How should I treat a reproductive‑age woman with excessive or irregular menstrual bleeding due to unopposed estrogen or a dysfunctional endometrium?

Treatment of Excessive or Irregular Menstrual Bleeding Due to Unopposed Estrogen or Dysfunctional Endometrium

For reproductive-age women with irregular or excessive menstrual bleeding from anovulation, use cyclic oral progesterone 400 mg daily at bedtime for 10-14 days per month to induce regular withdrawal bleeding, or consider a levonorgestrel IUD (20 μg/day) for superior bleeding reduction (71-95%) with minimal systemic effects. 1, 2

Initial Diagnostic Considerations

Before initiating progesterone therapy, you must:

• Exclude pregnancy with a pregnancy test 1
• Rule out structural causes including polyps, fibroids, adenomyosis, or malignancy through appropriate imaging (transvaginal ultrasound or saline infusion sonohysterography) 3, 4
• Screen for coagulopathies (particularly von Willebrand disease), thyroid dysfunction, hyperprolactinemia, and uncontrolled diabetes in women with persistent irregular bleeding 4
• Perform endometrial biopsy in women ≥35 years with recurrent anovulation, women <35 years with risk factors for endometrial cancer (obesity, PCOS, prolonged unopposed estrogen), or those with bleeding unresponsive to initial medical therapy 4

Treatment Algorithm

First-Line Medical Management

Cyclic Oral Progesterone:

• Dosing: 400 mg daily at bedtime for 10-14 days per month 2
• Expected outcome: 87% reduction in bleeding 1
• Mechanism: Induces organized endometrial shedding and regular withdrawal bleeding 5, 4
• Important administration detail: Take at bedtime with water while standing, as drowsiness, dizziness, blurred vision, and difficulty walking can occur 2
• Contraindication: Peanut allergy (progesterone capsules contain peanut oil) 2

Alternative: Levonorgestrel IUD:

• Dosing: 20 μg/day intrauterine delivery 1
• Expected outcome: 71-95% reduction in menstrual blood loss 1
• Advantages: Minimal systemic progesterone absorption, effective for 5 years, comparable efficacy to endometrial ablation 1
• Particularly suitable for women with hypertension or cardiovascular risk factors 1

Special Population: Hypertensive Women

Progestin-only methods are first-line and safe 1

• Combined hormonal contraceptives are absolutely contraindicated (6-9 fold increased MI risk, 8-15 fold increased stroke risk) 1
• Progestin-only methods show no increased cardiovascular risk 1
• Monitor blood pressure every 6 months while on any hormonal therapy 1

Management of Irregular Bleeding During Treatment

If irregular bleeding persists beyond 3 months on progesterone therapy:

• NSAIDs for 5-7 days during bleeding episodes (e.g., ibuprofen, mefenamic acid) 3, 6
• Low-dose combined oral contraceptives for 10-20 days (if no contraindications) 3, 6
• Reassess for underlying gynecological problems: medication interactions, sexually transmitted infections, pregnancy, or new pathologic uterine conditions 3, 6

Important counseling point: Enhanced counseling about expected bleeding patterns and reassurance that irregularities are generally not harmful significantly reduces discontinuation rates 3, 6

Amenorrhea Management

• Amenorrhea occurs in approximately 22% of women on progestin-only therapy and requires no medical treatment—reassurance only 6
• If regular bleeding pattern abruptly changes to amenorrhea, rule out pregnancy 3

Duration and Monitoring

• Continue treatment for 3-6 months, then reassess 1
• Blood pressure monitoring every 6 months (even with progestin-only methods) 1
• Annual pelvic exam, breast exam, and mammogram unless more frequent surveillance is indicated by family history or prior abnormal findings 2

Critical Contraindications to Exclude

Before prescribing progesterone, ensure the patient does NOT have:

• Undiagnosed abnormal genital bleeding 2
• Known or suspected breast cancer 2
• Active or history of venous thromboembolism 2
• Known liver dysfunction 2
• Pregnancy 2
• Peanut allergy (for oral progesterone capsules) 2

When Medical Management Fails

If bleeding persists despite 3-6 months of appropriate medical therapy:

• Re-evaluate for structural causes with imaging or hysteroscopy 4
• Consider endometrial biopsy if not previously performed 4
• Surgical options include polypectomy, fibroidectomy, uterine artery embolization, or endometrial ablation for identified structural lesions 4
• Hysterectomy remains the most definitive treatment for refractory cases 4

Common Pitfalls to Avoid

• Do not use combined estrogen-progestin therapy in hypertensive women (significantly increased cardiovascular risk) 1
• Do not prescribe NSAIs or tranexamic acid to patients with cardiovascular disease history (thrombotic risk) 1
• Do not attribute all bleeding to anovulation without ruling out structural causes, particularly in women ≥35 years 4
• Do not forget to counsel about expected side effects (headaches, breast pain, irregular spotting, nausea, fluid retention) to improve adherence 2

Evidence Quality Note

The evidence base for progesterone treatment in anovulatory bleeding is surprisingly limited, with Cochrane reviews finding no randomized trials comparing progestogens to placebo or combination therapy 7, 8. However, guideline consensus from the American College of Obstetricians and Gynecologists, Centers for Disease Control and Prevention, and American Heart Association strongly supports cyclic progesterone or levonorgestrel IUD as first-line therapy based on physiologic rationale and observational data 1, 6.