Approach

History

Menstrual history should include enquiry about:[21]

  • Frequency (≥24 and ≤38 days is considered normal)

  • Duration (≤8 days is considered normal)

  • Regularity (±4 days variation in cycle length is considered normal). Irregular cycles may indicate ovulatory dysfunction.

  • Volume, excessive bleeding that interferes with a woman’s physical, social, emotional, and/or material quality of life, is termed ‘heavy menstrual bleeding’.[22] Women may report passing blood clots or changing pads or tampons at least hourly.[5]

  • Presence of any intermenstrual bleeding.

Abnormal uterine bleeding (AUB) is considered chronic if symptoms have been present for >6 months.

Symptoms associated with AUB may help to narrow down the differential diagnosis. Leiomyomata may compress surrounding pelvic structures, causing urinary frequency, urgency or retention, bowel dysfunction or constipation, dyspareunia, low back pain, and pelvic pressure.[5] Adenomyosis can cause pelvic pain, dysmenorrhoea, dyspareunia, and subfertility.[23] Hirsutism and acne may indicate polycystic ovary syndrome; weight gain, cold intolerance, dry hair and skin, and fatigue may indicate hypothyroidism; galactorrhoea suggests hyperprolactinaemia.

A full gynecological and obstetrical history should be taken, including any previous episodes of AUB and any treatment received, age at menarche, and parity. Early menarche, infertility, and nulliparity are risk factors for endometrial cancer.[10]

A structured history to screen for a coagulation disorder is recommended.[17] The screen is positive if there is:[24]

  • Heavy menstrual bleeding since menarche, or

  • One of: postnatal haemorrhage, surgery-related bleeding, or bleeding associated with dental work, or

  • Two of: bruising greater than 5 centimetres once or twice per month, epistaxis once or twice per month, frequent gum bleeding, and family history of bleeding symptoms.

Medication

Many drugs can cause AUB. Possible iatrogenic causes include use of anticoagulants, tamoxifen, hormonal therapies, and copper intrauterine devices.[17] Tricyclic antidepressants and phenothiazines may cause AUB by disrupting dopamine metabolism. Herbal supplements (e.g., ginseng, ginkgo, and soy) may cause menstrual irregularities by altering oestrogen levels or coagulation parameters.[25][26]

Physical examination

Pelvic examination, including speculum and bi-manual examination, is a key part of the evaluation.[27] All potential bleeding sites should be examined, including the urethra, perineum, and anus.[5] Leiomyomata may be palpable as firm masses, or cause generalised uterine enlargement. A tender uterus may indicate leiomyomata or adenomyosis. Polyps may be visible at the cervical os. 

Physical examination of patients with heavy menstrual bleeding should include haemodynamic assessment, including pulse rate and orthostatic blood pressure.[28]

Obesity, hirsutism, acne, hypertension, scalp hair loss, oily skin, and acanthosis nigricans may be present in polycystic ovary syndrome.

Laboratory evaluation

Initial investigations should include urine or serum beta human chorionic gonadotropin to exclude pregnancy, and a full blood count (FBC) to detect anaemia.[28][21][22]

Subsequent blood tests

Depending on the suspected cause of AUB, further blood tests might be required.

  • Thyroid-stimulating hormone screening is reasonable if there are signs or symptoms of hypothyroidism.[22]

  • 17-hydroxyprogesterone should be measured to rule out non-classical congenital adrenal hyperplasia in women with suspected polycystic ovary syndrome (PCOS). Serum total and free testosterone and dehydroepiandrosterone sulfate may also be measured if an abnormal result would confirm the diagnosis.[29] Serum luteinising hormone (LH) and follicle stimulating hormone (FSH) can be measured to calculate the LH/FSH ratio. A ratio >3 suggests PCOS.

  • Serum prolactin should be measured if hyperprolactinaemia is suspected.

  • If the clinician is uncertain whether the patient is ovulating, serum progesterone can be measured in the estimated mid-luteal phase.[4]

  • Prothrombin time/activated partial thromboplastin time may indicate coagulopathy, but is rarely sufficient to rule-in most bleeding disorders. A haematologist should direct further testing if a coagulation disorder is suspected.[4]

  • Specific testing for von Willebrand disease (vWd) includes von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCoF), and factor VIII activity.[8] Patients with a positive screening result from a structured bleeding history should be considered for further evaluation, including haematology consultation and specific testing for von Willebrand disease.[8]

UK guidance recommends considering testing for coagulation disorders in women who have had heavy menstrual bleeding since starting menstruation as well as having a personal or family history suggesting a coagulation disorder.[22]

Routine testing for female hormones or serum ferritin in women with heavy menstrual bleeding is not recommended.[22]

Imaging

Imaging is indicated when there is suspicion of underlying structural lesions, such as uterine leiomyomata, adenomyosis, malignancy, or polyps.[4]

The National Institute for Health and Care Excellence (NICE) recommends that findings from the history and examination are taken into account when deciding whether to offer hysteroscopy or ultrasound as the first-line investigation.[22] Ultrasound is offered first if adenomyosis is suspected, if the uterus is palpable abdominally, if history or examination suggest a pelvic mass, or if examination is inconclusive or difficult (e.g., in women who are obese).[22]

The American College of Radiologists recommends a combined transabdominal and transvaginal approach for pelvic ultrasound.[30]

Transvaginal ultrasound provides a better view of individual pelvic organs and internal architecture of any pelvic masses, compared with transabdominal ultrasound.[31][32] It is particularly helpful in the presence of obesity, bowel gas, and incomplete bladder filling.[32]

Transvaginal ultrasound is highly sensitive for diagnosing submucosal fibroids, although it may not always be possible to distinguish between submucosal fibroids and endometrial polyps, and small lesions may not be detected.[33]

Transabdominal ultrasound provides an overview of pelvic anatomy and its wider field of view is particularly helpful when the uterus is significantly enlarged, or a uterine tumour is present.[30]

Colour and spectral Doppler are used to distinguish fluid from vascular soft tissue, and to help distinguish between normal endometrium and highly vascular polyps or tumours.[30]

Magnetic resonance imaging (MRI)

May be used if transvaginal ultrasound is declined or inappropriate.[4]

MRI can distinguish between leiomyomata and adenomyosis. Saline contrast sonohysterography can be used to further characterise an endometrial abnormality detected on transvaginal ultrasound.[34] Sterile saline is injected transcervically as an endometrial contrast agent. This procedure should not be performed in the secretory phase of the menstrual cycle, because there is a possibility that there is a fertilised egg in the uterine cavity, and the endometrium often has a polypoid outline in this phase.[35]

Endometrial biopsy

Endometrial biopsy is not required for all pre-menopausal patients.[36]

Women ≥45 years should have an endometrial biopsy.[4][10][17] Endometrial biopsy should also be considered for younger women with a history of unopposed oestrogen exposure, and women with persistent unexplained or unsuccessfully treated AUB.[4][10]

The NICE guidelines recommend that clinicians consider endometrial biopsy at the time of hysteroscopy for women at high risk of endometrial pathology, such as:[22]

  • Women with persistent intermenstrual or irregular bleeding

  • Women with infrequent heavy bleeding who are obese

  • Women with infrequent heavy bleeding who have PCOS

  • Women taking tamoxifen

  • Women for whom treatment for heavy menstrual bleeding has not been successful.

Endometrial biopsy can be obtained using suction catheters for endometrial sampling, or through cervical dilatation and endometrial curettage at the time of hysteroscopy.

For women with heavy menstrual bleeding, an endometrial sample should only be obtained in the context of diagnostic hysteroscopy.[22] Blind endometrial biopsy is not recommended for these patients.[22]

Hysteroscopy

Hysteroscopy permits direct visualisation of the endometrial cavity and acquisition of endometrial biopsies.

UK guidelines recommend that findings from the history and examination are taken into account when deciding whether to offer hysteroscopy or ultrasound as the first-line investigation.[22]

Hysteroscopy may be offered first if the history suggests submucosal fibroids, polyps, or endometrial pathology because the patient has symptoms such as persistent intermenstrual bleeding or risk factors for endometrial pathology.[17][22]

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