What is the typical rate of testicular size reduction in milliliters (ml) per year in cases of low testosterone, infection (e.g. epididymitis or orchitis), or varicocele?

Rate of Testicular Size Reduction in Low Testosterone, Infection, and Varicocele

Testicular atrophy from varicocele causes a mean volume loss of approximately 3.1 ml in fertile men and 2.5 ml in infertile men, but this represents cumulative atrophy rather than an annual rate, as the timeline of progression is not well-defined in the literature. 1, 2

Varicocele-Related Testicular Atrophy

Varicocele causes significant ipsilateral testicular atrophy/hypotrophy, with mean testicular volume differences of 3.1 ± 0.4 ml in fertile men and 2.5 ± 0.6 ml in infertile men with varicoceles, compared to 1.6 ± 0.3 ml in men without varicoceles. 1, 2 However, this volume loss does not correlate with fertility status or hormonal parameters, meaning the degree of atrophy alone cannot predict reproductive outcomes. 1, 2

Mechanisms and Progression

The pathophysiology involves multiple mechanisms that cause progressive testicular damage: 3, 1

• Higher scrotal temperature 3, 1
• Testicular hypoxia 3, 1
• Reflux of toxic metabolites 3, 1
• Increased DNA damage 3, 1

Progressive testicular atrophy is defined as a size difference >2 ml or 20% confirmed on two visits 6 months apart, which represents a strong indication for varicocele repair. 1 This guideline provides the only specific timeframe in the literature: meaningful progression occurs over a 6-month observation period. 1

Clinical Significance

Higher varicocele grade (particularly grade 3) is associated with worse semen parameters and greater testicular dysfunction. 3, 4, 5 In patients with bilateral grade 3 varicocele, left and right testicular volumes are highly significantly decreased compared to controls. 5

Approximately 80% of men with varicoceles remain fertile despite testicular atrophy, indicating that volume loss alone does not determine fertility outcomes. 1

Low Testosterone and Testicular Atrophy

Men with varicoceles have significantly lower testosterone levels (mean 416 ng/dL) compared to men without varicoceles (mean 469 ng/dL), and this difference persists across age groups. 6 The relationship between testosterone and testicular atrophy in varicocele patients shows a significant inverse linear correlation between age and plasma testosterone concentration. 7

Bilateral grade 3 varicocele is associated with highly significantly decreased serum testosterone in male infertility patients and significantly decreased testosterone in impotent patients compared to controls. 5

Reversibility

Microsurgical varicocele repair results in significant increases in serum testosterone levels in more than two-thirds of men, with mean increases from 358 ng/dL to 454 ng/dL postoperatively. 6 Of patients with postoperative improvement: 6

• 41% increased testosterone by ≤50%
• 19% increased by 51-100%
• 10% increased by >100%

Infection-Related Testicular Atrophy

Epididymo-orchitis can lead to progressive inflammation and testicular damage, though specific rates of volume loss per year are not established in the literature. 3, 8 Acute epididymo-orchitis is the most common cause of acute scrotal pain in adults and adolescent boys, with up to 20% concomitant rate for orchitis. 3

Rarely, acute epididymo-orchitis can be complicated by global testicular infarction, which represents catastrophic rather than gradual volume loss. 3

Trauma-Related Atrophy

Testicular atrophy following blunt scrotal trauma occurs in approximately 50% of patients, with significant reduction in volume observed at follow-up sonography. 9 The timeline for this atrophy development varies, but it represents a distinct mechanism from the gradual progression seen in varicocele or chronic conditions. 9

Critical Clinical Caveats

The literature does not provide specific annual rates of testicular volume loss (ml/year) for any of these conditions. The available data describes cumulative volume differences or progression over 6-month observation periods rather than annualized rates. 1, 2

Severe testicular atrophy (volumes ≤2 ml) is associated with non-obstructive azoospermia in the majority of cases, while moderate atrophy (volumes <12 ml but >2 ml) typically presents with oligospermia. 8 Testicular volumes <12 ml are definitively considered atrophic and associated with impaired spermatogenesis. 8

FSH levels >7.6 IU/L suggest underlying spermatogenic dysfunction and are negatively correlated with the number of spermatogonia, serving as a hormonal marker that accompanies testicular atrophy. 1, 8