What is the best course of action for an adult male with bilateral testicular atrophy (shrinkage of the testicles) without evidence of varicocele, infection, or hormonal abnormalities?

Bilateral Testicular Atrophy Without Varicocele, Infection, or Hormonal Abnormalities

You need immediate comprehensive evaluation including repeat hormonal testing with FSH, LH, and testosterone, semen analysis, genetic testing (karyotype and Y-chromosome microdeletion), scrotal ultrasound to confirm testicular volumes and exclude occult pathology, and assessment for testicular cancer risk factors—particularly if you are under 30-40 years old or have a history of cryptorchidism. 1, 2

Critical First Steps: Confirm the Diagnosis

Verify Testicular Volume Measurements

• Testicular volumes below 12ml are definitively considered atrophic and associated with significant pathology including impaired spermatogenesis and increased cancer risk 1, 2
• If ultrasound was performed, request repeat imaging using the Lambert formula (Length × Width × Height × 0.71) rather than the traditional ellipsoid formula (0.52 coefficient), as the latter systematically underestimates volume by 20-30% and may lead to misdiagnosis 2
• Use high-frequency probes (>10 MHz) to maximize resolution and accurate caliper placement 2
• Size discrepancy between testes greater than 2ml or 20% warrants further evaluation to exclude pathology, regardless of absolute volume 1, 2

Reconfirm "Normal" Hormonal Status

• FSH levels above 7.6 IU/L indicate spermatogenic failure, even if technically within the laboratory's reference range 1
• You stated hormones are normal, but if FSH is between 7.6-12 IU/L, this represents borderline-elevated levels suggesting reduced testicular reserve 1
• Measure complete hormonal panel: FSH, LH, total testosterone, and consider SHBG to calculate free testosterone, as the pattern helps distinguish primary testicular dysfunction from secondary causes 1

Essential Diagnostic Workup

Semen Analysis

• Obtain semen analysis immediately to assess sperm concentration, motility, and morphology, as testicular volume strongly correlates with total sperm count 1, 2
• The assessment of combined ejaculate parameters (concentration, motility, morphology, total count) is more predictive of testicular function than any single parameter 1

Genetic Testing

• Karyotype testing is strongly recommended for males with severe oligospermia or non-obstructive azoospermia, as chromosomal abnormalities are more common in this population 1
• Y-chromosome microdeletion testing should be offered if sperm concentration is <1 million/mL or azoospermia is present 1
• Klinefelter syndrome (47,XXY) is the most common chromosomal abnormality associated with testicular atrophy and spermatogenic failure 1

Imaging Confirmation

• Scrotal ultrasound provides accurate testicular volume assessment and can identify structural abnormalities, masses, or occult varicoceles 1, 2
• Ultrasound is particularly indicated when there is size discrepancy between testes, or when physical examination is difficult 2

Cancer Risk Stratification

High-Risk Features Requiring Urgent Evaluation

• If you are under 30-40 years old with testicular volume <12ml, you have a >34% risk of intratubular germ cell neoplasia (TIN) if testicular cancer develops 1, 2
• If untreated, invasive testicular tumor develops in 70% of TIN-positive testes within 7 years 2
• History of cryptorchidism is the single most important risk factor and substantially increases cancer risk 1

Surveillance Recommendations

• You should be taught testicular self-examination given increased cancer risk with smaller volumes 1, 2
• Men with testicular atrophy and testicular microcalcification should be offered testicular biopsy due to increased risk of testicular germ cell tumors 1
• Testicular microcalcifications increase testicular cancer risk 18-fold in this population 1

Evaluate for Underlying Causes

Medication and Substance History

• Chronic opioid use, corticosteroids, or anabolic steroids can suppress the hypothalamic-pituitary-gonadal axis, leading to testicular atrophy 1
• Even if current hormones appear "normal," prior suppression may have caused irreversible damage 1

Systemic Disease Assessment

• HIV/AIDS, diabetes, prior chemotherapy, or testicular radiation can cause progressive testicular damage 1
• Obtain detailed history focusing on cryptorchidism, prior testicular trauma, mumps orchitis, or family history of testicular cancer 1, 2

Exclude Occult Varicocele

• While you stated no varicocele is present, subclinical (non-palpable) varicoceles can only be detected by ultrasound 1
• However, treatment of subclinical varicoceles is not effective at improving fertility outcomes, so this is primarily for diagnostic completeness 1, 3

Management Based on Findings

If Semen Analysis Shows Abnormalities

• Microsurgical testicular sperm extraction (micro-TESE) may be considered for non-obstructive azoospermia to search for areas of preserved spermatogenesis 1
• Micro-TESE is 1.5 times more successful than non-microsurgical extraction in men with non-obstructive azoospermia 1
• Discuss fertility preservation options, such as sperm banking, particularly if you may undergo treatments that could further impair fertility 2

If High Cancer Risk Features Present

• Refer to urology for consideration of testicular biopsy if: age <30 years, history of cryptorchidism, bilateral small testes with infertility, or presence of testicular microcalcification 1, 2
• Contralateral testicular biopsy is strongly indicated if testicular cancer develops, given the 34% TIN risk 2

Ongoing Monitoring

• Repeat hormonal evaluation (FSH, LH, testosterone) every 6-12 months to monitor for progression 1
• Monitor for rapid testicular atrophy or development of palpable masses, which require urgent urology referral 1
• Changes in the contralateral testicle should be monitored, as bilateral involvement is common even in seemingly unilateral conditions 1

Critical Pitfalls to Avoid

• Do not accept "normal" hormones at face value—FSH >7.6 IU/L indicates spermatogenic failure even if within lab reference range 1
• Do not use the 0.52 ellipsoid formula for testicular volume—it systematically underestimates volume and may miss true atrophy 2
• Do not delay genetic testing if semen analysis shows severe oligospermia (<5 million/mL)—chromosomal abnormalities occur in 10% of these patients 1
• Do not ignore testicular atrophy in young men (<30-40 years)—cancer risk is substantially elevated and requires aggressive surveillance 1, 2