What SHBG is
Sex hormone binding globulin is a glycoprotein produced by the liver that binds sex hormones with high affinity in circulation. It serves as a transport protein and reservoir, regulating hormone bioavailability to tissues.
Binding biology
SHBG binds:
- Testosterone with high affinity
- DHT with high affinity
- Estradiol with moderate affinity
- DHEA weakly
SHBG-bound hormones cannot enter cells or activate receptors. They circulate as inactive reservoir.
What's bioavailable
Total testosterone in blood = SHBG-bound + albumin-bound + free
- SHBG-bound (~50-60%), inactive
- Albumin-bound (~40-45%), loosely bound, easily released to tissues
- Free (~1-3%), directly bioavailable
Bioavailable T = free + albumin-bound. This is what tissues actually access.
If SHBG is high, more T is sequestered as SHBG-bound, reducing bioavailable fraction even when total T is normal. Patient may have "normal" total T but symptoms of low T.
What raises SHBG
- Aging (modest increase)
- Hyperthyroidism
- Estrogen (oral estrogens, pregnancy, OCPs)
- Anorexia or significant caloric restriction
- Chronic alcohol use
- Liver disease
- HIV
- Some medications
What lowers SHBG
- Insulin resistance / hyperinsulinemia
- Obesity
- Hypothyroidism
- Androgen excess (PCOS, exogenous androgens)
- Growth hormone excess
- Cortisol excess
- Some medications
Insulin is the major driver in metabolic disease. High insulin suppresses hepatic SHBG production.
Interpreting SHBG
Common patterns:
- Low SHBG + normal total T, often metabolic syndrome / insulin resistance; free T may be okay or elevated
- High SHBG + normal total T, often aging or hyperthyroidism; free T may be low and patient may be symptomatic despite normal total
- Low SHBG + low total T, both metabolic and HPG axis dysfunction
- High SHBG + low total T, primary hypogonadism with high SHBG (less common pattern)
Therapeutic modulation
Raising SHBG (when too low):
- Treat insulin resistance (lifestyle, GLP-1 therapy, metformin)
- Reduce body fat
- Address hypothyroidism if present
Lowering SHBG (when too high):
- Reduce alcohol
- Address hyperthyroidism
- Adequate protein and avoid extreme caloric restriction
- Sometimes androgens (TRT) lower SHBG modestly
The clinical insight: Total testosterone alone is misleading without SHBG context. The same total T can mean very different bioavailable T depending on SHBG. Always test both.
Bottom line
SHBG modulates testosterone bioavailability. High SHBG sequesters T (reducing effective hormone); low SHBG releases more (raising effective). Understanding what moves SHBG explains lab patterns and informs treatment. Always interpret total T in context of SHBG.