6.7 – 25.7
|0.3 – 1.68
0.1 – 1.43
Testosterone is the primary androgen produced by the Leydig cells of the testes and is responsible for sexual differentiation and male secondary sex characteristics. Young men exhibit a diurnal pattern of testosterone secretion, with a peak at about 08:00 and a nadir at about 20:00. Levels increase after exercise. In women, levels are 5 to 10% of male levels.
Testosterone circulates in the blood 98% bound to protein. In men, approximately 40% is bound with high affinity to sex hormone binding globulin (SHBG) and approximately 60% is bound weakly to albumin. The testosterone fraction that is bound to albumin dissociates freely in the capillary bed, becoming available for tissue uptake. Only 2 to 3% of testosterone exists in the free state. All non-SHBG bound testosterone is considered to be bioavailable.
Measurement of serum testosterone concentration is useful in the evaluation of hypogonadism, infertility, impotence and replacement therapy monitoring in males and hirsutism and virilization in females. Testosterone levels may also be helpful in the evaluation of ambiguous genitalia and precocious puberty in children.
Testosterone dependent changes of puberty can begin from age 10 to 14. In early puberty, testosterone levels initially increase during the night and return to prepubertal levels by morning. As puberty progresses, testosterone levels eventually remain elevated throughout the day. Measurement of an early morning testosterone level is indicated as part of the work-up for precocious puberty, which is defined as the onset of pubertal changes before age 9, and in the work-up of delayed puberty, which is the lack of pubertal changes by age 14. Testosterone is usually increased in precocious puberty.
In adult men, serum testosterone is decreased in both testicular and pituitary failure. The manifestations of hypogonadism are loss of libido and reduced volume of ejaculate. Often hypogonadal men may not offer specific complaints, but may present with scant facial, axillary and pubic hair; pale, fine wrinkled skin; eunuchoid body habitus; small or atrophic testes or prostate; and mild normocytic anemia. The diagnosis is confirmed by a low serum testosterone concentration. If LH and FSH are elevated, the problem is primary testicular failure. Testosterone levels may also be decreased in hepatic cirrhosis and severe obesity.
Female hirsutism is caused by excess androgen secretion by either the adrenal glands or ovary. Virilization or rapidly progressive hirsutism suggests a tumor is present and requires prompt investigation. Testosterone is a good indicator of ovarian function, while dehydroepiandrosterone sulfate (DHEA-S) is a good indicator of adrenal function. A serum total testosterone level above 5.0 nmol/L is suggestive of ovarian stromal hyperthecosis (a benign condition) or an adrenal or ovarian tumor. If the total testosterone is less than 2.5 nmol/L then a tumor is unlikely.
The polycystic ovary syndrome is the most common hormonal cause of anovulation and hirsutism. Most women will have slightly elevated testosterone, elevated LH, and normal FSH. The differential diagnosis of polycystic ovary syndrome includes hyperprolactinemia, acromegaly and congenital adrenal hyperplasia.
Two conditions are associated with male sexual dysfunction and elevated total testosterone level: hyperthyroidism and the syndromes of androgen resistance. Hyperthyroidism causes an increase in SHBG, which elevates total but not free testosterone. Androgen resistance is associated with a defective androgen receptor or 5-alpha reductase deficiency.
Testosterone and Aging
As men age, their serum total testosterone concentrations fall, mostly due to a diminution of the early morning peak. The major cause of decreased testosterone production appears to be diminished testicular response to luteinizing hormone (LH). Alterations in pituitary function may also be partly responsible, because LH concentrations do not increase appropriately in response to falling testosterone concentration.
After the age of 40 years, men’s total testosterone levels begin to decline about 0.4% per year. The result is that 60 to 80 year old men have total serum testosterone concentrations that are about 70% of those of 20 to 40 year old men. Men with chronic illnesses have testosterone levels that are 10-15% below that of healthy age-matched men.
Serum concentrations of sex hormone binding globulin (SHBG) rise gradually with increasing age, so that serum free testosterone concentrations decrease even more dramatically than total testosterone. In 60 to 80 year old men, serum free testosterone concentrations are only 33 to 50% of those of 20 to 40 year old men.
Young men have a circadian rhythm of testosterone, with the zenith occurring in the morning between 0600 and 0800 h and the nadir in the late afternoon between 1700 and 1800 h. This circadian rhythm disappears in elderly men. The difference in testosterone levels between young and elderly men is most pronounced when measurements are made in the morning.
Decreased serum testosterone is associated with:
Some experts have likened this syndrome to menopause and named it andropause. However, several major differences exist. Testosterone levels in men decline much more gradually than estrogen levels in women and there does not appear to be a definitive testosterone level at which all men exhibit symptoms of hypogonadism. The efficacy of testosterone replacement therapy in reversing these age-related changes has not been established. Testosterone treatment has been associated with numerous adverse effects including polycythemia, gynecomastia, edema, prostate cancer, benign prostatic hyperplasia and coronary artery disease.
A symposium on “Issues in Testosterone Replacement in Older Men”, concluded that no well designed clinical trials have indicated that one testosterone assay is better than any other at determining whether an older man is androgen deficient (J CE & M 1998;83:3436-38). Total testosterone is as good a measurement, and less expensive, than the more complex and labor intensive measurement of free or bioavailable testosterone. Measurements of free or bioavailable testosterone should be considered experimental, until they are clearly shown to be a better marker of hypogonadism in elderly men than total testosterone levels.
The calcualtion of free and bioavailable testosterone requires an SHBG. If you would like to discuss doing this phone the Duty Biochemist on ext 2935
Monitoring of testosterone or antiandrogen therapy in older men and in females.
Can be added on to an existing request up to 4 days following sample receiptSpecimen Labelling Procedure