*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
1. Ruzicka L, Wettstein A: Synthesis of the testicular hormone (testosterone) (androstene 3-on-17-ol.) Helv Chim Acta 1935; 18: 1264-1275.
2. Butenandt A, Hanisch G: Testosterone. The transformation of dehydroandrosterone into androstendiol and testosterone: a method for producing testosterone from cholesterol. Hoppe-Seyler’s Z Physiol Chem 1935; 237: 89-98.
3. Griffin JE, Wilson JD: Zaburzenia dotyczące jąder. [In:] Fauci A (ed.): Interna Harrisona. Wyd. 14. T. 3. Czelej, Lublin 2000; 36: 3510-3516.
4. Liu PY, Death AK, Handelsman DJ: Androgens and cardiovascular disease. Endocrine Reviews 2003; 24: 313-340.
5. Hayes FJ, Crowley WF: Gonadotropin pulsations across development. Horm Res 1998; 49: 163-168.
6. Sriraman V, Anbalagan M, Rao AJ et al.: Hormonal regulation of Leydig cell proliferation and differentiation in rodent testis: A dynamic interplay between gonadotrophins and testicular factors. Reprod Biomed Online 2005; 11: 507-518.
7. Behre HM, Zitzmann M, Anderson RA et al.: Efficacy and safety of an injectable combination hormonal contraceptive for men. J Clin Endocrinol Metab 2016; 101(12): 4779-4788.
8. Lunenfeld B, Mskhalaya G, Zitzmann M et al.: Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male 2015; 18(1): 5-15.
9. Dohle GR, Arver S, Bettocchi C: Punab M. EAU Guidelines on male hypogonadism. 2015; www.uroweb.org/guidelines/online-guidelines/.
10. Tüttelmann F, Nieschlag E: Classification of Andrological Disorders. [In:] Nieschlag E, Behre HM, Nieschlag S (eds.): Andrology: male reproductive health and dysfunction. Springer-Verlag, Berlin Heidelberg 2010; 4: 87-92.
11. Hall SA, Esche GR, Araujo AB et al.: Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metab 2008; 93(10): 3870-3877.
12. Wu FC, Tajar A, Pye SR et al.: Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 2008; 93: 2737-2745.
13. Wu FC, Tajar A, Beynon JM et al.: Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010; 363(2): 123-135.
14. Nieschlag E, Swerdloff R, Behre HM: Investigation, treatment, and monitoring of late-onset hypogonadism in male: ISA, ISSAM, and EAU recommendations. J Androl 2006; 27: 135-137.
15. Scovell JM, Ramasamy R, Wilken N et al.: Hypogonadal symptoms in young men are associated with a serum total testosterone threshold of 400 ng/dL. BJU Int 2015; 116(1): 142-146. doi: 10.1111/bju.12970.
16. Diver MJ, Imtiaz KE, Ahmad AM et al.: Diurnal rhythms of serum otal, free and bioavailable testosterone and of SHBG in middleaged men compared with those in young men. Clin Endocrinol (Oxf) 2003; 58: 710-717.
17. Dudek P, Kozakowski J, Zgliczyński W: Late-Onset Hypogonadism. Menopause Review 2017; 16(2): 66-69.
18. Saad F, Aversa A, Isidori AM et al.: Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol 2011; 165(5): 675-685.
19. Caminiti G, Volterrani M, Lellamo F et al.: Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscleperformance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol 2009; 54(10): 919-927.
20. Tracz MJ, Sideras K, Boloña ER et al.: Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. J Clin Endocrinol Metab 2006; 91(6): 2011-2016.
21. Araujo AB, Dixon JM, Suarez EA et al.: Clinical review: endogenous testosterone and mortality in men: a systematic review and metaanalysis. J Clin Endocrinol Metab 2011; 96(10): 3007-3019.
22. Calof OM, Singht AB, Lee ML et al.: Adverse events associated with testosterone replacement in middle-aged and older men: ameta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 2005; 60(11): 1451-1457.
23. Comhaire FH: Andropause: hormone replacement therapy in the ageing male. Eur Urol 2000; 38(6): 655-662.
24. Wang C, Harnett M, Dobs AS et al.: Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial. J Androl 2010; 31(5): 457-465.
25. Lakshman KM, Basaria S: Safety and efficacy of testosterone gel in the treatment of male hypogonadism. Clin Interv Aging 2009; 4: 397-412.
26. Carter HB, Pearson JD, Metter EJ et al.: Longitudinal evaluation of prostate-specific antigen in men with and without prostate disease. JAMA 1992; 267: 2215-2220.
27. Dobs AS, Meikle AW, Arver S et al.: Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone transdermal system in comparison with bi-weekly injections of testosterone enanthate for the treatment of hypogonadal men. J Clin Endocrinol Metab 1999; 84: 3469-3478.
