High SHBG Does Not Cause Testicular Atrophy—Only Low Intratesticular Testosterone (ITT) Matters
Testicular atrophy is caused by low intratesticular testosterone (ITT), not by elevated SHBG reducing free testosterone in the bloodstream. Your total testosterone of 40 nmol/L (approximately 1150 ng/dL) is actually quite high, and even if SHBG is reducing your free testosterone, this does not directly cause testicular atrophy.
Understanding the Mechanism
Why ITT—Not Serum Testosterone—Controls Testicular Size
Intratesticular testosterone concentrations are approximately 40 times higher than serum levels (around 822 nmol/L vs. 22.8 nmol/L in healthy men), and this high local concentration is essential for maintaining spermatogenesis and testicular volume 1.
Testicular atrophy occurs when ITT drops dramatically, not when serum free testosterone is reduced by SHBG 1. In studies where men received hormonal contraception that suppressed ITT by 98% (down to levels similar to serum testosterone), sperm production collapsed from 65 million/mL to 1.3 million/mL, demonstrating that serum-level testosterone concentrations within the testes are insufficient to maintain normal testicular function 1.
SHBG elevation affects circulating free testosterone but does not directly impact ITT production 2. In chronic liver disease, where SHBG rises significantly, testicular atrophy occurs through suppression of the hypothalamic-pituitary axis by elevated estrogen (from increased peripheral aromatization), which then reduces LH secretion and subsequently lowers ITT 2.
The SHBG-Free Testosterone Relationship
High SHBG reduces free testosterone by binding more total testosterone, but this is a serum phenomenon 2. Free testosterone represents only 0.5-3% of circulating testosterone, with most bound to SHBG and albumin 3.
Your elevated total testosterone (40 nmol/L) suggests your testes are producing testosterone normally, as this level is well above the normal range (typically 10-30 nmol/L) 2. If you had primary testicular failure causing atrophy, your total testosterone would be low, not high.
What Actually Causes Testicular Atrophy
Primary Mechanisms
Suppression of LH secretion leads to reduced Leydig cell stimulation, which decreases ITT production 1. This can occur from:
Primary testicular failure from conditions like Klinefelter syndrome, where despite normal or even elevated ITT concentrations, structural testicular abnormalities exist 4. Interestingly, men with Klinefelter syndrome have significantly increased ITT despite reduced serum testosterone, possibly due to impaired vascular release of testosterone from the testes 4.
Cryptorchidism exposes testes to core body temperature, causing heat-induced damage to spermatogenesis 2.
Your Specific Situation
With total testosterone of 40 nmol/L, testicular atrophy from hypogonadism is extremely unlikely 2. Consider these possibilities:
If you have actual testicular atrophy on examination, measure LH and FSH levels 2:
- Low LH/FSH with high total testosterone suggests exogenous androgen use or an androgen-secreting tumor
- High LH/FSH suggests primary testicular failure (but this would typically show low total testosterone)
- Normal LH/FSH with high total testosterone and atrophy is unusual and warrants further investigation
If you're concerned about fertility despite high total testosterone, ITT may still be adequate even with elevated SHBG, as ITT production is driven by LH stimulation, not serum free testosterone levels 1.
Clinical Recommendations
Diagnostic Approach
Measure morning LH, FSH, and estradiol to determine if your hypothalamic-pituitary-testicular axis is functioning normally 2.
Assess free testosterone by equilibrium dialysis or calculation (using total testosterone, SHBG, and albumin) rather than direct immunoassay, which is inaccurate 2, 3.
Physical examination for testicular volume is essential—a history alone cannot predict hypogonadism or testicular pathology 5.
Key Pitfall to Avoid
Do not assume that high SHBG causing low free testosterone equals testicular atrophy. The testes respond to LH stimulation and maintain their own high ITT concentrations independent of serum free testosterone levels 1. Testicular atrophy requires either loss of LH stimulation or primary testicular pathology—not simply altered SHBG binding in the circulation 2, 4.
If you have genuine testicular atrophy on examination with total testosterone of 40 nmol/L, this represents an unusual clinical scenario requiring comprehensive endocrine evaluation including imaging and possibly genetic testing 2.