What are the risk factors, presenting symptoms, diagnostic strategies, treatment planning, and follow-up management for abnormal uterine bleeding in women of reproductive age?

Management of Abnormal Uterine Bleeding

Risk Factors

Women at highest risk for abnormal uterine bleeding include those with anovulatory conditions, structural uterine pathology, coagulopathies, and endometrial cancer risk factors. 1

Age-Specific Risk Patterns

• Adolescents: Coagulopathies (particularly von Willebrand disease) are more common than typically recognized and should be screened in all adolescents with menorrhagia 2
• Reproductive age women: Structural causes (polyps, adenomyosis, leiomyomas) and non-structural causes (ovulatory dysfunction, coagulopathies, iatrogenic causes) predominate 1
• Perimenopausal women: Anovulation is common, but structural causes must be excluded due to higher risk of endometrial hyperplasia and cancer 1, 3
• Postmenopausal women: Endometrial cancer is the primary concern and main focus of evaluation 1

Specific Risk Factors for Endometrial Cancer

• Age >45 years 3
• Obesity, diabetes, hypertension 3
• Unopposed estrogen exposure 3
• Tamoxifen use 3
• Lynch syndrome 3

Medical Conditions Increasing Risk

• Polycystic ovary syndrome, uncontrolled diabetes, thyroid dysfunction, hyperprolactinemia 4
• Coagulation disorders (von Willebrand disease most common) 2, 4
• Hypothyroidism, cirrhosis 2
• Use of antipsychotics, antiepileptics, anticoagulants, sex steroids, intrauterine devices 2

Presenting Symptoms

Abnormal uterine bleeding is defined as bleeding from the uterus that is abnormal in regularity, volume, frequency, or duration occurring in the absence of pregnancy. 1

Clinical Presentations

• Heavy menstrual bleeding (menorrhagia): Excessive volume during regular cycles 1, 5
• Irregular menstrual bleeding: Abnormal cycle regularity 5
• Intermenstrual bleeding: Bleeding between regular cycles 5
• Acute bleeding: Saturating a large pad/tampon hourly for ≥4 hours requires urgent evaluation 3

Associated Symptoms by Etiology

• Adenomyosis: Heavy menstrual bleeding, dysmenorrhea, dyspareunia; commonly affects women in their 40s 6, 1
• Fibroids: Heavy bleeding, pelvic pressure symptoms 1
• Anovulatory bleeding: Irregular, unpredictable bleeding patterns 4

Diagnostic Strategies

Pregnancy must be ruled out first in all reproductive-age women using β-hCG testing before proceeding with any further evaluation. 6, 3

Classification Framework

• Use the PALM-COEIN classification system to systematically categorize bleeding causes 6, 1, 3
  • PALM (structural): Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia 6, 1
  • COEIN (non-structural): Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified 6, 1

Initial Laboratory Assessment

• Pregnancy test (β-hCG) in all reproductive-age women 6, 3
• Complete blood count with platelets to assess for anemia and thrombocytopenia 6
• Thyroid-stimulating hormone and prolactin levels to exclude endocrine causes 6, 3
• Hemodynamic stability assessment 3

Imaging Studies

• Combined transabdominal and transvaginal ultrasound with Doppler is the first-line imaging study 6, 3
• Saline infusion sonohysterography has 96-100% sensitivity and 97% accuracy distinguishing leiomyomas from polyps; superior to endometrial biopsy alone for detecting focal lesions 6, 3
• MRI should be considered when ultrasound incompletely visualizes the uterus or findings are indeterminate 1, 3

Endometrial Sampling Indications

Endometrial biopsy is mandatory in the following patients: 3

• Age >45 years 3
• Postmenopausal status 3
• Risk factors for endometrial cancer (obesity, diabetes, hypertension, unopposed estrogen, tamoxifen, Lynch syndrome) 3
• Perimenopausal women (lower threshold due to higher cancer risk) 3
• Postmenopausal bleeding with endometrial thickness ≥4 mm 3

Advanced Diagnostic Procedures

• Hysteroscopy with biopsy is the reference method for definitive diagnosis and allows visualization of focal lesions potentially missed by endometrial sampling 6, 5
• Indicated when bleeding persists despite initial medical therapy 6

Coagulopathy Screening Indications

Screen for coagulopathy in: 2

• All adolescents with menorrhagia 2
• Women with anovulatory bleeding who fail medical/surgical therapy 2
• Women with ovulatory bleeding without anatomic uterine lesion 2
• Women with high-risk bleeding history 2

Treatment Planning

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

Medical Management Algorithm

First-Line Options for Most Patients

• Levonorgestrel-releasing IUD (LNG-IUD): 71-95% reduction in menstrual blood loss; efficacy equivalent to endometrial ablation 6, 7
• Combined hormonal contraceptives (CHCs): Effective for ovulatory dysfunction bleeding; can be combined with NSAIDs for further bleeding reduction 6, 4
• Oral progestins: Administer for 21 days per month for cyclic heavy bleeding related to menstrual cycle 6, 4

Non-Hormonal Options

• Tranexamic acid: High efficacy for heavy menstrual bleeding; non-hormonal alternative 6, 3, 4
• NSAIDs: Most effective for ovulatory menorrhagia, reducing bleeding by 20-50%; can be combined with hormonal methods 3, 4

Acute Bleeding Management

For acute abnormal uterine bleeding with normal uterus: 8

• Parenteral estrogen 8
• Multidose combined oral contraceptive regimen 8
• Multidose progestin-only regimen 8
• Tranexamic acid 8

Special Population Considerations

Cardiovascular Disease or Post-SCAD Patients

NSAIDs and tranexamic acid should be avoided due to MI and thrombosis risk; levonorgestrel-releasing IUD becomes the preferred option. 6

• Hormonal therapy is relatively contraindicated despite being first-line for most AUB cases 6
• Progestin-eluting IUDs preferred due to minimal systemic absorption 6

Patients on Antiplatelet Therapy

• Reassess indication for ongoing antiplatelet therapy and discontinue if appropriate before initiating AUB treatment 6
• Progestin-eluting IUDs preferred 6

Patients with Inherited Bleeding Disorders

• All hormonal methods and tranexamic acid can be used 8

Patients on Anticoagulation

• Progestin-only methods preferred 8
• GnRH agonists may be considered 8

Surgical Management

Endometrial Ablation

• Less invasive alternative to hysterectomy with efficacy comparable to LNG-IUD 6
• Appropriate for women with completed childbearing 3
• Important caveat: Long-term complications include postablation Asherman syndrome, synechiae, cervical stenosis, and potential delayed endometrial cancer diagnosis; thorough informed consent required 6

Hysterectomy

Hysterectomy is the most appropriate treatment when medical management fails or is contraindicated, providing definitive resolution with significantly better health-related quality of life compared to other therapies. 6, 1, 3

• Particularly appropriate for postmenopausal women with symptomatic fibroids 6, 1
• Accounts for three-quarters of fibroid treatment in the United States 1
• Choose the least invasive surgical route based on uterine size and surgical expertise 1, 3

Other Surgical Options

• Polypectomy, fibroidectomy for identified structural lesions 4
• Uterine artery embolization for fibroids (greater short-term benefits but increased long-term reintervention compared to hysterectomy) 1

Treatment of Specific Etiologies

Adenomyosis

• Frequently coexists with fibroids 6, 1
• LNG-IUD, hormonal contraceptives, or hysterectomy for definitive treatment 6

Fibroids

• GnRH antagonists (elagolix, linzagolix, relugolix) reduce bleeding symptoms and fibroid volume 1
• GnRH agonists reduce fibroid volume but symptoms return after discontinuation 1
• Tranexamic acid may reduce bleeding in patients with fibroids 1

Hyperplasia Without Atypia

• Cyclic or continuous progestin 4

Hyperplasia With Atypia or Adenocarcinoma

• Refer to gynecologist or gynecologic oncologist 4

Treatments NOT Recommended

• Ascorbic acid is not recommended for abnormal uterine bleeding 6

Follow-Up Management

If bleeding persists despite initial medical therapy, further investigation with imaging or hysteroscopy is indicated. 6

Monitoring Response to Medical Therapy

• Assess bleeding pattern changes within 3-6 months of initiating treatment 6
• Document hemoglobin improvement if anemia was present 6

Indications for Further Investigation

• Persistent bleeding despite medical therapy 6
• Failed medical management 3
• Development of new symptoms 6

Referral Indications

• Failed medical management 3
• Endometrial sampling showing hyperplasia or malignancy 3
• Postmenopausal bleeding with endometrial thickness ≥4 mm 3
• Structural pathology requiring surgery 3

Long-Term Considerations

• LNG-IUD: Monitor for device expulsion, infection; replace every 5-8 years depending on device 7
• Endometrial ablation: Counsel about potential for delayed endometrial cancer diagnosis; maintain surveillance 6
• GnRH agonists/antagonists: Symptoms return after discontinuation; not suitable for long-term management alone 1
• Hysterectomy: Definitive resolution; no further surveillance for AUB needed 1, 3

Age-Specific Follow-Up

• Perimenopausal women: Lower threshold for repeat endometrial sampling if bleeding recurs 3
• Postmenopausal women: Any recurrent bleeding requires immediate evaluation for malignancy 3