Differential Diagnosis of Hematospermia
The differential diagnosis of hematospermia varies significantly by age, with infection being the most common identifiable cause in men under 40 years, while iatrogenic causes from urogenital instrumentation dominate in men 40 years and older, though the majority of cases remain idiopathic. 1, 2
Age-Stratified Differential Diagnosis
Men Under 40 Years
Infectious/Inflammatory Causes (Most Common Identifiable Etiology):
- Sexually transmitted infections (chlamydia, gonorrhea) 2, 3
- Prostatitis (bacterial or non-bacterial) 3, 4
- Urethritis 2, 5
- Epididymitis or orchitis 3, 4
- Seminal vesiculitis 3, 4
Other Benign Causes:
- Idiopathic (most common overall, representing 80-90% of cases) 6, 3
- Prostatic or ejaculatory duct calcifications 1, 7
- Seminal vesicle or ejaculatory duct cysts 1, 7
- Prostatic utricle cysts 6
Men 40 Years and Older
Iatrogenic Causes (Most Common in This Age Group):
- Post-prostate biopsy 2, 3
- Post-urogenital instrumentation (cystoscopy, urethral catheterization) 2, 5
Structural/Anatomic Abnormalities:
- Benign prostatic hyperplasia 1, 7
- Prostatic calcifications or calculi 1, 7
- Ejaculatory duct obstruction 1, 4
- Seminal vesicle cysts or dilatation (width >1.7 cm) 1, 4
- Cowper gland masses 1, 7
Vascular Abnormalities:
- Prostatic or seminal vesicle varices 4, 8
- Arteriovenous malformations 4
- Internal pudendal artery hemorrhage 1
Neoplastic Causes (Must Not Miss):
- Prostate cancer 1, 2
- Bladder cancer (especially at trigone/bladder neck) 6
- Seminal vesicle tumors 3, 4
- Testicular cancer 3
- Urethral carcinoma 4
Systemic/Hematologic Disorders:
- Coagulopathy (inherited or acquired bleeding disorders) 7, 2
- Anticoagulation therapy 2, 4
- Thrombocytopenia 7
- Liver disease with portal hypertension 4, 8
- Severe hypertension 4, 8
Red Flag Features Requiring Urgent Investigation
Associated symptoms that mandate thorough workup regardless of age include: 2, 5
- Fever or chills (suggesting infection or systemic disease) 2, 4
- Weight loss or bone pain (concerning for malignancy) 2, 4
- Persistent or recurrent hematospermia beyond several weeks 1, 2
- Concurrent hematuria 4, 5
- Lower urinary tract symptoms (dysuria, frequency, urgency) 2, 5
- Painful ejaculation 4, 5
Common Pitfalls
A critical caveat is that TRUS demonstrates abnormalities in 82-95% of men with hematospermia, but many findings (prostatic calcifications, benign prostatic hyperplasia, nonobstructing cysts) are age-related changes also found in asymptomatic patients and may not represent the true cause. 1, 7 This can lead to overdiagnosis and unnecessary anxiety.
Another important consideration is distinguishing true hematospermia from postcoital bleeding from a sexual partner, which requires visual confirmation of blood in the ejaculate. 1
In men 40 years and older, prostate cancer screening with PSA testing is mandatory even when other causes seem apparent, as malignancy must not be missed. 1, 7