Is Low Free Testosterone Due to High SHBG the Likely Cause of Atrophy?
Yes, low free testosterone due to elevated SHBG can cause testicular atrophy and other hypogonadal symptoms, even when total testosterone appears normal or high, because free testosterone is the bioactive form that drives tissue function. 1
Understanding the Mechanism
The critical issue is that SHBG binds testosterone and renders it biologically inactive—only free testosterone can enter tissues and exert physiological effects. 2 When SHBG is elevated, less testosterone is available to tissues including the testes, brain centers regulating libido, and muscle, regardless of how high total testosterone measures. 1
Your LH of 7 mIU/mL (assuming normal range ~1.5-9.3) suggests your pituitary is appropriately responding to low free testosterone by increasing gonadotropin output, but the elevated SHBG is preventing adequate free testosterone delivery to tissues. 2 This represents a form of functional hypogonadism where the hormonal axis is working, but SHBG interference creates tissue-level androgen deficiency. 1
Clinical Significance for Atrophy
Testicular atrophy specifically requires sustained low intratesticular testosterone levels. 2 With normal LH signaling, your testes should maintain reasonable size unless there's primary testicular pathology or the SHBG elevation is so severe that even intratesticular testosterone production is compromised.
If you're experiencing muscle atrophy, reduced lean body mass, or loss of secondary sexual characteristics, these are more consistent with low free testosterone effects on peripheral tissues. 2 Testosterone deficiency causes reduced lean body mass, increased abdominal fat, and decreased muscle strength. 2
A subset of men with elevated SHBG and normal total testosterone will have frankly low free testosterone levels that cause symptomatic hypogonadism. 2 In one study of men with erectile dysfunction, 17.2% had normal total testosterone but low calculated free testosterone, with 74.2% of these being over 60 years old. 3
Diagnostic Confirmation Required
You must measure calculated free testosterone by equilibrium dialysis to confirm functional hypogonadism—total testosterone alone is insufficient and misses approximately half of diagnoses when SHBG is elevated. 1, 3, 4
Repeat morning (8-10 AM) measurements of total testosterone, SHBG, and calculated free testosterone on at least two separate occasions. 2, 1
A free testosterone index (total testosterone/SHBG ratio) <0.3 indicates functional hypogonadism. 1
Calculated free testosterone <6.5 ng/dL is considered low. 3
Common Causes of Elevated SHBG to Investigate
Before attributing symptoms solely to SHBG, rule out secondary causes: 2, 1
- Hyperthyroidism (check TSH, free T4)
- Liver disease (check liver function tests)
- Medications: oral estrogens, anticonvulsants, antiandrogens
- HIV infection (if risk factors present)
- Aging (SHBG increases steeply after age 60, with 52.5% of men over 60 having elevated SHBG) 3
Management Algorithm
If calculated free testosterone is confirmed low on repeat testing:
First-line: Address reversible causes 1
- Treat hyperthyroidism if present
- Discontinue SHBG-elevating medications if possible
- Optimize metabolic health and body composition (lower body fat increases free testosterone availability) 5
Second-line: Consider testosterone replacement therapy if free testosterone remains frankly low after addressing reversible causes 2, 1
Critical Pitfall to Avoid
Relying on total testosterone alone will miss your diagnosis if free testosterone is truly low. 3, 4 Current screening recommendations that use only total testosterone are inadequate when SHBG is elevated, particularly in men over 60 years where this pattern is most common. 3 The 2025 European Association of Urology guidelines recognize drug-induced increased SHBG as a cause of hypogonadism. 2