SHBG Testing in Males: Clinical Indications
Yes, SHBG testing is indicated in males when evaluating testosterone status, particularly when assessing for hypogonadism, erectile dysfunction, or when total testosterone levels are near the lower limit of normal. 1
Primary Indications for SHBG Testing
Testosterone levels should be measured in all men with organic erectile dysfunction, especially those who failed PDE5 inhibitor therapy, and SHBG should be measured alongside testosterone to accurately interpret androgen status. 2, 1
Specific Clinical Scenarios Requiring SHBG Measurement
Suspected hypogonadism with borderline total testosterone: When total testosterone is near the lower limit, determine free testosterone using calculations that require SHBG, total testosterone, and albumin. 1, 3
Symptoms of testosterone deficiency despite normal total testosterone: Men may have functional hypogonadism caused by elevated SHBG, where total testosterone appears normal but free testosterone is actually low. 1
Erectile dysfunction evaluation: The Princeton III Consensus and British Society for Sexual Medicine advocate testosterone and SHBG measurements in all men with ED. 2
Obesity-related hypogonadism: Men with obesity often have low total testosterone due to low SHBG but may have normal free testosterone levels, making SHBG measurement essential for accurate interpretation. 3
Why SHBG Matters: The Physiologic Rationale
SHBG binds testosterone with high affinity, reducing the amount of free testosterone available for biological activity. 1 When SHBG levels increase, a greater proportion of total testosterone becomes bound, decreasing the free and bioavailable testosterone fractions. 1
The pituitary gland primarily senses free testosterone levels rather than total testosterone when regulating the hypothalamic-pituitary-gonadal axis. 1 This means:
- Elevated SHBG can cause symptoms of testosterone deficiency despite normal total testosterone 1
- A free testosterone index (total testosterone/SHBG ratio) <0.3 indicates hypogonadism 1
- SHBG concentrations vary remarkably widely in clinical populations—nearly 20-fold differences from lowest to highest values 4
Recommended Testing Approach
Measure morning total testosterone (8-10 AM) using an accurate assay along with either free testosterone or calculating the free androgen index to accurately assess androgen status. 1, 3
The Endocrine Society recommends measuring both total and free testosterone when evaluating hypogonadism, especially when SHBG levels may be abnormal. 1
Conditions That Alter SHBG and Require Testing
SHBG Increases With:
- Aging (mean SHBG significantly higher in men ≥55 years: 36.6 nmol/L vs 27.7 nmol/L in younger men) 4
- Hyperthyroidism 1, 3
- Hepatic disease 1, 3
- Certain medications (anticonvulsants, estrogens, thyroid hormone) 1, 3
- HIV/AIDS 1, 3
SHBG Decreases With:
- Obesity and insulin resistance 1
- Hypothyroidism 1
- Certain medications (glucocorticoids, testosterone, anabolic steroids) 1
- Acromegaly and Cushing's disease 1
Critical Clinical Pitfalls to Avoid
Relying solely on total testosterone measurements can miss cases of functional hypogonadism caused by elevated SHBG. 1 This is the most common error in testosterone assessment.
Not considering the impact of medications and medical conditions on SHBG levels leads to incorrect interpretation of testosterone test results. 1
In men with elevated SHBG and testicular atrophy, do not attribute the atrophy solely to SHBG elevation—investigate underlying causes such as liver disease with elevated estrogens suppressing the hypothalamic-pituitary axis. 3
Clinical Utility Beyond Testosterone Assessment
SHBG measurement helps discriminate subjects with excessive androgen activity from normal individuals and identifies women with hirsutism more likely to respond to estrogen therapy. 5 The testosterone:SHBG ratio correlates well with both measured and calculated values of free testosterone. 5
Routine SHBG testing should be considered for men suspected of testosterone deficiency given the wide interindividual variability in SHBG concentrations that greatly influences hormone test interpretation. 4