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					Heavy Menstrual Bleeding



     Max Brinsmead PhD FRANZCOG
                    January 2011
This presentation will cover:

Definitions & Diagnosis
The evidence base for recommended
management
What tests are necessary & when
Treatment
 – Medical & Surgical
 – Indications & Options
 – Risks & Side Effects
          Resources:
NICE Guidelines “Heavy menstrual
bleeding” (January 2007)

Cochrane database

Pubmed

Personal experience
                  A Few Definitions


Menorrhagia
– Excessive menstrual loss at regular intervals

Metrorrhagia
– Excessive menstrual loss without evidence of any cycling
– Typical of anovulatory bleeding at the extremes of reproductive life

Intermenstrual bleeding (IMB)
– Episodes of bleeding between menstrual periods
– Postcoital bleeding is a type of IMB

The generic modern terms are Heavy
Menstrual Bleeding (HMB) & Abnormal
Uterine Bleeding (AUB)
Heavy menstrual bleeding is defined as:


Excessive menstrual blood loss which
interferes with a woman’s…
–   physical
–   emotional
–   social or
–   material quality of life
This implies that the woman herself is the
primary judge of severity
And there can be substantial variation in
tolerance to this dis - ease
While a pathological description is impractical:


 That is, the menstrual loss of an amount of blood loss
 that is likely to lead to health sequelae
 Because treatment options have risk & cost implications,
 a health provider is obliged to indicate to patients some
 criteria for diagnosis
 My criteria:
  –   Sufficient to cause iron deficiency (exclude other causes)
  –   Escapes from accepted menstrual protection
  –   Requires changes > 4 hourly
  –   Up at night more than once
  –   Passage of large clots
  –   Lasts for >7 days (full flow)
  Menstrual Bleeding – What is Normal?

One study of 179 normal women found that 97%
menstruate for 3-8 days but the range is 1 – 19 days
Most studies demonstrate an effect of age on the duration
and amount of bleeding, as well as cycle length
– For teenagers mean menstrual loss is 4.7 days, the mean cycle length
  is 30.8 days (10th to 90th centile range is 25 – 31days)
– For ♀ >40 yrs mean menstrual loss is 4.1 days, the mean cycle
  length is 28.4 days (10th to 90th centile range is 25 – 32 days)
– Mean measured loss is 34 ml at 15 yrs, peaks at 50 ml at 30 years
  then declines to 43 at 45 years
Excessive blood loss is variously reported as >45, >80 or
>120 ml based on when anaemia & iron deficiency begins
But at least 30% of women who complain of HMB will
have <80 ml blood loss
Incidence of Heavy Menstrual Bleeding
        The Impact on Women
 Cross sectional studies indicate that 5 – 50% of women
 will complain of “heavy periods”
 Quantified studies show that ≈ 10% of women will have
 menstrual losses that ≥ 80 ml
 Many studies indicate that the condition is associated
 with…
 – Reduced employment options
 – Work absences
 – Decreased earning capacity that for women are more important than
   such psychological effects as…
 – Depression and anxiety
 – Mood changes, irritability
 – As well as effects on social life, hobbies etc
 Can be summarised in “Quality of Life” measures
Some Causes of Heavy Menstrual Bleeding

  Fibroids
  Adenomyosis
  Endometriosis & Chronic PID
  Endometrial cancer
  Bleeding disorders
   – Idiopathic and acquired thrombocytopenia
   – Other known & undiagnosable disorders of coagulation
  Physiological
   – Includes dysfunctional uterine bleeding
   – All studies show >50% have no identified pathology
        Some History-taking Tips
How many days does your period last for
How many heavy days? What do you mean by heavy
What do you use for menstrual protection
How often do you change? Why do you change so often
What do you use at night
Do you change at night? How many nights
Do you pass clots? How big are the clots? How often
Any accidents (escape from menstrual protection)
What do you mean by flooding
Do you have to modify your life when you have your periods
What do you do for contraception in your relationship
Do you experience any other bleeding or bruising
Are you taking iron tablets
    Other History-taking Essentials
Consider the cultural context
Explore parity, fertility requirements etc
Consider occupation and activities
The extent of examination and investigations will depend on
 – Age >45
 – Intermenstrual bleeding
 – Any pelvic pain or pressure symptoms
Details of any previous gynaecological interventions
Other illnesses or conditions may influence treatment options
Other symptoms may influence treatment choices
 – Infertility
 – Prolapse
 – Urinary incontinence
Family History
                  Examination
A general examination of all patients
– Height & weight
– Signs of anaemia
– Signs of endocrinopathy
    • Thyroid
    • Androgen excess
Abdominal examination
– For significant uterine enlargement
    • Only rewarding in slim patients
    • A palpable uterus is >12w size
A vaginal examination is not required in primary care if
there is no palpable uterus & a Pap smear is not required
    • Unless a Mirena is planned
And patients should not be sent for US without prior VE
Laboratory Tests in Primary Care
A Full Blood Count (FBC) for all patients
– Look for iron-deficiency anaemia
– Check the platelet count
S Ferritin
–   Is the most sensitive indicator of Iron deficiency
–   But it is an acute phase reactant
–   Not required in primary care in the UK
–   Required in NZ for subsidised Mirena
Thyroid function tests
– Only when clinically indicated
Female hormones
– Have no role
– Even when the diagnosis is dysfunctional uterine bleeding
          Indications for Tests
       of Coagulation Disorders

Symptoms from menarche
Positive Family History
Other personal bleeding or bruising
There is thrombocytopenia
Tests to do:
– Renal and Liver Function Tests
– Bleeding time and Coagulation time
– Seek specialist haematological advice
The most commonly identified abnormality is von
Willebrands Disease
         Imaging in Primary Care

Ultrasound is the imaging of choice
– But is not required unless the uterus is enlarged
– Required for uncertainty after pelvic examination
– Required after a failure of primary medical treatment
Required information from this examination include:
– Uterine size including length of the endometrial cavity
– Myometrial abnormalities
– Any adnexal pathology
Considerable caution is required when...
– Comments about endometrial thickness are reported as abnormal
– Fibroids <4 cm in size are reported
– Multiple fibroids are reported but there is no clinical evidence of an
  irregular uterus
– Adnexal cysts <5 cm diameter are reported
What is the risk of significant pathology?

 This is mostly about the risk of endometrial cancer
 There are many studies…
  – Most do not distinguish between HMB and AUB
 The risk of endometrial Ca is age dependent
  – For women <30 yrs age the risk is 1:10,000
  – For those >45 years the risk is 8:10,000
  – And the risk of endometrial hyperplasia is ≈ 4X higher
 Who is at risk of Endometrial Cancer?
  –   Those with intermenstrual bleeding
  –   Those with irregular cycles – PCO disorder
  –   Infertility
  –   Obesity
  –   Positive Family History
What is the chance of any pathology?
 There are many studies…
  – Most use ultrasound and hysteroscopy for Ix
 Overall about 30% have “significant fibroids”
  – But only ≈50% of patients with “significant fibroids” have HMB
 About 10% have endometrial polyps
  – But there is evidence that polyps cause HMB
 About 15% have endometriosis
  – But pain is more important for this disease
 Up to 50% of patients undergoing hysterectomy have
 Adenomyosis
  – But these are a selected group
  – And there is debate about what constitutes adenomyosis on histology
 Up to 20% patients with HMB have a coagulation disorder
        Indications for Referral

Patient is >45 years of age
There is irregular or intermenstrual bleeding
The uterus is >10 weeks size
There are symptoms or signs suggestive of such
pelvic conditions as endometriosis, PID , adnexal
pathology etc.
Ultrasound suggests uterine fibroids >4 cm or
distortion of the uterine cavity
Failure of primary pharmaceutical treatment
Patient request
                  Patient Choice

Information about the condition and options for
treatment should be given prior to the specialist’s
visit
Written information to include...
– expected outcome and its duration of effect
– the type and frequency of risks, side effects and complications of all
  methods of treatment
– any potential impact on fertility
The patient should be involved in the treatment
choice
– But safety and cost effectiveness need to be borne in mind
This may require time
A second specialist opinion is sometimes required
   How is pathology identified?

There is no gold standard short of hysterectomy &
histology
The tools of investigation are best regarded as
complementary and should be used selectively
D&C is no longer regarded as an acceptable investigation
Most studies have compared:
– Transvaginal ultrasound (TVS)
– Saline hysterography (SHG)
– Hysteroscopy
    • Which can be inpatient or outpatient
    • Electrolyte , non-electrolyte distension medium or CO2
    • Fixed or fibreoptic
– With attention to the role of Endometrial Biopsy to exclude Ca
           Which Test?
        What is the Evidence?
Systematic Review of TVS (10 studies), Saline Hysterography
(SHG, 11 studies) and Hysteroscopy (3 studies) for the
identification of any pathology
TVS
 – Sensitivity 48 – 100%
 – Specificity 12 – 100%
SHG
 – Sensitivity 85 – 100%
 – Specificity 50– 100%
Hysteroscopy
 – Sensitivity 90 – 97%
 – Specificity 62 – 93%
Ultrasound better for the identification of fibroids
HSG and Hysteroscopy better for the identification of polyps
Exclusion of Endometrial Cancer


Hysteroscopy with biopsy will identify >99.5% of
endometrial cancers
Pipelle endometrial biopsy (an outpatient
procedure) has an overall sensitivity of only 70%
for endometrial pathology
– Because it will often be negative with benign endometrial
  polyps
But Pipelle has a 99% negative predictive value
for endometrial cancer
   Pipelle Endometrial Biopsy


Is best done in association with ultrasound
Indications:
– Prior to therapy in patients at increased risk of endometrial
  cancer
– Age >45
– Those with intermenstrual bleeding
– Obese, Family history etc.
Will be unsuccessful in up to 20% of patients
No sample will be obtained in up to 50%
– But that in itself may be diagnostic enough
 Who Requires Hysteroscopy?
High risk patient who has had a failed Pipelle

Negative Pipelle but continuing symptoms

Ultrasound findings inconclusive for
submucous fibroid or endometrial pathology
– A post menstrual study is required
Failure of primary treatment

Prior to endometrial ablation
 Medical Options for the Treatment
   of Heavy Menstrual Bleeding
Hormonal
   •   Levonorgestrel IUS (“Mirena”)
   •   Combined COC
   •   Cyclical oral Progestins
   •   Injected Progestin (“Depo Provra”)
   •   Danazol
   •   GnRH analogues


Non Hormonal
   • NSAIDs
   • Tranexamic Acid (“Cyclokapron”)
    Surgical Treatment Options
   for Heavy Menstrual Bleeding
Endometrial Ablation
   • Hysteroscopic endometrial resection
   • 2nd generation techniques
       – Thermal balloon endometrial ablation (TBEA)
       – Microwave endometrial ablation (MEA)

Myomectomy
Uterine Artery Embolisation
Hysterectomy
   • Abdominal, vaginal or laparoscopic
   • Subtotal or total
   • With or without bilateral oophorectomy
         Potential unwanted outcomes
Information for women about treatment for HMB
         Potential unwanted outcomes
Information for women about treatment for HMB
       The Mirena IUS for HMB
        What is the Evidence?
Systematic Review of 10 RCT’s that compare Mirena with other
hormonal methods of treatment, endometrial ablation & hysterectomy
Reduces mean menstrual loss by 71 – 96%
Up to 50% of patients amenorrhoeic after 6m depending on age
≈ 85% patients are satisfied (and continuation rate)
≈ 1% rate of troublesome hormonal side effects
When compared to endometrial ablation (EA)
 – Mean reduction in blood loss is greater with EA
 – But overall satisfaction equal
 – And Mirena better in the longer term (1 small study)
When compared to hysterectomy
 – Overall satisfaction rates are equal
 – But Mirena is half the cost even when up to 40% of patients go on to
    hysterectomy
       Oral Hormones for HMB
       What is the Evidence?
Only one RCT of 45 patients for Combined oral contraceptive (COC)
Mean blood loss (MBL) was reduced by 43%
Better than Danazol and one NSAID but not another trialled
Risks in older women and smokers plus side effects limit its use

Progestin e.g. Norethisterone 5 mg TDS from Day 5 to 27 of a cycle is
effective in reducing (MBL)
 – Luteal phase progestins are not effective
Not as effective as NSAIDs and Tranexamic acid
But MBL was reduced by 83% with long term use in 44 women CF
Mirena (94%) and this difference is not significant
Side effects are limiting – weight gain, headaches, acne, mood
changes, mastalgia
They are of most use in the short term treatment of DUB at the
extremes of reproductive life
   IM Depo Provera for HMB

≈10% of patients are amenorrhoic after 3m of
150 mg every 12w

≈50% amenorrhoic after 12m

Continuation rates are low, however,
presumably due to side effects

And there is a small risk of bone mineral loss
with long term use
    GnRH analogues for HMB

Most studies have been directed at the reduction of
uterine size with these agents that induce a “reversible
menopause”
Reductions in uterine size up to 75% over 6m can occur
And up to 90% of patients achieve amenorrhea
This can be very useful prior to hysterectomy
Oestrogen-deficiency symptoms i.e. hot flushes,
vaginal atrophy and bone loss are limiting
But these can be overcome with add-back therepy
using small doses of oral oestrogen, COC, progestin or
tibilone
GnRH are currently very expensive drugs
Tranexamic Acid (Cyklokapron) for
             HMB
Inhibits plasminogen activation but has no effect on
blood clotting in healthy vessels
Reduces fibrin breakdown in spiral arterioles
Systematic reviews confirm that mean blood loss
during menstruation is reduced by ≈ 50%
12% of women experience side effects
    •   Nausea, vomiting, dyspepsia
    •   Diarrhoea
    •   No apparent risk of thromboembolism
    •   Visual side effects are rare
Dose 1G every 6 – 8 hours
It is not contraceptive nor cycle regulating
            NSAIDs for HMB

Systematic reviews confirm that mean menstrual blood
loss during menstruation is reduced by ≈ 30%
Mefanamic acid e.g. Naprosyn better than Ibufren e.g.
Indocid
Side effects are well known but risk is reduced by
intermittent use
Dose 1 – 2 tablets 4 – 6 hourly
Particularly useful when dysmenorrhoea is also a
problem
Not recommended if there is a known bleeding disorder
loss
Summary of Non-Hormonal Drugs Rx

 Cyclokapron is more effective than NSAIDs
 But both can be used together
 And either can be continued long term if benefit is
 obtained
 But should be stopped if there is no response after 3
 cycles
 Neither are contraceptive or cycle regulating
 NSAID is the drug of 1st choice when there is
 concomitant dysmenorrhoea
 All of the trials excluded women with fibroids so their
 role in menorrhagia with fibroids is uncertain
 Endometrial Ablation or Hysterectomy
      What is the Evidence?

Systematic review 1999 of 5 RCTs with 706 patients
Hysterectomy reduced MBL more (OR 0.12, CI 0.06 – 0.25)
Greater patient satisfaction at 12m & 24m (OR 0.46, CI 0.24 –
0.88)
Less pelvic pain on follow up (p<0.007)
Better social functioning (p<0.007)
Endometrial ablation had shorter hospital stay
Fewer adverse outcomes
More likely to require further surgery (OR 7.33, CI 4.18 –
12.86)
As a result hysterectomy is as cost effective as EA
Information for Patients that compares
 Endometrial Ablation & Hysterectomy
 Endometrial Ablation Techniques

All techniques are equivalent for outcomes but 2nd
generation techniques are:
– Safer & Quicker
– Easier to learn & perform
Reduces MBL by 10 – 40 %
Problems include:
–   Equipment failure
–   Continuing pelvic pain
–   Infection & Haematometra
–   Uterine perforation & fluid overload with hysteroscopic EA
TBEA does not require prior endometrial thinning
MEA best done in the 1st half of the cycle
 NICE Recommendations on Surgical
            Options
Endometrial resection by a 2nd generation technique be
offered to all women with HMB provided that they have
completed their family
If the uterus is <10w in size and or fibroids < 3 cm
diameter
A hysteroscopic technique is used when there are
submucous fibroids
Practitioners and institutions be trained and competent
for EA
Hysterectomy, uterine artery embolisation or
myomectomy be considered for fibroids >4 cm or
uterus >10w size
    Uterine Artery Embolisation (UAE) or
               Hysterectomy?
5 RCT’s 157+ patients showed that UAE better than
hysterectomy in terms of:
–   Procedure time (Mean 16min less)
–   Less blood loss (minimal with UAE CF av. 400 ml for hysterectomy )
–   Fewer lood transfusions
–   Shorter hospital stay (Mean 3.3 days less)
–   Quicker return to normal duties (Mean 27 days less)
–   Cheaper (UAE costs 65% those of hysterectomy)
No difference between UAE and hysterectomy in terms of:
– Patient satisfaction
– Complication rates
But UAE result in more readmissions (OR 6.00, CI 1.14 -
31.53)
And 13 – 30% UAE patients require further surgery
   Uterine Artery Embolisation (UAE) or
              Myomectomy?
One RCT (n=?) and one cohort study (n=111)
Myomectomy performed against UAE as for
hysterectomy in terms of operating time, blood
loss, hospitalisation and return to normal
activities
Equivalent results in terms of mean menstrual
blood loss and complications
But myomectomy better in terms of pelvic pain on
follow up
And fewer required re operation
NICE Recommendations for Uterine Fibroids

  For patients with heavy menstrual bleeding and fibroids
  >3 cm size (and especially those with pelvic pain or
  other symptoms) then…
  – Hysterectomy, Uterine artery embolisation (UAE) and
    myomectomy should all be offered
  – Myomectomy recommended if fertility is desired
  – Hysteroscopic resection of the entire fibroid with endometrial
    resection is appropriate if the fibroid (s) are submucous
  Pre treatment with GnRH analogue for 3 - 4m is
  worthwhile before hysterectomy and myomectomy
  – Reduces uterine size and makes surgery easier
  – Better HB pre op and less bleeding
  But GnRH analogues are contraindicated before UAE