Abnormal Uterine Bleeding

Abnormal uterine bleeding (AUB) is bleeding from the uterine corpus that is abnormal in regularity, volume, frequency or duration, outside pregnancy. Normal menstruation: cycle 24 to 38 days, duration up to 8 days, cycle-to-cycle variation up to 7 to 9 days, blood loss up to 80 mL per cycle.

Heavy menstrual bleeding (HMB) is excessive loss that interferes with physical, social, emotional or material quality of life, and is the main complaint in about 30% of women of reproductive age. Intermenstrual bleeding, postcoital bleeding and postmenopausal bleeding need separate attention because of cancer risk.

The causes are classified by the PALM-COEIN scheme:

• Structural (PALM): Polyp, Adenomyosis, Leiomyoma (submucosal and other), Malignancy and hyperplasia
• Non-structural (COEIN): Coagulopathy, Ovulatory dysfunction, Endometrial disorders, Iatrogenic, Not otherwise classified

Common causes by age:

• Adolescence: anovulation (immature hypothalamic-pituitary-ovarian axis) and bleeding disorders (von Willebrand disease in about 13 to 20% of adolescents with HMB, platelet function defects)
• Reproductive years: ovulatory dysfunction (PCOS, thyroid disease, hyperprolactinaemia, stress, weight change), polyps, fibroids, adenomyosis, coagulopathy, endometrial causes, contraceptive breakthrough bleeding, and pregnancy complications
• Perimenopause: anovulation, fibroids, polyps, hyperplasia, endometrial cancer
• Postmenopause: atrophy (60 to 80%), polyps, hyperplasia, endometrial cancer (5 to 10%), hormone therapy

Pregnancy related causes (ectopic, miscarriage, molar pregnancy) must be excluded in every woman of reproductive age. Anticoagulants, tamoxifen, copper IUD and antipsychotics (via prolactin) are other causes.

• History: bleeding pattern (last menstrual period, cycle length, duration, pads or tampons used, clots larger than 2.5 cm, flooding, nocturnal bleeding, intermenstrual or postcoital bleeding), associated pain (dysmenorrhoea suggests adenomyosis or endometriosis), pelvic pressure or urinary symptoms (fibroids), anaemia symptoms (fatigue, dyspnoea, pica, palpitations), medication (anticoagulants, hormones, tamoxifen), personal and family history of bleeding disorders (heavy bleeding since menarche, bruising, epistaxis, dental or surgical bleeding, postpartum haemorrhage), cervical screening history, thyroid symptoms, PCOS features (hirsutism, acne, obesity), and galactorrhoea.
• Examination: vital signs, pallor, thyroid, BMI, hirsutism, abdominal mass, speculum and bimanual examination (cervical lesions, polyps, bleeding source, uterine size and mobility).
• Acute heavy bleeding causes haemodynamic instability and needs resuscitation.

Initial tests:

• Urine or serum beta-hCG in every woman of reproductive age
• Full blood count and ferritin (ferritin below 30 micrograms/L indicates iron deficiency)
• Thyroid function; prolactin if oligomenorrhoea or galactorrhoea; androgens and LH/FSH if PCOS suspected
• Coagulation screen and von Willebrand testing (antigen, ristocetin cofactor activity, factor VIII) in adolescents and in women with a suggestive history; repeat if borderline because oestrogen and stress alter levels
• Swabs for chlamydia and gonorrhoea when indicated; cervical screening

Imaging: transvaginal ultrasound is first line (endometrial thickness, polyps, fibroids, adenomyosis with heterogeneous myometrium, globular uterus and subendometrial cysts). Saline infusion sonography or hysteroscopy defines intracavitary lesions. MRI is used for adenomyosis and fibroid mapping.

Endometrial sampling (outpatient pipelle biopsy) is indicated at age 45 or over with persistent AUB, in younger women with risk factors for hyperplasia or cancer (obesity, PCOS, chronic anovulation, tamoxifen, Lynch syndrome), after failed medical therapy, and for persistent intermenstrual bleeding. In postmenopausal bleeding, sample when endometrial thickness is 4 to 5 mm or more, or when bleeding recurs.

Acute heavy bleeding. Resuscitate with IV access, fluids and blood products. Options:

• Tranexamic acid 1 g IV every 8 hours, or 1 to 1.3 g orally every 8 hours
• Conjugated oestrogens 25 mg IV every 4 to 6 hours for up to 24 hours (avoid with thrombosis risk)
• Combined oral contraceptive containing 30 to 35 micrograms ethinylestradiol, one pill three times daily for 3 to 7 days, then taper to once daily
• Norethisterone 5 mg three times daily for 10 days, or medroxyprogesterone acetate 20 mg three times daily for 7 days then daily for 21 days
• Intrauterine balloon tamponade (Foley with 30 to 60 mL), curettage, hysteroscopic resection, uterine artery embolisation or hysterectomy if medical therapy fails
• Iron replacement and transfusion as needed; correct any coagulopathy

Chronic heavy menstrual bleeding without a structural cause. In order of effectiveness:

1. Levonorgestrel intrauterine system (52 mg, releasing about 20 micrograms/day): reduces menstrual blood loss by 70 to 95%; first choice, especially when contraception is also wanted; effective for at least 5 years
2. Tranexamic acid 1 g orally three to four times daily during the first 4 days of bleeding (maximum 4 g/day): reduces loss by 30 to 55%
3. NSAIDs: mefenamic acid 500 mg three times daily during bleeding, or naproxen 500 mg then 250 mg every 6 to 8 hours: reduces loss by 20 to 35% and relieves dysmenorrhoea
4. Combined oral contraceptive (reduces loss by 35 to 50%), including an oestradiol valerate/dienogest quadriphasic pill
5. Cyclical oral progestogen: norethisterone 5 mg three times daily from day 5 to day 26 (less effective); medroxyprogesterone 10 mg for 10 to 14 days per month in anovulatory bleeding
6. Etonogestrel implant or depot medroxyprogesterone (often causes amenorrhoea; long term use reduces bone density)
7. GnRH antagonist with add back therapy (elagolix 300 mg twice daily with oestradiol/norethindrone, or relugolix 40 mg with oestradiol 1 mg and norethindrone 0.5 mg daily) for fibroid related bleeding, up to 24 months
8. Desmopressin (intranasal 300 micrograms or IV 0.3 micrograms/kg) for von Willebrand disease and platelet function disorders

Structural causes. Polyps: hysteroscopic polypectomy. Submucosal fibroids: hysteroscopic myomectomy. Large or multiple fibroids: GnRH antagonist, myomectomy, uterine artery embolisation, MRI-guided focused ultrasound or hysterectomy. Adenomyosis: LNG-IUS, hormonal therapy, embolisation or hysterectomy. Hyperplasia without atypia: LNG-IUS or oral progestogen with repeat biopsy at 6 months. Atypical hyperplasia or cancer: hysterectomy, or specialist fertility sparing progestin therapy.

Endometrial ablation or resection. For women with completed families and failed medical treatment: reduces bleeding substantially, with amenorrhoea in 30 to 50%. It needs reliable contraception, and pathology must be excluded first.

Hysterectomy. Definitive treatment when other measures fail or by the woman's choice.

Iron deficiency. Ferrous sulfate 200 mg (65 mg elemental iron) once daily or on alternate days; IV ferric carboxymaltose 15 mg/kg up to 1,000 mg, repeated after 7 days if needed, for intolerance or poor response.