What are the causes of testicular atrophy?

Causes of Testicular Atrophy

Testicular atrophy results from diverse etiologies including congenital conditions, vascular compromise, inflammatory processes, iatrogenic injury, systemic diseases, and malignancy-related factors, with cryptorchidism, testicular torsion, mumps orchitis, and Klinefelter syndrome representing the most clinically significant causes.

Congenital and Developmental Causes

• Cryptorchidism (undescended testis) is a major cause of testicular atrophy, reflecting prenatal testicular damage that results in an "incompetent" small testis even after surgical orchiopexy 1, 2
• Cryptorchidism is associated with smaller testicular volumes and impaired spermatogenesis even after surgical correction 3
• Klinefelter syndrome (47,XXY) is probably the most frequent cause of small testicles, presenting with a spectrum from eunuchoid hypogonadism to normally virilized but sterile males 2

Vascular and Ischemic Causes

• Testicular torsion causes testicular atrophy through twisting of the spermatic cord and compromising blood flow, particularly when surgical exploration is delayed beyond 6-8 hours 1
• Inguinal hernioplasty causes testicular atrophy due to thrombosis of spermatic cord veins from surgical dissection trauma, not from incorrect reconstruction or infection 4
• Chronically incarcerated inguinal hernias can cause ischemic orchitis and subsequent testicular atrophy through compression of testicular vessels, particularly in long-standing hernias of years' duration 5
• Varicocele is associated with testicular dysfunction and atrophy, present in 15% of normal males and 35-40% of men with infertility, with higher varicocele grade and age correlating with worse semen parameters 1

Traumatic Causes

• Blunt scrotal trauma causes testicular atrophy in approximately 50% of cases, with significant volume reduction observed months to years following injury 6
• Trauma from testicular torsion represents a painful event leading to subsequent atrophy 2

Infectious and Inflammatory Causes

• Mumps orchitis is a classic infectious cause resulting in testicular atrophy as a consequence of the painful inflammatory event 2
• Epididymoorchitis can lead to progressive inflammation and testicular damage 1

Iatrogenic Causes

• Chemotherapy causes testicular atrophy, though spermatogenesis may recover 1-4 years after treatment in some cases 3
• Radiation therapy leads to testicular atrophy, with prostate bed radiation causing atrophy in 71% of men versus 28% without radiation, particularly within 3 years post-radiation 7
• Immunosuppressive drugs may lead to testicular atrophy as a side effect 2
• Surgical injury to blood vessels during orchiopexy can result in a small testis postoperatively 2

Systemic Disease-Related Causes

• Liver cirrhosis is associated with testicular atrophy as a consequence of extratesticular disease 2
• Chronic alcoholism causes testicular atrophy through systemic effects 2
• Hemochromatosis leads to testicular atrophy as part of its systemic manifestations 2
• Curschmann-Steinert dystrophic myotonia is associated with testicular atrophy 2

Malignancy-Related Causes

• Testicular cancer survivors have higher risk of testicular atrophy, with approximately 5-30% having atrophy in the contralateral testis, reaching 30% in men with testicular volume <12ml and age <40 years 8
• Testicular microcalcification is observed in men with testicular atrophy and associated with increased risk of germ cell tumors 1

Clinical Significance and Volume Thresholds

• Testicular volumes <12ml are definitively considered atrophic and associated with impaired spermatogenesis, higher risk of intratubular germ cell neoplasia, and potential infertility 1, 9
• Severe testicular atrophy (volumes ≤2ml) is associated with non-obstructive azoospermia in the majority of cases 3
• In men under 30 years with testicular volume <12ml, there is a >34% risk of intratubular germ cell neoplasia in the contralateral testis if testicular cancer is present 9, 8

Important Clinical Caveats

• Age-related atrophy occurs more commonly in men >70 years (38%) compared to those <70 years (7%) in the absence of other risk factors 7
• Testicular atrophy does not necessarily preclude sperm retrieval, as up to 50% of men with non-obstructive azoospermia and testicular atrophy have retrievable sperm with microsurgical testicular sperm extraction 8
• Size discrepancy between testes >2ml or 20% warrants ultrasound evaluation to exclude pathology, regardless of absolute volume 9