What are the possible causes of asymptomatic bilateral testicular atrophy in an adult male with testicular volumes of approximately 9 mL?

Asymptomatic Bilateral Testicular Atrophy: Causes and Evaluation

Understanding Your Testicular Volume

Testicular volumes of 9 mL bilaterally represent definitive testicular atrophy, as volumes below 12 mL are considered atrophic and associated with significant pathology including impaired spermatogenesis. 1, 2

Your testicular size is approximately 25% below the normal threshold, which warrants comprehensive evaluation even without symptoms.

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Primary Causes of Bilateral Testicular Atrophy

Genetic and Chromosomal Abnormalities

• Klinefelter syndrome (47,XXY) is the most common chromosomal abnormality causing bilateral testicular atrophy and spermatogenic failure 1
• Y-chromosome microdeletions (AZFa, AZFb, AZFc regions) can cause progressive testicular atrophy with oligospermia or azoospermia 1, 3
• Karyotype abnormalities and structural chromosomal anomalies are established genetic causes 3

Hormonal Causes

• Hypogonadotropic hypogonadism (low LH/FSH with low testosterone) from pituitary dysfunction causes bilateral atrophy 1
• Exogenous testosterone or anabolic steroid use suppresses the hypothalamic-pituitary-gonadal axis, causing reversible testicular atrophy and azoospermia 1, 3
• Chronic opioid or corticosteroid use can suppress gonadotropin production leading to atrophy 1

Congenital and Developmental Factors

• History of cryptorchidism (undescended testicles) is the single most important risk factor, substantially increasing both atrophy risk and testicular cancer risk 1, 2
• Even the contralateral descended testis in unilateral cryptorchidism may have structural abnormalities including smaller volume 1

Acquired Conditions

• Varicocele can cause progressive bilateral testicular damage, particularly when bilateral hypotrophy is present 4
• Scrotal trauma causes testicular atrophy in 50% of cases at long-term follow-up 5
• Systemic diseases including HIV/AIDS, diabetes, prior chemotherapy, or testicular radiation cause progressive testicular damage 1
• Cystic fibrosis with CFTR mutations has been associated with bilateral testicular atrophy 6

Environmental and Occupational Exposures

• Exposure to toxins such as lead and cadmium 3
• Occupational exposures including oil and natural gas extraction 3

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Essential Diagnostic Workup

Hormonal Evaluation (First Priority)

• Measure FSH, LH, and total testosterone on morning samples on at least two separate occasions to distinguish primary testicular dysfunction from secondary hypogonadism 1
• FSH >7.6 IU/L with testicular atrophy strongly suggests spermatogenic failure 1, 3
• Low or low-normal LH with low-normal testosterone suggests secondary hypogonadism requiring prolactin measurement 1

Semen Analysis

• Obtain at least two semen analyses separated by 2-3 months, as single analyses can be misleading due to natural variability 1
• Testicular volume of 9 mL strongly correlates with impaired spermatogenesis, reduced total sperm count, and decreased sperm concentration 2, 7
• Sperm count and motility decrease in accordance with testicular volume, with bilateral atrophy showing the lowest mean values 7

Genetic Testing (Mandatory if Severe Oligospermia or Azoospermia)

• Karyotype analysis is strongly recommended for males with severe oligospermia or non-obstructive azoospermia, as chromosomal abnormalities occur in 10% of these patients 1, 2
• Y-chromosome microdeletion testing should be offered if sperm concentration is <1 million/mL or azoospermia is present 1, 3

Physical Examination Priorities

• Assess for palpable varicocele on standing examination, as bilateral hypotrophy with varicocele predicts severe impairment 4
• Evaluate testicular consistency, epididymal abnormalities, and vas deferens patency 1
• Check for signs of hypogonadism including reduced secondary sexual characteristics 1

Imaging

• Scrotal ultrasound is indicated to accurately assess testicular volume using the Lambert formula (Length × Width × Height × 0.71) 1, 2
• High-frequency probes (>10 MHz) should be used to maximize resolution and accurate caliper placement 1
• Evaluate for testicular microcalcifications, which increase testicular cancer risk 18-fold in this population 1, 8

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Critical Cancer Risk Considerations

Men with testicular volume <12 mL have significantly increased risk of testicular cancer and intratubular germ cell neoplasia (TIN). 1, 2

Specific Risk Factors

• If age <30-40 years with volume <12 mL, there is a >34% risk of TIN in the contralateral testis 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 with atrophic testes warrants testicular biopsy to screen for TIN 2

Surveillance Recommendations

• Teach testicular self-examination given increased cancer risk with smaller volumes 1, 2
• Consider testicular biopsy if: age <30 years with history of cryptorchidism, testicular microcalcifications present, or testicular cancer develops 1, 2

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Fertility Implications and Preservation

Current Fertility Status

• Bilateral testicular atrophy with volumes of 9 mL typically presents with oligospermia rather than complete azoospermia 3
• FSH levels >7.6 IU/L indicate impaired but not necessarily absent spermatogenesis 1, 3

Fertility Preservation Strategy

• Bank sperm immediately if any sperm are present in ejaculate, preferably 2-3 separate collections with 2-3 days abstinence between collections 1
• This provides insurance against technical failures, poor post-thaw recovery, or progressive decline 1
• Once azoospermia develops, even microsurgical testicular sperm extraction (micro-TESE) only achieves 40-50% sperm retrieval rates 1

Critical Avoidance

• Never use exogenous testosterone or anabolic steroids if fertility is desired, as these cause complete azoospermia through negative feedback that can take months to years to recover 1, 3

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Treatment Considerations Based on Underlying Cause

If Secondary Hypogonadism Identified

• Human chorionic gonadotropin (hCG) injections as first-line treatment can restore testosterone production and spermatogenesis 1
• FSH analogues may be added if sperm counts remain low after testosterone normalizes on hCG 1

If Varicocele Present

• Varicocele repair is strongly indicated with clinical (palpable) varicocele, documented testicular atrophy, and elevated FSH 4
• Correction can halt progression of testicular atrophy and potentially reverse some damage 4
• Men with bilateral hypotrophy and varicocele are nearly 9 times more likely to have severely impaired semen quality 4

If Non-Obstructive Azoospermia Develops

• Microsurgical testicular sperm extraction (micro-TESE) offers the best chance of retrieving sperm, with success rates of 40-50% despite elevated FSH 1, 3
• Micro-TESE is 1.5 times more successful than conventional TESE 1

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Common Pitfalls to Avoid

• Do not treat subclinical varicoceles found only on ultrasound, as only palpable varicoceles improve fertility outcomes after repair 1
• Do not rely on single semen analysis due to natural variability—always obtain at least two samples separated by 2-3 months 1
• Do not use the traditional ellipsoid formula (0.52 coefficient) for testicular volume calculation, as it systematically underestimates volume by 20-30% 2
• Do not assume normal fertility based on testicular size alone—semen analysis is essential to correlate volume with actual reproductive function 2