What Is The Difference Between Free And Total Testosterone

// Published October 30, 2019 by James Washington

The laboratory determination in the blood of the hormone testosterone, the main androgen in men, in many diseases has not only important diagnostic and prognostic value, but also therapeutic and prophylactic.

The hormone is synthesized from cholesterol and acetic acid. In men, it is produced in the testes by Leydig cells (95-98%) and, in a small amount, in the cortical layer of the adrenal glands (3-5%). Testosterone is also partially formed as a result of peripheral metabolism. Its almost complete destruction and transformation into 17-ketosteroids occurs in the liver and partially in the tissues.

Testosterone Fractions and Their Normal Values

In the blood, the hormone circulates in three forms, or fractions:

1. Strongly associated with SHBG (sex steroid-binding globulin) and constitutes 54-70%.
2. Albumin bound protein by an unstable bond is about 25-43%.
3. Free testosterone, which is the most bioavailable and active form – from 1 to 4%.

Biologically active are the second and third forms. Only they are able to penetrate into cells and bind directly to specific receptors or transform into active 5α-dihydrotestosterone. A strong connection with GPSS does not allow testosterone to penetrate into the cells, and therefore it is not able to show its biological activity.

Total testosterone is the sum of all fractions of the hormone, including free testosterone.

In most laboratory diagnostic centers, only total testosterone is determined, which is normal in men at 12-33 nmol / L. In some cases, this is enough. However, only such a study is uninformative and limits the doctor’s ability to conduct early and differential diagnostics in cases, for example, patients having obesity, metabolic syndrome, type 2 diabetes mellitus.

In this regard, the optimal is an additional definition:

• • biologically active fractions, the average norms of which are 3.5-12 nmol / l;

• • free testosterone – 4.25-42 pg / ml.

Testosterone Age and Norms

All of the above indicators of the norm of the hormone are average. They do not take into account fluctuations in different age periods. The concentration of total testosterone in men begins to decline from 50-55 years of age by 0.8-1.6% annually and by the age of 80 is an average of 60%, compared with 20-year-old men. The content of biologically active hormone in the blood is maximum at 25-35 years of age, after which it decreases by 2-3% annually.

Factors Affecting Blood Testosterone

Laboratory indicators of normal testosterone levels are very variable even in people of the same age. They are influenced by the specifics of the diagnostic equipment of laboratories, laboratory errors associated with the lack of standardization in commercial institutions, and other reasons that should be taken into account when evaluating analyzes.

The main reasons that affect the content of both total and biologically active testosterone are:

• • Time of day and region of residence. Daily changes in total testosterone reach 45%, free – 68%, bioavailable – 57%. The content of the hormone in the blood from 4 to 8 in the morning is maximum, minimum – from 4 to 8 in the evening. Therefore, the optimal time for blood sampling for the study is the morning hours. The daily rhythm of testosterone may differ in individuals working at different times of the day (shift work), which requires correction of the time of blood sampling for analysis (after waking up) and its assessment. Fluctuations in testosterone levels during the day are smoothed as age increases, which should also be taken into account when evaluating test results.

• • Season. In autumn, the level of the hormone in the blood is the highest, the lowest – in the summer. Seasonal fluctuations in total testosterone reach 19%, free – 31%.

• • Nature of food: meal time and its composition. Significant amounts of protein and fat in foods contribute to the reduction of GPS (read more “The 8 Best Supplements to Boost Testosterone Levels”).

• • Stressful conditions and constant high physical activity. Frequent and prolonged psychoemotional and heavy physical exertion inhibit the production of sex hormone. At the same time, immediately after exercise, the level of the hormone in the blood rises.

• • Acute or chronic diseases (arterial hypertension, coronary heart disease, diabetes mellitus, liver disease, etc.), as well as chemo- or radiation therapy. Chronic pathology leads to a decrease in total testosterone or only its free fraction.

• • A number of drugs and narcotic drugs.

In the case of lower (compared with the age norm) values of the hormone in the test results, it is necessary to conduct another 1-2 repeated studies of the level of testosterone. Further, other, already targeted diagnostic tests are carried out to identify the causes of deviations of the hormonal level. For example, blood glucose measurement, total cholesterol and low density lipoprotein, ECG, blood pressure monitoring, coronary cardiography, measurement of bone mineral density, etc.

Indications for testing free testosterone levels

Determination of serum free testosterone in men is recommended for:

• • impaired sexual development and synthesis of testosterone, as well as with early puberty in boys;

• • Reifenstein’s syndrome;

• • pathology of the hypothalamic-pituitary system;

• • cryptorchidism and myotonic dystrophy;

• • dysfunction of the adrenal cortex;

• • suspected adrenal or testicular swelling;

• • pathology of the genital glands after a trauma to the testicles, viral mumps;

• • chronic alcoholism;

• • taking antiandrogenic drugs and gonadoliberins;

• • old age.

Read more about “Testing your testosterone: It’s tricky”.

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