What is the best course of action for an adult male with ongoing testicular atrophy of unknown cause, potentially related to a history of testicular injury, infection, or hormonal imbalances?

Management of Ongoing Testicular Atrophy of Unknown Cause

For an adult male with ongoing testicular atrophy of unknown etiology, the immediate priority is comprehensive diagnostic evaluation with testicular ultrasound, hormonal assessment (testosterone, LH, FSH), and tumor markers (AFP, β-HCG, LDH) to identify the underlying cause and assess cancer risk, followed by treatment decisions based on whether the atrophy is unilateral or bilateral and the functional status of the contralateral testis. 1, 2

Diagnostic Workup

Imaging Assessment

• Perform scrotal ultrasound with high-frequency probes (>10 MHz) as the mandatory first-line imaging to confirm testicular volume using three-dimensional measurements (length × width × height × 0.71), with volumes <12 mL defining atrophy 1, 2
• Ultrasound must also evaluate for underlying pathology including testicular masses, microcalcifications, and assess the contralateral testis 1

Hormonal Evaluation

• Measure serum testosterone, LH, and FSH in the morning to distinguish primary testicular failure from secondary hypogonadism 1, 2
  • Elevated FSH (>7.6 IU/L) with low testosterone indicates primary testicular failure and suggests spermatogenic failure 3
  • Low or low-normal LH with low testosterone suggests secondary hypogonadism from pituitary dysfunction 3
• Obtain tumor markers (AFP, β-HCG, LDH) before any surgical intervention if malignancy is suspected 1, 2

Etiologic Investigation

• Evaluate for history of cryptorchidism, testicular torsion, trauma, infection (orchitis), varicocele, or prior inguinal surgery 1, 4, 5
  • Cryptorchidism is the single most important risk factor and substantially increases cancer risk 3
  • Testicular torsion, even if salvaged, leads to atrophy in approximately 47% of cases on long-term follow-up 5
  • Inguinal hernioplasty can cause testicular atrophy through thrombosis of spermatic cord vessels from surgical trauma 6, 7
• Screen for chronic medication use including opioids, corticosteroids, or anabolic steroids that suppress the hypothalamic-pituitary-gonadal axis 3
• Assess for systemic diseases including HIV/AIDS, diabetes, prior chemotherapy, or testicular radiation 3

Genetic Testing (If Indicated)

• Offer karyotype testing if severe oligospermia or non-obstructive azoospermia is present, as chromosomal abnormalities (particularly Klinefelter syndrome) are more common with testicular atrophy 3
• Consider Y-chromosome microdeletion testing if sperm concentration is <1 million/mL or azoospermia 3

Treatment Algorithm Based on Clinical Scenario

Unilateral Atrophy with Normal Contralateral Testis

• Offer orchiectomy if the contralateral testis demonstrates normal hormonal function and spermatogenesis, as this eliminates the increased cancer risk associated with the atrophic testis 8, 1
• Consider orchidopexy only if biochemical hypogonadism or spermatogenic failure is present and the procedure is technically feasible, though this carries a weak recommendation 8
• The 2025 European Association of Urology guidelines specifically recommend orchiectomy for unilateral undescended/atrophic testes when the contralateral testis is normal, given the 2.75-8 fold increased cancer risk 8

Bilateral Atrophy or Unilateral Atrophy with Compromised Contralateral Testis

• Pursue organ-preserving approaches when possible to maintain androgen production and fertility potential 1
• If testosterone deficiency is confirmed (typically <300 ng/dL on two morning measurements), initiate testosterone replacement therapy 4
  • Start with testosterone gel 50 mg applied topically once daily to shoulders/upper arms 4
  • Measure morning pre-dose testosterone at 14 days; increase to 100 mg daily if levels remain <300 ng/dL 4
• Discuss sperm cryopreservation before any surgical intervention or testosterone therapy that might further compromise fertility 1

Cancer Risk Stratification and Surveillance

• Offer testicular biopsy to patients with atrophic testes (<12 mL) who have additional risk factors including infertility, bilateral atrophy, history of cryptorchidism, or testicular microcalcifications 8, 3
• Teach testicular self-examination to all patients with testicular atrophy due to increased cancer risk, which may allow early detection of testicular germ cell tumors 8, 1
• Do not perform routine testicular biopsy, tumor markers, or imaging in isolated testicular atrophy without associated risk factors 8

Fertility Considerations

• Consider microsurgical testicular sperm extraction (micro-TESE) for men with non-obstructive azoospermia, as it is 1.5 times more successful than conventional extraction 3
• Elevated FSH >7.6 IU/L with testicular atrophy strongly predicts spermatogenic failure, but focal areas of preserved spermatogenesis may still exist 3

Long-Term Monitoring

• Monitor testosterone levels regularly in patients with bilateral atrophy or post-orchiectomy, as these patients are at high risk for developing hypogonadism 1, 5
  • Testicular torsion with salvage or orchiectomy has negative long-term impact on serum testosterone 5
• Perform annual physical examination with attention to the contralateral testis to detect changes in volume or consistency 1, 2
• Reassess testicular volume periodically, as progressive atrophy may occur even after initial stabilization 1

Critical Pitfalls to Avoid

• Do not fail to consider fertility preservation before definitive treatment, as this is the most common regrettable oversight 1
• Do not overlook the increased testicular cancer risk, particularly in patients with cryptorchidism history where the relative risk is 2.75-8 fold higher 8, 3
• Do not treat subclinical varicoceles found incidentally on ultrasound, as only palpable varicoceles benefit from surgical repair 8, 3
• Do not assume bilateral atrophy has the same management as unilateral atrophy—bilateral cases require more conservative, organ-preserving approaches 1
• Do not delay evaluation in progressive atrophy, as the underlying cause (particularly malignancy) requires prompt identification 1, 2