How should I evaluate and manage an unexplained shrinking testicle?

Evaluation and Management of Unexplained Testicular Shrinkage

Order an immediate scrotal ultrasound with color Doppler to quantify testicular volume, assess architecture, and exclude masses—this is the single most important first step because volumes <12 mL are definitively atrophic and associated with impaired spermatogenesis and increased cancer risk. 1, 2

Immediate Diagnostic Workup

Imaging

• Use high-frequency ultrasound (>10 MHz) with both grayscale and color/power Doppler to measure testicular volume using the Lambert formula (Length × Width × Height × 0.71), as this provides the most accurate volume estimates. 2, 3
• Measure both testes because a size discrepancy >2 mL or >20% warrants further evaluation to exclude pathology, regardless of absolute volume. 2, 3
• Ultrasound achieves 98-100% accuracy for distinguishing intratesticular from extratesticular processes and is nearly 100% sensitive for detecting intratesticular masses. 1, 3

Laboratory Evaluation

• Draw morning serum FSH, LH, and total testosterone between 08:00-10:00 hours on two separate occasions to differentiate primary testicular failure (elevated FSH/LH) from secondary hypogonadism (low/normal FSH/LH). 2, 4
• Order karyotype analysis if FSH is elevated and testicular volume is <12 mL to screen for Klinefelter syndrome (47,XXY), the most common genetic cause of primary testicular failure. 2
• Measure serum prolactin to exclude hyperprolactinemia as a cause of secondary hypogonadism. 2
• Obtain semen analysis to assess sperm concentration, motility, and morphology, as testicular volume strongly correlates with total sperm count. 2

Critical History Elements to Elicit

• Prior undescended testes (cryptorchidism) dramatically raises the risk of both atrophy and testicular cancer—men with this history have 3.6-7.4 times higher risk of germ cell tumors. 2, 5
• Use of anabolic steroids, exogenous testosterone, chronic opioids, or glucocorticoids—these suppress the hypothalamic-pituitary-gonadal axis and can cause complete azoospermia that may take months to years to recover. 2
• History of chemotherapy or pelvic/testicular radiation, which causes irreversible testicular shrinkage and impaired spermatogenesis for up to 2 years following treatment. 2
• Systemic diseases including type 2 diabetes, chronic liver disease (cirrhosis), chronic kidney disease, or HIV infection—all are associated with functional hypogonadism and reduced testicular volume. 2
• Family history of Klinefelter syndrome or other hypogonadal disorders. 2

Physical Examination Findings to Document

• Assess for varicocele presence, testicular consistency, epididymal abnormalities, and vas deferens patency. 2
• Check for scrotal skin erythema, presence of hydrocele, and inguinal lymphadenopathy. 4
• Examine for signs of hypogonadism including gynecomastia, reduced body hair, and eunuchoid body proportions. 2

Risk Stratification Based on Volume and Age

High-Risk Scenarios Requiring Urgent Urology Referral

• Age <30-40 years with testicular volume <12 mL carries a ≥34% risk of intratubular germ cell neoplasia (TIN) in the contralateral testis if testicular cancer develops. 2
• If TIN is left untreated, approximately 70% progress to invasive testicular cancer within 7 years. 2
• History of cryptorchidism combined with volume <12 mL mandates intensified surveillance and consideration of contralateral testicular biopsy. 2
• At the time of orchidopexy for adult cryptorchidism, testicular biopsy is recommended to exclude TIN, particularly when testicular volume is <12 mL. 2

Borderline Volumes (12-15 mL)

• Volumes of 12-15 mL are considered borderline-small and warrant clinical correlation with fertility status, hormonal parameters, and symptoms. 2
• An elevated FSH (>7.6 IU/L) in a patient with borderline volume indicates reduced testicular reserve and impaired spermatogenic capacity. 2

Common Etiologies by Hormonal Pattern

Primary Testicular Dysfunction (Elevated FSH/LH)

• Klinefelter syndrome (47,XXY)—most common genetic cause, presents with small firm testes <12 mL. 2
• Bilateral cryptorchidism, especially when uncorrected or surgically corrected after puberty. 2, 5
• Myotonic dystrophy (types I and II) can present with painless bilateral testicular atrophy. 2
• Autoimmune orchitis may affect both testes and produce relatively painless atrophic process. 2
• Sickle-cell disease with recurrent vaso-occlusive crises leads to chronic testicular hypoperfusion. 2

Secondary Testicular Dysfunction (Low/Normal FSH/LH)

• Chronic opioid use suppresses GnRH secretion, resulting in low gonadotropins and bilateral atrophy. 2
• Anabolic-steroid or exogenous testosterone use causes complete suppression of spermatogenesis. 2
• Hyperprolactinemia from pituitary adenoma or prolactin-raising medications. 2
• Kallmann syndrome or idiopathic hypogonadotropic hypogonadism. 2

Fertility Preservation and Counseling

• Discuss sperm banking before any surgical intervention or initiation of testosterone therapy, as testicular volume <12 mL strongly correlates with impaired spermatogenesis. 2
• Never start testosterone replacement without first clarifying the patient's fertility intentions, because exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis and can cause complete azoospermia. 2
• Repeat semen analysis every 6-12 months to detect early decline in sperm parameters, as single analyses can be misleading due to natural variability. 2

Critical Pitfalls to Avoid

• Do not rely on physical examination alone—ultrasound is essential because 90% of intratesticular masses are malignant, and palpable intratesticular lesions are highly likely to be malignant. 1, 6
• Do not use the traditional ellipsoid formula (0.52 coefficient) for volume calculation, as it systematically underestimates volume by 20-30% and may lead to inappropriate classification of testicular atrophy. 2
• Do not order ultrasound or other imaging prior to referral in boys with cryptorchidism, as these studies rarely assist in decision-making and surgical exploration is required. 1
• Do not use hormonal therapy to induce testicular descent, as evidence shows low response rates and lack of long-term efficacy. 1

Surveillance and Follow-Up

• Teach testicular self-examination given increased cancer risk with smaller volumes—men should examine monthly for new masses or changes in consistency. 2
• Monitor with repeat ultrasound every 6-12 months if volume is borderline (12-15 mL) and patient has risk factors. 2
• Urgent urology referral is indicated if: palpable testicular mass develops, rapid testicular atrophy occurs, or severe oligospermia (<5 million/mL) develops. 2

When to Consider Testicular Biopsy

• Age <30 years with volume <12 mL and history of cryptorchidism. 2
• Development of testicular mass on examination or ultrasound. 2
• Progression to azoospermia in the setting of previously documented sperm production. 2
• Presence of testicular cancer requiring evaluation of contralateral testis when volume <12 mL. 2