What is the appropriate management for a female patient of reproductive age presenting with abnormal uterine bleeding?

Management of Abnormal Uterine Bleeding in Reproductive-Age Women

For reproductive-age women with abnormal uterine bleeding, start with a pregnancy test, assess hemodynamic stability, and obtain combined transabdominal/transvaginal ultrasound with Doppler, then initiate medical management with a levonorgestrel-releasing IUD as first-line therapy, which reduces menstrual blood loss by 71-95% with efficacy comparable to endometrial ablation. 1, 2

Immediate Assessment and Risk Stratification

Hemodynamic Evaluation

• Urgent evaluation is required if bleeding saturates a large pad or tampon hourly for at least 4 consecutive hours 1
• Assess for signs of hemodynamic instability including orthostatic symptoms, tachycardia, and hypotension 1
• Perform abdominal examination to palpate for enlarged uterus or masses 1

Essential Initial Testing

• Pregnancy test (β-hCG) is mandatory in all reproductive-age women before any other workup 1, 2
• Order thyroid-stimulating hormone and prolactin levels 1, 2
• Obtain complete blood count with platelets to assess for anemia and coagulopathy 2
• Perform speculum examination to visualize cervix/vagina and exclude cervical or vaginal bleeding sources 1
• Complete bimanual examination to assess uterine size, contour, mobility, and adnexal masses 1

Diagnostic Imaging Algorithm

First-Line Imaging

Combined transabdominal and transvaginal ultrasound with Doppler is the most appropriate initial imaging study to identify structural causes including polyps, adenomyosis, leiomyomas, and endometrial hyperplasia/malignancy 1, 3

Advanced Imaging When Indicated

• Saline infusion sonohysterography has 96-100% sensitivity and 94-100% negative predictive value for uterine and endometrial pathology, distinguishing between leiomyomas and endometrial polyps with 97% accuracy 1
• MRI pelvis should be considered when ultrasound incompletely visualizes the uterus or findings are indeterminate, with sensitivity up to 79% and specificity up to 89% for endometrial cancer 1

Classification Using PALM-COEIN System

Structural Causes (PALM)

• Polyp: More common in women over 40 years 1, 4
• Adenomyosis: Frequent in premenopausal women in their 40s, often coexists with fibroids, presents with heavy menstrual bleeding, dysmenorrhea, and dyspareunia 4, 2
• Leiomyoma: Most common structural cause in women under 40 years 1, 4
• Malignancy/hyperplasia: Most serious etiology requiring endometrial sampling 1, 4

Non-Structural Causes (COEIN)

• Coagulopathy: Evaluate for von Willebrand disease and other bleeding disorders 5
• Ovulatory dysfunction: Including PCOS, thyroid dysfunction, hyperprolactinemia 1, 5
• Endometrial: Primary endometrial disorders with molecular deficiencies in hemostasis regulation 1
• Iatrogenic: Anticoagulants (70% of women on anticoagulation experience heavy menstrual bleeding), IUDs, exogenous hormones 1, 4
• Not yet classified 1, 4

Medical Management Algorithm

First-Line Therapy

The levonorgestrel-releasing IUD (LNG-IUD) is the most effective first-line medical treatment, reducing menstrual blood loss by 71-95% with efficacy comparable to endometrial ablation 2, 6, 7

Alternative First-Line Options

• Combined hormonal contraceptives (CHCs): Effective for ovulatory dysfunction bleeding, particularly in younger women desiring contraception 1, 4, 2
• Tranexamic acid: Non-hormonal alternative reducing menstrual blood loss by 20-60%, particularly useful in patients with fibroids or those unable to use hormonal therapy 1, 4, 2
• NSAIDs: Can reduce bleeding volume by 20-50% and may be combined with hormonal methods 4, 2
• Oral progestins: Administer for 21 days per month for women with cyclic heavy bleeding 2, 5

Second-Line Medical Options

• GnRH antagonists (elagolix, linzagolix, relugolix): Effectively reduce bleeding symptoms and fibroid volume when fibroids are present 4
• GnRH agonists: Reduce fibroid volume but cause temporary medical menopause with symptom return after discontinuation 4

Critical Caveats for Special Populations

Cardiovascular Disease or Post-SCAD Patients

Avoid NSAIDs and tranexamic acid due to increased risk of MI and thrombosis 1, 2

• LNG-IUD becomes the preferred option in this population due to minimal systemic absorption 2
• Hormonal therapy is relatively contraindicated despite being first-line for most AUB cases 2

Patients on Anticoagulation

• Reassess indication for ongoing antiplatelet therapy and discontinue if appropriate before initiating AUB treatment 1, 2
• Progestin-eluting IUDs are preferred due to minimal systemic absorption 2
• Oral anticoagulants (particularly rivaroxaban) cause abnormal uterine bleeding in 9-14% of reproductive-age women, with 27% experiencing prolonged bleeding >8 days 1
• Avoid combined hormonal contraceptives due to increased thromboembolic risk 8

Patients Desiring Contraception

Concomitant use of tranexamic acid with hormonal contraceptives increases thromboembolic risk—advise patients to use effective alternative (nonhormonal) contraceptive methods 8

Indications for Endometrial Sampling

Perform endometrial biopsy in the following scenarios:

• Women ≥35 years with recurrent anovulation 5
• Women <35 years with risk factors for endometrial cancer (obesity, diabetes, hypertension, unopposed estrogen exposure, tamoxifen use, Lynch syndrome or family history) 1, 5
• Postmenopausal bleeding with endometrial thickness ≥4 mm 1
• Excessive bleeding unresponsive to medical therapy 5

Important caveat: Endometrial biopsy alone has variable sensitivity for focal lesions—saline infusion sonohysterography has superior sensitivity and negative predictive value for intracavitary pathology 2

Surgical Management

When to Consider Surgery

• Failed medical management after adequate trial 1, 4, 2
• Endometrial sampling showing hyperplasia or malignancy 1
• Postmenopausal bleeding with endometrial thickness ≥4 mm 1
• Patient preference after completing childbearing 2

Surgical Options in Order of Invasiveness

Endometrial Ablation

• Less invasive alternative to hysterectomy with efficacy comparable to LNG-IUD 2
• Long-term complications include: postablation Asherman syndrome, synechiae, cervical stenosis, and potential delayed endometrial cancer diagnosis—thorough informed consent required 2

Uterine Artery Embolization (UAE)

• Effective for patients with fibroids and adenomyosis desiring uterus preservation 4
• 94% short-term symptom improvement and 85% long-term improvement 4
• 7% require subsequent hysterectomy for persistent symptoms 4
• Meta-analysis shows significantly greater short-term benefits compared to hysterectomy but increased percentage of long-term reintervention 4

Hysterectomy

• Most definitive treatment providing complete resolution of all fibroid-related symptoms and eliminating recurrence risk 1, 4, 2
• Accounts for three-quarters of fibroid treatment in the United States 4
• Provides significantly better health-related quality-of-life advantage compared to other therapies 1, 4
• Choose the least invasive surgical route (vaginal > laparoscopic/robotic > abdominal) based on uterine size and surgical expertise 4
• Vaginal and laparoscopic approaches associated with shorter hospital stays, faster recovery, and lower complication rates compared to abdominal hysterectomy 4

Management of Persistent Bleeding Despite Treatment

If bleeding persists despite initial medical therapy:

• Perform hysteroscopy to visualize endometrial cavity and endocervix, diagnosing focal lesions possibly missed by endometrial sampling 2
• Consider further imaging with MRI if ultrasound findings are indeterminate 1
• Reassess diagnosis using PALM-COEIN classification 2

Referral Indications to Gynecology

Refer to gynecologist in the following scenarios:

• Failed medical management 1
• Endometrial sampling showing hyperplasia or malignancy 1
• Postmenopausal bleeding with endometrial thickness ≥4 mm 1
• Hyperplasia with atypia or adenocarcinoma (refer to gynecologic oncologist) 5