Testosterone is the main male sex hormone that is produced in the Leydig interstitial cells of the testes. But also in women, small amounts of this hormone are synthesized in the adrenal gland and in the ovaries.
How is testosterone production controlled – and does it depend on age and time of day?
There is a negative biological feedback between the brain and testosterone production in the testicles: the concentration of testosterone in the blood is continuously measured in two areas of the brain, a part of the diencephalon (hypothalamus) and the pituitary gland (pituitary); at low concentrations, the hypothalamus and pituitary provide messengers (gonadotropins) to boost testosterone production in the testicles.
In the opposite case, the production of these gonadotropins is reduced. This negative biological feedback only awakens with the onset of puberty, usually from the age of 10. The external signs of the change are growth of the testicles, pubic and axillary hair as well as the appearance of acne and broken voice.
This negative biological feedback weakens in the course of life so that in men over the age of 40, testosterone levels drop by about 1 percent a year (left side figure below). The aging-related drop in testosterone levels involves both a dry production of testosterone in the Leydig cells of the testes and a change in the frequency and amount of gonadotropins released.
Low testosterone levels can be associated with loss of libido, muscular weakness, marked overweight, increased sadness, lack of concentration, sweating, erectile dysfunction, osteoporosis and anemia in advancing age.
When assessing serum testosterone levels, the daily fluctuations must be taken into account, since the testosterone concentration in the morning hours is 20 to 40 percent higher than in the evening. Highest values can be found between 6 a.m. and 10 a.m. and lowest values between 5 p.m. and 9 p.m. (top right).
How is testosterone transported in the blood and what happens to it in the target cells?
In the blood, testosterone is bound to various transport proteins, especially the sex hormone-binding globulin (SHBG). Only about 1 to 2 percent of the circulating testosterone is unbound and actually biologically active as free testosterone. In the cells, testosterone is converted to the more biologically active dihydrotestosterone (DHT).
However, the fat cells also have the ability to convert testosterone into the most important female sex hormone, estradiol, and thus, in a way, to feminize a man and counteract the effects of testosterone.
How is blood testosterone measured?
Since the free testosterone usually agrees well with the total testosterone, the determination of the free testosterone, which is methodically very complex, is not standard and unnecessary. However, if the concentrations of the SHBG change, either increased or decreased total testosterone values are measured, although the free or biologically active portion of the testosterone has remained largely normal:
So it typically occurs with an underactive thyroid, with a treatment such. B. with cortisone and with pronounced obesity to a significant drop in SHBG and total testosterone, so that the diagnosis of a testosterone deficiency can be erroneously made. The additional determination of the free androgen index (FAI), in which a quotient of total testosterone and SHBG is formed, can help to avoid a misjudgment regarding a testosterone deficiency.
Do physical activity, diseases, and medications affect testosterone levels?
Short, intense physical exertion can lead to an increase in testosterone, but long-term muscular activity and high-performance sports can lead to a drop in testosterone. Almost all chronic diseases, especially the liver, kidneys, and heart, as well as stress, anesthesia, and many medications can cause a drop in testosterone.
Examples include the anabolic steroids, which are also used by recreational athletes to improve physical performance and supposedly optimize physical appearance: These substances inhibit the messenger substances in the hypothalamus and pituitary gland – and thus testosterone production in the testicles.
Since a sufficient testosterone level is also essential for the maturation of the sperm in the Sertoli cells of the testicles, there is also a drop in the sperm count and thus infertility. Fortunately, this unwanted infertility is usually reversible after stopping the anabolic steroids. An increase in prolactin can also lead to a drop in testosterone levels and sperm count in men since this pituitary hormone also inhibits the release of messenger substances; This hormone is known primarily as a breastfeeding hormone for women.
But also in men, different medications (especially psychotropic drugs) or an almost always benign pituitary tumor can trigger an increase in prolactin in the blood and lead to temporary infertility with testosterone and sperm deficiency. It is not uncommon for these men to come to us because the hormonal effects of this hormone have been shown to them: real breast tissue or gynecomastia has developed. Fortunately, these changes are traceable through medication or surgical removal of the pituitary tumor.
What should be considered when determining testosterone in the blood?
We hope that you can now understand why a testosterone deficiency cannot be derived from testosterone determination alone. It is important that blood samples are taken on two days in the morning, preferably between 8 and 10 a.m.
To evaluate the testosterone values are essential: weight, medication, data on previous or concomitant diseases, information on the current life situation and the additional determination of the gonadotropins, SHBG, and prolactin, as explained above. Otherwise, statements about the presence of a testosterone deficiency can also be compared to the predictions from the famous glass ball.
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