What are the differential diagnoses for a female of reproductive age with left lower quadrant pain resolved with Non-Steroidal Anti-Inflammatory Drugs (NSAID) use, experiencing bleeding between periods, and no guarding or masses on palpation?

Differential Diagnoses for Left Lower Quadrant Pain Resolved with NSAIDs and Intermenstrual Bleeding

The most likely diagnosis is primary dysmenorrhea with intermenstrual bleeding (metrorrhagia), though you must systematically exclude secondary causes including IUD-related bleeding, endometriosis, uterine structural abnormalities (polyps, fibroids), cervical pathology, and early pregnancy complications. 1, 2

Primary Differential Diagnoses

Most Likely: Primary Dysmenorrhea with Intermenstrual Bleeding

• NSAIDs effectively treat primary dysmenorrhea by inhibiting prostaglandin synthesis, which causes the characteristic cramping pain 3, 4
• The fact that NSAIDs provide complete pain resolution strongly suggests prostaglandin-mediated pain, characteristic of primary dysmenorrhea 3, 4
• Intermenstrual bleeding (metrorrhagia) can coexist with primary dysmenorrhea as a separate menstrual irregularity 2
• Absence of guarding or palpable masses on examination makes inflammatory or structural pathology less likely but does not exclude it 5

IUD-Related Bleeding and Pain

• If the patient uses a copper IUD, unscheduled spotting and left lower quadrant pain responsive to NSAIDs is an expected side effect, especially within the first 3-6 months of use 1
• NSAIDs are specifically recommended for 5-7 days to treat Cu-IUD-related bleeding and cramping 1
• However, if symptoms persist beyond 3-6 months of IUD use, you must investigate for IUD displacement, sexually transmitted disease, pregnancy, or new uterine pathology (polyps or fibroids) 1

Endometriosis

• Endometriosis should be strongly considered when dysmenorrhea persists despite treatment with NSAIDs and hormonal agents 6
• Left-sided endometriotic implants can cause lateralized left lower quadrant pain 6
• Endometriosis commonly presents with intermenstrual bleeding and pain that initially responds to NSAIDs but eventually becomes refractory 6
• The absence of palpable masses does NOT exclude endometriosis, as lesions may be microscopic or on peritoneal surfaces 6

Uterine Structural Abnormalities

• Submucous leiomyomas (fibroids), endometrial polyps, and adenomyosis can all cause intermenstrual bleeding with cramping pain that responds to NSAIDs 1, 2
• These conditions may not produce palpable masses on examination, especially if lesions are small or intracavitary 2

Cervical Pathology

• Cervical polyps, cervical erosion, and cervicitis can cause intermenstrual bleeding with associated cramping 2
• These are typically painless but can cause secondary uterine cramping that responds to NSAIDs 2

Early Pregnancy Complications

• Any reproductive-age woman with abnormal uterine bleeding and pelvic pain must have pregnancy excluded first 2
• Threatened abortion, incomplete abortion, or ectopic pregnancy can present with left lower quadrant pain and bleeding 2
• Pain from early pregnancy complications may transiently improve with NSAIDs before worsening 2

Critical Next Steps in Evaluation

Immediate Assessment Required

• Obtain urine or serum β-hCG to exclude pregnancy before proceeding with any other workup 2
• Determine if patient uses an IUD, as this dramatically changes the differential diagnosis 1
• Assess timing: if symptoms occur only during menstruation, primary dysmenorrhea is most likely; if pain is continuous or occurs between periods, consider endometriosis or structural pathology 6, 7

When to Obtain Imaging

• If the patient has no clinical improvement within 3-6 months of NSAID therapy, obtain transvaginal ultrasound to evaluate for structural abnormalities 6
• Transvaginal ultrasound is the preferred initial imaging modality for reproductive-age women with suspected gynecologic pathology 1
• If ultrasound is equivocal or suggests endometriosis, MRI provides superior tissue characterization 7

When to Consider Laparoscopy

• Laparoscopy should be considered if dysmenorrhea persists despite 3-6 months of combined NSAID and hormonal therapy, particularly when no other etiology is identified on imaging 6
• Endometriotic lesions in reproductive-age women may appear clear or red rather than the classic "powder burn" appearance, making visual diagnosis challenging 6

Common Pitfalls to Avoid

• Do not assume benign primary dysmenorrhea without excluding pregnancy first—this is the most critical error 2
• Do not continue empiric NSAID therapy beyond 3-6 months without investigating for secondary causes 6
• Do not rely on physical examination alone to exclude structural pathology—absence of palpable masses does not rule out polyps, fibroids, or endometriosis 6
• Do not dismiss IUD-related symptoms as "normal" if they persist beyond 6 months or worsen over time—investigate for displacement or new pathology 1
• Do not assume that pain responsive to NSAIDs excludes serious pathology—endometriosis and even early ectopic pregnancy may initially improve with NSAIDs 6, 4