The way to prevent osteoporosis in men with partial age-related androgen deficiency (padam)

 

(57) Abstract:

The invention relates to medicine, in particular to urology and endocrinology. How is that lower levels of parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), 1,25(OH)2D3, alkaline phosphatase, calcium, thyroid-stimulating hormone (TSH),4, adrenocorticotropic hormone (ACTH), cortisol, increase the levels of calcitonin, phosphate in the blood plasma, restore pulse mode secretion of TSH, T4, ACTH, cortisol by individual selection of doses of testosterone to normalize the levels of luteinizing hormone (LH), total testosterone, free testosterone, globulin that binds sex hormones, index of free androgens, 5-dihydrotestosterone, 17-estradiol, recovery pulse secretion of LH and total testosterone. The way you can affect pathogenetic aspects of osteoporosis prevention.

The invention relates to medicine, in particular to urology and endocrinology. The prototype of the invention is the purpose men with hypogonadism to reduce the risk of osteoporosis 200 mg testosterone prolonged action month (Lavi is ariew optimal doses of androgens, which would be observed restore hormonal regulation of bone metabolism.

The purpose of the invention is to develop a pathogenetic way to prevent osteoporosis in men with partial age-related androgen deficiency (PADAM).

The invention consists in the decrease in men with partial age-related androgen deficiency (PADAM) levels of parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), 1.25 (OH)2D3, alkaline phosphatase, calcium, thyroid-stimulating hormone (TSH),4, adrenocorticotropic hormone (ACTH), cortisol, increased levels of calcitonin phosphate in the blood plasma, in the restoration of the pulse mode of secretion of TSH, T4, ACTH, cortisol, resulting from the assignment of one of the drugs testosterone with individual selection of doses to normalize the levels of LH, total testosterone, free testosterone, bioavailable testosterone, globulin that binds sex hormones, index of free androgens, 5-dihydrotestosterone, 17-estradiol, recovery pulse secretion of LH and total testosterone. The daily dose of testosterone is divided into two steps: 2/3 - in the morning (7-8 hours) and 1/3 day (16 cha who's hormones, LH and low levels of total testosterone, free testosterone, bioavailable testosterone and index of free androgens (or a combination of these changes with normal values of LH and total testosterone), as well as the absence or reduced pulse rhythm education total testosterone, LH dose of testosterone increase.

Due to the interdependence of neurohumoral regulatory processes age-related decline in the production of testosterone, in addition to increasing the production of LH, gonadotropin-releasing hormone violation of their physiological pulse mode of education is reflected throughout the hypothalamic-pituitary regulation and affects the activity of growth factors (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 370 and 371, 877-898).

In response to a decrease in total testosterone compensatory increases the formation of 5-dihydrotestosterone, and 17-estradiol (Pechersk A. C., Mazur C. I., Semiglazov C. F., Karpischenko A. I., Mikhailichenko centuries, Udintsev A. C. Open No. 175 “Regularity reduce the formation of 5-dihydrotestosterone and 17-estradiol in men with partial age-related androgen deficiency (PADAM) and benign prostatic hyperplasia pri years, bone mass, all people gradually decreases. The rate of bone loss after 30 years is higher among women than men (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 460). Increased risk of osteoporosis in men with primary hypogonadism in women with estrogen deficiency at menopause is caused by increased sensitivity of the cells of the parathyroid gland to calcium, resulting in disrupted the mechanism of suppression of PTH secretion in response to hypercalcemia. The resulting cells of the parathyroid glands secrete excessive amounts of PTH. Accordingly decreases the secretion of calcitonin. The secretion is also affected by changes in the concentration of magnesium (Mg2+) in the blood (Lavin N. Endocrinology. - M.: The Practice, 1999. - C. 414, 417, 418, 420, 426, 464). The lack of magnesium (Mg2+) can significantly degrade the effectiveness of PTH (cattail C. M., Arch R. A. Pathophysiology of the endocrine system. - SPb-M.: Nevsky dialect", 2001. - S. 153).

Excess PTH accelerates bone resorption and increases the leaching of calcium from the bones, which leads to hypercalcemia. Under the influence of excess PTH threshold decreases resorption of phosphate in the kidney; this results in phosphaturia and hypophosphatemia. Tubular resorption of calcium increases, but this effect of PTH leveled povisiatsa (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 420). The PTH receptors are present on osteoblasts and osteocytes, but not in osteoclasts. However, when the level of PTH activates osteoclasts and increased bone resorption. This effect of PTH is mediated by osteoblasts under the influence of PTH they start hard to secrete IGF-1 and cytokines that in turn activate osteoclasts. This contributes to the rapid proliferation of precursor cells of osteoclasts (the cells bear receptors PTH) (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 414, 430), at a constant elevated PTH levels of the bone resorption predominates over her education, which leads to osteopenia. With increasing PTH secretion observed increase in the activity of alkaline phosphatase (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 412, 422). Alkaline phosphatase is produced in bone by osteoblasts, and its content increases during periods of enhanced osteoliticescoy activity. The activity of osteoblasts and osteoclasts closely associated with each other, so any increase metabolic processes in the bones increases the concentration of the alkaline phosphatase (cattail C. M., Arch R. A. Pathophysiology of endocrine sistemin N. Endocrinology. - M.: The Practice, 1999. - S. 414). The receptor for IGF-1 is similar to the insulin receptor, therefore, IGF-1 can bind to insulin receptors and activate them. Increased levels of IGF-1 and insulin in patients with PADAM is a compensatory reaction in response to the development of insulin resistance, impaired glucose tolerance. The latter is caused by increased levels of IGF-1 - binding proteins that inhibit the binding of IGF-1 and insulin receptors and thereby inhibit their action on target cells (Lavin N. Endocrinology. - M.: The Practice, 1999. - C. 42, 43, 102, 104, 691). Insulin resistance of the liver cells promotes production of glucose (by increasing gluconeogenesis). As a result of increasing levels of fasting blood glucose. Insulin resistance in skeletal muscle increases glucose levels in the blood after a meal, because the utilization of glucose in the muscles is the main mechanism of removal of glucose from the blood (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 865). Hyperglycemia leads to increased insulin levels, which in turn stimulates the secretion of somatoliberin and suppresses the secretion of somatostatin, which leads to increased levels STH and therefore IGF-1 level chap who etiologia endocrine system. - SPb-M.: Nevsky dialect", 2001. - S. 175).

The hormonal action of insulin (insulin resistance) is accompanied by decreased activity of osteoblasts, which also contributes to osteoporosis (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 464, 465).

Blockade of insulin receptors disrupts the implementation of the hormonal activity of insulin and, in particular, disrupted transport and utilization of glucose. "Imaginary hypoglycemia" neurons in the hypothalamus secrete into the portal system of the pituitary somatoliberin and corticoliberin. Somatoliberin stimulates the secretion continuarea hormone STH. Corticoliberin causes the release of ACTH, which increases the secretion of another continuarea hormone cortisol in the adrenal cortex (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 966).

Glucocorticoids inhibit the activity of osteoblasts and inhibit calcium absorption in the intestine that stimulates PTH and, accordingly, osteoclasts (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 462).

Excess PTH and hypophosphatemia stimulate the synthesis of 1.25(OH)2D3in the renal tubules. On the formation of 1.25(OH)2D3also affected by the levels of calcitonin, estrogen, insulin (Lavin N. Endocrinology. - M: PR is e increases hypercalcemia (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 420).

Calcitonin inhibits bone resorption by reducing the activity of osteoclasts and stimulating osteoblasts. At lower levels of sex hormones, in particular in women with estrogen deficiency due to menopause, and men when PADAM, the secretion of calcitonin is reduced, which contributes to accelerated bone resorption (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 417, 464).

The increase in 17-estradiol causes an increase in the concentration of thyroxine-binding globulin; a reciprocal decrease in free T3T4increases education tiroliberina and TSH. The secretion of total T3and T4increases and their content in serum is increased until, until levels return to normal free T3and T4(Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 519-521).

Excessive formation of thyroid hormones stimulate mainly the osteoclasts, which leads to increased bone resorption (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 456).

Older people are sensitive to even mild hypercalcemia. Peak hypercalcemia accounts for 60-70 years. The clinical picture is dominated by the CNS, with age, when bone density in both men and women begins to decline. In women, this process is considerably accelerated during menopause. Men relatively steep drop curve decrease in bone mass does not occur does not occur because of a sharp decrease in the content of sex hormones as women in menopause. The appointment of estrogen prevents women hypercalcemia and further loss of bone mass (cattail C. M., Arch R. A. Pathophysiology of the endocrine system. - SPb-M.: Nevsky dialect", 2001. - S. 170-173; Lavin S. 420, 426).

The PTH receptors found not only in bone and kidney, but also in many other tissues and organs, in which PTH is involved in the metabolism of calcium and phosphorus (Lavin N. Endocrinology. - M.: The Practice, 1999. - S. 415, 418). Apparently, increased sensitivity to calcium during menopause in women and PADAM men applies not only to the parathyroid gland, but also on other fabrics, containing PTH receptors. Creates the effect of "imaginary hypocalcemia", comperatore causing intense synthesis of PTH parathyroid glands, as well as neocomitidae production of PTH analog-, PTH-like peptides in peripheral tissues. Stimulation of the synthesis of PTH str is - The .420).

The purpose of androgen-replacement therapy to men with partial age-related androgen deficiency (PADAM) leads to lower levels of parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), 1.25(OH)2D3, alkaline phosphatase, calcium, thyroid-stimulating hormone (TSH),4, adrenocorticotropic hormone (ACTH), cortisol, increased levels of calcitonin, phosphate in the blood plasma, to restore the pulse mode of secretion of TSH, T4, ACTH, cortisol.

The way to prevent osteoporosis in men with partial age-related androgen deficiency (PADAM), namely, that reduce the levels of parathyroid hormone (PTH), insulin-like growth factor-1 (IGF-1), 1,25(OH)2D3, alkaline phosphatase, calcium, thyroid-stimulating hormone (TSH),4, adrenocorticotropic hormone (ACTH), cortisol, increase the levels of calcitonin, phosphate in the blood plasma, restore pulse mode secretion of TSH, T4, ACTH, cortisol by individual selection of doses of testosterone to normalize the levels of luteinizing hormone (LH), total testosterone, free testosterone, globulin that binds sex hormones, index of free androgens, 5-

 

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