Total Testosterone

SHBG is a glycoprotein that transports testosterone and estradiol in the blood. SHBG is synthesised in the liver and has a high binding affinity with 17-hydroxysteroid hormones.

Less than 2% of biologically active steroids are free in the circulation, the remainder being bound mainly to SHBG and albumin.

The concentration of SHBG in plasma is regulated by, among other things, the androgen/estrogen balance, thyroid hormones, insulin and dietary factors.
SHBG production is stimulated by oestradiol and inhibited by testosterone. As a result, SHBG concentrations are higher in women than in men.

Pregnant women have significantly higher serum SHBG levels due to their increased oestrogen production.

Plasma SHBG levels are influenced by a number of medical conditions, with elevated levels observed in hyperthyroidism, hypogonadism, androgen insensitivity and liver cirrhosis in men. Low levels are seen in myxedema, hyperprolactinaemia and excessive androgen activity syndromes.

Measurement of SHBG is useful in the assessment of mild disorders of androgen metabolism and can identify women with hirsutism who are more likely to respond to oestrogen therapy.

The ratio of testosterone to SHBG is also known as the Free Androgen Index (FAI) or the Free Testosterone Index (FTI). This ratio correlates closely with measured and calculated values of free testosterone and can be used to distinguish subjects with excessive androgen activity from normal individuals.

Testosterone is the main androgenic steroid.

In men, it is secreted by the Leydig and interstitial cells of the testes, stimulated by luteinising hormone (LH).
Testosterone secretion is controlled by a negative feedback loop in the hypothalamus, where the secretion of gonadotropin-releasing hormone promotes the synthesis and release of LH and follicle-stimulating hormone (FSH) by the anterior pituitary gland.

In women, testosterone is secreted by the follicular theca and interstitial cells of the ovaries and is also produced by the metabolism of adrenal androgens. Testosterone concentrations are generally 10 to 20 times lower in women than in men.

In the circulation, around 97% of testosterone is transported by proteins, notably by binding to sex hormone-binding globulin (SHBG).
Testosterone concentration in an individual fluctuates over 24 hours.

The pulsatile release of LH during the night generally leads to a peak in testosterone concentration in the morning. Time of day, age, sex, puberty, pre-menopause and post-menopause, as well as medical conditions, all have an influence on testosterone levels and must be taken into account when interpreting individual results.

Clinical assessment of serum testosterone, as well as serum LH, facilitates the detection of hypogonadism in men. The main causes of low testosterone in men are hypogonadotropic hypogonadism, testicular failure, hyperprolactinaemia, hypopituitarism, certain types of liver and kidney disease and severe illness.