What is the recommended management for abnormal uterine bleeding due to anovulation (AUB-A)?

Management of Abnormal Uterine Bleeding Due to Anovulation (AUB-A)

Combined oral contraceptives or cyclic progestins are first-line medical therapy for anovulatory abnormal uterine bleeding, with the levonorgestrel-releasing intrauterine system offering the highest efficacy (71-95% reduction in menstrual blood loss) when hormonal contraception is acceptable. 1, 2

Initial Diagnostic Requirements Before Treatment

Before initiating therapy for suspected AUB-A, you must exclude:

• Pregnancy in all reproductive-age women using β-hCG testing 1
• Endocrine causes by measuring thyroid-stimulating hormone and prolactin levels, as hyperprolactinemia and thyroid dysfunction are common reversible causes of anovulation 1
• Structural pathology using combined transabdominal and transvaginal ultrasound with Doppler as first-line imaging 1
• Endometrial hyperplasia or malignancy through endometrial biopsy in high-risk patients (see below) 1, 3

Mandatory Endometrial Sampling Criteria

Perform endometrial biopsy if the patient has any of these risk factors, even if younger than 45 years:

• Age >45 years 1
• Obesity combined with diabetes and chronic anovulation 1
• Unopposed estrogen exposure 1
• Tamoxifen use 1
• Lynch syndrome 1
• Failed medical therapy 1

The combination of obesity, diabetes, and chronic anovulation markedly increases endometrial cancer risk due to peripheral aromatization of androgens to estrogen, creating persistent unopposed estrogen stimulation. 1

First-Line Medical Management Algorithm

Option 1: Combined Oral Contraceptives (COCs)

• Preferred for most patients with anovulatory DUB who also need contraception 1, 3
• Provide cycle regulation and reduce bleeding volume 1
• Can be combined with NSAIDs for additional bleeding reduction 2
• Contraindicated in patients with cardiovascular disease, history of spontaneous coronary artery dissection, or thrombotic risk 2

Option 2: Cyclic Progestins

• Administer medroxyprogesterone acetate orally for 21 days per month 2, 3
• Reduces menstrual blood loss by approximately 87% 2
• Appropriate when estrogen is contraindicated (cardiovascular disease, migraine with aura, thrombophilia) 1
• Particularly effective for women with heavy cyclic bleeding related to anovulation 2

Option 3: Levonorgestrel-Releasing Intrauterine System (LNG-IUS)

• Most effective medical treatment available, reducing menstrual blood loss by 71-95% 1, 2
• Efficacy comparable to endometrial ablation 1, 2
• Preferred option for patients with cardiovascular disease due to minimal systemic absorption 2
• Delivers 20 µg/day of levonorgestrel with primarily local endometrial effect 2
• Highly effective for adolescents with anovulatory bleeding, though may cause irregular bleeding patterns initially 1

Special Population Considerations

Adolescents

• Medroxyprogesterone acetate 10 days per month for ≥3 months with close monitoring 4
• Progestin-only contraception including LNG-IUS is highly effective despite potential irregular bleeding 1
• Anovulation is physiologic in the first 2-3 post-menarchal years due to hypothalamic-pituitary-ovarian axis immaturity 5

Perimenopausal Women

• Higher risk for endometrial hyperplasia/cancer requires lower threshold for endometrial sampling 1
• Cyclic progestin or low-dose COCs (if nonsmoker without vascular disease) 4
• May use cyclic conjugated equine estrogens for 25 days with medroxyprogesterone acetate days 18-25 4

Patients with Cardiovascular Disease

• Avoid NSAIDs and tranexamic acid due to MI and thrombosis risk 2, 6
• LNG-IUS is the preferred option because systemic hormonal therapy is relatively contraindicated 2
• Careful clinical judgment required before prescribing any systemic hormonal therapy 2

Non-Hormonal Alternatives

When hormonal therapy is contraindicated or declined:

• Tranexamic acid reduces bleeding by 20-60% but should be avoided in cardiovascular disease 2, 6
• NSAIDs reduce bleeding by 20-50%, most effective for ovulatory menorrhagia rather than anovulatory bleeding 1, 3

Critical Management Pitfalls

• Do not prescribe progestogen therapy without assessing contraceptive needs, as ovulation may still occur in up to 20% of patients despite treatment 2
• If bleeding does not improve during progestogen therapy, systematically investigate for alternative etiologies rather than escalating doses 2
• Do not rely on endometrial biopsy alone to rule out focal lesions; saline infusion sonohysterography has 96-100% sensitivity for polyps and leiomyomas 1
• Exclude coagulopathy (especially von Willebrand disease, present in ~1% of the population) in adolescents with heavy bleeding from menarche 4

When Medical Management Fails

If bleeding persists despite appropriate medical therapy:

• Perform hysteroscopy to diagnose focal lesions potentially missed by endometrial sampling 2
• Consider endometrial ablation as a uterus-sparing option for completed childbearing 1
• Hysterectomy provides definitive resolution and significantly better health-related quality of life compared to other therapies, appropriate when medical management fails or is contraindicated 1, 2