What is the differential diagnosis and treatment plan for a 26-year-old female, gravida 0, para 0 (G0P0), presenting with new intermenstrual bleeding without abdominal pain, fever, nausea, or vomiting?

Intermenstrual Bleeding in a 26-Year-Old Nulligravid Woman

Immediate Priority: Rule Out Pregnancy and Infection

The first step is to obtain a urine pregnancy test and screen for sexually transmitted infections, particularly cervical infections, as these are the most critical diagnoses to exclude in a reproductive-aged woman with new intermenstrual bleeding. 1, 2

Differential Diagnosis Using PALM-COEIN Classification

The PALM-COEIN system categorizes causes of abnormal uterine bleeding into structural and non-structural etiologies 1, 3:

Structural Causes (PALM):

• Polyp: Endometrial or endocervical polyps causing irregular bleeding 1, 4
• Adenomyosis: Less common in nulliparous women but possible 1, 4
• Leiomyoma: Submucosal fibroids can cause intermenstrual bleeding 1, 4
• Malignancy/Hyperplasia: Rare at age 26 but must be considered with persistent bleeding 1

Non-Structural Causes (COEIN):

• Coagulopathy: Inherited bleeding disorders (von Willebrand disease, platelet dysfunction) 1, 5
• Ovulatory dysfunction: Most common cause in reproductive-aged women, including polycystic ovary syndrome 1, 3, 4
• Endometrial: Primary endometrial disorders 1
• Iatrogenic: Hormonal contraception, IUD, anticoagulation 1, 4
• Not yet classified: Cervicitis, cervical polyp, vaginal laceration 1

Diagnostic Workup

Essential Laboratory Tests:

• Urine pregnancy test (β-hCG): Mandatory first step 1
• Complete blood count with platelets: Assess for anemia and thrombocytopenia 5
• STI screening: Gonorrhea and chlamydia testing 2
• TSH and prolactin levels: Evaluate for thyroid disease and hyperprolactinemia 1

Imaging:

• Transvaginal ultrasound: Initial and often only imaging needed to identify structural causes (polyps, fibroids, adenomyosis) 4
• Saline infusion sonohysterography: If transvaginal ultrasound is inconclusive, this has 96-100% sensitivity for intracavitary pathology 1

When to Consider Endometrial Biopsy:

• Generally not indicated in women under 35 without risk factors for endometrial hyperplasia or cancer 1
• Consider if bleeding persists despite treatment or if risk factors present (obesity, PCOS, chronic anovulation) 1

Treatment Plan

First-Line Medical Management:

Combined oral contraceptives containing 30-35 μg ethinyl estradiol with levonorgestrel or norgestimate are the recommended first-line treatment for intermenstrual bleeding after excluding structural pathology. 1, 2

• Mechanism: Induces regular shedding of thinner endometrium, reduces menstrual blood loss 2
• Additional benefits: Improves acne, reduces risk of endometrial and ovarian cancers 2
• Dosing: Monophasic formulation preferred 2

Alternative First-Line Options:

• NSAIDs: For 5-7 days during bleeding episodes to acutely reduce blood flow 6, 2
• Progestin-only contraception: If estrogen contraindicated 1

Important Counseling Points:

• Reassure patient: Unscheduled bleeding is common during first 3-6 months of hormonal therapy and generally not harmful 2
• Re-evaluate: If bleeding persists beyond 3-6 months, reassess for underlying gynecological problems 2

Second-Line Options if First-Line Fails:

• Depot medroxyprogesterone acetate (DMPA): Consider if oral contraceptives ineffective or not tolerated 6
• Levonorgestrel intrauterine system: Highly effective for heavy menstrual bleeding 7
• Tranexamic acid: Antifibrinolytic agent for 5 days during bleeding episodes 6, 7

Safety Considerations:

• Assess thrombotic risk factors: Before prescribing combined oral contraceptives, as they increase venous thromboembolism risk 3-4 fold 2
• Monitor blood pressure: At follow-up visits for patients on hormonal methods 6, 2

Surgical Management

If medical treatment fails, is contraindicated, or not tolerated, or if concomitant significant intracavitary lesions are present, surgical options include endometrial ablation and hysterectomy. 1

• Hysteroscopy: Allows visualization of endometrial cavity and can diagnose focal lesions missed by endometrial sampling 1
• Myomectomy: If fibroids identified and fertility preservation desired 1

Follow-Up Protocol

• No routine follow-up visit required: Patients should return if experiencing side effects or concerns 6, 2
• At follow-up visits: Assess satisfaction with method, any changes in health status, and monitor blood pressure for patients on hormonal methods 6, 2
• Further investigation: If medical treatment fails, perform imaging or hysteroscopy to identify missed structural pathology 1

Common Pitfalls to Avoid

• Failing to exclude pregnancy: Always perform pregnancy test first, regardless of contraceptive use 1, 2
• Missing cervical pathology: Perform speculum examination to visualize cervix and exclude cervicitis, polyps, or lesions 3, 8
• Premature endometrial biopsy: Not routinely indicated in women under 35 without risk factors 1
• Discontinuing treatment too early: Bleeding irregularities typically resolve after 3-6 months of hormonal therapy 2