What is the first‑line treatment for abnormal uterine bleeding in a reproductive‑aged woman without contraindications to estrogen?

Combined Hormonal Contraceptives for Abnormal Uterine Bleeding

Combined hormonal contraceptives (CHCs) are an effective first-line treatment for abnormal uterine bleeding in reproductive-aged women without estrogen contraindications, particularly when ovulatory dysfunction is the cause, though the levonorgestrel-releasing IUD demonstrates superior efficacy with 71-95% reduction in menstrual blood loss. 1

Treatment Hierarchy for Reproductive-Aged Women

Most Effective First-Line Option

• The levonorgestrel-releasing intrauterine device (LNG-IUD) is recommended as the most effective first-line medical treatment, reducing menstrual blood loss by 71-95% with efficacy comparable to endometrial ablation. 1, 2
• The LNG-IUD is strongly recommended as the initial option for patients who wish to preserve the uterus. 2

Combined Hormonal Contraceptives as First-Line Alternative

• CHCs containing 30-35 µg ethinyl estradiol are recommended as first-line therapy for anovulatory dysfunctional uterine bleeding when pregnancy prevention is desired, as they regulate the menstrual cycle and provide effective contraception. 2
• CHCs are particularly effective for ovulatory dysfunction bleeding and reduce menstrual blood loss by 40-50%. 1, 3
• Adding an NSAID to the CHC regimen can further decrease menstrual blood loss when needed. 1, 2

Other First-Line Options

• Oral progestins administered for 21 days per month reduce menstrual blood loss and are effective for women with cyclic heavy bleeding related to the menstrual cycle. 1
• Tranexamic acid provides a non-hormonal reduction in blood loss of 20-60% and is useful when hormonal therapy is contraindicated. 2

Management Algorithm for CHC Use

Initial CHC Therapy

• Prescribe a combined oral contraceptive containing 30-35 µg ethinyl estradiol for women with anovulatory bleeding who need contraception. 2
• Counsel patients that bleeding is common during the first three months of OCP use; reassurance is adequate during this time period. 4

If Bleeding Persists Beyond 3 Months on CHC

• Add tranexamic acid to the combined oral contraceptive regimen if bleeding persists on COC alone. 2
• Alternatively, supplement with estrogen and/or an NSAID. 4
• Consider changing to an OCP with higher estrogen content or a different progestin formulation. 4

If Combination Therapy Fails

• Discontinue the COC and proceed with LNG-IUD insertion. 2
• In selected cases, combine COC with desmopressin (DDAVP) as an adjunctive measure. 2

Refractory Bleeding

• A combined regimen of DDAVP, COC, and tranexamic acid may be employed for refractory bleeding. 2

Management of Breakthrough Bleeding on Extended-Cycle CHCs

• If breakthrough bleeding occurs during an extended-cycle COC regimen, institute a short hormone-free interval of 3-4 days, provided it is not taken during the first 21 days of the cycle and is limited to no more than one interval per month. 2
• For persistent heavy bleeding after the hormone-free interval, add a course of NSAIDs for 5-7 days to reduce blood loss. 2

Critical Contraindications and Special Populations

Cardiovascular Disease

• Avoid CHCs in patients with cardiovascular disease or history of spontaneous coronary artery dissection due to increased thrombotic risk. 2
• Also avoid NSAIDs and tranexamic acid in these patients due to increased risk of myocardial infarction and thrombosis. 1, 5, 2
• In cardiovascular disease patients, the LNG-IUD is the preferred option because of its minimal systemic hormone exposure. 1, 2

Anticoagulation Therapy

• Approximately 70% of women receiving anticoagulant therapy experience heavy menstrual bleeding. 5, 2
• Re-evaluate the necessity of ongoing antiplatelet agents and discontinue when clinically appropriate. 5, 2
• Progestin-eluting IUDs are favored in anticoagulated patients due to limited systemic absorption. 1, 2

Common Pitfalls to Avoid

• Always perform pregnancy testing before initiating CHC therapy, even in patients using contraception or with irregular cycles, as pregnancy is a frequent cause of abnormal bleeding. 5, 2, 4
• Do not prescribe NSAIDs or tranexamic acid to women with cardiovascular disease without assessing thrombotic risk. 5, 2
• Abnormal uterine bleeding is a major cause for discontinuation of hormonal contraception and resultant unplanned pregnancy; adequate counseling about expected bleeding patterns in the first 3 months improves compliance. 4

When to Refer or Escalate Treatment

• Refer to gynecology if medical management fails after an adequate trial period. 2
• Refer if endometrial sampling reveals hyperplasia or malignancy. 2
• Refer when endometrial thickness is ≥4 mm on ultrasound with persistent bleeding. 2
• Consider endometrial ablation or hysterectomy after failed medical management, with hysterectomy providing definitive symptom resolution and significantly better health-related quality of life. 1, 2