*Piotr Dudek, Jarosław Kozakowski
Testosterone suplementation in men
Suplementacja testosteronu u mężczyzn
Department of Endocrinology, Centre of Postgraduate Medical Education, Bielański Hospital, Warsaw
Head of Department: Professor Wojciech Zgliczyński, MD, PhD
Streszczenie
Androgeny odgrywają istotną rolę na każdym etapie życia mężczyzny i pełnią ważną funkcję w jego czynnościach rozrodczych i seksualnych. Hipogonadyzm u mężczyzn jest zespołem klinicznym spowodowanym niedoborem androgenów, który może niekorzystnie wpływać na funkcje wielu narządów i jakość życia.
Hipogonadyzm spowodowany jest niewydolnością jąder lub zaburzeniemi na jednym lub kilku poziomach osi podwzgórze – przysadka – gonady. Hipogonadyzm u mężczyzn jest głównym wskazaniem do suplementacji testosteronem. Na rynku dostępnych jest kilka preparatów, różniących się drogą podawania, farmakokinetyką i mogącymi występować działaniami niepożądanymi. Wybór powinien być wspólną decyzją zarówno pacjenta, jak i lekarza. Preparaty o krótkotrwałym działaniu są preferowane do podawania w początkowej fazie leczenia, a zatem wszelkie działania niepożądane, które mogą wystąpić, obserwowane są wcześnie i leczenie można przerwać w razie potrzeby. Obecnie w Polsce dostępne są preparaty testosteronu podawane domięśniowo oraz w postacji żelu trandermalnego. Uzupełnianie niedoboru testosteronu może przynosić szereg korzyści związanych z zmianą składu ciała, poprawą kontroli metabolicznej oraz parametrów psychologicznych i seksualnych.
Summary
Androgens are important in every phase of human life and play a important role in male reproductive and sexual function. Male hypogonadism is a clinical syndrome caused by androgen deficiency which can adversely affect multiple organ functions and quality of life.
Hypogonadism results from testicular failure, or is due to the disruption of one or several levels of the hypothalamic-pituitary-gonadal axis. Male hypogonadism is the main indication for testosterone supplementation. Several preparations are available, which differ in the route of administration, pharmacokinetics and adverse events. The selection should be a joint decision by both the patient and the physician. Short-acting preparations are preferred to long-acting depot administration in the initial treatment phase, so that any adverse events that may develop can be observed early and treatment can be discontinued if needed. Nowadays, in Poland the available agents are intramuscular injections or transdermal gel.
Testosterone therapy may present several benefits regarding body composition, metabolic control, psychological and sexual parameters.
The role of androgens
Androgens are important in every phase of human life and play a important role in male reproductive and sexual function. During the embryonal stage, testosterone determines the differentiation of the sexual organs, during puberty, the further development toward the adult male phenotype which is then maintained along with important anabolic functions such as body composition, muscle formation, bone mineralization amd fat metabolism.
The method of synthesizing testosterone from cholesterol was first described in 1935 by Adolf Butenandt and Leopold Ruizka (1, 2). In men testosterone is synthesized mainly in the testes (95%), in Leydig cells. Less than 1% of testosterone is produced in cells of the adrenal cortex and less than 5% comes from the peripheral metabolism of its precursors (3, 4). Testosterone production is regulated by the hypothalamic-pituitary-gonadal axis. Gonadotropin-releasing hormone (GnRH) is produced by neurons of the arcuate nucleus in the hypothalamus (5). GnRH is secreted into the circulation of the pituitary gland and causes LH and FSH release from the anterior pituitary cells. LH stimulates Leydig cells to produce testosterone. Testosterone inhibits LH secretion by negative feedback (6). The biological effect of testosterone is due to the conection of the hormone with the androgen receptor. A small portion of the circulating testosterone (less then 10%) becomes a precursor to the production of two other hormones: through 5α-reduction it gives rise to the highly biologically active hormone 5α-dihydrotestosterone (DHT), and through aromatization to oestradiol.
Male hypogonadism is the main indication for testosterone suplementation. The other possible applications are constitutionally delayed puberty, male hormonal contraception (experimental use) and in anemia (7). Because of its erythropoetic effect testosterone is used to the treatment of aplastic and renal anemia, but lost ground to erythropoetin after the latter was introduced.
Hypogonadism
Male hypogonadism is a clinical syndrome caused by androgen deficiency which can adversely affect multiple organ functions and quality of life (8).
Hypogonadism results from testicular failure, or is due to the disruption of one or several levels of the hypothalamic-pituitary-gonadal axis.
Male hypogonadism can be classified in accordance with disturbances at the level of:
– the testes (primary hypogonadism); primary testicular failure is the most frequent cause of hypogonadism and results in low testosterone levels, impairment of spermatogenesis and elevated gonadotrophins,
– the hypothalamus and pituitary (secondary hypogonadism); central defect of the hypothalamus or pituitary causes secondary testicular failure,
– the hypothalamus or pituitary and gonads (late-onset hypogonadism); combined primary and secondary testicular failure results in low testosterone level and variable gonadotrophins levels,
– the androgen target organs (androgen insensitivity or resistance) (9, 10).
Androgen deficiency increases slightly with age also in healthy men (9). In middle-aged men, the incidence of biochemical hypogonadism varies from 2.1-12.8% (9, 11). The incidence of low testosterone and symptoms of hypogonadism in men aged 40-79 varies form 2.1-5.7% (11, 12).
The diagnosis of hypogonadism requires the presence of characteristic symptoms and signs in combination with decreased serum concentration of testosterone.
According to the various recommendations of the scientific societies and the “working groups”, the lower values of total testosterone below which substitution therapy is suggested are ranging from 2.5 to 4.0 ng per ml (8-13.9 mmol per l) (13-15). It is preferred to obtain a serum sample for testosterone determination between 07.00 and 11.00 h in the fasting state. Total testosterone assessment should be repeated at least on two occasions. In addition, in men with total testosterone levels beetwen 2.5 to 4.0 ng per ml, the free testosterone level should be measured to strengthen the laboratory assessment (9, 16).
The clinical manifestation of hypogonadism is determined by the age of onset and the severity of hypogonadism.
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Piśmiennictwo
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