Approach

Evaluation of women with abnormal uterine bleeding necessitates a medical history and physical exam, and imaging tests and studies as required.[23]

History

Menstrual history should include enquiry about:[24]

  • 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 which interferes with a woman’s physical, social, emotional, and/or material quality of life is termed "heavy menstrual bleeding".[25] Women may report passing blood clots or changing pads or tampons at least hourly.​

  • 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.[26][27]​​ Adenomyosis can cause pelvic pain, dysmenorrhea, dyspareunia, and subfertility.[9] Hirsutism and acne may indicate polycystic ovary syndrome; weight gain, cold intolerance, dry hair and skin, and fatigue may indicate hypothyroidism; galactorrhea suggests hyperprolactinemia.

A full gynecologic and obstetric history should be taken, including any previous episodes of AUB and any treatment received, age at menarche, parity, and use of an intrauterine device. Early menarche, infertility, and nulliparity are risk factors for endometrial cancer.

A structured history to screen for a coagulation disorder is recommended.[18] The screen is positive if there is:[28]

  • Heavy menstrual bleeding since menarche, or

  • One of: postpartum hemorrhage, surgery-related bleeding, or bleeding associated with dental work, or

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

Drug history should include enquiry about use of:

  • anticoagulants, tamoxifen or hormonal therapies.[18][23]​​

  • antidepressants (e.g., SSRIs and tricyclic antidepressants) or phenothiazines.[23]​​

  • recently started medications which may affect the pharmacodynamics of the patient’s existing medication.

    • For example, strong inhibitors of P- glycoprotein or CYP3A4 (or both) increase circulating levels of direct-acting oral anticoagulants.[17][16]​​

  • herbal supplements (e.g., ginseng, ginkgo, and motherwort).[29][30] ​

    • may cause menstrual irregularities by altering estrogen levels or coagulation parameters.

Physical examination

Pelvic examination, including speculum and bimanual examination, is a key part of the evaluation.[23][31]​​​ All potential bleeding sites should be examined, including the urethra, perineum, and anus. Leiomyomata may be palpable as firm masses, or cause generalized 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 hemodynamic assessment, including pulse rate and orthostatic blood pressure.[20]

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

Laboratory evaluation

Initial investigations include urine or serum beta human chorionic gonadotropin to exclude pregnancy, and a complete blood count (CBC) to detect anemia.[20][23]​​​​[24][25]​ Routine testing for female hormones or serum ferritin in women with heavy menstrual bleeding is not recommended.[25]​​​​

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.[25]

  • Serum prolactin should be measured if hyperprolactinemia is suspected.

  • In women with suspected polycystic ovary syndrome (PCOS):

    • 17-hydroxyprogesterone should be measured to rule out nonclassical congenital adrenal hyperplasia.[32]

    • If hirsutism is absent, serum total and free testosterone may be measured to evaluate for hyper-androgenism. Androstenedione levels may occasionally be helpful if other androgens are normal; checking dehydroepiandrosterone sulfate (DHEAS) is of little value.[33][34]​​

    • Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) can be measured to calculate the LH/FSH ratio. A ratio >3 suggests PCOS, but is helpful only if positive, and is not diagnostic.

  • If the clinician is uncertain whether the patient is ovulating, serum progesterone can be measured in the estimated mid-luteal phase.[1]

  • ​If there is a positive screening history for a coagulation disorder, imaging testing is indicated.[25] Initial tests should include a CBC with platelets, prothrombin time, and partial thromboplastin time (fibrinogen or thrombin time are optional).[23]​​​

  • If a coagulation disorder is suspected further evaluation, including hematology consult and specific testing for von Willebrand disease is recommended.[1][35]​​​ ​

Imaging

Imaging is indicated when there is suspicion of underlying structural lesions, such as uterine leiomyomata, adenomyosis, malignancy, or polyps.[1]

Ultrasound is the preferred imaging modality.[23][25]​​​​

The American College of Radiologists recommends a combined transabdominal and transvaginal approach for pelvic ultrasound.[36]

Transvaginal ultrasound provides a better view of individual pelvic organs and internal architecture of any pelvic masses, compared with transabdominal ultrasound.[37][38]​ It is particularly helpful in the presence of obesity, bowel gas, and incomplete bladder filling.[38]

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.[39]

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 tumor is present.[36]

Color and spectral Doppler are used to distinguish fluid from vascular soft tissue, and to help distinguish between normal endometrium and highly vascular polyps or tumors.[36]

Sonohysterography can be used to further characterize an endometrial abnormality detected on transvaginal ultrasound.[36] 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 fertilized egg in the uterine cavity and the endometrium often has a polypoid outline in this phase.[40]

Magnetic resonance imaging (MRI)

May be used if transvaginal ultrasound is declined or inappropriate.[1][23]​​[25]​​​ MRI can distinguish between leiomyomata and adenomyosis.

Endometrial biopsy

Endometrial biopsy is not required for all premenopausal patients.[41]

Women ages ≥45 years with abnormal uterine bleeding should have an endometrial biopsy.[1]​​​​[18]​​[23]​​​​ Endometrial biopsy should also be considered for younger women with a history of unopposed estrogen exposure, and women with persistent unexplained or unsuccessfully treated AUB.[1]​​

In the UK, guidelines recommend that clinicians consider endometrial biopsy at the time of hysteroscopy for women at high risk of endometrial pathology, such as:[25]

  • 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.[25] Blind endometrial biopsy is not recommended for these patients.[25]

Hysteroscopy

Hysteroscopy permits direct visualization 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.[25] 

Hysteroscopy may be offered first if the history (persistent intermenstrual bleeding or risk factors for endometrial pathology) suggests submucosal fibroids, polyps, or endometrial pathology.[18][23]​​[25]​​

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