What is the course of diagnosis and treatment for a female patient presenting with abnormal uterine bleeding?

Diagnosis and Treatment of Abnormal Uterine Bleeding

Initial Assessment and Stabilization

All reproductive-age women presenting with abnormal uterine bleeding must undergo pregnancy testing before any further evaluation or treatment. 1, 2, 3

Urgent Evaluation Criteria

• Assess hemodynamic stability immediately in patients bleeding through a large pad or tampon hourly for ≥4 hours 2
• Perform abdominal examination to detect enlarged uterus or masses and assess for signs of instability 2
• Complete speculum examination to exclude cervical or vaginal bleeding sources 2
• Bimanual examination to evaluate uterine size, contour, mobility, and adnexal masses 2

Essential Laboratory Workup

• Complete blood count with platelets to assess for anemia and thrombocytopenia 3
• Thyroid-stimulating hormone and prolactin levels to exclude thyroid dysfunction and hyperprolactinemia 2, 3
• Coagulation studies if bleeding disorder suspected (von Willebrand disease is the most common) 4

Diagnostic Classification Using PALM-COEIN

The PALM-COEIN system categorizes bleeding into structural versus non-structural causes 1, 2, 3:

Structural Causes (PALM)

• Polyp: More common in women >40 years 2
• Adenomyosis: Frequently coexists with fibroids, presents with dysmenorrhea and dyspareunia, typically affects women in their 40s 1, 2
• Leiomyoma (fibroids): Most common structural cause in women <40 years 2
• Malignancy and hyperplasia: Primary concern in postmenopausal women 2

Non-Structural Causes (COEIN)

• Coagulopathy: Von Willebrand disease most common 4
• Ovulatory dysfunction: Causes irregular, heavy bleeding; assess for PCOS (acne, hirsutism), diabetes, thyroid dysfunction 3, 4
• Endometrial: Primary endometrial disorders with molecular hemostasis deficiencies 2
• Iatrogenic: 70% of women on anticoagulation experience heavy bleeding; rivaroxaban causes prolonged bleeding (>8 days) in 27% 2
• Not yet classified 1

Imaging Strategy

Combined transabdominal and transvaginal ultrasound with Doppler is the mandatory first-line imaging study for all patients with abnormal uterine bleeding. 2, 3

Imaging Algorithm

• Transvaginal ultrasound (TVUS) is primary modality for evaluating endometrium and myometrium 2
• Transabdominal ultrasound is essential when uterus is significantly enlarged (TVUS has limited field of view) 3
• Doppler imaging identifies vessels within endometrial polyps or cancer (62-98% specificity for polyps) 3

Endometrial Thickness Thresholds

• Postmenopausal women: Endometrial thickness <4 mm has nearly 100% negative predictive value for cancer 2, 3
• Postmenopausal women: Endometrial thickness ≥5 mm mandates endometrial tissue sampling 3

Advanced Imaging

• Saline infusion sonohysterography: 96-100% sensitivity and 94-100% negative predictive value for uterine pathology; distinguishes leiomyomas from polyps with 97% accuracy 2
• MRI pelvis: Reserved for when ultrasound incompletely visualizes uterus or findings are indeterminate; sensitivity up to 79% and specificity up to 89% for endometrial cancer 2
• MRI pelvis: Also used for preprocedural workup of leiomyomas prior to uterine artery embolization to map vascular anatomy 3

Endometrial Sampling Indications

Mandatory Biopsy Criteria

• All women >45 years with abnormal uterine bleeding 4, 5
• All postmenopausal women with bleeding 5
• Women ≥35 years with recurrent anovulation 4
• Women <35 years with risk factors for endometrial cancer 4
• Postmenopausal women with endometrial thickness ≥4 mm on ultrasound 2

Risk Factors for Endometrial Cancer

• Obesity, diabetes, hypertension 2
• Unopposed estrogen exposure 2
• Tamoxifen use 2
• Lynch syndrome or family history of endometrial cancer 2

Important Caveat

Endometrial biopsy alone should not be used to rule out focal lesions due to variable sensitivity; saline infusion sonohysterography has superior sensitivity and negative predictive value for intracavitary pathology. 1

Medical Management Algorithm

First-Line Treatment: Levonorgestrel-Releasing Intrauterine Device (LNG-IUD)

The levonorgestrel-releasing intrauterine device is the most effective first-line medical treatment, reducing menstrual blood loss by 71-95% with efficacy comparable to endometrial ablation. 1, 3

• Mandatory preferred option in patients with cardiovascular disease or post-SCAD (NSAIDs and tranexamic acid carry unacceptable MI and thrombosis risks) 1, 3
• Preferred in patients on antiplatelet therapy due to minimal systemic absorption 1

Alternative Medical Options

Combined Hormonal Contraceptives (CHCs)

• Effective for ovulatory dysfunction bleeding 1, 3
• Can be combined with NSAIDs to further reduce bleeding volume 3
• First-line for mild to moderate bleeding in adolescents (95% of adolescent AUB is dysfunctional) 3
• Use multidose regimen in acute abnormal uterine bleeding 6

Oral Progestins

• Administer for 21 days per month for menstrual blood loss reduction 1, 3
• Effective for women with cyclic heavy bleeding related to menstrual cycle 1
• Progestin-only options as alternatives in adolescents 3

Tranexamic Acid

• Viable option with high efficacy for heavy menstrual bleeding 1, 3
• Absolutely contraindicated in patients with cardiovascular disease or post-SCAD due to thrombosis risk 1, 3

NSAIDs

• May be utilized with hormonal methods to decrease menstrual bleeding 3, 6
• Absolutely contraindicated in patients with cardiovascular disease or post-SCAD due to MI risk 1, 3

Ulipristal Acetate (UPA) for Fibroids

• Bridges to surgery, improves quality of life, and shrinks fibroids when surgery is delayed 3
• Fibroid volume reductions of approximately 30% after single course, up to 70% after 4 courses 3
• Does not increase difficulty of hysteroscopic or laparoscopic myomectomy 3
• In perimenopausal women, pulsatile courses can help transition into menopause while avoiding surgery 3
• Important caveat: UPA can induce fibroid migration; image uterine cavity as part of preoperative workup 3
• Ovulation rate up to 20% occurs at fibroid-treatment doses—counsel patients about concurrent nonhormonal contraception 3

Special Population Considerations

Patients with Cardiovascular Disease

• LNG-IUD is the mandatory preferred option 1, 3
• Hormonal therapy is relatively contraindicated despite being first-line for most AUB cases 1
• Avoid NSAIDs and tranexamic acid completely 1, 3

Patients on Antiplatelet Therapy

• Reassess indication for ongoing antiplatelet therapy and discontinue if appropriate before initiating AUB treatment 1, 2
• Progestin-eluting IUDs preferred due to minimal systemic absorption 1

Patients on Anticoagulation

• 70% experience heavy menstrual bleeding 2
• Consider progestin-only methods 6
• GnRH agonists can be used to treat heavy menstrual bleeding 6

Patients with Inherited Bleeding Disorders

• All hormonal methods and tranexamic acid can be used 6

Surgical Management

Hysteroscopy

If bleeding persists despite initial medical therapy, perform hysteroscopy to visualize the endometrial cavity and diagnose focal lesions potentially missed by endometrial sampling. 1, 3

Endometrial Ablation

• Less invasive alternative to hysterectomy with efficacy comparable to LNG-IUD 1, 3
• Critical caveat: Long-term complications include postablation Asherman syndrome, synechiae, cervical stenosis, and potential delayed endometrial cancer diagnosis 1
• Thorough informed consent regarding these complications is mandatory 1, 3

Hysterectomy

Hysterectomy is the definitive treatment when medical management fails or is contraindicated, particularly in postmenopausal women with symptomatic fibroids. 1, 3

• Provides complete resolution of symptoms and significantly better health-related quality of life compared to other therapies 2
• Most appropriate for patients who have completed childbearing and desire permanent resolution 1

Other Surgical Options

• Polypectomy for endometrial polyps 4
• Myomectomy for fibroids in patients desiring fertility; type and route depend on fibroid size and myoma-serosa distance 3
• Uterine artery embolization for leiomyomas 4

Gynecology Referral Criteria

Refer to gynecologist when 2:

• Failed medical management
• Endometrial sampling showing hyperplasia or malignancy
• Postmenopausal bleeding with endometrial thickness ≥4 mm

Women with hyperplasia with atypia or adenocarcinoma should be referred to a gynecologist or gynecologic oncologist, respectively. 4

Management of Specific Histologic Findings

Hyperplasia Without Atypia

• Treat with cyclic or continuous progestin 4

Hyperplasia With Atypia or Adenocarcinoma

• Immediate referral to gynecologist or gynecologic oncologist 4