What could be causing my perceived testicular atrophy with normal testosterone levels, but high Sex Hormone-Binding Globulin (SHBG) and no evidence of varicocele or infection?

Perceived Testicular Atrophy with High SHBG and Normal Total Testosterone

Your perceived testicular atrophy with high SHBG but normal total testosterone most likely reflects either true testicular dysfunction with compensatory hormonal changes, or a measurement artifact where high SHBG is masking low bioavailable testosterone—the critical next step is obtaining a morning free testosterone by equilibrium dialysis, repeat semen analysis, and scrotal ultrasound to measure actual testicular volume. 1, 2

Understanding Your Hormone Profile

Your situation is diagnostically complex because high SHBG creates a disconnect between total and bioavailable testosterone:

• High SHBG binds testosterone tightly, reducing the free (bioavailable) fraction that actually enters cells and supports spermatogenesis, even when total testosterone appears normal or elevated 1, 3
• Intratesticular testosterone concentrations are 50-100 times higher than serum levels and are essential for normal spermatogenesis—these are maintained by LH stimulation of Leydig cells, independent of circulating total testosterone or SHBG levels 2
• If your LH is elevated or high-normal, this suggests your pituitary is compensating for testicular resistance or dysfunction, which could explain perceived atrophy 2

Essential Diagnostic Workup

Immediate Laboratory Testing

• Measure morning free testosterone by equilibrium dialysis (8-10 AM, fasting)—this is the gold standard method and will reveal if high SHBG is masking true hypogonadism 1
• Obtain LH and prolactin levels to determine if this represents primary testicular dysfunction versus secondary hypogonadism 1, 2
• Check thyroid function (TSH, free T4) as hyperthyroidism directly increases SHBG production and can disrupt spermatogenesis—even subtle thyroid over-replacement significantly affects SHBG 2
• Assess metabolic factors: fasting glucose, HbA1c, lipid panel, as metabolic stress affects the hypothalamic-pituitary-gonadal axis 2

Imaging and Physical Assessment

• Scrotal ultrasound with testicular volume measurement is the definitive way to confirm or refute testicular atrophy—subjective perception is unreliable 1, 4
• Testicular volumes <12 mL are definitively atrophic and associated with significant spermatogenic dysfunction 4, 5
• Ultrasound can identify varicocele (present in up to 15% of men), which causes progressive testicular atrophy and is reversible with microsurgical repair 6, 7
• Look for heterogeneous testicular echogenicity which may indicate prior subclinical orchitis, trauma, or torsion 5

Semen Analysis

• Perform at least two semen analyses separated by 2-3 months to correlate hormone levels with actual reproductive function—single analyses are misleading due to natural variability 2, 8
• If sperm concentration is <5 million/mL, obtain karyotype analysis and Y-chromosome microdeletion testing (AZFa, AZFb, AZFc regions) 2, 8

Most Likely Diagnostic Scenarios

Scenario 1: High SHBG Masking True Hypogonadism

• If free testosterone by equilibrium dialysis is low (<50-70 pg/mL), you have functional hypogonadism despite "normal" total testosterone 1
• Causes of elevated SHBG include: hyperthyroidism, liver disease, medications (anticonvulsants), aging, and genetic factors 1, 2
• This pattern can impair spermatogenesis even with normal total testosterone, as bioavailable testosterone is what matters for testicular function 2

Scenario 2: Compensated Primary Testicular Dysfunction

• If LH is elevated (>9-10 IU/L) with high-normal total testosterone, this indicates your pituitary is working overtime to compensate for testicular resistance 2
• This pattern suggests progressive testicular dysfunction that may eventually lead to overt hypogonadism and further atrophy 2, 7
• Varicocele is a common reversible cause—microsurgical varicocelectomy improves testosterone levels in men with varicocele and borderline-low testosterone 7

Scenario 3: Subclinical Testicular Pathology

• Prior subclinical orchitis, trauma, or torsion can cause testicular atrophy without obvious clinical history 5, 9
• Cryptorchidism history (even if corrected in childhood) leads to progressive testicular atrophy and dysfunction 9
• Ultrasound findings of heterogeneous echogenicity, calcifications, or volume asymmetry >20% support this diagnosis 5

Critical Management Principles

What NOT To Do

• Never start exogenous testosterone therapy if fertility is a concern—it will completely suppress LH and FSH through negative feedback, eliminating intratesticular testosterone production and causing azoospermia that can take months to years to recover 2
• Do not rely on total testosterone alone when SHBG is elevated—you must measure free testosterone by equilibrium dialysis 1

Addressing Reversible Causes

• Optimize thyroid function if TSH is abnormal—bring TSH into the lower portion of the reference range if currently in the upper half 2
• Weight optimization and metabolic control can normalize gonadotropins and improve testosterone levels in functional hypogonadism 2
• Varicocele repair should be considered if palpable varicocele is present, as microsurgical varicocelectomy improves both testosterone levels and semen parameters 7

Fertility Preservation Considerations

• If testicular volumes are <12 mL bilaterally and semen analysis shows oligospermia, strongly consider sperm cryopreservation now—the risk of progressive spermatogenic failure is high 2, 4
• Once azoospermia develops, even microsurgical testicular sperm extraction (micro-TESE) only achieves 40-50% sperm retrieval rates 2
• Collect at least 2-3 ejaculates for cryopreservation if possible, as this provides backup samples 2

Common Pitfalls to Avoid

• Assuming normal total testosterone means normal testicular function when SHBG is elevated—this is the most common diagnostic error 1, 2
• Relying on subjective assessment of testicular size—ultrasound measurement is essential for accurate diagnosis 4, 5
• Failing to check thyroid function in men with high SHBG—thyroid hormone directly increases SHBG production 2
• Not obtaining repeat semen analyses—single analyses are insufficient due to high biological variability 8

Next Steps Algorithm

1. Obtain morning free testosterone by equilibrium dialysis, LH, prolactin, TSH, and free T4 1, 2
2. Schedule scrotal ultrasound with testicular volume measurement 1, 4
3. Perform two semen analyses separated by 2-3 months 2, 8
4. If free testosterone is low: address reversible causes (thyroid, metabolic factors, varicocele) before considering testosterone replacement 2, 7
5. If testicular volumes <12 mL and oligospermia present: discuss sperm cryopreservation urgently 2, 4
6. If semen analysis shows severe oligospermia (<5 million/mL): obtain genetic testing (karyotype, Y-chromosome microdeletions) 2, 8