Dr Graham Jones
Department of Chemical Pathology

Sex Hormone Binding Globulin (SHBG) is the major binding protein for testosterone in the serum, accounting for about 60% of testosterone binding with serum albumin accounting for the remainder. SHBG is a dimeric glycoprotein of molecular weight 90,000 MW comprising 373 amino acids. SHBG is secreted from the liver with production with production strongly regulated by a number of hormonal and other factors. Before puberty SHBG concentrations are similar in males and females, but due to the effects of sex hormones the adult female concentrations are approximately twice those of adult males.

The concentration of SHBG affects the bioavailability of testosterone, with high concentrations binding more testosterone leaving less free for interaction with tissue receptors, and conversely low SHBG concentrations leading to higher free testosterone concentrations. In women the effect of SHBG on testosterone is assessed with the Free Androgen Index (FAI) which is equal to the total testosterone concentration divided by the SHBG concentration. The FAI is not a suitable tool for use in males.

Pathology     

Causes of elevated serum SHBG

• High oestrogen states (eg pregnancy)
• Low androgens (hypogonadism), androgen insensitivity
• Increasing age
• Drugs: oral contraceptive pill, hormone replacement therapy, tamoxiphen, phenytoin, carbamazepine.
• Other: thyrotoxicosis, cirrhosis, anorexia nervosa (women only)

Causes of decreased serum SHBG

• Obesity.
• Cushing’s syndrome,  hypothyroidism, acromegaly, hyperprolactinaemia
• Drugs: corticosteroid treatment, androgen treatment, Danazol.
• Other: nephrotic syndrome, congenital deficiency.

SydPath Reference Intervals

• Female: 30-90 nmol/L
• Pregnancy: 200-500 nmol/L
• Male: 10-50 nmol/L