Sex hormone-binding globulin (SHBG) is a protein produced primarily by the liver that binds to testosterone in the bloodstream. Testosterone bound to SHBG cannot enter cells or bind to androgen receptors, it is biologically inactive. Because SHBG levels vary significantly between individuals and change with age, two men with identical total testosterone can have completely different amounts of active testosterone at the cellular level.

A man with a total testosterone of 500 ng/dL and high SHBG may have less biologically active testosterone than a man with 350 ng/dL and low SHBG. This is why total testosterone alone is an incomplete picture of androgen status.

How Testosterone Is Distributed in the Blood

Total testosterone circulates in three forms:

  • Bound to SHBG: approximately 40-50%, inactive
  • Bound to albumin: approximately 40-50%, loosely bound and biologically available
  • Free testosterone: approximately 2-3%, unbound and immediately active

Free testosterone is the most direct measure of available androgen activity. Albumin-bound testosterone is also considered bioavailable because the albumin binding is loose enough that testosterone can dissociate and enter cells at the tissue level. The sum of free plus albumin-bound testosterone is called bioavailable testosterone.

What Affects SHBG Levels

SHBG is not a fixed value. Multiple factors increase or decrease it:

Increases SHBG:

  • Aging (SHBG rises approximately 1-2% per year after age 40)
  • High estrogen levels (including from obesity-related aromatase activity)
  • Thyroid dysfunction, particularly hyperthyroidism
  • Liver disease (the liver produces SHBG; liver disease paradoxically can increase SHBG)
  • Certain medications including anticonvulsants and some antifungals

Decreases SHBG:

  • Obesity and insulin resistance, high insulin suppresses SHBG production in the liver
  • Type 2 diabetes
  • Hypothyroidism
  • High androgen levels (exogenous testosterone use)
  • Protein-calorie malnutrition

This last point explains a clinically common scenario: an obese man with low total testosterone but also low SHBG. His free testosterone may actually be within a normal range because less testosterone is bound. His low total testosterone reflects both low production and low SHBG, not purely an androgenic deficiency.

When to Measure SHBG

SHBG should be measured when total testosterone is borderline, in the 250-400 ng/dL range, and symptoms suggest possible deficiency. Adding SHBG to the panel allows calculation of free testosterone and bioavailable testosterone, which provide more clinically useful information than total testosterone alone.

Reference ranges for free testosterone are approximately 9-30 ng/dL, though laboratory methods differ and ranges vary by laboratory.

The Endocrine Society recommends measuring free or bioavailable testosterone in patients with borderline total testosterone and conditions known to affect SHBG, including obesity, diabetes, liver disease, and thyroid dysfunction.

High SHBG: Symptoms and Approach

A man with high SHBG and a total testosterone that appears normal on a standard test may have free testosterone well below the reference range. Symptoms would mirror those of low total testosterone: reduced libido, fatigue, difficulty building muscle, mood changes.

Treatment approaches for high SHBG-related low free testosterone depend on the underlying cause. If elevated SHBG stems from thyroid disease, treating the thyroid often normalizes SHBG. If it reflects aging-related increases without a correctable cause, the clinical decision is whether the free testosterone level is low enough to warrant TRT.

Some clinicians prescribe testosterone replacement based on low free testosterone even when total testosterone is within range, particularly when symptoms are present. Others follow total testosterone thresholds strictly. This is an area of clinical disagreement, and the Endocrine Society guidelines do not fully resolve it.

How to Calculate Free Testosterone

Free testosterone can be measured directly (equilibrium dialysis is the most accurate method) or calculated using total testosterone and SHBG values with validated formulas. The calculated free testosterone from the Vermeulen formula, which most labs use, correlates well with measured free testosterone and is the standard approach in clinical practice.

For more on how to interpret the full hormone panel, see How to Read a Hormone Blood Panel. For context on what testosterone levels mean across age groups, see Testosterone Levels by Age: What the Numbers Actually Mean.