Testosterone is produced by the testes in a percentage of more than 90%, the rest of the insignificant amount is produced by the adrenal glands. It is possible to disrupt the flow of androgen into the blood under the influence of external and internal factors.

Conditions for lowering testosterone:

Drinking beer containing phytoestrogen, as well as smoking, poisoning the body, has a negative effect. With prolonged exposure to testosterone deficiency syndrome, it is possible to reduce the vegetation on the body and change the timbre of the voice.

FACT... Irregular sex life suppresses sexual reflexes - testosterone in the blood decreases.

What to do in such a situation? Medicines or folk remedies?

Herbs and other natural ingredients are used when testosterone decreases over a short period of time. The hormonal background is most easily corrected after the elimination of destabilizing factors, especially alcohol abuse, exposure to nervous tension and malnutrition.

However, there are prerequisites for the need for drug treatmentif significant physiological disorders are diagnosed.

Rationality of therapy for:

1. mechanical damage to the genitals;
2. genetic diseases;
3. pituitary tumors;
4. orchitis and cryptorchidism;
5. varicocele, spermatocele and hydrocele.

Infectious inflammation of the scrotum organs, which often occur when infected with sexually transmitted diseases, are also dangerous. Against the background of pronounced damage to the skin, balanoposthitis and epididymitis occur.

When infected with mycoplasmosis and trichomoniasis in men, testosterone levels also decrease simultaneously with a deterioration in spermatogenesis.

Chlamydia provokes inflammation of the appendages, bladder and impaired potency.

The destruction of extraneous pathogens is carried out mainly by taking powerful antibiotics, and only then therapy is carried out to restore the balance of testosterone in the blood.

With diagnosed asthenospermia (the number of motile sperm is less than half of their total number) and azoospermia (active germ cells are completely absent), the help of natural components will no longer be enough.

Congenital forms of male hormone deficiency are called Kallman syndrome and Klinefelter syndrome.... In the latter case, not only testosterone deficiency is observed, but also poorly developed genitals.

Andrologists in such situations prescribe medications that force the return of a healthy hormonal background. In old age, you need to be prepared for the appearance of andropause: after 50 years, a significant decrease in androgen is a natural process that can only be corrected with medication.

WARNING... For men with prostate cancer or other diseases of the prostate gland, an increase in the concentration of testosterone in the blood is contraindicated.

Tactics for treating a lack of testosterone in men: exercises, recommendations, medications

Phytoproducts are used as conservative methods to restore healthy hormone levels. Tinctures of ginseng, eleutherococcus, schisandra chinensis and leaves of the ginkgo tree have a strong tonic effect.

A tangible help is provided by the use of multi-complexes (Vitrum, Alphabet, Multitabs), containing vitamins from which testosterone is built (B, C, E, D), and trace elements (zinc and selenium). As for the products, andrologists advise to "lean" on nuts, ginger, dried fruits, garlic, eggs and seafood.

Physical activity is similarly included in the list of what is called a must-have in androgen deficiency syndrome.

Helpful Exercises to Boost Testosterone Production:

• warm-up (5 to 10 minutes);
• barbell lifting exercises (10 to 40 minutes);
• strength training for large muscles (legs, chest, back);
• abdominal exercises (10–20 min).

Male rivalry is a traditional source of testosterone boost. Since ancient times, dominance has made men feel euphoric after victories in wars or hunting.

In modern conditions, these methods may be viewed as barbaric and unethical by some men, so it is rational to choose more civilized methods of uplifting.

Participation in sports - from running to boxing - can be helpful in treating insufficient androgen levels in the blood using the most natural methods.

Career success is also seen as an element of social dominance that restores a man's natural strength. The peak rise in testosterone is observed during the period of promotion, with active self-development and career achievements.

The production of the hormone occurs in the same way when contemplating a female naked body, therefore, to strengthen the sexual constitution, the number of sexual contacts should be increased.

Less androgen is formed during verbal communication with the opposite sex without erotic contact.

Along with the above recommendations, you should increase physical activity - the best option becomes an enrollment in the gym. Muscle tension automatically activates the male reflex to produce more testosterone.

If conservative methods are ineffective, then the doctor has the right to prescribe medicines androgenic group. Common injection options: Sustanon 250, Nebido, Testosterone propionate, Omnadren. Andriol can be prescribed as tablets, Androgel ointments.

Duration of taking testosterone products:

1. ampoules - within 7-10 days;
2. tablets are taken up to 1 month;
3. gel - 1–3 months.

These drugs inject artificially created testosterone into the bloodstream, but there are also medications that force the reproductive system to reanimate the production of its own hormone.

Medicines in this group: Arimatest, Evo-Test, Vitrix, Tribulus, Animal Test... By suppressing aromatase, a testosterone antagonist, anabolic substances lead to a sharp increase in the male hormone, but their intake is recommended in conjunction with a trip to fitness clubs or sports complexes.

WARNING... Lifelong administration of injections is possible only with congenital insufficient development of the testicles - hypogonadism - or the loss of their functions by the testicles already in the process of life.

Conclusion

Treatment of patients with low testosterone is necessary: \u200b\u200bthe long presence of a weak hormonal background leads to obesity, impotence and even premature aging of a man.

Maintaining the production of sufficient concentrations of androgen helps to prolong well-being and permanently consolidate the behavioral and physiological qualities that are truly inherent in the stronger sex.

In conclusion, watch a video about drugs for increasing testosterone in men based on tribulus:

Severe androgen deficiency can develop in men for various reasons and at any age.

Testosterone replacement therapy is prescribed to restore the endocrine system of the male body and improve the quality of life.

A decrease in the concentration of testosterone in the blood serum negatively affects the functioning of various organs and systems of the male body. Testosterone decline is slow and begins to develop after age 30. By the age of forty, many men become overweight, their belly begins to grow and their sex drive decreases. Testosterone deficiency in men leads to the development of cardiovascular disease and osteoporosis. Testosterone replacement therapy enables men suffering from male hormone deficiency to avoid negative consequences.

The only way to know about the lack of male hormone in the blood serum is to measure its level in the blood. To find out its exact amount, several samples are taken. Blood is taken for analysis from 8 to 9 in the morning, when it is at the highest level. With the right dosages after long-term use of androgenic hormone, the health of men with symptoms of testosterone deficiency improves. They restore their weight, their blood pressure normalizes, libido and potency return.

Why does testosterone deficiency occur?

The decline in testosterone levels does not always occur naturally over the years. There can be various reasons for the decrease in its production by the endocrine glands. Injuries to the testes can lead to a lack of male hormone. The cause is genetic diseases and the development of oncological neoplasms. Excess iron in the body suppresses the production of testosterone by the endocrine system. Pituitary dysfunction and the use of various hormonal drugs can cause a developing deficiency. Chronic diseases associated with alcoholism, nicotine addiction and drug use lead to early aging of the body and a decrease in the production of androgenic hormone.

When to start treatment with testosterone drugs

All men with symptoms of androgen deficiency and the elderly after 50 years of age are advised to undergo a diagnostic examination for hormonal levels in blood serum. The test readings give true information about the production of hormones in the body. Replacement therapy is prescribed in the presence of symptoms of androgen deficiency, tests confirming an insufficient amount of testosterone in the blood and in the absence of malignant tumors in the prostate gland. Laboratory diagnostics should exclude or confirm the presence of prostate cancer. With a lack of testosterone, the likelihood of developing carcinoma of this male organ increases. For men with a history of cancer, testosterone preparations are contraindicated. The therapy will worsen the patient's condition. After collecting all the necessary information, testosterone preparations are prescribed.

The symptoms of androgen deficiency syndrome are:

1. Prostration.
2. Decreased stamina and performance.
3. Decreased growth.
4. Long-term depression.
5. Increased irritability.
6. Erectile dysfunction.
7. Need for afternoon naps.
8. Increase in body fat mass.
9. Breast growth.
10. Anemia.
11. Osteoporosis.
12. Increased cholesterol.

If there are 3 or more symptoms in the history, then you should consult a doctor for examination.

How to properly administer testosterone therapy

Replacement therapy with testosterone preparations should be carried out only as directed by a physician and under constant medical supervision. Uncontrolled use of hormonal drugs leads to an addiction of the body, which reduces the natural production of testosterone by the organs of the endocrine system. The most common hormonal treatment option is intramuscular administration of drugs containing the hormone.

In addition to injections, there are other types of administration of medicinal hormonal agents into the human body. Preparations containing testosterone are produced by manufacturers in the form of tablets, gels and patches.

Pharmaceutical companies offer crystal implants for use, which are inserted under the skin, making an incision in the abdomen. This drug, dissolving, provides a uniform release of testosterone for about six months. The implant is placed and removed surgically.

Replacement therapy using different types preparations containing testosterone lasts for life. The effectiveness of treatment can be seen after the body has accumulated the necessary concentration of testosterone and the symptoms of androgen deficiency are eliminated. If testosterone is taken under medical supervision, the therapy will be safe. It allows men of any age with androgen deficiency to maintain their health by leading an active lifestyle.

Hypogonadism therapy

Male hypogonadism is a functional failure of the testicles. The development of the disease is accompanied by a low level of testosterone in the serum and characteristic clinical manifestations.

The causes of the development of the disease can be testicular injury or disorders of the hypothalamic-pituitary system. Development pathologies can be genetically determined. Treatment of the disease involves mandatory use substitution therapy testosterone.

Signs of hypogonadism often begin to develop in boys during childhood. If the developing disease is not treated, then the teenager will have a delay in the development of secondary sexual characteristics. Adult men with hypogonadism have insufficient muscle development, a high-pitched voice, and a small scrotum and testicles.

They have a small penis, rare hair on the pubis and in the armpits. Breast growth and eunuchoid body composition may be observed.

Hormone replacement therapy for this disease is recommended from adolescence and continues for life, because androgen deficiency will accompany a man suffering from hypogonadism throughout his life.

There are various techniques for eliminating testosterone deficiency in this disease, which the doctor uses during treatment.

Substitution therapy in the elderly

Hormone replacement therapy in older men is performed to improve the quality of life. Everything more menhaving crossed the 40-year mark, they want to look young and strong. They do not accept old age and agree to substitution therapy if there are indications for use.

The main goal is to reduce the symptoms of age-related androgen deficiency. Such men are recommended to wear patches, intramuscular injections, gels and capsules for insertion.

Studies have shown that such therapy leads to a decrease in blood cholesterol, reduces the risk of heart attacks and cardiovascular diseases.

Side effects of replacement therapy

Testosterone therapy can lead to the development of side effects... Skin that becomes oily develops acne. Careful hygiene should be observed during treatment. Using lotions with the addition of alcohol, hard brushes for the body, gels for oily skin will help eliminate the development of acne.

Retention of fluids in the body may occur due to urinary retention, an increase in the size of the testicles. All these phenomena indicate an overabundance of the hormone. Testosterone therapy will be temporarily canceled if the doctor discovers the development of side effects. With the normalization of the condition, testosterone treatment continues, but the doctor reduces the dose of the injected drug.

Therapy results

When carrying out testosterone replacement therapy, the conditions that develop in various somatic diseases are improved. Reduction of signs of male hormone deficiency occurs in men of different ages. One month after starting replacement therapy, resistance to stress increases, an increase in stamina during exercise and a decrease in cholesterol levels, which is required to produce testosterone. Substitution therapy has a positive effect on the cardiovascular system. It reduces the symptoms of heart failure in elderly patients, normalizes blood pressure, and reduces the number of angina attacks. Numerous studies have shown that testosterone therapy improves myocardial contractile function and accelerates myocardial recovery after a heart attack.

Replacement therapy with hormonal drugs helps many men cope with inferiority complexes, find the joy of fatherhood, and stop the onset of old age. If there are any symptoms of male hormone deficiency in the body, you should consult an andrologist for advice and treatment.

26 February 2010

Until recently, diseases such as atherosclerosis, hypertension, diabetes mellitus, disorders of the lower urinary tract and erectile dysfunction, characteristic of elderly and old men, were considered separate diseases. Recently, however, there is more and more data indicating that these and other age-related diseases are closely interrelated and, as a rule, accompany a decrease in testosterone levels in an aging body. This indicates the need for an integrated approach to the treatment of diseases in older men and the inclusion of an analysis of the level of testosterone in blood plasma in the corresponding diagnostic protocols.

Comparison of age-related and classical hypogonadism

Symptoms of hypogonadism include erectile dysfunction, abdominal fat accumulation, mood swings, and decreased muscle and bone strength. Usually, hormone replacement therapy has pronounced positive effects on the condition of young patients with this disease. Comparison of data on similar symptoms developing in elderly men, as well as on a statistically proven decrease in testosterone levels in old age, led to the emergence of the terms "age-related hypogonadism" and "age-related androgen deficiency" and suggestions that normalization of testosterone levels in the bloodstream can slow the aging of the male body ... However, to date, there is no reliable evidence that the symptoms described above are actually manifestations of testosterone deficiency. Unfortunately, the data currently available regarding the positive effects of testosterone replacement therapy on the health of aging men cannot be considered scientifically proven. The reason for this lies in the imperfection of research methods, as a result of which they are obtained. Research of this kind should be carried out in a double-blind, placebo-controlled manner. In addition, to assess the results, it is necessary to use not the data on the dynamics of surrogate markers of a particular disease, but the final clinical outcomes. For example, is the risk of developing diabetes mellitus and cardiovascular disease in patients who have had an improvement in metabolic syndrome symptoms as a result of testosterone administration? Or - does the increased bone mineral density as a result of hormone therapy reduce the risk of fractures?

What does testosterone deficiency mean in old age?

A large number of healthy men have testosterone levels in the blood 5-20% lower than taken normal values, therefore, it is very difficult to draw a clear line between hypogonadal and normal body status. Moreover, the threshold level of the hormone at which a man begins to show symptoms of hypogonadism is very individual and ranges from extremely low values \u200b\u200bto values \u200b\u200babove the lower limit of normal values \u200b\u200bfor young men. The factors that determine this symptomatic threshold are not known, however, it is possible that genetic polymorphism of the androgen receptor plays an important role in this mechanism, causing variations in tissue sensitivity to testosterone. The effect of aging and acquired chronic disease on testosterone threshold levels is not yet fully understood. At the same time, the results of most population studies indicate that obesity, various comorbidities and lifestyle have a pronounced effect on testosterone levels.

Thresholds and dose-dependence of androgenic effects

Empirical evidence supporting the concept of testosterone thresholds in the development of symptoms of hypogonadism has begun to emerge quite recently. In addition, studies in older men have shown that different levels of the hormone circulating in the blood correspond to different symptoms of testosterone deficiency. So, according to one of the studies, the decrease in libido and muscle strength associated with the level of testosterone was most pronounced with a decrease in the level of the hormone below 15 nmol / l, and the development of depression and type 2 diabetes mellitus - with its concentration in the blood below 10 nmol / l. The authors of this study divided patients into three groups according to their symptoms of testosterone deficiency: psychosomatic complaints, signs of metabolic syndrome and sexual problems. Since the patients of these groups differed in a number of parameters (testosterone content in the blood, age and body mass index), the observed symptoms could not be unambiguously associated with hormonal levels. The situation is further complicated by the multifactorial nature of the disorders observed with a decrease in testosterone levels. For example, the cause of erectile dysfunction, in addition to hypogonadism, can be impaired functioning of the arterial endothelium and nervous systemas well as psychological and other factors. And given the disagreement about the threshold for the development of symptoms of hypogonadism, the concentration in the blood plasma of total testosterone (according to various sources - from 7.5 to 12 nmol / l), the diagnosis of this disease cannot be made only on the basis of the results of the analysis of hormonal status, without a comprehensive study of somatic and psychological aspects. (Total testosterone includes the free form of the hormone and the complex of the hormone with a carrier protein.)

Diagnostics of the age-related hypogonadism

The decision on the diagnosis of age-related hypogonadism and the appointment of hormone therapy must be made with great caution, taking into account the mutual dynamics of the increase in symptoms and changes in the level of testosterone in the patient's blood. Testosterone is by no means a panacea for all the psychological and somatic problems facing aging men, and its uncontrolled use can have serious negative consequences.

If hypogonadism is suspected, patients should undergo a serious physiological and biochemical examination. In men of any age, periods of transient testosterone decline are possible, which must be excluded by a detailed study of clinical information and a reassessment of hormonal status. It is necessary to take into account the risk factors for the development of hypogonadism, which include many chronic diseases (including diabetes, chronic obstructive pulmonary disease, inflammatory diseases joints, kidney disease and diseases associated with HIV), obesity, metabolic syndrome and hemochromatosis.

Benefits of Testosterone Replacement Therapy

Restoring testosterone levels to normal levels with replacement therapy can reduce many of the symptoms of hypogonadism in young adults. There is evidence that hormone replacement therapy has a short-term positive effect on the health of older people, including their psychological state, sexual function, body weight, muscle strength, erythropoiesis, bone mineral density, cognitive function and cardiovascular health. systems. Below are the main regularities identified in the study of the effect of hormone replacement therapy on the health of older men.

Metabolic syndrome, type 2 diabetes and cardiovascular disease

Many symptoms of metabolic syndrome (obesity, hypertension, fat and carbohydrate metabolism and tissue resistance to insulin) are also characteristic of hypogonadism. Low testosterone levels are also associated with surrogate markers for cardiovascular disease and increased mortality from these diseases. According to the research results, the introduction of testosterone to elderly men improved the indicators of fat and carbohydrate metabolism, which, together with the correction of diet and physical exercise, led to the normalization of body weight and a decrease in body fat in the abdomen.

Low testosterone levels in men are associated with an increased likelihood of developing cardiovascular disease. However, there is no evidence that high levels of the hormone would be consistent with a decrease in this risk. It is possible that the inverse correlation between the level of testosterone and the severity of coronary heart disease, revealed by scientists, can be explained by the concomitant accumulation of fat in the abdomen, associated with an increased risk of problems in the cardiovascular system and the development of impaired tissue sensitivity to glucose and non-insulin dependent diabetes mellitus.

According to the results of studies carried out to date, the administration of physiological doses of testosterone has a positive or neutral effect on the state of the cardiovascular system of older men. There is evidence of an improvement in the functional state of the vascular endothelium and blood supply to the myocardium, but none of the studies has shown the effect of therapy on the likelihood of developing diseases such as heart attack, stroke and angina pectoris, as well as on mortality rates from them.

Thus, despite the fact that a decrease in testosterone levels is associated with the development of metabolic syndrome and an increased risk of developing cardiovascular diseases, to study the effect of androgen replacement therapy on the incidence of these diseases and the mortality associated with them, it is necessary to conduct carefully planned clinical trials of an adequate scale and duration.

Bone mineral density

Osteopenia, osteoporosis, and increased fragility of bones are common in both young patients with hypogonadism and aging men with normal hormonal levels. With testosterone deficiency, the risk of fractures doubles. However, the role of age-related hypogonadism in increasing the risk of fractures needs detailed study, as well as the long-term effects of hormone therapy with testosterone. Testosterone increases the activity of bone-forming cells - osteoblasts and suppresses the activity of osteoclasts performing the opposite function. There is evidence that its administration in sufficient doses increases bone density (but does not provide normal values) in men of all ages with hypogonadism. However, in general, studies on the effect of testosterone replacement therapy have yielded conflicting results, which can be explained by insufficient sample sizes and duration of observations.

Muscle mass and strength

The aging process is accompanied by significant changes in body composition, characterized by an increase in the amount of adipose tissue and its redistribution. This can lead to physical limitations and increased mortality. Maximum muscle strength is proportional to muscle mass regardless of age. Testosterone not only directly stimulates protein synthesis and muscle cell growth, but also increases the expression of the similarly acting insulin-like growth factor-1 (IGF-1). Therefore, age-related decline in testosterone levels may be one of the factors contributing to a decrease in muscle mass and, accordingly, physical strength.

Most of the studies to date indicate that testosterone supplementation generally has a positive effect on the health of older men: it reduces body fat, increases muscle mass, increases the strength of various muscle groups, and generally improves physical performance. Only a small amount of data indicates that there is no effect of testosterone replacement therapy on the functional state of muscles. Despite the fact that testosterone administration is considered a promising approach to combat aging physical weakness, at the present stage it is still impossible to speak unambiguously about the positive effect of such treatment on the physical condition of elderly men with a deficiency of this hormone.

Increased sex drive, sexual function and performance

The likelihood of developing erectile dysfunction increases significantly with age. Older men require higher testosterone levels than younger men to maintain libido and maintain normal erections. However, erectile dysfunction and / or decreased sex drive, both with normal and low testosterone levels, can be caused by other comorbidities or medications.

The administration of adequate doses of testosterone can prevent premature drainage of blood from the corpus cavernosum, which is a common cause of erectile dysfunction in old age. According to a review of evidence from randomized clinical trials, testosterone replacement therapy has a positive effect on the sexual health of older men with testosterone deficiency. The positive effects include not only an increase in self-esteem and sex drive, but also the frequency of intercourse and erections that occur during sleep.

Condition of the urinary tract

In addition to improving sexual function, testosterone therapy has a positive effect on the functional state of the lower urinary tract in men with age-related hypogonadism, which is manifested by an increase in the capacity and elasticity of the bladder wall and a decrease in the pressure of its sphincter with maximum urine flow.

Mood, energy and quality of life

Men over 50 years of age with low levels of free testosterone in their blood often complain of a deterioration in quality of life, which usually manifests itself with symptoms that overlap with those of major depression, including decreased sex drive, increased anxiety, fatigue, and irritability. When examining the effect of testosterone replacement therapy on the severity of these symptoms, different groups of researchers received differing results, ranging from a significant improvement in the quality of life to the absence of any recorded changes. The reason for this may be genetic polymorphism of androgen receptors, which determines the population of men who are prone to developing depression when testosterone levels drop below a certain level.

Cognitive function

The age-related decline in free testosterone levels is a predictor of deterioration in visual and verbal memory. There is also evidence of a strong relationship between testosterone levels and a number of aspects of cognitive function, such as the ability to orientate in space and perform mathematical calculations. However, there are data that contradict these observations. For example, in men undergoing hormone therapy for prostate cancer, suppression of endogenous testosterone synthesis and blocking of androgen receptors had a positive effect on verbal memory, but impaired the ability to orientate in space.

All clinical studies to date on the effects of androgen replacement therapy on cognition and memory have involved relatively small patient populations and have been relatively short-lived. The data obtained in this case contradict each other in some aspects, but in general they indicate that hormone therapy in men with hypogonadism, especially in elderly patients, has a positive effect on their cognitive abilities.

Improving symptoms of anemia

It is known that endogenous androgens stimulate the formation of erythrocytes in the bone marrow, increase the number of reticulocytes and the level of hemoglobin in the blood, while castration has the opposite effect. Testosterone deficiency leads to a decrease in hemoglobin levels by 10-20%, which can be the cause of anemia. For young men with hypogonadism, the content of erythrocytes and hemoglobin in the blood is lower than for healthy individuals of the same age. A similar decrease in these indicators can be observed in healthy older men.

The safety of giving testosterone to older men

To obtain reliable information about the effect of testosterone replacement therapy on the health status of elderly men with hypogonadism, it is necessary to conduct clinical studies with the participation of 5-7 thousand men, which should be monitored for at least 5-7 years. Carrying out work of this scale is quite problematic, so today, to assess the safety of androgen replacement therapy, one has to be content with the results of smaller studies. The main side effects of testosterone administration are described below.

Polycythemia
(a chronic disease of the blood system, characterized by an increase in the absolute number of erythrocytes, and in some cases also leukocytes and platelets).

In men not receiving testosterone therapy, there is a non-linear relationship between testosterone levels and plasma hemoglobin concentration. Testosterone affects erythropoiesis through several mechanisms. It activates the synthesis of erythropoietin in the kidneys, and also directly stimulates the formation of colonies of erythrocyte progenitor cells in the bone marrow. The results of a number of studies indicate that the increase in the values \u200b\u200bof hemoglobin and hematocrit (the volume percent of erythrocytes relative to whole blood) is dose-dependent even when testosterone is administered. Moreover, this effect is more pronounced when treating elderly patients.

Elevated hematocrit is associated with a high risk of stroke and coronary heart disease. However, a large-scale meta-analysis of placebo-controlled clinical trials in which testosterone was administered to elderly patients did not generally find an association between hormone-induced hematocrit increases and the likelihood of stroke and other cardiovascular diseases. Thus, polycythemia is a controlled side effect of testosterone administration, provided that hemoglobin and hematocrit are monitored and an adequate dosage of the hormone is selected.

The functional state of the lower urinary tract and prostate disease

In the framework of several studies, when monitoring the condition of men receiving hormone replacement therapy, no cases of difficulty urinating due to benign prostatic hyperplasia were detected. Moreover, the incidence of complications such as urinary retention in experimental groups was the same as in the control groups.

Despite the inconsistency of the data of individual studies, a meta-analysis of the results of studies on the possible effect of testosterone administration on the likelihood of developing prostate cancer also showed no pronounced relationship. However, according to its results, men undergoing hormone therapy are more likely to undergo prostate biopsies. The same applies to the safety of testosterone administration to older men with no history of prostate cancer. At the same time, there are at least three publications, according to which in 17 patients (in total in all studies), who had previously been cured of prostate carcinoma, the administration of testosterone did not cause tumor recurrence.

Today, it is believed that giving testosterone to older men is a reasonable practice, provided that existing guidelines are followed. This consensus is based on expert opinion, who, however, underscore the need for long-term studies of the safety of therapy.

Diseases of the cardiovascular system

A decade ago, experts were of the opinion that androgens are atherogenic, so it was believed that the introduction of testosterone could increase the risk of developing cardiovascular diseases. Several studies over the past decade have provided evidence that testosterone is not the cause of circulatory disease. However, recent epidemiological studies have shown that low level testosterone is a predictor of mortality, and numerous reviews that have appeared over the past two years describe a significant relationship between decreased testosterone concentration and the likelihood of developing cardiovascular diseases.

The study of the results of testosterone replacement therapy did not reveal the development of such side effects as peripheral edema, exacerbation of hypertension and congestive heart failure. However, given that the existing data are obtained mainly from the observation of relatively healthy elderly men, when treating patients with chronic diseases and generally sick individuals, it is necessary to take into account the possibility of fluid retention in the body.

Sudden cessation of breathing during sleep (apnea)

Obstructive sleep apnea syndrome is characterized by snoring and repeated episodes of closure of the upper airway, leading to decreased blood oxygen levels, sleep fragmentation, and increased daytime sleepiness. This condition is characterized by decreased libido and (in 10-60% of cases) erectile dysfunction. In addition, it is associated with an increased risk of hypertension, arrhythmias, myocardial infarction, stroke, and sudden death. It is not uncommon for patients with sleep apnea to have obesity and metabolic syndrome, which can underlie sexual problems.

Typically, men with sleep apnea have low plasma testosterone levels, but this can be attributed to obesity and metabolic syndrome. A large meta-analysis of placebo-controlled trials of hormone therapy in older men found no significant differences between the incidence of sleep apnea in the experimental and control groups. However, obstructive pulmonary disease in obese men or heavy smokers should be considered a relative contraindication to hormone therapy.

conclusions

To date, there have been many studies showing that hormone replacement therapy reduces the symptoms of metabolic syndrome and increases bone mineral density, mood and sexual function in older men with reduced testosterone levels. However, only a few of these studies have been carried out according to generally accepted scientific standards. In addition, comparison of the results of these studies is hampered by the lack of generally accepted normal hormone levels used to diagnose hypogonadism. Another obstacle to an adequate interpretation of the results is the pronounced genetic polymorphism of androgen receptors, due to which the same testosterone levels can form completely different hormonal statuses in different men.

There is strong evidence that testosterone is not a major determinant of prostate cancer in older men. Therefore, subject to the protocols developed by specialists, the administration of testosterone to patients with age-related hypogonadism is quite safe.

Currently, the most popular form of therapy for androgen deficiency is testosterone replacement therapy.

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The first reports on the successful treatment of androgen deficiency were dated back to the 40s of the last century. However, the drugs of that time had many side effects and did not have the full spectrum of action of natural testosterone.

The first popular synthetic testosterone preparations were sold in the form of tablets (methyltestosterone, fluoxymesterone, etc.). Oral administration exposed testosterone to metabolism in the liver, as a result of which most of it was destroyed, while exerting a strong toxic and carcinogenic effect on the liver. In this regard, in most countries, drugs based on these derivatives of testosterone are prohibited for use, giving way to modern analogues.

A great influence on the development of synthetic forms of testosterone is played by its role in sports. Despite the fact that the use of anabolic steroids is prohibited, drug control incidents continue to rage at the Olympic Games and other major events.

Forms of administration of testosterone preparations

The methods of administration of androgens are divided into the following:

• oral (tablets, capsules);
• injection (injection);
• transdermal (patches, gels, creams);
• subcutaneous (implant).

Table 1 - Exogenous testosterone preparations (S. Yu. Kalinchenko, I. A. Tyuzikov, 2009)

GROUP OF PREPARATIONS	CHEMICAL NAME	TRADENAME	DOSAGE
Injection forms	Testosterone Cypionate	Depot testosterone cypionate	200-400 mg every 3-4 weeks
	Testosterone Enanthate	Delasteril Testosterone Depot	200-400 mg every 2-4 weeks
	Testosterone Ester Blend	Sustanol-250 Omnadren-250	250 mg every 2-3 weeks
	Testosterone Undecanoate	Nebido	1000 mg every 3 months
Oral forms	Fluoxymesterone *	Halotestin	5-20 mg daily
	Methyltestosterone *	Metadrene	10-30 mg daily
	Testosterone undecanoate	Andriol	120-200 mg daily
	Mesterolone ***	Proviron Vistinone Vistimon	25-75 mg daily
	Buccal tablets	Striant	30 mg 3 times a day
Subcutaneous forms	Implants	Testosterone implants	1200 mg every 6 months
Transdermal forms	Testosterone gel	Androgel	25-75-100 mg daily
	Testosterone patches (scrotal and cutaneous) **	Androderm Testoderm	2.5-7.5 mg daily
	Testosterone cream	Andromenes	10-15 mg daily
	Dihydrotestosterone Gel (DHT Gel)	Andractim	Individually

Notes: * - hepatotoxic and prohibited in a number of countries; ** - not registered in Russia; *** - out of production.

Choosing a drug

Figure: 1 - The share of various forms of androgenic drugs in the pharmaceutical market of Russia (2007) (source "Practical Andrology", S. Yu. Kalinchenko I. A. Tyuzikov, 2009).

Intramuscular testosterone injections are the most commonly used replacement therapy method. The most famous testosterone esters, testosterone cypionate and testosterone enanthate, have their own characteristic features: getting into the bloodstream, the testosterone level reaches its maximum value 2-3 days after injection, after which it gradually decreases over 2 weeks and reaches its minimum. This causes the so-called. The roller-coaster effect, when mood, well-being and libido rise along with the level of androgens in the blood, and just as sharply declines when it is at the minimum level. The same properties are possessed by preparations containing a mixture of testosterone esters (Sustanol, Omnadren).

A sharp change in the concentration of androgens in the blood, often felt by the patient himself, is an undesirable effect when using testosterone preparations.

Nevertheless, both individual testosterone esters and their mixtures are still successfully used due to their low cost, availability and effectiveness. In particular, testosterone esters are loved by strength athletes and bodybuilders for their anabolic properties and for their ability to create high concentrations of testosterone in the blood.

Testosterone undecanoate (Nebido) is currently the injectable drug of choice for hormone replacement therapy (HRT). It differs from other testosterone esters in its prolonged action (1 injection every 10-12 weeks) and the absence of pathological surges in the level of androgens. The drug Nebido has the full spectrum of testosterone action and does not cause hepatotoxic and hepatocarcinogenic effects.

Oral medications have little effect compared to injectables, even at high doses. Therefore, it is advisable to use oral testosterone in cases where there is a slight decrease in androgens. The drug of choice for HRT is Andriol. Compared to the old analogues (methyltestosterone, fluoxymesterolone), when using Andriol, most of the testosterone bypasses the metabolism in the liver and enters the systemic circulation directly, which contributes to the rapid achievement of the required hormone concentration. However, this also causes a fast half-life of the drug (3-4 hours), which forces the patient to take it again (3-4 times a day).

Transdermal forms of testosterone preparations (gels, patches) are gaining more and more popularity. They quickly create the necessary level of androgens in the blood, but at the same time they do not undergo hepatic metabolism as oral drugs, and at the same time do not create a supraphysiological level of testosterone, as is the case with the use of testosterone esters (cypionate, enanthate) and a mixture of esters (Sustanol, Omnadren) ... The advantage of transdermal forms is their non-invasiveness, the possibility of independent use, and the absence of pronounced side effects.

In some countries, implants are a common treatment for androgen deficiency. With the help of surgical intervention, the implant is placed subcutaneously in the patient, releasing the hormone evenly over 6 months. Testosterone implants are not registered in Russia.

Figure: 2 - Pharmacokinetics of various testosterone preparations.

Table 2 - Characteristics of various forms of testosterone preparations

	INJECTION	ORAL	TRANSDERMAL	SUBCUTANEOUS
The effectiveness of therapy	+ Highly effective. The ability to create high concentrations of the hormone in the blood	— Effective only for mild androgen deficiency	+ Effective enough to overcome different degrees androgen deficiency	+ Effective
Availability	+ A wide variety of testosterone esters available on the market	+ Availability by prescription	+/- Only testosterone gel (AndroGel) is on sale. Testosterone patches are not registered in Russia	— Testosterone implants are not registered in Russia
Duration of action	+ Nebido has the longest duration of action of all testosterone preparations (1 injection every 3 months)	— Daily from 2-4 times a day (Andriol)	— Daily, once a day	+ The duration of action of one implant is 6 months.
Possibility of urgent stopping of therapy	—	+	+	—
Sharp fluctuations in hormone levels	+ Not detected when using Nebido-It is noted when using testosterone propionate, testosterone enanthate and a mixture of esters	— Have a fast half-life	+ Absorbs evenly throughout the day, keeping hormone levels within normal limits	+ Uniform release of testosterone throughout the life of the implant
The possibility of independent use	+/- The procedure is performed by a specialist, but the possibility of independent use is not excluded	+	+	— Requires surgical intervention
Feature of side effects	Depending on the dosage	Have some liver toxicity, especially older drugs	May cause skin reactions where the drug comes in contact with the skin	Complications caused by surgery

In the next issue of the program "An Hour with a Leading Urologist" Stepan Sergeevich Krasnyak, employee of the Department of Andrology and Human Reproduction, Research Institute of Urology and Interventional Radiology. N. A. Lopatkina of the Ministry of Health of Russia, spoke about the problems associated with the appointment of hormone replacement therapy with testosterone drugs in men.

As Stepan Sergeevich noted at the beginning of his speech, the topic of testosterone therapy is extremely controversial and raises many questions from both doctors and patients. The prevalence of the use of testosterone therapy today is growing at a high rate, but the negative aspects of such treatment, according to the guest of the program, are often forgotten.

S.S. Krasnyak recalled the main areas of influence of testosterone on the male body. In particular, this hormone provokes the growth of body hair, participates in the synthesis of serum proteins in the liver, induces an enlargement of the penis and triggers spermatogenesis, affects thinking and mood, helps to increase strength and muscle mass, on the part of the kidneys it is involved in the synthesis of erythropoietin, and supports the growth of bones in length and increase in their density. Accordingly, the less testosterone in the body, the less pronounced male sexual characteristics. Fortunately, according to Stepan Sergeevich, usually the decrease in the amount of this hormone is reversible.

The border of norm and pathology

It's no secret that testosterone levels tend to decline with age. However, is this process a norm or a pathology, and where is the border that allows you to distinguish between these two states? Most often, testosterone problems occur in men over the age of 45-50. There are a number of criteria for identifying age-related hypogonadism. Among them, a decrease in serum testosterone (total<11 нмоль/л, свободный <220 пмоль/л), эректильная дисфункция, снижение либидо и частоты утренних эрекций (данные EMAS). Доктор подчеркнул, что препараты тестостерона назначаются для лечения не сексуальной дисфункции или ожирения, а гипогонадизма как такового. Порог уровня тестостерона для назначения гормонозаместительной терапии — 9,7-10,4 и 6,9 нмоль/л.

Stepan Sergeevich noted the importance of a personalized approach to the patient: there are people with high receptor sensitivity, in whom even a low testosterone level does not cause clear clinical manifestations. Accordingly, the question arises as to whether hormone therapy is needed in such patients. The current clinical guidelines suggest that, as a rule, they are not needed. In practice, according to the lecturer, it is necessary to proceed from a combination of clinical symptoms, probably associated with low testosterone levels, and laboratory confirmation. At the same time, it is important to avoid uncontrolled and excessive prescription / intake of testosterone.

In general, there are frequent cases of mismatch of symptoms (20-40% of the general population) and low levels of circulating testosterone (20% of men\u003e 70 years). According to these criteria, only 2% of those aged 40 to 80 years have age-related hypogonadism and really need testosterone therapy.

Hormone replacement therapy - billions of dollars

Today, testosterone replacement therapy is widely used worldwide to treat hypogonadism and related isolated symptoms. A disturbing aspect of this trend, however, is that it has developed without any solid scientific evidence of the swinging benefits and risks of this type of therapy.

Today, injectable and gel testosterone preparations are mainly tried on. In the United States, sales of testosterone drugs between 2005 and 2010 has doubled and continues to grow. Similar trends can be seen around the world. From 2000 to 2011, total sales of testosterone in the world increased 12 times to $ 1.8 billion. According to forecasts, in 2018 the sales of testosterone drugs in the United States alone will amount to $ 3.8 billion. Inevitably, as Stepan Sergeevich noted, the question arises: is it really Have men become so much more likely to suffer from hypogonadism recently? It is possible that there is a large-scale over-treatment.

The doctor also spoke about the presence of scattered, but numerous data indicating a trend towards an increase in the number of obese patients associated with testosterone intake.

Substitution therapy, emphasized Stepan Sergeevich, should be offered to the patient only after a conversation about the fact that in the long term, the beneficial and unfavorable consequences of this treatment for him are unknown. So, in 2017, at the congress of the American Urological Association, the so-called urological "trial" was held, where, with the participation of practicing lawyers, the case of prescribing testosterone preparations to a patient with a high risk of cardiovascular diseases was examined, which eventually led to his death. It is interesting that practically no somatic diseases are contraindications to the appointment of hormone therapy. However, the doctor stressed, this does not mean that you need to prescribe it to everyone, including the most severe patients. Patients with a high risk of concomitant diseases must necessarily undergo specialized studies.

Noteworthy is the fact that many of the currently available studies on the topic included men without symptoms of hypogonadism, while various testosterone thresholds, drugs, and dosing regimens were used for the assessment. Thus, it is very difficult to bring together the data that would allow an objective assessment of the safety of testosterone therapy.

About pitfalls

At the very least, there are absolute contraindications for the appointment of HRT. These are prostate and breast cancers, as well as liver tumors. Relative contraindications include prostate-specific antigen (PSA) levels\u003e 4 ng / ml (or 3 ng / ml in men at high risk for prostate cancer); hematocrit\u003e 50%; severe symptoms of the lower urinary tract caused by benign prostatic hyperplasia (above 19 points on the IPSS scale); and poorly controlled congestive heart failure and sleep apnea.

There is some evidence that testosterone supplementation increases the volume of the prostate gland, eventually causing a moderate increase in PSA levels in older men. In 2005, the Journal of Gerontology published a report according to which the total number of adverse events associated with the prostate gland (prostate biopsy, cancer, serum PSA level above 4 ng / ml, increased IPSS scores) was significantly higher in the group of patients. receiving testosterone than those receiving placebo (odds ratio 1.90; 95% CI 1.11-3.24; p<0,05). Также есть данные, показывающие результаты применения препаратов тестостерона у пациентов с местно-распространенным и метастатическим раком предстательной железы (РПЖ). Согласно этим данным, у пациентов с агрессивной и неагрессивной формой заболевания достоверно отличались уровни общего тестостерона и глобулина, связывающего половые гормоны: у больных с агрессивной формой РПЖ уровень тестостерона был значительно выше. Неясно, можно ли тут говорить о причинно-следственной связи, но факт корреляции выявлен.

Another significant factor is hepatotoxicity. It is because of her that in most countries today oral forms of testosterone preparations are prohibited. The development of hepatic failure, benign and malignant neoplasms of the liver, intrahepatic cholestasis, hepatic purpura, hepatocellular adenoma, and carcinoma were associated with their intake.

In addition, a factor such as polycythemia is noted. A very common complication of taking testosterone drugs is erythrocytosis (hematocrit is more than 50%). Two meta-analyzes performed in recent years have shown significant negative effects of testosterone therapy in this respect compared to placebo. There is a correlation between high testosterone levels and high hemoglobin levels. Erythrocytosis is more often dose-dependent and develops in older men during therapy with injectable forms of testosterone. The risk of such complications is especially high in the presence of other chronic diseases, for example, chronic obstructive pulmonary disease. Therefore, when prescribing testosterone medications, control blood tests should be performed.

As for the effect of testosterone preparations on the cardiovascular system, this issue remains controversial. In connection with the steady increase in the rates of cardiovascular mortality, it becomes especially acute. There is, in particular, evidence that testosterone intake is correlated with the progression of heart failure, but the causal relationship remains a matter of debate. The use of testosterone in coronary artery disease is believed to have a stimulating atherogenic effect due to its negative effect on the lipid profile. However, normal physiological testosterone levels have been shown to be beneficial for the male heart, and low levels are associated with an unfavorable risk of coronary artery disease outcomes. But, as S.S. Krasnyak emphasized, it is impossible to guarantee that the physiological level of testosterone will be achieved in a particular patient without serious hesitation.

In 2006, the New England Journal of Medicine published a study of 106 elderly men, an average age of 74, with low total testosterone, mobility limitations, high prevalence of hypertension, obesity, diabetes, preexisting heart disease, and hyperlipidemia. For 6 months, the patients underwent testosterone therapy in daily doses from 5 to 15 g. A placebo group was also allocated. The incidence of cardiovascular events was significantly higher in patients taking testosterone preparations (23% versus 5%). Thus, Stepan Sergeevich summed up, it is impossible to assert the safety of such therapy, especially long-term, in patients with existing diseases.

Testosterone and fertility

Another serious issue is the effect of testosterone preparations on male fertility. There is evidence of a decrease in patients' testes in volume and a decrease in the number of sperm cells up to their complete absence (azoospermia) while taking testosterone preparations. In this case, the sperm count most often returns to the initial level within 6 months after stopping therapy, but this does not always happen. This is especially important for young men, some of whom are taking hormonal drugs to achieve a rapid improvement in physical and sports performance. Today there are even development of the use of testosterone preparations as a means of male contraception.

Other factors

An important factor is also changes in the psyche: psychotic symptoms, excessive libido and aggression, in addition to physical and psychological dependence with a withdrawal syndrome is quite rare, but still noted by the attending physicians in patients taking testosterone. In this sense, as the doctor noted, the hormone, like many things in the world, has dark and light sides. Taking testosterone can increase the patient's level of enterprise and courage, but it can also lead to aggression and suspicion. Much depends on the innate qualities of the man himself.

A known side effect of testosterone drugs is gynecomastia. It is associated with the aromatization of testosterone to estradiol in peripheral adipose and muscle tissue. At the same time, the ratio of estradiol to testosterone, as a rule, remains normal.

In addition, testosterone replacement therapy has been linked to worsening sleep apnea. Its severe forms are a relative contraindication for the appointment of therapy. In the event of the occurrence or exacerbation of obstructive apnea, a decrease in the dosage of the drug or discontinuation of therapy is required.

Like any anabolic steroids, testosterone preparations can cause nitrogen, sodium and water retention - a mineralocorticoid effect. Edema in such cases can worsen the condition of patients with diseases of the heart, liver and kidneys.

With the use of cutaneous forms of testosterone, the phenomenon of hyperandrogenism in sexual partners of patients is associated. Transdermal formulations can be associated with a variety of skin reactions, mainly erythema and pruritus, which are also common with patches. Intramuscular testosterone injections, in turn, can cause local pain and bruising.

Non-drug ways to increase testosterone

In addition to hormone replacement therapy, physical exercise, proper nutrition and regular visits to a urologist contribute to maintaining and increasing testosterone levels at any age. Controlling stress levels also plays a role. Many patients benefit from shorter working hours, for example. If you have large amounts of overtime, you should reduce the working day to 10 hours. It is useful to spend at least 2 hours a day doing something you love and not related to work: for example, reading or listening to music.

Regarding physical activity, there is a recent Japanese study (Kumagawa et al., 2015) that showed that after 12 weeks, against the background of high physical activity, there is a significant increase in testosterone levels without the appointment of hormone replacement therapy. Another study involving 83 men (Trumble, Benjamin C. et al.) Showed that one hour of wood chopping increased testosterone levels by 48% (R<0,001). Еще одна работа реализована с участием 30 молодых мужчин в возрасте 18-27 лет (Devi S. et al., 2014). Они занимались на велотренажере 15 минут в день с пульсом 125- 150 ударов в минуту. Через 12 недель таких занятий наблюдалось повышение уровня тестостерона до 20%.

There is also evidence that testosterone levels correlate well with waist circumference. Thus, getting rid of excess fat mass in any case will lead to an adjustment in the level of this hormone. It is weight loss that can be considered as a first-line therapeutic measure in patients with obesity-related hypogonadism. There is a possibility that with successful weight loss, the appointment of hormone replacement therapy in the future will not be required for a man.

In the 21st century, life extension and maintenance of its quality come to the fore among the tasks of medicine. Accordingly, patients should be given a number of simple guidelines to help reduce the risk of metabolic syndrome and testosterone problems. First of all, a man should change his diet and give up excessive alcohol consumption, and approach this systematically, and not as a temporary measure. However, the doctor emphasized, the patient does not need to be severely restricted in the intake of fats, including saturated ones: they are involved in the production of sex steroids, including testosterone. There is evidence of a strong correlation between high density lipoprotein (HDL) levels and free testosterone levels (Heller, R.).

There are also a number of herbal remedies that have an evidence base in terms of increasing testosterone levels. For example, a 14-day intake of Eurycoma longifolia extract has been shown to increase circulating testosterone levels by 30.2%. In another study, the same extract increased the number of men with normal testosterone levels from 35.5% to 90.8%. In addition, 6-week consumption of Peruvian maca extract showed an increase in testosterone production by Leydig cells (Ohta Y. et al., 2016).

Stepan Sergeevich, however, noted that he understands the skepticism of some doctors regarding methods other than hormone replacement therapy. But, as he recalled, many of the active ingredients of the preparations synthesized today were first obtained from plant materials. Therefore, the use of herbal supplements in addition to changing the amount of physical activity, adjusting the diet and reducing the level of daily stress may well pay off.

Stepan Sergeevich Krasnyak
employee of the department of andrology and human reproduction
Research Institute of Urology and Interventional Radiology
them. N. A. Lopatkina Ministry of Health of Russia