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SHBG – Sex Hormone-Binding Globulin Explained

SHBG (Sex Hormone-Binding Globulin) is a transport protein in the blood that binds sex hormones such as testosterone and estrogen, regulating their availability in the body.

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Things worth knowing about "SHBG"

SHBG (Sex Hormone-Binding Globulin) is a transport protein in the blood that binds sex hormones such as testosterone and estrogen, regulating their availability in the body.

What is SHBG?

SHBG stands for Sex Hormone-Binding Globulin. It is a glycoprotein transport protein produced primarily by the liver and released into the bloodstream. SHBG binds the sex hormones testosterone, estradiol (a form of estrogen), and dihydrotestosterone (DHT) with high affinity, thereby regulating how much of these hormones are biologically active and available to the body's tissues.

Function and Mechanism of Action

Sex hormones in the blood circulate in three forms:

Bound to SHBG: These hormones are biologically inactive and cannot enter cells.
Bound to albumin: This binding is loose, allowing hormones to be released relatively easily.
Free (unbound) hormones: Only a small fraction circulates freely and is biologically active.

Only free hormones and those loosely bound to albumin can enter target cells and exert their biological effects. A high SHBG level therefore means less free testosterone or estrogen is available, while a low SHBG level increases the amount of active hormones in circulation.

Reference Values

SHBG levels vary depending on sex and age:

Men: approx. 10–57 nmol/l
Women (non-pregnant): approx. 18–114 nmol/l
Pregnant women: significantly elevated values are considered normal

Exact reference ranges may vary between laboratories.

Causes of Altered SHBG Levels

Elevated SHBG

Hyperthyroidism (overactive thyroid)
Liver disease (e.g., cirrhosis)
Use of estrogens or oral contraceptives
Anorexia nervosa and significant weight loss
Aging (SHBG naturally increases with age in men)
HIV infection

Low SHBG

Insulin resistance and type 2 diabetes
Obesity
Polycystic ovary syndrome (PCOS)
Hypothyroidism (underactive thyroid)
Use of androgens or anabolic steroids
Metabolic syndrome

Clinical Significance

Measuring SHBG levels is essential for accurately assessing free testosterone and free estrogen, as these are the biologically active fractions. Measuring total testosterone alone can be misleading when SHBG levels are abnormal. The Free Androgen Index (FAI) is often calculated from total testosterone and SHBG to estimate the amount of biologically available testosterone.

SHBG plays a role in the following clinical contexts:

Hypogonadism: reduced function of the gonads with decreased hormone production
PCOS: women with PCOS often have low SHBG, resulting in elevated free androgens
Male fertility assessment
Hormone replacement therapy (HRT): monitoring therapy for menopausal symptoms
Diabetes risk: low SHBG is recognized as an independent risk factor for developing type 2 diabetes

Diagnosis and Laboratory Testing

SHBG is measured through a simple blood draw. The test is often ordered alongside total testosterone, LH (luteinizing hormone), FSH (follicle-stimulating hormone), and other hormone markers. No special preparation is typically required, though testing in the morning is recommended as hormone levels fluctuate throughout the day.

Factors That Influence SHBG Levels

Several lifestyle factors can affect SHBG levels:

Diet: A high-fiber diet may increase SHBG; a high-sugar diet may lower it.
Body weight: Overweight and obesity are associated with lower SHBG levels.
Physical activity: Regular exercise may help increase SHBG.
Alcohol: Moderate alcohol consumption may slightly raise SHBG.
Medications: Corticosteroids, insulin, and certain anticonvulsants can influence SHBG levels.

References

Selby C. - Sex hormone binding globulin: origin, function and clinical significance. Annals of Clinical Biochemistry, 1990; 27(6): 532–541.
Hammond GL. - Diverse roles for sex hormone-binding globulin in reproduction. Biology of Reproduction, 2011; 85(3): 431–441.
Hillier SG, Lasley BL, Sauer MV - Reproductive Endocrinology and Infertility. In: Strauss JF, Barbieri RL (eds.) - Yen and Jaffe's Reproductive Endocrinology, 8th edition. Elsevier, 2019.

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