MusculeX
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Hypogonadism is known to occur in approximately 5 adult men out of 1000 (in most European countries). Despite fairly clear clinical manifestations of testosterone deficiency in adult men, which include decreased libido, erectile dysfunction, oligospermia or azoospermia, decreased bone density, regression of secondary sexual characteristics, loss of muscle mass and muscle strength, and impaired mood, they are not always recognized by clinicians or attributed to other diseases. However, with the accumulation of information about the importance of the role of androgens in the development, function and health of the male body, testosterone deficiency is receiving more and more attention as hypogonadism in adult men is related to health issues, economic viability and quality of life. Men of advanced age have climacteric disorders in the foreground, diagnosis and treatment of which represent obvious difficulties, taking into account age polymorrhagic character. Scientific researches of great importance in clinical practice give more and more evidence of benefit of testosterone replacement therapy usage in adult men.
Physiological effects of androgens
Endogenous androgens include testosterone and its more active metabolite, dihyde-rotestosterone. They have different functions in different periods of life. During embryonic development, androgens play a key role in the differentiation of the male genital organs-prostate, seminal vesicles, penis and scrotum. Testosterone is necessary to stimulate sexual behavior and functions, initiate sperm production, and develop male secondary sexual characteristics: specific body hairiness (on the face, pubis, chest and armpits), throat growth and vocal cord thickening. Androgens also cause a growth spurt in adolescence and possible growth arrest due to the closure of epiphyseal growth plates.
At maturity, androgens are essential for the maintenance of reproductive function and secondary male sexual characteristics. In addition, testosterone affects muscle mass and strength, fatty tissue distribution, bone mass, erythropoiesis, spermatogenesis, and libido and potency. Moreover, androgens may have a nonspecific effect on the general metabolism, mood and well-being.
Thus, androgens not only play the most important role in adolescent growth and development, but also are involved in maintaining the health of a man in his adulthood and determine the course of menopause. Hormones in this group have a significant physiological impact on many organs and tissues, including reproductive organs tissues, sexual function and behavior, the hematopoietic system, muscles, bones, skin and hair.
Despite the fact that the biological effect of androgens varies depending on the period of life, the regulation of hormone production by testicles and mechanisms of hormonal action at different stages, from early embryonic development to old age, are the same.
Testosterone, the predominant androgen in male blood plasma, is produced predominantly (95%) by the testes from cholesterol, and in much smaller quantities by the adrenal cortex. In turn, the precursor of testosterone, cholesterol, may be produced de novo in Leydig cells or derived from plasma lipoproteins. Only a small amount of testosterone is stored in the testicles. Therefore, a complete turnover of testosterone in blood occurs approximately 200 times per day, and the daily amount of testosterone released into the blood plasma is approximately 6 mg.
Testosterone is transported in plasma by the sex-steroid-binding globulin or in bound form with albumin or other proteins; only small part of it remains in free form in dynamic equilibrium with bound fractions. Circulating testosterone in plasma is largely converted to dihydrotestosterone in the target tissues (including skin, liver, and prostate) by the enzyme 5a-reductase. Testosterone is also metabolized to estradiol through the aromatase enzyme complex in the testicles, brain and adipose tissues. In many tissues, testosterone activity depends on its reduction to dihydrotestosterone, which is also bound by cytosolic androgen receptors. At this point, the steroid-receptor complex translocates into the nucleus, where it activates transcription and changes at the cellular level related to the action of androgens. Testosterone production is controlled by hypothalamic-pituitary hormones.
Impulsive releases from hypothalamus of LH releasing hormone (LHRH) which is also called gonadotropin-releasing hormone (GHRH) stimulate hypophysis to release luteinizing (LH) and follicle stimulating (FSH) hormones. As for the main effects of these gonadotropins in the male body, the luteinizing hormone stimulates testosterone production by Leydig cells and promotes testicular development, while the follicle stimulating hormone together with testosterone regulates spermatogenesis and sperm maturation. In addition, the latter increases the activity of luteinizing hormone and testosterone synthesis.
The release of luteinizing and follicle stimulating hormones is regulated by testosterone through negative feedback. In addition, follicle stimulating hormone release is selectively inhibited by inhibin, a polypeptide produced by Sertoli cells located in the testicles, and stimulated by activin.
Male hypogonadism is a deficiency or absence of endogenous testosterone. Such terms as "testosterone insufficiency" and "hypoandrogenism" can be used in different classifications of hypogonadism and serve for more precise description of clinical manifestations resulting from insufficient stimulation of androgen-dependent functions.
The incidence of testosterone deficiency is unknown. Because there are many forms of it, and clinical manifestations are sometimes poorly pronounced, hypogonadism is considered to be a difficult disease to diagnose. Of the approximately 4-5 million men who have hypogonadism in the United States, only 5% receive regular testosterone replacement therapy. In clinical practice, the symptoms of male hypogonadism are often masked by other complaints of the patient and not recognized by the doctor. Therefore, estimation of the frequency of testosterone deficiency is based on identifying men with hypogonadism who have risk factors.
Klinefelter syndrome, the most common hereditary form of primary hypogonadism, is found in 1-2.5 out of 1000 newborn boys. Klinefelter syndrome occurs in 35-50% of men with hypogonadism who require androgen replacement therapy. In the general population, hypogonadism is found in about 5 out of 1,000 men. However, recent data suggest that these estimates represent only a fraction of the actual cases of male hypogonadism. It is not always the case that abnormalities associated with age-related changes in androgen production are registered.
Decreased testosterone levels were found in 20-50% of men with femur fractures, indicating that the frequency of acquired forms of hypogonadism is significantly higher than the frequency of congenital forms. Hypogonadism is the most common cause of secondary osteoporosis in men, which, in turn, is the most common cause of morbidity, mortality and disability due to increased risk of fractures.
Infertility as a symptom or form of hypogonadism in the general population is present in 5-10% of men, which indicates a rather high frequency of hypogonadism. In addition, erectile dysfunction of varying degrees is observed in more than half of men over 40 years of age in the United States, and endocrine disorders, mainly hypogonadism, are found in 5-35% of cases in selected populations.
A large study (n = 890) was conducted to determine the proportion of adult men with decreased plasma levels of total (or free) testosterone. The study showed a progressive increase in the frequency of low total testosterone and free testosterone index (IST = T/CCG) determination with age as compared to the levels in the general population of men aged 20-40 years. The incidence of hypogonadism determined by low total testosterone levels was 12,19, 28, and 49% in men aged 50-59, 60-69, 70-79, and 80-89 years. The free testosterone index was decreased in 9, 34, 68, and 91% of men in the given age groups, respectively.
Physiological effects of androgens
Endogenous androgens include testosterone and its more active metabolite, dihyde-rotestosterone. They have different functions in different periods of life. During embryonic development, androgens play a key role in the differentiation of the male genital organs-prostate, seminal vesicles, penis and scrotum. Testosterone is necessary to stimulate sexual behavior and functions, initiate sperm production, and develop male secondary sexual characteristics: specific body hairiness (on the face, pubis, chest and armpits), throat growth and vocal cord thickening. Androgens also cause a growth spurt in adolescence and possible growth arrest due to the closure of epiphyseal growth plates.
At maturity, androgens are essential for the maintenance of reproductive function and secondary male sexual characteristics. In addition, testosterone affects muscle mass and strength, fatty tissue distribution, bone mass, erythropoiesis, spermatogenesis, and libido and potency. Moreover, androgens may have a nonspecific effect on the general metabolism, mood and well-being.
Thus, androgens not only play the most important role in adolescent growth and development, but also are involved in maintaining the health of a man in his adulthood and determine the course of menopause. Hormones in this group have a significant physiological impact on many organs and tissues, including reproductive organs tissues, sexual function and behavior, the hematopoietic system, muscles, bones, skin and hair.
Despite the fact that the biological effect of androgens varies depending on the period of life, the regulation of hormone production by testicles and mechanisms of hormonal action at different stages, from early embryonic development to old age, are the same.
Testosterone, the predominant androgen in male blood plasma, is produced predominantly (95%) by the testes from cholesterol, and in much smaller quantities by the adrenal cortex. In turn, the precursor of testosterone, cholesterol, may be produced de novo in Leydig cells or derived from plasma lipoproteins. Only a small amount of testosterone is stored in the testicles. Therefore, a complete turnover of testosterone in blood occurs approximately 200 times per day, and the daily amount of testosterone released into the blood plasma is approximately 6 mg.
Testosterone is transported in plasma by the sex-steroid-binding globulin or in bound form with albumin or other proteins; only small part of it remains in free form in dynamic equilibrium with bound fractions. Circulating testosterone in plasma is largely converted to dihydrotestosterone in the target tissues (including skin, liver, and prostate) by the enzyme 5a-reductase. Testosterone is also metabolized to estradiol through the aromatase enzyme complex in the testicles, brain and adipose tissues. In many tissues, testosterone activity depends on its reduction to dihydrotestosterone, which is also bound by cytosolic androgen receptors. At this point, the steroid-receptor complex translocates into the nucleus, where it activates transcription and changes at the cellular level related to the action of androgens. Testosterone production is controlled by hypothalamic-pituitary hormones.
Impulsive releases from hypothalamus of LH releasing hormone (LHRH) which is also called gonadotropin-releasing hormone (GHRH) stimulate hypophysis to release luteinizing (LH) and follicle stimulating (FSH) hormones. As for the main effects of these gonadotropins in the male body, the luteinizing hormone stimulates testosterone production by Leydig cells and promotes testicular development, while the follicle stimulating hormone together with testosterone regulates spermatogenesis and sperm maturation. In addition, the latter increases the activity of luteinizing hormone and testosterone synthesis.
The release of luteinizing and follicle stimulating hormones is regulated by testosterone through negative feedback. In addition, follicle stimulating hormone release is selectively inhibited by inhibin, a polypeptide produced by Sertoli cells located in the testicles, and stimulated by activin.
Male hypogonadism is a deficiency or absence of endogenous testosterone. Such terms as "testosterone insufficiency" and "hypoandrogenism" can be used in different classifications of hypogonadism and serve for more precise description of clinical manifestations resulting from insufficient stimulation of androgen-dependent functions.
The incidence of testosterone deficiency is unknown. Because there are many forms of it, and clinical manifestations are sometimes poorly pronounced, hypogonadism is considered to be a difficult disease to diagnose. Of the approximately 4-5 million men who have hypogonadism in the United States, only 5% receive regular testosterone replacement therapy. In clinical practice, the symptoms of male hypogonadism are often masked by other complaints of the patient and not recognized by the doctor. Therefore, estimation of the frequency of testosterone deficiency is based on identifying men with hypogonadism who have risk factors.
Klinefelter syndrome, the most common hereditary form of primary hypogonadism, is found in 1-2.5 out of 1000 newborn boys. Klinefelter syndrome occurs in 35-50% of men with hypogonadism who require androgen replacement therapy. In the general population, hypogonadism is found in about 5 out of 1,000 men. However, recent data suggest that these estimates represent only a fraction of the actual cases of male hypogonadism. It is not always the case that abnormalities associated with age-related changes in androgen production are registered.
Decreased testosterone levels were found in 20-50% of men with femur fractures, indicating that the frequency of acquired forms of hypogonadism is significantly higher than the frequency of congenital forms. Hypogonadism is the most common cause of secondary osteoporosis in men, which, in turn, is the most common cause of morbidity, mortality and disability due to increased risk of fractures.
Infertility as a symptom or form of hypogonadism in the general population is present in 5-10% of men, which indicates a rather high frequency of hypogonadism. In addition, erectile dysfunction of varying degrees is observed in more than half of men over 40 years of age in the United States, and endocrine disorders, mainly hypogonadism, are found in 5-35% of cases in selected populations.
A large study (n = 890) was conducted to determine the proportion of adult men with decreased plasma levels of total (or free) testosterone. The study showed a progressive increase in the frequency of low total testosterone and free testosterone index (IST = T/CCG) determination with age as compared to the levels in the general population of men aged 20-40 years. The incidence of hypogonadism determined by low total testosterone levels was 12,19, 28, and 49% in men aged 50-59, 60-69, 70-79, and 80-89 years. The free testosterone index was decreased in 9, 34, 68, and 91% of men in the given age groups, respectively.