Aetiology

The International Federation of Gynecology and Obstetrics (FIGO) classification system can be used to identify the nine main causes of abnormal uterine bleeding (AUB), which are arranged according to the acronym PALM-COEIN:[1] 

  • Polyp

  • Adenomyosis

  • Leiomyoma

  • Malignancy and hyperplasia

  • Coagulopathy

  • Ovulatory dysfunction

  • Endometrial

  • Iatrogenic

  • Not otherwise classified.

AUB may be due to more than one of these causes.

Polyp

Endometrial and endocervical polyps are focal proliferations of glandular, vascular, fibromuscular, and connective tissue.[1] Many polyps are asymptomatic and do not cause AUB; however, they may cause intermenstrual bleeding, menorrhagia, or postmenopausal bleeding.[3]​ Prevalence of endometrial polyps in the general adult female population is 10% to 15%. Prevalence in women with AUB is 20% to 30%.[4] Incidence increases with age and the vast majority of symptomatic polyps are benign.[5][6]​​

Adenomyosis

Adenomyosis is the presence of endometrial tissue within the myometrium. Estimates of prevalence are very variable and further research is needed into the association between adenomyosis and AUB.[1] Symptoms typically include prolonged, heavy, and/or painful menstrual bleeding, although many women with radiological evidence of adenomyosis are asymptomatic.[7][8][9]

Leiomyomata (uterine fibroids)

Leiomyomata, also known as uterine fibroids, are common benign tumours of uterine smooth muscle tissue. Prevalence increases with age until menopause. Up to 80% of women have leiomyomata by age 50 years, although many are asymptomatic.[10]​ Leiomyomata may be classified according to location as subserosal, intramural (with the myometrium), or submucosal (just below the endometrium). Symptoms are influenced by the number, size, and location of the leiomyomata. Heavy menstrual bleeding is one of the most common symptom.[11]​​

Malignancy and hyperplasia

Endometrial cancer and atypical hyperplasia are relatively uncommon causes of abnormal uterine bleeding because most cases present after menopause.[1]​​ Unopposed oestrogen exposures increase risk. These include unopposed oestrogen therapy, tamoxifen therapy, early menarche, nulliparity, and infertility or failure to ovulate. Other risk factors include age >50 years, family history of endometrial cancer or hereditary non-polyposis colon cancer, smoking, and obesity. 

Rarely, ovarian cancer may present with AUB. Persistent intermenstrual bleeding may indicate cervical cancer.[12]

Coagulopathy

Systemic disorders of haemostasis may be associated with abnormal uterine bleeding, although the extent of their contribution to symptoms is unclear.[1] The prevalence of von Willebrand disease is increased in women with heavy menstrual bleeding, compared with the general population.[13] Symptoms of easy bruising, bleeding after dental extractions, and postnatal bleeding may indicate von Willebrand disease.[13]

Ovulatory dysfunction

Causes of ovulatory dysfunction include endocrine disorders (such as polycystic ovary syndrome, hypothyroidism, and hyperprolactinaemia), weight loss, anorexia nervosa, obesity, mental stress, extreme exercise, and medications. Otherwise unexplained ovulatory disorders occur at the extremes of reproductive age (adolescence and menopause).[1] Absence of cyclical progesterone secretion from the corpus luteum can cause changes to the regularity, frequency, volume, and duration of menstruation. Symptoms range from amenorrhoea and light, infrequent uterine bleeding to frequent, very heavy uterine bleeding.[1] See Assessment of primary amenorrhoea and Assessment of secondary amenorrhoea.

Endometrial

Refers to endometrial dysfunction that cannot be detected using imaging or histopathology. The timing of menstruation is predictable and cyclical, suggesting normal ovulatory function, and there is no evidence of structural causes such as polyps, adenomyosis, leiomyomata, and malignancy.[1] Consequently, endometrial dysfunction is usually a diagnosis of exclusion. Alterations in endometrial production of vasoactive substances contribute to heavy menstrual bleeding.[14][15]

Iatrogenic

Iatrogenic causes include unscheduled ‘breakthrough’ bleeding that occurs with gonadal hormone use, anticoagulant drugs, tamoxifen, and drugs that interfere with dopamine metabolism (e.g., tricyclic antidepressants, phenothiazines).[1][16]​​ Missed, delayed, or erratic use of contraception may cause an episode of AUB.[1] It is important to ask about recently started medicines, which may affect the pharmacodynamics of the patient’s existing medicine. For example, strong inhibitors of P- glycoprotein or CYP3A4 (or both) increase circulating levels of direct-acting oral anticoagulants, resulting in AUB.[16][17]​​

Not otherwise classified

This category contains conditions that are rare, poorly defined, do not easily fit within the other categories, or whose contribution to AUB requires further research. Examples include chronic endometritis, arteriovenous malformations, and myometrial hypertrophy.[1]

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