What are the potential causes of bilateral testicular tenderness or alternating pain between each testicle?

Bilateral or Alternating Testicular Pain: Differential Diagnosis

Bilateral testicular tenderness or alternating pain between testicles is most commonly caused by bilateral epididymitis/epididymo-orchitis, though you must urgently exclude bilateral or sequential testicular torsion, which can occur in approximately 2% of torsion cases. 1, 2

Primary Causes to Consider

Infectious/Inflammatory Etiologies

Bilateral Epididymitis/Epididymo-orchitis is the leading cause of bilateral testicular pain, particularly in sexually active men under 35 years:

• In men <35 years: Most commonly caused by Chlamydia trachomatis or Neisseria gonorrhoeae, usually accompanied by asymptomatic urethritis 3
• In men >35 years: More frequently caused by gram-negative enteric organisms (e.g., E. coli) associated with urinary tract infections or recent urinary instrumentation 3
• Men who practice receptive anal intercourse: Consider enteric organisms as causative agents 3
• Characterized by gradual onset of pain, positive Prehn sign (pain relief with testicular elevation), and increased blood flow on Doppler ultrasound 1

Surgical Emergencies

Bilateral or Sequential Testicular Torsion is rare but critical:

• Bilateral torsion occurs in approximately 2% of testicular torsion cases 2
• Sequential torsion (one side, then the other at different times) can present as alternating pain
• Presents with sudden onset of severe unilateral pain that may alternate sides if sequential 3, 1
• Requires surgical intervention within 6-8 hours to prevent permanent testicular loss 1, 4
• More common in adolescents with bimodal distribution (neonates and postpubertal boys), though can occur in adults 4

Bilateral Torsion of Testicular Appendages:

• Most common cause of acute scrotal pain in prepubertal boys 1
• Bilateral occurrence rate of 1.8% 2
• May present with the pathognomonic "blue dot sign" visible through scrotal skin in only 21% of cases 1, 4

Less Common but Important Causes

Viral Orchitis:

• Can cause bilateral involvement, particularly mumps orchitis
• Consider in context of systemic viral illness 5

Testicular Tumors:

• Must be excluded if swelling and tenderness persist after completion of antimicrobial therapy 3

Other Considerations:

• Testicular abscess, infarction, tuberculosis, or fungal epididymitis should be considered if symptoms fail to improve within 3 days of appropriate treatment 3, 5

Critical Diagnostic Approach

Immediate evaluation required:

• Obtain urethral Gram stain showing >5 polymorphonuclear leukocytes per oil immersion field to diagnose urethritis 3
• Culture or nucleic acid amplification test for N. gonorrhoeae and C. trachomatis 3
• First-void urine examination for leukocytes if urethral Gram stain is negative 3
• Duplex Doppler ultrasound of bilateral scrotum is the first-line imaging modality with 96-100% sensitivity for torsion 3, 1

Key ultrasound findings:

• Epididymitis: Increased blood flow, enlarged epididymis, possible hydrocele 1
• Torsion: Decreased/absent blood flow, "whirlpool sign" of twisted spermatic cord (96% sensitivity), heterogeneous testicular appearance 3, 4

Management Algorithm

If clinical suspicion for torsion is high (sudden severe pain, negative Prehn sign, absent cremasteric reflex):

• Proceed directly to emergency urological consultation and surgical exploration without waiting for imaging 3, 4
• Do not delay surgery for imaging studies when clinical presentation strongly suggests torsion 6

If epididymitis is suspected (gradual onset, positive Prehn sign, urethritis symptoms):

• Initiate empiric antibiotic therapy immediately before culture results 3
• For men <35 years or sexually transmitted etiology: Ceftriaxone 250 mg IM once PLUS Doxycycline 100 mg orally twice daily for 10 days 3
• For men >35 years or enteric organisms: Ofloxacin 300 mg orally twice daily for 10 days OR Levofloxacin 500 mg orally once daily for 10 days 3
• Adjunctive therapy: Bed rest, scrotal elevation, and analgesics until fever and inflammation subside 3

Critical pitfall: Failure to improve within 3 days of treatment initiation requires complete reevaluation of diagnosis and consideration of alternative etiologies including tumor, abscess, or atypical infections 3, 5

Follow-up considerations: Treat sexual partners if epididymitis is confirmed or suspected to be caused by N. gonorrhoeae or C. trachomatis 3