Anovulatory Abnormal Uterine Bleeding

Anovulatory abnormal uterine bleeding is irregular, unpredictable and often heavy or prolonged bleeding caused by failure of ovulation, with continued oestrogen stimulation of the endometrium without progesterone. It results from polycystic ovary syndrome, obesity, immaturity of the hypothalamic axis in adolescence, perimenopause, thyroid disease, hyperprolactinaemia and weight change. It matters because the thickened, unstable endometrium bleeds heavily, causing anaemia, and long exposure to unopposed oestrogen leads to hyperplasia and cancer.

• Risk factors: polycystic ovary syndrome, obesity, age under 20 or above 40 years, thyroid disease, hyperprolactinaemia, hypothalamic suppression, diabetes.
• Bleeding follows weeks to months of no period, then heavy loss.
• The endometrium may be thickened on ultrasound.

Women have long gaps without a period followed by heavy prolonged bleeding, or frequent irregular bleeding, without premenstrual symptoms. Examination may show hirsutism, obesity and acanthosis nigricans.

• Unpredictable cycle length, from 20 days to 3 months.
• Absence of cyclical breast tenderness and cramps.
• Differential diagnosis: polycystic ovary syndrome, thyroid disease, hyperprolactinaemia, perimenopause, premature ovarian insufficiency, endometrial hyperplasia or cancer, endometrial polyp, fibroids, miscarriage or ectopic pregnancy, bleeding disorder, ovarian tumour.
• Complications: severe anaemia, endometrial hyperplasia and cancer, infertility, hospital admission and transfusion, metabolic syndrome, anxiety.

The approach is to confirm anovulation, exclude pregnancy and assess the endometrium.

• Urine hCG; menstrual diary; weight, body mass index, blood pressure, hirsutism score.
• Full blood count; thyroid stimulating hormone, prolactin, follicle stimulating hormone, luteinising hormone, testosterone, sex hormone binding globulin; midluteal progesterone below 6 nmol/L confirms anovulation.
• Transvaginal ultrasound for ovarian morphology and endometrial thickness; fasting glucose and lipids.
• Endometrial sampling if age is 45 years or above, or for women with obesity, persistent bleeding or endometrial thickness above 12 mm.

The principle is to stop the bleeding with a progestogen, then to protect the endometrium with regular progestogen exposure and treat the cause.

• Supportive: weight loss of 5 to 10 percent; exercise; regular meals; stress management; iron rich diet; menstrual diary; counselling about the risk of hyperplasia if cycles remain absent.
• Pharmacological: to stop bleeding: norethisterone 5 mg oral 8-hourly for 10 days, with a withdrawal bleed expected within 3 days of stopping; tranexamic acid 1 g oral 8-hourly for 4 days; to regulate: medroxyprogesterone 10 mg oral once daily for 12 to 14 days every month, or combined oral contraceptive pill with ethinylestradiol 30 micrograms and levonorgestrel 150 micrograms oral once daily for 21 days then 7 days free, or levonorgestrel intrauterine system 52 mg for 5 years; metformin 500 mg oral once daily increased weekly to 500 mg 3 times daily (maximum 2000 mg daily); ferrous sulphate 200 mg oral 12-hourly for 3 months; for fertility: letrozole 2.5 mg oral once daily on days 3 to 7, increased by 2.5 mg each cycle to 7.5 mg; endometrial hyperplasia without atypia: levonorgestrel intrauterine system 52 mg for 6 months or more, or medroxyprogesterone 10 mg oral once daily for 12 to 14 days each month for 3 to 6 months.
• Procedures: endometrial sampling or hysteroscopy; dilatation and curettage for failed medical control in unstable bleeding; endometrial ablation after childbearing; hysterectomy for atypical hyperplasia.
• Special groups: adolescents with severe bleeding have a bleeding disorder screen and iron correction, with norethisterone or the combined pill; women who cannot use oestrogen (migraine with aura, hypertension, previous clot) use progestogen-only methods; women with endometrial hyperplasia with atypia need hysterectomy.
• Red flags: haemoglobin below 8 g/dL, syncope, endometrial thickness above 12 mm, bleeding after months of amenorrhoea that is very heavy, atypical hyperplasia, age above 45 years.
• Follow-up: review at 3 months with diary and haemoglobin; endometrial biopsy after 3 to 6 months of treatment for hyperplasia; yearly review of weight, glucose and lipids; fertility review if pregnancy is wanted.