Nice guidelines for dub 2007

Definition

 Dysfunctional uterine bleeding (DUB) is defined as abnormal uterine bleeding in the absence
of organic disease.2
 It usually presents as heavy menstrual bleeding (menorrhagia).
 The diagnosis of DUB can only be made once all other causes for abnormal, or heavy,
uterine bleeding have been excluded. The pathophysiology is largely unknown.
 80% of women treated for heavy menstrual bleeding have no anatomical pathology.3
 Menorrhagia is clinically defined as a total menstrual blood loss of more than 80 mls per
menstruation.
 NICE defines heavy menstrual bleeding as "excessive menstrual blood loss which interferes
with the woman's physical, emotional, social and material quality of life, and which can
occur alone or in a combination with other symptoms."

Epidemiology

 Dysfunctional uterine bleeding (DUB) is more common around the menarche and
perimenopause.
 The perception of what is heavy menstrual bleeding is subjective and 30% of women
consider their bleeding to be excessive.4
 Only half of women complaining of heavy menstrual bleeding fit the clinical criteria of more
than 80 mls blood loss per cycle.5
 Pictorial blood-loss assessment charts are available.6
 Among women aged 30-49, one in 20 consults her GP each year with menorrhagia.2
 Heavy menstrual bleeding accounts for 12% of all gynaecology referrals in the UK. 7
 Each year around £7 million is spent in the UK on prescriptions in primary care to treat
menorrhagia.2

Other causes of heavy menstrual bleeding

 Uterine pathology: polyps, fibroids, carcinoma, infection - including pelvic inflammatory

disease (PID), endometriosis.
 Systemic disease: hypothyroidism, liver disease, obesity, polycystic ovarian syndrome
(PCOS), haematological disorders, e.g. von Willebrand's disease.
 Iatrogenic causes: intrauterine device, anticoagulant treatment.

History

 Menstrual history: cycle length, number of bleeding days, intermenstrual or postcoital

bleeding, degree of blood loss (number of pads/tampons changed per day; Pictorial blood-
loss assessment charts); passage of clots; pain associated with bleeding (dysmenorrhoea).
 Contraception: current method; need; family complete?
 Symptoms suggesting underlying pathology:
o Metabolic disorders: symptoms suggesting PCOS and hypothyroidism.
o Haematological disorders: excessive bleeding after childbirth or tooth extraction,
easy bruising.
o PID/infection: pelvic pain, pain on intercourse (dyspareunia), vaginal discharge.
o Endometriosis: pelvic pain, dysmenorrhoea.
o Postcoital and intermenstrual bleeding also suggests pelvic pathology.

Examination
  Signs of underlying pathology: bruising, typical hypothyroid features, features of PCOS
(hirsutism, acne, overweight), pallor, koilonychia.
 Abdominal examination: tenderness, palpable masses (uterine, ovarian).
 Pelvic examination: vulval inspection, speculum examination, bimanual palpation for
masses.
 Cervical smear: as appropriate.
 Infection screening: high vaginal and endocervical swabs as appropriate.

Routine investigations

 Every woman presenting with heavy menstrual bleeding should have a full blood count
taken.1
 Serum ferritin, female hormone testing and thyroid testing are not routinely recommended.
Only carry out these blood tests if there is strong clinical suspicion of underlying pathology. 1

When to refer to secondary care

Referral to secondary care for further gynaecological assessment and examination should be made:

 In women over 45 years with heavy menstrual bleeding.

 If there is persistent intermenstrual bleeding.
 If an abnormality is suspected on physical examination (other than fibroids < 3 cm in
diameter).
 If there is suspicion from the history of increased risk of pathology, such as carcinoma (e.g.
family history or endometrial or colonic cancer, nulliparity, obesity, tamoxifen or
unopposed oestrogen therapy, abnormal smear, PCOS).
 If there is treatment failure.

A woman with heavy menstrual bleeding referred to specialist care should be given information
before her outpatient appointment.1 NICE's information for patients - 'Understanding NICE guidance'
- is available from the link below.

Further investigations that usually take place in secondary care:

 Pelvic ultrasound scan: first-line diagnostic tool for identifying structural abnormalities.
Endometrial thickness may also be assessed.
 Endometrial biopsy.
 Hysteroscopy.

Management of dysfunctional uterine bleeding

Pharmacological management of dysfunctional uterine bleeding (DUB)
Once organic causes for heavy menstrual bleeding have been excluded, the first-line management
of DUB is pharmaceutical treatment. Treatments should be considered in the following order:

 First-line: levonorgestrel-releasing intrauterine system, provided long-term use (at least 12

months) is anticipated.
 Second-line: tranexamic acid or non-steroidal anti-inflammatory drugs (NSAIDs) or
combined oral contraceptive pills (COCPs).
 Third-line: norethisterone (15 mg) daily from days 5 to 26 of the menstrual cycle, or
injected long-acting progestogens.1,3

If hormonal treatments are not acceptable to the woman, then either tranexamic acid or NSAIDs
can be used.
1. Levonorgestrel-releasing intrauterine system (LNG-IUS)

 Prevents endometrial proliferation.

 Also acts as a contraceptive.
 Doesn't impact future fertility.
 Unwanted outcomes: irregular bleeding that can last for six months; amenorrhoea;
progestogen-related problems such as breast tenderness, acne and headaches; uterine
perforation at insertion (1 in 100,000 chance).
 As equally effective in improving quality of life and psychological well-being as
hysterectomy.8,9

2. Tranexamic acid

 Oral antifibrinolytic.
 If no improvement, stop after three cycles.
 Can be used in parallel with investigations.
 Not a contraceptive.
 Unwanted outcomes: indigestion; diarrhoea; headache.
 Has been reluctance to prescribe due to potential increased risk of thrombosis.
 Studies in Sweden have shown that incidence of thrombosis in women treated with
tranexamic acid is comparable with the spontaneous frequency of thrombosis in women.
10A Cochrane Review showed that there are no data available within randomised

controlled trials which record the frequency of thromboembolic events during treatment
with tranexamic acid.11
 Dose: 500 mg tablets. 2 to 3 tablets three to four times daily for three to four days.
Therapy is indicated only after heavy bleeding has started.12

3. NSAIDs

 Commonly used examples: mefenamic acid.

 Oral tablets that reduce production of prostaglandin.
 If no improvement, stop after three cycles.
 Can be used in parallel with investigations.
 Preferred over tranexamic acid in dysmenorrhoea.
 Not a contraceptive.
 Unwanted outcomes: indigestion; diarrhoea; worsening of asthma in sensitive individuals;
peptic ulcer.
 Dose: mefenamic acid 500 mg tablets. 1 tablet three times daily during heavy bleeding.

4. COCPs

 Prevent proliferation of the endometrium.

 Also act as a contraceptive.
 Do not impact future fertility.
 Unwanted outcomes: mood change; headache; nausea; fluid retention; breast tenderness;
deep vein thrombosis; myocardial infarction; cerebrovascular event.

5. Oral progestogen (norethisterone)

 Prevents proliferation of the endometrium.

 Also acts as a contraceptive.
 Does not impact future fertility.
 Dose: 15 mg daily on days 5-26 of the cycle.
 Unwanted outcomes: weight gain; bloating; breast tenderness; headaches; acne;
depression.
  A recent Cochrane Review showed that this regime of progestogen results in a significant
reduction in menstrual blood loss but that women find the treatment less acceptable
than intrauterine levonorgestrel.3

6. Injected progestogen (depot-medroxyprogesterone acetate)

 Prevents proliferation of the endometrium.

 Also acts as a contraceptive.
 Does not impact on future fertility.
 Unwanted outcomes: weight gain; irregular bleeding; amenorrhoea; bloating; fluid
retention; breast tenderness; bone density loss.
 Due to the potential for bone density loss, current guidance is that depot-
medroxyprogesterone acetate should only be used in adolescents if other treatments for
heavy menstrual bleeding are unsuitable, ineffective or unacceptable. In women of all
ages, careful re-evaluation of the risks and benefits of use should be carried out at two
years. If there are significant risk factors for osteoporosis, alternative treatment for
heavy menstrual bleeding should be considered first.13

Surgical management of DUB

This should only be considered if:

 Pharmacological management has failed.

 There is severe impact on quality of life.
 There is no desire to conceive.
 The uterus is normal (or there are just small fibroids < 3 cm).

1. Endometrial ablation
Second-generation: non-hysteroscopic, general anaesthetic not required, can be done as day
case, easier, quick recovery period.

o Impedance-controlled bipolar radiofrequency ablation (bipolar radiofrequency

electrode placed through the cervix and radiofrequency energy is delivered to the
uterus).
o Balloon thermal ablation (balloon inserted through cervix to endometrial cavity,
inflated with a pressurised solution then heated to destroy the endometrium).
o Microwave ablation (microwave probe inserted into the uterine cavity to heat the
endometrium, and moved side-to-side to destroy it).
o Free fluid thermal ablation.

First-generation: hysteroscopic, general anaesthetic usually used.

o Rollerball ablation (a current is passed through a rollerball electrode that is moved

around the endometrium).
o Transcervical resection of the endometrium (the endometrial lining ± small fibroids
are removed using a cutting loop).

Unwanted outcomes: vaginal discharge; increased period pain even if no further bleeding;
need for additional surgery; infection; perforation (very rare).Contraception after
endometrial ablation is still advised even though fertility is usually not retained.

2. Hysterectomy

 Not first-line surgical management for DUB. Only consider when:

o Other treatments have failed, are contra-indicated or declined.
o There is desire for amenorrhoea.
o The woman is fully informed and requests it.
 o There is no desire to retain the uterus and fertility.
 First-line is vaginal hysterectomy, second-line is abdominal.
 Healthy ovaries should not be removed.
 Unwanted outcomes: infection; intraoperative haemorrhage; damage to other organs, such
as urinary tract and bowel; urinary dysfunction; thrombosis; menopausal-like symptoms if
ovaries are removed.

Complications of dysfunctional uterine bleeding

 Iron deficiency anaemia.

 Psychological sequelae: depression, embarrassment.
 Social implications for woman: cost of pads and tampons, time off work.

Arresting very heavy bleeding

 In the acute situation, a bleeding episode may be so disabling for the woman that treatment
with high-dose norethisterone (30 mg daily) needs to be used. This is continued until
bleeding is controlled, but is then tailed off.