SHBG — Sex Hormone-Binding GlobulinSex Hormone-Binding Globulin)
Normal values by sex and age
- Adult man 10–57 nmol/L (reference values vary by laboratory) + gradually decreases with age up to 50 years + then increases after 60 years (decrease in total testosterone + relative increase in SHBG)
- Adult woman (non-pregnant): 18–144 nmol/L + values higher in women than men due to estrogenic stimulation of SHBG synthesis in the liver
- Pregnant woman up to 5–10 times the normal value → physiological hyperestrogenism of pregnancy → very high SHBG → elevated total testosterone but normal or low free fraction
- Combined oral contraceptives (COCs) increase SHBG 2 to 4 times → reduction in free testosterone → anti-androgen effect sought for PCOS + acne + hirsutism → SHBG can remain elevated for several months after stopping COCs (liver memory effect)
- Pre-pubescent child Higher values than in adults → gradually decrease at puberty under the effect of androgens
Causes of low SHBG
| Cause | Mechanism | Clinical consequences |
|---|---|---|
| Obesity and Metabolic Syndrome | Hyperinsulinemia → inhibition of hepatic synthesis of SHBG (FOXO1 pathway) → SHBG low, proportional to BMI and insulin resistance | Elevated free testosterone (hyperandrogenism) → acne + hirsutism in women + low SHBG = marker of insulin resistance → increased cardiovascular and metabolic risk |
| PCOS (polycystic ovary syndrome) | Hyperinsulinemia + hyperandrogenism → double inhibition of hepatic SHBG | Low SHBG → high free testosterone (FT) → worsening of hirsutism + acne + anovulation → FT measurement essential in PCOS workup |
| Type 2 diabetes and prediabetes | Insulin resistance → hyperinsulinemia → low SHBG | Low SHBG = independent predictive factor for the risk of developing type 2 diabetes (prospective studies) → useful as a marker of metabolic risk |
| Hypothyroidism | Thyroid hormone deficiency → reduced stimulation of hepatic SHBG synthesis | Low SHBG → increased free testosterone → possible signs of hyperandrogenism in women → systematic TSH in evaluation |
| Androgens (endogenous or exogenous) | Androgens directly inhibit hepatic SHBG synthesis | Exogenous testosterone (TRT) + anabolic steroids → very low SHBG → high free testosterone → amplified androgenic effects |
| Glucocorticoids (cortisol + exogenous corticosteroids) | Inhibition of hepatic SHBG synthesis | Cushing's syndrome + prolonged corticosteroid therapy → low SHBG → relative androgenic effects |
| Hepatic steatosis (MASLD) | Liver dysfunction → reduced SHBG synthesis | Low SHBG → marker of liver fat severity in some studies |
| Acromegaly | Excess IGF-1 → inhibition of SHBG synthesis | Low SHBG → relative hyperandrogenism |
Causes of high SHBG
- Hyperthyroidism excess thyroid hormones → major stimulation of hepatic SHBG synthesis → very high SHBG → elevated total testosterone but normal or low free testosterone → functional hypogonadism → systematic TSH if unexplained elevated SHBG
- Combined oral contraceptives + exogenous estrogens: ethinyl estrogens → strong stimulation of hepatic SHBG → reduced free testosterone → anti-androgenic effect → discontinuation of COCs → SHBG may remain elevated for 3–6 months
- Cirrhosis of the liver and liver failure: Paradoxically, cirrhosis can increase SHBG by reducing hepatic SHBG catabolism → normal or elevated total testosterone but low free testosterone → biochemical hypogonadism is frequent in advanced cirrhosis
- Anorexia nervosa and severe malnutrition: catabolism + caloric deficit → high SHBG → hypogonadism + hypothalamic amenorrhea
- Male aging: after 60 years → SHBG gradually increases → total testosterone may remain normal but free testosterone decreases → late-onset hypogonadism in men (LOH) → measure free or calculated testosterone + do not rely on total testosterone alone
- Enzyme-inducing antiepileptics: phenytoin + carbamazepine + phenobarbital → hepatic CYP3A4 induction → increased SHBG → reduced free testosterone → iatrogenic hypogonadism + suspect if erectile dysfunction in an epileptic
- HIV on antiretroviral treatment: Certain ARVs (efavirenz) → enzyme induction → increased SHBG → low free testosterone
Free Androgen Index (FAI) — Calculation and Interpretation
- Formula: Total Testosterone (nmol/L) / SHBG (nmol/L) × 100
- Normal values: Male: 30–150 + Female: 0.5–6.5 (values vary by laboratory)
- Clinical relevance in women (PCOS + hirsutism): High IAL (> 6.5–10) = biochemical hyperandrogenism even if total testosterone is within the normal range + indicator of PCOS severity + guides the intensity of anti-androgen treatment
- Clinical interest in humans (aging): Low free testosterone → functional hypogonadism → assess symptoms + consider testosterone replacement therapy
- Calculated free testosterone: Vermeulen formula (using total testosterone + SHBG + albumin) → more accurate than the calculated free testosterone (cFT) + available via validated online calculators (recommended by the EAU and the Endocrine Society)
Consult a doctor if a hormonal assessment shows abnormally low SHBG associated with normal or elevated total testosterone in a woman presenting with acne + hirsutism + menstrual irregularities + or infertility — these signs suggest functional hyperandrogenism in the context of PCOS or insulin resistance. Similarly, an older or aging man with symptoms of hypogonadism (fatigue + erectile dysfunction + reduced libido) despite normal total testosterone should have SHBG and free testosterone measured. For a complete hormonal assessment (SHBG + total testosterone + IAL + TSH), Clinique Omicron offers consultations at its service points in Quebec and via telemedicine. To make an appointment, visit cliniqueomicron.ca.
Consult at Clinique Omicron
Clinique Omicron's physician assistants and nurse practitioners (PAs and NPs) prescribe and interpret SHBG in the appropriate clinical context—PCOS assessment + hirsutism + hyperandrogenism + male hypogonadism + thyroid assessment + metabolic syndrome assessment—calculate the Free Androgen Index (FAI) and calculated free testosterone (Vermeulen formula), differentiate biochemical hyperandrogenism from clinical hyperandrogenism, and refer to endocrinology or gynecology based on the results. Consultations are available at several service points in Quebec and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is for informational purposes only and does not replace the advice of a doctor or endocrinologist. SHBG should always be interpreted in conjunction with total testosterone and within the patient's clinical context—a single SHBG value has no diagnostic significance without clinical data and other hormonal parameters. SHBG reference values vary by laboratory.
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