Heavy Menstrual Bleeding

Max Brinsmead MB BS PhD

Mayy 2015

This presentation will cover:

Definitions & DiagnosisThe evidence base for recommended managementWhat tests are necessary & whenTreatment– 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 severityAnd 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 sequelaeBecause treatment options have risk & cost implications, a health provider is obliged to indicate to patients some criteria for diagnosisMy 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 WomenCross 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

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 Causes of Heavy Menstrual Bleeding

How many days does your period last forHow many heavy days? What do you mean by heavyWhat do you use for menstrual protectionHow often do you change? Why do you change so oftenWhat do you use at nightDo you change at night? How many nightsDo you pass clots? How big are the clots? How oftenAny accidents (escape from menstrual protection)What do you mean by floodingDo you have to modify your life when you have your periodsWhat do you do for contraception in your relationshipDo you experience any other bleeding or bruisingAre you taking iron tablets

Some History-taking Tips

Consider the cultural contextExplore parity, fertility requirements etcConsider occupation and activitiesThe 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 optionsOther symptoms may influence treatment choices

– Infertility– Prolapse– Urinary incontinence

Family History

Other History-taking Essentials

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

But patients should not be sent for US without prior VE

Examination

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

Laboratory Tests in Primary Care

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

Indications for Tests of Coagulation Disorders

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

Imaging in Primary Care

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

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

Indications for Referral

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

Patient Choice

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

Hormonal• Levonorgestrel IUS (“Mirena”)• Combined COC• Cyclical oral Progestins• Injected Progestin (“Depo Provra”)• Danazol• GnRH analogues

Non Hormonal• NSAIDs• Tranexamic Acid (“Cyclokapron”)

Medical Options for the Treatment of 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

Surgical Treatment Options for Heavy Menstrual Bleeding

Potential unwanted outcomes Information for women about treatment for HMB

Potential unwanted outcomes Information for women about treatment for HMB

The Mirena IUS for HMBWhat 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 HMBWhat 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 tibiloneGnRH 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 problemNot 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) (1:5 patients go on to hysterectomy)

As a result hysterectomy is as cost effective as EA

But is associated with ↑rate of long term urinary symptoms

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

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