What are the possible causes of unexplained testicular atrophy and how should it be evaluated?

Evaluation of Unexplained Testicular Atrophy

Testicular atrophy without an obvious cause requires a systematic evaluation focusing on hormonal status, anatomical abnormalities, and prior surgical or traumatic history, with the primary goal of identifying reversible causes and assessing fertility potential. 1, 2

Initial Clinical Assessment

Your evaluation should focus on these specific findings:

Physical Examination Priorities

• Measure testicular volume bilaterally – atrophic testes (typically <15 mL) suggest primary testicular failure, while normal-sized testes point toward obstruction or other causes 2

• Palpate for vas deferens bilaterally – absence indicates congenital bilateral absence of vas deferens (CBAVD), which can be diagnosed by physical examination alone 3, 2

• Assess for varicoceles – palpable varicoceles are a treatable cause of testicular atrophy and impaired spermatogenesis 3

• Evaluate secondary sexual characteristics – assess hair distribution, breast development, and body habitus for signs of hypogonadism 2

• Document any history of scrotal trauma, inguinal hernia repair, or testicular torsion – these are well-established causes of secondary testicular atrophy 4, 5, 6, 7

Essential Laboratory Testing

The hormonal profile will guide your differential diagnosis:

• Serum testosterone and FSH are mandatory first-line tests – elevated FSH (>7.6 IU/L) with low testosterone indicates primary testicular failure, while low testosterone with low/normal FSH suggests hypogonadotropic hypogonadism 3, 2

• Add LH measurement to complete the hormonal assessment and distinguish primary from secondary hypogonadism 2

• If considering fertility evaluation, obtain a semen analysis – this will determine whether atrophy has resulted in azoospermia or oligospermia 2

Imaging Studies

Do not order routine scrotal ultrasound unless the physical examination is inadequate or you suspect a testicular mass – imaging rarely changes management for testicular atrophy alone 8, 1, 2

However, ultrasound is indicated when:

• Physical examination is difficult or inconclusive 2
• You suspect a testicular tumor (testicular microcalcifications carry an 18-fold higher cancer risk in infertile men) 2
• You need to quantify testicular volume objectively 2
• Color Doppler can assess blood flow – atrophied testes typically show decreased arterial velocity and increased resistive index 2

Differential Diagnosis Based on Findings

Primary Testicular Failure Pattern

• Atrophic testes + elevated FSH (>7.6 IU/L) + low testosterone 2
• This indicates irreversible spermatogenic failure
• Genetic testing is mandatory: karyotype and Y-chromosome microdeletion analysis 2

Hypogonadotropic Hypogonadism Pattern

• Atrophic testes + low testosterone + low/normal FSH and LH 3, 2
• This is potentially reversible with appropriate hormonal therapy
• Critical pitfall: Never prescribe testosterone replacement if fertility is desired – it will suppress spermatogenesis further 2

Post-Surgical or Post-Traumatic Atrophy

• History of inguinal hernia repair, orchiopexy, or testicular torsion 4, 5, 6
• Atrophy results from ischemia due to vascular compromise during surgery or from the initial torsion event 4
• Scrotal trauma causes atrophy in approximately 50% of cases 7

Hormone-Secreting Tumors (Rare but Important)

• Estrogen-secreting adrenal tumors can cause testicular atrophy in men, along with gynecomastia 8
• Consider if you find gynecomastia on examination

Common Pitfalls to Avoid

• Do not assume bilateral disease means symmetric pathology – unilateral atrophy from torsion or trauma does not cause "sympathetic orchiopathy" of the contralateral testis; bilateral findings suggest primary bilateral disease 4

• Do not order imaging as your first step – physical examination and hormonal testing are more informative and cost-effective 8, 1

• Do not miss acquired cryptorchidism – a previously descended testis that has ascended carries the same fertility and cancer risks as congenital undescended testes 1

• Do not delay genetic testing if azoospermia is confirmed – results impact counseling and treatment decisions before assisted reproduction 3, 2

Long-Term Surveillance

• Men with testicular atrophy require lifelong surveillance for testicular cancer, with relative risk 2.75-8 times higher than the general population 1

• Teach monthly testicular self-examination after puberty for early detection of malignancy 1

• If fertility is a concern and primary testicular failure is confirmed, refer to reproductive endocrinology for discussion of sperm retrieval techniques (testicular sperm extraction with ICSI) 2