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Androgen deficiency in men (male hypogonadism) is a clinical and biochemical syndrome characterized by a decrease in the level of male sex hormones (primarily testosterone) that occurs against the background of functional insufficiency of the testicles.
Recent scientific studies have convincingly proved the huge role of deficiency of the main male sex hormone — testosterone - in the formation and development of most urological diseases in men, including prostate and kidney cancer.
There is a strong opinion that problems associated with low testosterone occur only in older men. In fact, this is far from the case. Modern data show that the development of androgen deficiency can occur at any age.
The first modern multicenter mega-study of the global significance of age-related androgen deficiency MMAS (2000) revealed the main trends towards a decrease in the level of total testosterone in the blood of men by 0.8% per year. Along with this, the concentration of sex hormone binding globulin (GSPS) increases by 1.6% per year, which makes it possible to position GSPS as a diagnostic factor of age-related androgen deficiency.
Further study of the problem showed that the level of androgen deficiency in men aged 41-80 years is more than 35%, which is a serious indicator. According to the research of C. McHenry Martin (2013), more than 6 million American men have a low concentration of the hormone testosterone in the blood, which is manifested by depression, decreased performance and cardiovascular diseases. And a study conducted in Sweden among men aged 33-46 years showed that the frequency of erectile dysfunction in these groups reflected a low level of total testosterone in the blood, which was lower in 45-year-old subjects compared with men aged 33 years.
Thus, androgen deficiency is a significant factor for every man and requires constant attention both from the patient himself and from doctors of various specialties.
They are usually divided into acquired and congenital.
The symptoms of androgen deficiency include the following signs:
If androgen deficiency occurred before puberty, then the body acquires a characteristic tallness with eunuchoid proportions. At the same time, the span of the arms exceeds the length of the body, and the legs are longer than the trunk. As a result, such patients look short when sitting ("sedentary dwarfism"), and very tall when standing ("standing gigantism").
Prolonged androgen deficiency leads to bone fragility (osteoporosis), which can be accompanied by pathological fractures of the vertebrae and femurs, back pain.
Androgen deficiency does not directly lead to an increase in subcutaneous adipose tissue, but the distribution of fat acquires a feminine character (deposits on the hips, buttocks, lower abdomen). The muscle mass of the body, on the contrary, decreases.
In the event that androgen deficiency occurs before puberty, the length of the larynx does not increase and the coarsening of the voice does not occur.
Despite the high growth, such patients are mistaken for women, especially over the phone, which gives them additional complexes.
The straight border of the hair above the forehead remains, the beard does not grow or grows very poorly, almost does not require shaving. Body hair is very sparse.
Another typical sign is the early appearance of fine wrinkles around the eyes and mouth. In addition, as a result of the lack of stimulation of the sebaceous glands, the skin remains dry. Anemia and poor blood supply determine the severe pallor of the skin.
Also an important sign is a decrease or complete absence of the ability to distinguish odors (the likelihood of Kalman syndrome). Such patients are not able to sense, for example, the smell of vanilla, lavender and other aromas, but retain the ability to distinguish substances that irritate the trigeminal nerve (ammonia).
A decrease in testosterone levels can cause breast enlargement in men. In most cases, gynecomastia is bilateral, very rarely unilateral. With pronounced, especially unilateral enlargement, the patient is referred for mammography to exclude breast cancer.
Breast enlargement is accompanied by a feeling of tightness in the chest and increased sensitivity of the nipples. Gynecomastia often develops in boys at puberty (at the age of 12-14 years), but disappears after 2-3 years. With obesity, the picture becomes brighter and lasts longer. Sometimes breast enlargement occurs in men with aging.
In combination with small dense testicles, gynecomastia is typical of Klinefelter syndrome.
The rapid development of gynecomastia may indicate the presence of a hormone-active testicular tumor. A characteristic triad of symptoms includes gynecomastia, loss of libido and testicular tumor. The cause of gynecomastia may also be common diseases: cirrhosis of the liver or kidney failure.
The pathogenesis of androgen deficiency is diverse and depends on specific causes. Let's consider the main points of the pathogenesis of androgen deficiency.
Pathogenetic links of age-related androgen deficiency in men are triggered, first of all, by atherosclerotic factors that gradually obliterate (overgrow) the vessels concerned. This leads to a decrease in blood flow in the male gonads, respectively, to a decrease in testosterone synthesis by Leydig cells.
As the process progresses, the sensitivity of the posterior part of the brain — the hypothalamus — to testosterone increases.
In parallel, there is an increase in the concentration of gonadotropins in the blood, which further aggravates the situation.
The mechanism of development of pathological disorders in Kalman syndrome is interesting. During the development of a normal fetus, the precursors of gonadotropin-releasing-dependent hormones - special neurons - move from the olfactory epithelium of the nasal mucosa to their permanent point in the hypothalamus. In an embryo with Kalman syndrome linked to the X chromosome, this movement is disrupted. The precursors of gonadotropin-releasing-dependent hormones do not come out of the olfactory epithelium and therefore do not affect specific pituitary cells.
The main characteristic of Kalman syndrome is incomplete puberty or its complete absence. The average volume of testicles in patients with Kalman syndrome is no more than 3 ml.
Modern studies have shown the enormous importance of vitamin D deficiency in men, in the development of androgen deficiency and a decrease in testosterone levels. Vitamin D deficiency is a new epidemic of the XXI century, which is caused by a significant decrease in the sun exposure of people who live north of the 35th parallel.
By and large, vitamin D is not a vitamin at all. Rather, it is a provitamin, more precisely, a hormone that regulates many processes in the body. The concept of "vitamin D" implies several identical forms of vitamin D, belonging to the class of sexosteroids - D1, D2, D3, D4, D5. Only D3 is a true vitamin D.
Vitamin D is formed from food and under the influence of sunlight (ultraviolet). To be converted into an active form, it must undergo a two-stage hydroxylation process:
Recent work on the synthesis of testosterone has shown a direct correlation (relationship) between the ratio of vitamin D levels and androgen deficiency in men.
Thus, a large-scale European study by EMAS (2012) proved direct correlations between vitamin D and testosterone concentrations in men. The level of 25-(OH) vitamin D3 correlated well with the level of total and free testosterone and did not interact sufficiently with the concentration of estradiol and luteinizing hormone (LH), taking into account age.
Vitamin D deficiency significantly reflected the dynamics in men with compensated and secondary hypogonadism.
There is an opinion that vitamin D deficiency and related androgen deficiency are important endocrinological mechanisms in men that violate the ratio of fat-synthesizing (prolactin, insulin, cortisol) and fat-burning hormones (growth hormone, catecholamines, sex and thyroid hormones). This problem is under extensive study.
In stressful situations, the sympathoadrenal system is overstressed in the body, a large number of various hormones and biologically active substances are produced in the adrenal cortex:
Cortisol is synthesized in stressful situations, which are combined with poor nutrition and concomitant physical overload, trying to maintain blood glucose levels.
In the case of prolonged chronic stress, an increase in its physiological concentration is formed, which negatively affects the main male hormone - testosterone - and sharply reduces its concentration in the blood.
According to the level of the main male hormone testosterone:
By the nature of the defeat:
Taking into account the detection time in relation to puberty:
Depending on the reason:
Mainly clinical manifestations:
In the absence of full-fledged therapy of a patient with androgen deficiency, the symptoms worsen, and those symptoms that manifested themselves to a mild degree become direct complications of an increasing androgen deficiency.
The complications of androgen deficiency include:
Attention is drawn to a decrease in the overall tone of the body, poor growth of beard and mustache, the absence of spontaneous morning and night erections, a weakening of sexual desire and erotic fantasies.
It turns out what diseases the patient suffered from throughout his life, whether there were injuries, testicular damage, whether there were similar problems with parents and close relatives.
It is necessary to know what medications the patient has taken and is taking now, whether he has been subjected to sudden thermal and chemical influences.
You should also take into account the intensity of physical activity and bad habits (smoking, addiction to alcohol).
When examining the patient, it is necessary to pay attention to the clinical manifestations of androgen deficiency (hair loss, weight loss, breast enlargement, etc.).
Testicles normally have a dense consistency. In the absence of the stimulating effect of LH and FSH, they become soft. The volume of the testicles is determined by palpation and compared with balls of certain sizes (Prader's orchidometer).
In healthy men, the volume of each testicle averages 18 ml and ranges from 12 to 30 ml. A decrease in the volume of the testicles may indicate the presence of androgen deficiency.
The penis in hypogonadism, which occurs before puberty, remains very small (infaltile). If hypogonadism with androgen deficiency occurred after puberty (puberty), then the size of the penis does not change. In men of the European race, the length of the penis in the state of erection ranges from 11 to 15 cm.
The prostate gland during rectal examination (through the anus) has a smooth surface and the shape of a chestnut. With androgen deficiency, the volume of the gland remains small and does not increase with age. A dough-like soft consistency indicates prostatitis, a general increase indicates benign hyperplasia, a bumpy surface and a hard consistency indicates cancer.
Ultrasound examination of the scrotum (ultrasound) allows you to get an image of the contents of the scrotum without having a harmful effect on the testicles.
Normal testicles and their appendages on the echogram look homogeneous (homogeneous) structures.
Ultrasound can reliably determine the volume of the testicles, which is very important. According to the ellipsoid volume formula, accurate results are obtained that are of great importance for the control of treatment (for example, in the treatment of hypogonadism with gonadotropins).
Doppler echography allows you to assess the blood flow in the testicle and spermatic cord.
Transrectal ultrasound examination of the prostate gland is used in the differential diagnosis of andrological diseases. TRUZI is used in the diagnosis of prostatitis, prostate hyperplasia and cancer. With the help of transrectal examination, cysts, fibrosis, stones inside the gland and other formations can be detected.
Thermography allows you to detect an elevated temperature on the side of the damaged testicle, its overheating as a result of venous stagnation and against the background of varicocele (varicose veins of the testicular vein). Thermography is performed using a thermosensitive film or a portable sensor with a thermal meter continuously for 24 hours.
Measurement of bone mineral density (densitometry) allows using ultrasound or X-ray to detect even minimal bone loss (up to 2%).
With the help of laboratory tests, the following indicators are determined:
The main goal of treatment is to improve the patient's well-being and sexual health by restoring testosterone levels in the blood to normal values.
The choice of therapy method is determined by the form of the disease, risk factors and the patient's plans for the birth of a child.
It should be borne in mind a temporary decrease in testosterone levels against the background of acute or chronic diseases, which should be excluded with a thorough examination and repeated measurement of androgen levels. Therapy consists of an appointment:
Indications for the appointment of testosterone preparations:
Contraindications to the appointment of testosterone replacement therapy:
The choice of a testosterone drug should be a conscious decision of the patient. The attending physician should show the patient the advantages and disadvantages of various forms of substitution therapy and focus on the optimal option.
Short-acting testosterones may be more effective than prolonged forms at the initial stage of substitution therapy.
To compensate for androgen deficiency, there are various forms of testosterone preparations:
All of them have different concentrations of testosterone and different bioavailability.
It should be understood that each person is individual, therefore, constant monitoring of testosterone growth against the background of androgen replacement therapy becomes an important task. It also takes into account the fact that an average adult male produces 8-15 mg of endogenous testosterone per day.
Currently, tablet forms for the correction of androgen deficiency are practically not used due to their low effectiveness and effect on the mucous membrane of the gastrointestinal tract. Subcutaneous implants are also not widely used.
Of the injectable forms, drugs with a long-lasting androgenic effect have become widespread: "Nebido" and "Omnadren 250". Short— and medium-acting testosterones - "Testosterone Propionate" and "Sustanon 250" retain their value.
Of the skin preparations, Androgel has proven itself well.
"Testosterone Propionate" is a "reference" short-acting testosterone preparation (works up to 2-3 days). It can be used to treat androgen deficiency in cases where it is necessary to quickly and effectively raise the level of testosterone:
"Testosterone Propionate" is the very first and "oldest" testosterone drug in the world, which is prescribed to this day. Already in 1940, immediately after the synthesis of testosterone from cholesterol by Nobel laureates A. Butenandt and L. Ruzhichkois (1939), the drug began to treat male menopause.
"Testosterone Propionate" is the "gold standard" for all androgenic and steroid drugs. It is from him that all manufacturers are repelled when creating new drugs of the androgenic group.
The androgenic/anabolic index of "Testosterone Propionate" is 1/1, that is, it is equally anabolic and androgenic. The effectiveness of the drug is high due to the fact that the specific gravity of the short propionate ester is less than that of the long esters. And the shorter the ether, the less testosterone works in the body, and the greater its concentration. For example, after injection of 100 mg of testosterone cypionate, 69.90 mg of the active substance enters the body, the remainder is the mass of ether. When injecting "Testosterone Propionate", the mass of the main testosterone will be equal to 83.72 mg, the mass of the propionate ether, in turn, is much less.
The course of therapy is individual, it must be calculated for each patient individually. However, it should be understood that the actual effective dosage is at least 400 mg per week for an adult male. The period of activity of the substance lasts up to three days. The course of therapy can be up to six weeks.
The drug does not cause such fluid retention as "long" testosterone esters. In general, it has fewer side effects than other testosterones, precisely because of its short period of activity.
When using testosterone, certain disadvantages of therapy may appear:
Sustanon 250 is a powerful steroid with great androgenic power. It is a unique combination of four testosterone esters. This combination significantly increases the bioavailability and distribution of the drug in the body. For 40 years it has been used by athletes of various power sports.
The androgenic effect occurs 2-3 days after the first injection. The optimal frequency of injections is 1 time in 3 weeks. The preferred course of treatment is 6-8 weeks, maximum - 10 weeks. After a medical pause, a repeated course of injections of the drug is possible.
Sustanon 250 was developed by the Dutch pharmaceutical company Organon back in the 1970s for the gradual distribution of testosterone in the body. This is achieved due to the different distribution and excretion rates of testosterone esters included in the preparation: the half-life of testosterone propionate is 23-49 hours, phenylpropionate is 47-100 hours, isocapronate is 119-132 hours, decanoate is up to 11 days. The maximum concentration of testosterone in the body is observed two days after the introduction of Sustanon.
In general, the drug is well tolerated, but it, like all testosterones, has a "but"…
Esters of testosterone, which are part of Sustanon 250, are quickly converted into estradiol— a female sex hormone from the group of estrogens. An increased concentration of estrogen leads to side effects such as edema, an increase in fat mass and breast glands. Anti-estrogens - clomiphene, tamoxifen - can prevent these undesirable effects.
Sometimes it is necessary to alternate the intake of Sustanon with aromatase antagonists, for example, with Arimidex, which effectively blocks the production of estrogens.
Other side effects of the drug should include:
For better assimilation of the drug and prevention of mental reactions (depression and nervous breakdowns), it is mandatory to visit the gym - at least 3 times a week.
"Omnadren 250" is a complete analogue of the drug "Sustanon 250", produced under license by the Polish pharmaceutical company Jelfa S.A.
"Nebido" is the most popular castor oil depot drug for intramuscular injections containing testosterone undecanoate. After injection, the drug is gradually released and then cleaved by serum esterases into testosterone and undecanoic acid.
The increase in the concentration of testosterone is determined the very next day after the injection. 1 ml contains 250 mg of the drug, recently a dose of 1000 mg (4 ml) is usually used.
The drug is in the body for up to three months. The frequency of injection is 1 time in 10-14 weeks. "Nebido" has all the usual side effects of testosterone.
Androgel is produced in the form of a gel packed in sachets. One such sachet (sachet) contains 50 mg of pure testosterone. In addition, vials of this drug with a dispenser appeared. It is applied daily to the skin of the forearms and abdomen in the morning and after a shower. It is absorbed into the body only up to 15% of the applied dose.
The concentration of testosterone levels begins to rise from the first hour, reaching a maximum at the end of the day. If the gel is poorly absorbed into the skin, it can potentially be transferred to people in contact with the patient (spouse, children) and cause undesirable phenomena (hair growth at the point of contact). Therefore, you need to make sure that the gel dries well.
A good "bonus" is the local effect of "myolifting", which other drugs do not have. When applying the gel to problem areas of the body, the functional state of the skin and muscles in this area improves, excess fat deposits "go away". This effect allows the use of Androgel in complex therapy, together with prolonged forms of testosterone.
In addition, the drug can be used in the complex therapy of chronic prostatitis, the exacerbations of which coincide with seasonal fluctuations in testosterone. Androgel helps to eliminate the imbalance and improve the condition.
With prolonged use, Androgel can have negative effects inherent in testosterone:
An interesting question is about the use of so-called testosterone boosters (testobusters) - chemical and biological additives that stimulate the production of their own endogenous testosterone. And although extensive international clinical studies on testobusters have not been conducted, and sometimes data on the effects are quite contradictory, their use may be justified with minor and transient fluctuations in testosterone levels in the blood.
The most popular testobusters:
When vitamin D deficiency is replenished, androgen metabolism indicators return to normal fairly quickly, and testosterone levels increase.
The drugs that correct the level of vitamin D include:
The dosage of the drugs is selected individually, depending on the level of vitamin D deficiency.
Possible overdose of vitamin D preparations.
Early signs of vitamin D hypervitaminosis include:
The late symptoms of vitamin D hypervitaminosis include:
Contraindications to the use of vitamin D preparations:
Male drugs containing hCG increase the production of testosterone in the testicles by stimulating Leydig cells. Such drugs include:
When prescribing hCG drugs, therapy that stimulates spermatogenesis should be carried out.
With timely treatment, the prognosis is favorable (with the exception of hereditary forms of androgen deficiency and critical stages of age-related androgen deficiency).
The methods of prevention of androgen deficiency include:
