SHBG

Sex Hormone Binding Globulin (SHBG) is a liver-synthesised β-globulin that binds circulating testosterone, DHT, and estradiol with high affinity and transports them through serum. SHBG-bound hormone is biologically inactive — only the unbound fraction (free testosterone) and the weakly-albumin-bound fraction (together termed “bioavailable testosterone”) can enter tissues and activate receptors.

Standard reference ranges, adult male:

– Total testosterone: 300–1000 ng/dL
– Free testosterone: 50–200 pg/mL (sensitive LC-MS/MS)
– Bioavailable testosterone: 100–500 ng/dL
– SHBG: 10–57 nmol/L

Factors elevating SHBG (reducing free testosterone):

– Ageing — SHBG rises approximately 1% per year after age 40
– Hyperthyroidism
– Hepatic dysfunction — the cirrhotic liver paradoxically overproduces SHBG as other synthetic functions fail
– Caloric restriction, prolonged fasting
– Anticonvulsants (phenytoin, carbamazepine)
– Exogenous estrogens

Factors suppressing SHBG (elevating free testosterone):

– Insulin resistance and type 2 diabetes — the “high free T with low total T” pattern in metabolic syndrome
– Obesity
– Hypothyroidism
– High-dose androgens — especially stanozolol and oxandrolone
– Anabolic doses of methandrostenolone (less pronounced than stanozolol)
– Carbohydrate-rich diets (transient effect; resolves within 4–8 weeks at stable body composition)

The stanozolol-SHBG interaction — why the compound punches above its AR affinity:

Stanozolol shows Ki ≈ 0.25 relative to testosterone, a modest number. Clinical effect routinely exceeds what the binding number predicts. The dominant mechanism is aggressive SHBG suppression: adding 25 mg/day stanozolol to an existing testosterone-cypionate protocol can reduce SHBG by 40–60% within three weeks, elevating the free fraction of all circulating androgens (testosterone, DHT, the stanozolol itself) by a comparable amount. The synergy is pharmacokinetic, not receptor-level. This is also why “low-dose” stanozolol during a testosterone cycle feels disproportionately strong — the stanozolol is unlocking testosterone that was previously sequestered.

Why age-related “testosterone decline” is often SHBG rise:

Ageing men show falling bioavailable testosterone alongside stable or modestly declining total testosterone. The gap is SHBG. The 65-year-old with total T of 450 ng/dL and SHBG of 65 nmol/L has lower bioavailable T than the 35-year-old with total T of 450 ng/dL and SHBG of 25 — despite matching total values. Treating “low T” in this population without addressing SHBG treats a label, not a physiology.

Measured vs calculated free T:

Direct free-T measurement by equilibrium dialysis or ultrafiltration is the reference method — expensive and rarely available outside academic labs. Most clinical “free testosterone” values are calculated via the Vermeulen equation from total T, SHBG, and albumin. The calculation is reliable in the mid-range but loses accuracy at extremes, particularly with SHBG below 15 nmol/L or above 80, where direct measurement is warranted.

Bloodwork framing:

Always request total testosterone, free testosterone (or calculated free), SHBG, and albumin on the same draw. SHBG explains the majority of cases where symptoms and total-T numbers do not match.