What are the causes of testicular atrophy in an adult male, aside from varicoceles?

Causes of Testicular Atrophy Beyond Varicoceles

Testicular atrophy in adult males has numerous etiologies beyond varicoceles, including cryptorchidism, Klinefelter syndrome, testicular torsion, chemotherapy/radiation, anabolic steroid use, chronic opioid use, autoimmune orchitis, and systemic diseases such as cirrhosis, chronic kidney disease, and HIV infection. 1, 2

Primary Testicular Dysfunction (Hypergonadotropic Hypogonadism)

Genetic and Congenital Causes

• Klinefelter syndrome (47,XXY) is the most common genetic cause of primary testicular failure and should be considered when testicular volume is <12 mL with elevated FSH. 2
• History of cryptorchidism (undescended testes), especially when uncorrected or surgically corrected after puberty, markedly increases the risk of testicular atrophy and is the single most important risk factor to identify. 1, 2
• Myotonic dystrophy (type I and II) can present with painless bilateral testicular atrophy due to primary gonadal failure. 2

Acquired Testicular Damage

• Testicular torsion and atrophy can result in permanent testicular damage if not promptly treated. 1
• Prior chemotherapy or pelvic/testicular radiation is a recognized cause of irreversible testicular shrinkage, with spermatogenesis usually recovering 1–4 years after chemotherapy but DNA damage persisting for up to 2 years. 1, 2
• Autoimmune orchitis may affect both testes and produce a relatively painless atrophic process. 2
• Sickle-cell disease with recurrent vaso-occlusive crises can lead to chronic testicular hypoperfusion and atrophy. 2
• Surgical trauma from inguinal hernioplasty can cause testicular atrophy due to thrombosis of the veins of the spermatic cord from surgical dissection. 3

Secondary Testicular Dysfunction (Hypogonadotropic Hypogonadism)

Exogenous Hormone Suppression

• Anabolic steroid or exogenous testosterone use causes complete suppression of spermatogenesis through negative feedback and can produce persistent atrophy for months to years after cessation. 2, 4
• Chronic opioid use suppresses GnRH secretion, resulting in low gonadotropins and bilateral testicular atrophy. 2, 4

Pituitary and Hypothalamic Disorders

• Hyperprolactinemia from pituitary adenoma or prolactin-raising medications leads to secondary hypogonadism and testicular shrinkage. 2
• Kallmann syndrome or idiopathic hypogonadotropic hypogonadism present with low LH/FSH and small testes. 2

Systemic Conditions Associated with Testicular Atrophy

• Type 2 diabetes mellitus/metabolic syndrome is linked to functional hypogonadism and reduced testicular volume. 2
• Chronic liver disease (cirrhosis) contributes to secondary hypogonadism and testicular atrophy. 2
• Chronic kidney disease is associated with decreased testosterone production and testicular size. 2
• HIV infection can cause both primary and secondary gonadal dysfunction leading to atrophy. 2

Diagnostic Workup Algorithm

Laboratory Evaluation (Priority Order)

1. Morning serum FSH, LH, and total testosterone on two separate days (08:00–10:00 h) to differentiate primary from secondary hypogonadism. 2
2. Karyotype analysis when FSH is elevated and testicular volume is <12 mL to screen for Klinefelter syndrome. 2, 4
3. Serum prolactin to exclude hyperprolactinemia as a cause of secondary hypogonadism. 2
4. Y-chromosome microdeletion testing if sperm concentration is <1 million/mL or azoospermia is present. 4, 5

Imaging

• Scrotal ultrasound with Doppler to quantify testicular volume, assess architecture, and rule out masses; volumes <12 mL are considered definitively atrophic. 2, 4

Critical History Elements to Elicit

• Prior undescended testes dramatically raises the risk of atrophy and testicular cancer. 1, 2
• Use of anabolic steroids, testosterone, opioids, or glucocorticoids should be elicited as potential etiologic factors. 2, 4
• History of chemotherapy or radiation to the pelvis/testes warrants focused evaluation. 1, 2
• Family history of Klinefelter syndrome or other hypogonadal disorders is a pertinent clue. 2
• Presence of systemic disease (diabetes, liver disease, chronic infection) should be documented. 2

Cancer Risk Considerations

Men younger than 30–40 years with testicular volume <12 mL have a ≥34% risk of concurrent testicular intraepithelial neoplasia (TIN) in the contralateral testis if testicular cancer develops. 1, 2

• If TIN is left untreated, approximately 70% progress to invasive testicular cancer within 7 years. 1, 2
• History of cryptorchidism combined with testicular volume <12 mL markedly increases malignancy risk and mandates intensified surveillance. 1, 2
• Testicular biopsy should be considered for men with atrophic testes (<12 mL), age <30 years, history of cryptorchidism, or presence of testicular microcalcifications. 1, 4

Common Pitfalls to Avoid

• Never initiate testosterone replacement without first clarifying fertility intentions, as exogenous testosterone can cause complete azoospermia that may take months to years to recover. 2, 4
• Do not treat subclinical (non-palpable) varicoceles, as treatment is not effective at increasing chances of spontaneous pregnancy. 1, 5
• Approximately 80% of men with varicoceles remain fertile despite testicular atrophy, so normal sperm count does not exclude varicocele as a cause but does not mandate treatment. 5, 6
• Obtain at least two semen analyses separated by 2–3 months for accurate diagnosis, as single analyses can be misleading due to natural variability. 4