Introduction

Dysfunctional uterine bleeding (DUB) is a common condition in women of reproductive age. It is defined as anovulatory bleeding in pre-menopausal women that is not due to pregnancy or any identifiable uterine or systemic conditions. The hallmark of DUB is unpredictable, irregular bleeding that can range from spotting to larger volume bleeding. The pathophysiology of DUB is thought to relate to aberrant ovarian cycle hormones, and treatment may be medical or surgical depending on the severity of the symptoms and patient preference.

Epidemiology

  • Incidence: 750.00 cases per 100,000 person-years
  • Peak incidence: 30-40 years
Condition Relative
incidence
Uterine fibroids2.67
Dysfunctional uterine bleeding1
<1 1-5 6+ 16+ 30+ 40+ 50+ 60+ 70+ 80+

Aetiology

Pathophysiological changes relate to chronic unopposed exposure of the endometrium to oestrogen in an anovulatory woman.

  • An anovulatory woman remains in the follicular stage of the ovarian cycle, and consequently the only hormone stimulation the endometrium receives is oestrogen. This maintains the endometrium in the proliferative phase of the endometrial cycle.

  • Over time, the uninterrupted oestrogen signals in the absence of periodic progesterone causes hyperplasia and structural instability of the stroma.

  • Histology demonstrates proliferative endometrium, with areas of stromal breakdown and platelet/fibrin repair, associated with increased and dilated venous capillaries.

  • Once initiated, the process is exacerbated by local release of lysosomal proteolytic enzymes from surrounding epithelia, migratory leukocytes, and prostaglandins.

  • More common in states of increased unopposed oestrogen exposure
    • Polycystic ovarian syndrome
    • Peri-menopausal period
    • Post-menarche adolescence

Clinical features

The key clinical feature is unpredictable menstrual bleeding, and not just increased volume of menstrual bleeding (menorrhagia), although this may also be a feature.

  • Typically, infrequent and irregular, unpredictable menstrual bleeding
  • Varies in amount, duration and character
  • Not necessarily preceded by premenstrual symptoms (breast fullness/tenderness, bloating, mild mood swings)
  • Ask the patient if there is any possibility she may be pregnant

  • In a woman aged >40, peri-menopausal period may include DUB, and other symptoms such as:
    • Hot flushes
    • Night sweats
    • Vaginal dryness or itching
    • Mood changes
    • Sleep disturbance

  • In women of reproductive age, polycystic ovarian syndrome (PCOS) can cause DUB. Signs and symptoms include:
    • Obesity
    • Acne
    • Hypertension
    • Acanthosis nigricans

  • Anaemia is be present in 20-60% women with DUB. Signs of symptoms of anaemia may include:
    • Fatigue
    • Dizziness
    • Conjunctival pallor
    • Tachycardia

  • Systemic symptoms such as weight loss, fever, as well as dysmenorrhea are not typical and are more suggestive of other uterine pathology.

Investigations

Important to rule out structural uterine pathology and screen for blood test results indicating alternative diagnoses.

Blood tests
Essential tests:
  • Pregnancy test
    • Essential to rule out pregnancy as differential and before any treatment is given
  • Full blood count
    • May show anaemia
    • UTI causing bleeding may show high WCC
    • Abnormalities should prompt further tests such as Factor VIII and von Willebrand factor antigen.

If indicative symptoms:
  • Thyroid function tests
    • If clinical history suggestive of hypo- or hyperthyroidism
  • FSH and LH levels
    • Peri-menopausal women (typically aged 40-60) may experience irregular bleeding
    • Two levels at least 1 week apart are recommended
    • Elevated levels indicates patient is perimenopausal
  • Prolactin level
    • If clinical history suggests hyperprolactinaemia as a cause for anovulatory bleeding
  • Androgen levels
    • Can aid in the diagnosis of co-existent poly-cystic ovarian syndrome (PCOS), a strong risk factor for DUB

Imaging
A transvaginal ultrasound is the first-line investigation in DUB as it can delineate endometrial pathology such as polyps or fibroids which may be causing abnormal bleeding.
  • Furthermore, an endometrial biopsy can be done to rule out neoplasm if ultrasound findings indicate myometrium thickness >12mm, or 5-12mm with history of unopposed oestrogen exposure (e.g. poly-cystic ovarian syndrome)
  • Identification of intra-uterine pathology e.g. fibroids or endometrial cancer may require further imaging such as direct hysteroscopy or MRI.

Differential diagnosis

The International Federation of Gynaecology and Obstetrics (FIGO) introduced a classification system for abnormal uterine bleeding. DUB is not included in this classification, but is generally understood to be part of the ‘ovulatory dysfunction’ category. The other categories therefore provide good differentials for DUB.

  • Pregnancy related bleeding
    • Pregnancy should be excluded when departure from normal bleeding pattern occurs
    • Threatened or inevitable miscarriage, and ectopic pregnancy should be excluded if positive

  • Uterine fibroids (leiomyoma)
    • Fibroids can cause increased menstrual bleeding
    • Mass may be palpable on abdominal examination, confirmed on ultrasound imaging
    • May be managed medically or surgically

  • Iatrogenic uterine bleeding
    • Oral combined contraceptive pill or oral anticoagulants may cause irregular bleeding

  • Endometrial or cervical malignancy
    • Regional lymphadenopathy and systemic symptoms such as weight loss may be present
    • Screen for specific risk factors: obesity, family history, exogenous oestrogen use for endometrial cancer; HPV infection, smoking for cervical cancer
    • Biopsy and histological diagnosis

  • Clotting disorder
    • Family history important
    • May also report frequent bruising, epistaxis, bleeding from gums

  • Non-uterine bleeding
    • E.g. urethritis, lesions of the cervix or vulva
    • May be suggested by clinical history
    • UTI may present with systemic symptoms such as fever, malaise

Management

DUB is managed principally with progesterone therapy to regulate the chronic oestrogenic proliferation of the myometrium. Non-hormonal and surgical options are also available, depending on patient preference. Intra-uterine devices can often be inserted and managed in primary care. Further therapy, or surgery, requires input at a centre with a tertiary gynaecology service.

Hormonal management
The aim is to restore regular cyclical bleeding
  • Progestogens
    • Antagonise action of oestrogen
    • Intra-uterine device (IUD) e.g. Mirena most common option
    • Otherwise, norethisterone 5 mg orally three times daily on days 5-25 of cycle
    • Subdermal progestogen implant also available
  • Combined oestrogen and progestogen therapy
    • Oral combined contraceptive pill may help if progestogen therapy alone ineffective

Non-hormonal options
  • NSAIDS e.g. mefenamic acid or ibuprofen have anti-prostaglandin effects
  • Tranexamic acid (e.g. 1g PO TDS during menstruation) reduces rate of bleeding
  • Gonadotropin-releasing hormone analogues
    • Expert-guided treatment following referral to specialist centre
    • E.g. leuprorelin
    • Ovarian suppression therapy to cease oestrogen influence on proliferating endometrium.

Surgical options
  • Must be discussed fully with the patients taking in to account their desire for future fertility, risks and effect of current condition on their wellbeing.
  • Endometrial ablation
  • Hysterectomy - can be performed laparoscopically, trans-vaginal, or via laparotomy.