Dr. Mohammed Abdalla

1
Post-Menopausal Bleeding

• Dr. Mohammed Abdalla
• Egypt, Domiat general hospital

2
Menopause

• is the permanent cessation of menstruation
  resulting from loss of ovarian follicular
  activity.
• It can only be determined after 12 months'
  spontaneous amenorrhoea.
• Mean age is 51 years.

3
Menopause transition

• is the period of time in which the ovaries are
  beginning to fail, where endocrine, biological,
  and clinical changes are seen. It ends with the
  final menstrual period.
• Length of the transition is approximately 4 years

4
Perimenopause

• is the time period over which the ovaries are
  failing (when symptoms begin) up until the
  cessation of menstruation, and ends 12 months
  after the final menstrual period.

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Postmenopause

• is the time after the menopause, that is, after
  the permanent cessation of menstruation. It can
  only be determined after 12 months of spontaneous
  amenorrhoea.
• In practice this definition is difficult to
  apply, especially in women who have started
  hormone replacement therapy (HRT) in the
  perimenopause. It has been estimated that by the
  age of 54 years, 80 of women are postmenopausal
  McKinlay et al, 1992 DTB, 1996.

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Surgical menopause

• occurs after bilateral oophorectomy with or
  without hysterectomy.
• Premature menopause may also be radiation- or
  chemotherapy-induced, or occur after hysterectomy
  with ovarian conservation.

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Primary Premature menopause

• A premature menopause is one that occurs before
  the age of 40 years.
• Primary premature menopause may occur at any age
  and present as amenorrhoea. Not all women have
  acute symptoms. FSH levels are elevated.
  Spontaneous fertility may recur.

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• It is possible to discontinue the HRT or COC pill
  and measure the follicle-stimulating hormone
  (FSH) level after 6-8 weeks. The POP does not
  affect FSH levels and so does not need to be
  stopped for FSH testing Gebbie, 1998.
• An FSH value over 30 IU/L is in the
  postmenopausal range, but should be repeated 4-8
  weeks later to confirm this.
• Even if the FSH levels are in the postmenopausal
  range, this may not reliably indicate
  infertility, and contraception should be
  continued for a further 1 year if the woman is
  over 50 years old, or a further 2 years if she is
  under 50 years old .

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Risk assessment

• Benign conditions is most frequent causes of PMB
  but endometrial cancer is the most serious
  potential underlying cause

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Risk assessment

• 75 of women with endometrial cancer are
  postmenopausal.

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Risk factors for endometrial cancer

• are conditions typically associated with chronic
  elevations of endogenous estrogen levels or
  increased estrogen action at the level of the
  endometrium. These include
• Obesity.
• history of chronic anovulation.
• diabetes mellitus.
• estrogen-secreting tumors.
• exogenous estrogen unopposed by progesterone .
• tamoxifen use.
• a family history of Lynch type II syndrome
  (hereditary nonpolyposis colorectal, ovarian, or
  endometrial cancer).

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Risk assessment

• Investigate all bleeding during menopause unless
  the patient is on cyclic replacement therapy with
  normally anticipated withdrawal bleeding.
• The duration or amount (staining vs gross) of
  bleeding does not make any difference.

13
Tamoxifen use
Risk assessment

• Tamoxifen therapy is associated with a two- to
  threefold increased risk of endometrial cancer in
  postmenopausal women. TVUS of patients on this
  therapy typically shows an increased endometrial
  thickness.
• Risk appears to increase with higher cumulative
  doses of tamoxifen and longer duration of
  treatment.

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Postmenopausal bleeding and HRT

• The occurrence of uterine bleeding or spotting
  after the initiation of HRT is not unusual. More
  than half of HRT users will have some spotting or
  bleeding at the beginning of therapy.
• Usually such bleeding is lighter than a
  menstrual period and lessens with time after 6
  months, it stops completely in most women.

15
Postmenopausal bleeding and HRT

• Sequential (or cyclical) combined regimens cause
  scheduled bleeding in most users. Continuous
  combined regimens are associated with a reduced
  relative risk of endometrial cancer but may cause
  unpredictable spotting or bleeding during initial
  use.

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Systemic conditions

• Abnormalities of the hematologic system also must
  be considered as a possible cause of
  postmenopausal bleeding.
• On rare occasions, AUB will be the first sign of
  leukemia or a blood dyscrasia.
• Overuse of anticoagulant medications such as
  aspirin, heparin, and warfarin-which are taken
  with greater frequency by patients in this age
  group-may contribute to postmenopausal bleeding.

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Pathophysiology

• Once menopause occurs, estrogen and progesterone
  are no longer produced by the ovaries nor are
  they produced in any appreciable amounts by the
  liver and fat. The endometrium regresses to some
  degree, and no further bleeding should occur.
  When bleeding does resume, therefore, endometrium
  must be evaluated.

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Endometrial evaluation
19

• Endometrial evaluation is called for when
• any menopausal woman not taking HRT develops
  uterine bleeding after more than 1 year of
  amenorrhea.
• any postmenopausal woman on HRT for 6 months or
  more with persistent uterine bleeding.
• and any previously amenorrheic woman on HRT who
  begins bleeding without apparent cause.

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Endometrial evaluation

• As TVUS is a non invasive test with 91
  sensitivity and 96 specificity . it should be
  done for all women with postmenopausal bleeding.
• if the endometrial thickness is gt5mm. and if the
  patient pre test probability is low ,office
  endometrial biopsy and SIS should be done to
  determine whether the endometrium is
  symmetrically thickened.
• BUT if the patient pre test probability is high ,
  a fractional curettage biopsy or a hysteroscopic
  guided biopsy is recommended.

21
TVUS
endometrial thickness is gt 5mm
endometrial thickness is lt 5mm
If high risk
If low risk
follow
D/C biopsy OR hysteroscopy
office endometrial biopsy and SIS
But symptoms persist
In women with continued bleeding after a negative
initial evaluation, further testing with
hysteroscopically directed biopsy is essential,
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Diagnostic tools
23

• Vaginal ultrasonography.
• Hydrosonography.
• Endometrial biopsy.

• Office biopsy.
• D/C biopsy.
• Hysteroscopic guided biopsy.

24

• Sensitivity and specificity are often used to
  summarise the performance of a diagnostic test.
  Sensitivity is the probability of testing
  positive if the disease is truly present.
  Specificity is the probability of testing
  negative if the disease is truly absent.

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Vaginal ultrasound
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Vaginal ultrasound

• Transvaginal ultrasound has a good correlation
  with pathologic endometrial findings. Using an
  endometrial thickness from myometrium to
  myometrium of 5 mm (considered the upper limit of
  normal) sensitivity is 91 percent and specificity
  is 96 percent.
• Although the test is very specific , it isn't
  sensitive. Many women without endometrial cancer
  will have an endometrial thickness of 5 mm or
  more

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Vaginal ultrasound

• Identification and measurement of the endometrial
  echo and descriptions of the echogenicity and
  heterogeneity of the endometrium are key to
  defining endometrial health

28
A cut-off threshold of 3 mm or 5mm ?

• A negative TVUS result for a local cut-off
  point of 3 mm is therefore less likely to miss
  cancer (i.e. have a greater sensitivity) than
  cut-offs of 5 mm.
• But unfortunately a lower cut-off points also
  result in a greater proportion of false
  positives requiring further investigation.

29
A cut-off threshold of 3 mm or 5mm ?

• Adopting more than one cut off value may allow
  the interpretation of the test to be tailored to
  the patients pre-test probability (i.e. the
  patient risk group).

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the patient risk group

• Low pre-test probability
• On HRT
• On tamoxifen therapy

• High pre-test
• Probability (high risk)

Cut off threshold 5mm
Cut off threshold 3mm
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• If both pre-and post test probability are
  reassuring, no further action need be taken.
  Further investigations should be carried out if
  symptoms recur.

32

• If both pre-and post test probabilities are not
  satisfactory with this level of reassurance,
  further investigation is justified. This should
  include an endometrial biopsy to obtain a
  histological assessment.

33

• For women on sequential combined HRT presenting
  with unscheduled bleeding, or those who are
  tamoxifen users, TVUS using a cut-off point of 5
  mm or less should be used to exclude endometrial
  cancer.

34
Vaginal ultrasound
35
Vaginal ultrasound

• One of the difficulties with using the
  endometrial stripe as a criterion for further
  diagnostic tests (eg, endometrial biopsy) is that
  several conditions may be present that give a
  false reading on the endometrial stripe. This is
  particularly true in a patient who might have an
  endometrial polyp or who has been taking
  tamoxifen.

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saline-infusion sonography
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saline-infusion sonography

• The introduction of intrauterine fluid
  (saline-infusion sonography) during transvaginal
  ultrasound is one of the most significant
  advances in ultrasonography of the past decade.

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saline-infusion sonography

• Uterine fibroids and adenomyomas generally are
  apparent on ultrasound. Uterine polyps may appear
  as a thickened endometrial stripe, but these and
  submucous myomas can be clearly identified as
  filling defects when a sonohysterography is
  performed

39
saline-infusion sonography

• At transvaginal US, when the endometrium cannot
  be accurately measured or when there is a
  nonspecific thickened central endometrial
  complex, sonohysterography can provide additional
  information and can be used to direct the patient
  to a visually guided hysteroscopic procedure
  rather than a potentially unsuccessful blind
  biopsy procedure.

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• At transvaginal ultrasonography , the finding of
  a thickened central endometrial complex, with or
  without cystic changes, is often nonspecific.

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The Thickened endometrium may be a polyp
CYST
POLYP
With polyps the endometrial-myometrial interface
is preserved
well-defined, homogeneous, isoechoic to the
endometrium
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The Thickened endometrium may be a polyp
catheter
POLYP
With polyps the endometrial-myometrial interface
is preserved
43
The Thickened endometrium may be a Submucosal
leiomyomas
With myomas the endometrial-myometrial interface
is distorted
broad-based, hypoechoic,
44

The Thickened endometrium may be an endometrial
hyperplasia
Endometrium thickness A-B
A
B
diffuse thickening of the echogenic endometrial
stripe without focal abnormality
45
Endometrial cancer
Endometrial cancer is typically a diffuse
process, but early cases can appear as a polypoid
mass
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Endometrial biopsy
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Endometrial biopsy
Dilatation and curettage

• The role today of the formal DC probably is very
  limited because the diagnosis usually can be made
  in the office.

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Endometrial biopsy
Hysteroscopic-directed biopsy

• Hysteroscopic visualization has several
  advantages
• immediate office evaluation,
• visualization of the endometrium and endocervix,
• the ability to detect minute focal endometrial
  pathology and to perform directed endometrial
  biopsies.

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Thank you