Endocrinology & Clinical Biochemistry & Family Medicine

SHBG : Sex Hormone-Binding Protein (Sex Hormone-Binding Globulin)

Conduct this analysis

Blood draws at our service locations in Quebec. A healthcare professional can also review your results with you.

Blood draw Make an appointment 514 606-3350

Sex hormone-binding globulin (Sex Hormone-Binding Globulin, sex hormone-binding globulin) is a plasma transport glycoprotein synthesized primarily by the liver, whose main function is to bind and transport sex steroid hormones in the bloodstream, primarily testosterone (with high affinity) and estradiol (with moderate affinity), thereby regulating the biologically active free fraction of these hormones available to enter target cells and exert their biological effects via nuclear receptors. Sex hormones circulate in three forms: bound to SHBG (non-bioavailable, 40–70 % depending on sex) + bound to albumin (low affinity, considered bioavailable because it is easily released, 20–50 %) + and free (unbound, 1–3 %, biologically active). «Bioavailable testosterone» includes the free fraction and the albumin-bound fraction (easily released), while «total testosterone» includes all fractions, including those strongly bound to SHBG (non-bioavailable). SHBG is thus a major physiological regulator of androgenic and estrogenic activity: high SHBG reduces the free fraction of hormones → functional hypogonadism or relative hypoestrogenism + low SHBG increases the free fraction → functional hyperandrogenism (acne + hirsutism + virilization) even if total testosterone is within normal limits. Hepatic synthesis of SHBG is positively regulated by estrogens + thyroid hormones + physical activity + and negatively regulated by insulin (via the PI3K/Akt signaling) + androgens + glucocorticoids + obesity + hepatic steatosis, making SHBG an indirect marker of insulin resistance and metabolic syndrome. Its measurement is essential for correctly interpreting total testosterone and calculating free testosterone or the free androgen index (FAI).

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)
Prepubertal 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 SHBG synthesis (FOXO1 pathway) → low SHBG levels 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 → dual inhibition of hepatic SHBG	Low SHBG → high free testosterone (IAL) → worsening hirsutism, acne, and anovulation → measurement of IAL is essential in the evaluation of PCOS
Type 2 Diabetes and Prediabetes	Insulin resistance → hyperinsulinemia → low SHBG	Low SHBG = an independent predictor of 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 → elevated free testosterone → possible signs of hyperandrogenism in women → routine TSH testing as part of the workup
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 → a marker of the severity of fatty liver disease in some studies
Acromegaly	Excess IGF-1 → inhibition of SHBG synthesis	Low SHBG → relative hyperandrogenism

Causes of Elevated 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
Liver cirrhosis 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 antiepileptic drugs: phenytoin + carbamazepine + phenobarbital → hepatic CYP3A4 induction → increased SHBG → reduced free testosterone → iatrogenic hypogonadism + suspect if erectile dysfunction in an epileptic
HIV on antiretroviral therapy: 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 significance in women (PCOS + hirsutism): Elevated IAL (> 6.5–10) = biochemical hyperandrogenism even if total testosterone is within the normal range + indicator of PCOS severity + guides the intensity of antiandrogen therapy
Clinical relevance 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)

ℙ️ A normal total testosterone level does not mean the absence of hyperandrogenism, and an elevated total testosterone level does not necessarily indicate an excess of biologically active androgens. SHBG is the missing link: a woman with a borderline-high total testosterone level but very low SHBG (obesity + PCOS) may have markedly elevated free testosterone (IAL) and be clinically hyperandrogenic. Conversely, a woman on oral contraceptives with normal total testosterone and very high SHBG may have virtually undetectable free testosterone. Always interpret testosterone levels in relation to SHBG.

Medical consultation recommended

Consult a doctor if a hormone panel 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, and reduced libido) despite normal total testosterone levels should have his SHBG and free testosterone levels measured. For a comprehensive hormonal workup (SHBG + total testosterone + IAL + TSH), Clinique Omicron offers consultations at its locations in Quebec and via telemedicine. To schedule an appointment, visit cliniqueomicron.ca.

Consult at Clinique Omicron

The physicians and specialized nurse practitioners (SNPs) at Clinique Omicron order and interpret SHBG tests in the appropriate clinical context, PCOS evaluation + hirsutism + hyperandrogenism + male hypogonadism + thyroid evaluation + metabolic syndrome evaluation, calculate the free androgen index (FAI) and calculated free testosterone (Vermeulen formula), distinguish between biochemical hyperandrogenism and clinical hyperandrogenism, and refer patients to endocrinology or gynecology based on the results. Consultations are available at several locations in Quebec and via telemedicine. To schedule an appointment, visit cliniqueomicron.ca.

The content on this page is provided for informational purposes only and is not a substitute for the advice of a doctor or endocrinologist. SHBG levels should always be interpreted in conjunction with total testosterone and within the patient’s clinical context, an isolated SHBG value has no diagnostic significance without clinical data and other hormonal parameters. SHBG reference ranges vary by laboratory.

Omicron Clinic

Need to consult a doctor?

In-person or via telemedicine, anywhere in Quebec.

No appointment necessary Private clinic Family doctor

We accept insurance. Telemedicine consultations available 7 days a week. No family doctor required.

Health assessments

Our programs