• Menometrorrhagia metrorrhagia associated with
  80 mL
• Polymenorrhea frequent menstrual bleeding.
  Strictly, menses occur q 21 d or less
• Oligomenorrhea Menses are 35 d apart. Most
  commonly caused by PCOS, pregnancy, and
  anovulation

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Abnormal Uterine Bleeding Differential Diagnosis

• Structural
• Cervical or vaginal laceration
• Uterine or cervical polyp
• Uterine leiomyoma
• Adenomyosis
• Cervical stenosis/Ashermans (hypomenorrhea)
• Hormonal
• Anovulatory bleeding
• Hypogonadotropic hypogonadism
• Pregnancy
• Hormonal Contraception (i.e. OCPs, Depo-Provera)
• Malignancy
• Uterine or Cervical cancer
• Endometrial hyperplasia (potentially
  pre-malignant)
• Bleeding disorders
• von Willebrands Disease, Hemophilia/Factor
  deficiencies, platelet disorders

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Abnormal Uterine Bleeding Workup

• History
• Timing of bleeding, quantity of bleeding,
  menstrual hx including menarche and recent
  periods, associated sxs, family hx of bleeding
  disorders
• Physical
• R/o vaginal or cervical source of bleeding.
  Bimanual may reveal bulky uterus/discrete
  fibroids
• Assess for obesity, hirsutism, stigmata of
  thyroid disease (hypothyroidism associated with
  anovulation), signs of hyperprolactinemia (visual
  field testing, galactorrhea)
• Pap smear
• Endometrial biopsy, if appropriate
• Pregnancy Test
• Imaging
• Pelvic ultrasound
• Sonohystogram or hysterosalpingogram
• Surgical
• Hysteroscopy
• D C

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Normal Menstrual Cycle
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Normal Ovulatory Cycle

• Follicular development ? ovulation (d14) ? corpus
  luteal function ? luteolysis
• Endometrium is exposed to
• ovarian production of estrogen ?
• (proliferation)
• Combination of estrogen and progesterone ?
• (secretory phase)
• Estrogen and progesterone withdrawal
• (desquamation and repair)

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Anovulatory Bleeding

• Corpus luteum is not produced
• Ovary fails to secrete progesterone, although
  estrogen production continues
• Result is continuous, unopposed E stimulation of
  endometrium
• endometrial proliferation without P-induced
  differentiation / stabilization
• Endometrium becomes excessively vascular without
  stromal support ? fragility and irregular
  endometrial bleeding

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Anovulatory BleedingEtiologies

• Hyperandrogenic anovulation (PCOS, CAH,
  androgen-producing tumors)
• Hypothalamic dysfunction (stress, anorexia,
  exercise)
• Hyperprolactinemia
• Hypothyroidism
• Primary pituitary disease
• Premature ovarian failure
• Iatrogenic (secondary to radiation or chemo)

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Anovulatory Bleeding Adolescents (13-18 years)

• Anovulatory bleeding may be normal physiologic
  process, with ovulatory cycles not established
  until 1-2 yrs after menarche (immature HPG axis)
• Screen for coagulation disorders (PT/PTT, plts)
• May be caused by leukemia, ITP, hypersplenism
• Consider endometrial bx in adolescents with 2-3
  year history of untreated anovulatory bleeding,
  especially if obese

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Anovulatory Bleeding Management in Adolescents

• High dose estrogen therapy for acute bleeding
  episodes (promotes rapid endometrial growth to
  cover denuded endometrial surfaces) conjugated
  equine estrogens PO up to 10 mg/d in 4 divided
  doses or IV 25 mg q 4 hrs for 24 hrs
• Treat pts with blood dyscrasias for their
  specific diseases, r/o leukemia
• Prevent recurrent anovulatory bleeding with
• cyclic progestogen (i.e. Provera)
• or
• low dose ( 35 µg ethinyl estradiol) oral
  contraceptive
• suppresses ovarian and adrenal androgen
  production and increases SHBG ? decreasing
  bioavailable androgens

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Anovulatory Bleeding Reproductive Age (19-39
years)

• Anovulatory bleeding not considered physiologic,
  evaluation required
• 6-10 of women have hyperandrogenic chronic
  anovulation (i.e. PCOS), characterized by
  noncyclic bleeding, hirsutism, obesity (BMI 25)
• Underlying biochemical abnormalities noncyclic
  estrogen production, elevated serum testosterone,
  hypersecretion of LH, hyperinsulinemia.
• h/o rapidly progressing hirsutism with
  virilization? suggests tumor
• Lab testing HCG, TSH, fasting serum prolactin
• If androgen-producing tumor is suspected, serum
  DHEAS and testosterone levels
• If POF suspected, serum FSH
• Chronic anovulation resulting from hypothalamic
  dysfunction (dxd by low FSH level) may be due to
  excessive psychologic stress, exercise, or weight
  loss

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Anovulatory BleedingReproductive Age (19-39 yrs)

• When is endometrial evaluation indicated?
• Sharp increase in incidence of endometrial CA
  from 2.3/100,000 ages 30-34 yrs ? 6.1/100,000
  ages 35-39 yrs
• Therefore, endometrial bx to exclude CA is
  indicated in any woman 35 yrs old with
  suspected anovulatory bleeding
• Pts 19-35 who dont respond to medical therapy or
  have prolonged periods of unopposed estrogen 2/2
  anovulation merit endometrial bx

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Anovulatory Bleeding Reproductive Age (19-39 yrs)

• Medical therapies
• Can be treated safely with either cyclic
  progestogen or OCPs, similar to adolescents.
• Estrogen-containing OCPs
• relatively contraindicated in women with HTN or
  DM
• contraindicated for women 35 who smoke or have
  h/o thromboembolic dz
• If pregnancy is desired, ovulation induction with
  clomid is initial tx of choice
• Can induce withdrawal bleed with progestogen
  (i.e. provera), followed by initiation of therapy
  with Clomid, 50 mg/d for 5 days, starting b/t
  days 3 and 5 of menstrual cycle

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Anovulatory BleedingLater Reproductive Age
(40-Menopause)

• Incidence of anovulatory bleeding increases
  toward end of reproductive years
• In perimenopausal women, onset of anovulatory
  cycles is due to declining ovarian function.
• Can initiate hormone therapy for cycle control
• When is endometrial evaluation indicated?
• Incidence of endometrial CA in women 40-49 years
  36.2/100,000
• All women 40 yrs who present with suspected
  anovulatory bleeding merit endometrial bx after
  excluding pregnancy

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Anovulatory BleedingLater Reproductive Age
(40-Menopause)

• Medical therapy
• Cyclic progestogen, low-dose OCPs, or cyclic HRT
  are all options
• Women with hot flashes secondary to decreased
  estrogen production can have symptomatic relief
  with ERT in combination with continuous or cyclic
  progestogen

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Anovulatory BleedingLater Reproductive Age
(40-Menopause)

• Surgical therapy
• Surgical options include hysterectomy and
  endometrial ablation
• Surgical tx only indicated when medical mgmt has
  failed and childbearing complete
• Some studies suggest hysterectomy may have higher
  long-term satisfaction than ablation
• Endometrial ablation NovaSure, thermal balloon
• YAG laser and rollerball less widely-used
  currently
• 45 of women achieve amenorrhea after YAG laser
  or resectoscope. 12 month post-op satisfaction is
  90. Only 15 of women achieve amenorrhea after
  thermal balloon ablation, and 1 yr satisfaction
  rate still 90
• Long-term satisfaction with ablation may be
  lower
• in 3-year f/u study, 8.5 of women who had
  undergone ablation were re-ablated, an additional
  8.5 had hyst
• In a 5-year follow up study, 34 of women who
  underwent ablation later had a hyst.