Андрология и генитальная хирургия. 2015; 16: 95-101
Возрастной андрогенный дефицит у мужчин: этиология, клиника, диагностика, лечение
https://doi.org/10.17650/2070-9781-2015-1-95-101Аннотация
В обзоре приведены современные представления об этиологии, клинических проявлениях, диагностике и лечении возрастного андрогенного дефицита (ВАД). ВАД является мультидисциплинарной проблемой, поскольку с клиническими проявлениями этого заболевания – остеопорозом, анемией, депрессией, ожирением, сахарным диабетом 2-го типа, эректильной дисфункцией – приходится сталкиваться врачам различных специальностей, которые не всегда связывают с ВАД имеющиеся у пациента разрозненные жалобы. ВАД оказывает негативное влияние на качество жизни, и без коррекции дефицита андрогенов зачастую не получается помочь пациенту. В то же время у врачей различных специальностей существуют опасения в отношении безопасности заместительной терапии тестостероном, связанные с дефицитом актуальной информации по этому вопросу. Для практических врачей приведены диагностические критерии ВАД, как клинические, так и лабораторные, представлены формулы для пересчета единиц измерения основных мужских половых гормонов. На основании рекомендаций ISSAM (International Society for the Study of the Aging Male – Международного общества по изучению старения мужчин) изложены представления о современных возможностях лечения ВАД, приведены все имеющиеся на сегодняшний день в арсенале практического врача препараты тестостерона (пероральные, инъекционные, трансдермальные), представлена их сравнительная характеристика, особенности фармакодинамики, преимущества и недостатки. Описаны показания и противопоказания к заместительной терапии андрогенами, представлены данные о высокой эффективности, доказанной безопасности данной терапии, приведены стандартные схемы лечения ВАД, сроки развития ожидаемых результатов лечения и алгоритм динамического наблюдения за пациентами, получающими лечение.
Список литературы
1. Bhasin S., Buckwater J.G. Testosterone supplementation in older men: a rational idea whose time has not yet come. J Androl 2001;22(5):718–31.
2. Feldman H.A., Longcope C., Derby C.A. et al. Age trends in the level of serum testosterone and other hormones in middleaged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002;87(2):589–98.
3. Harman S.M., Metter E.J., Tobin J.D. et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86(2):724–31.
4. Mitchell R., Hollis S., Rothwell C., Robertson W.R. Age related changes in the pituitary-testicular axis in normal men; lower serum testosterone results from decreased bioactive LH drive. Clin Endocrinol (Oxf) 1995;42(5):501–7.
5. Wu F.C., Tajar A., Pye S.R. et al. Hypothalamic-pituitary-testicular axis disruptions in older man are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 2008;93(7):2737–45.
6. Wang C., Nieschlag E., Swerdloff R. et al.; International Society of Andrology; International Society for the Study of Aging Male; European Association of Urology; European Academy of Andrology; American Society of Andrology. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur Urol 2009;55(1):121–30.
7. Gray A., Berlin J.A., McKinlay J.B., Longcope C. An examination of research design effects on the association of testosterone and male aging: results of meta-analysis. J Clin Epidemiol 1991;44(7):671–84.
8. Gray A., Feldman H.A., McKinlay J.B., Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991;73(5):1016–25.
9. Kaufman J.M., Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005;26(6):833–76.
10. Nieschlag E., Behre H., Nieschlag S. Testosterone: action, deficiency, substitution. Cambridge: Cambridge University Press, 2004.
11. Bross B., Javanbahkit M., Bhasin S. Anabolic interventions for agingassociated sarcopenia. J Clin Endocrinol Metab 1999;84(10):3420–30.
12. Wu F.C., Tajar A., Beynon J.M. et al.; EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010;363(2):123–35.
13. Khat K.T., Barret-Connor E. Lower endogenous androgens predict central adiposity in men. Ann Epidemiol 1992;2(5):675–82.
14. Ringe J., Dorst A. Osteoporose bei Mannern. Dtsch Med Wochenschr 1994;119:943–7.
15. Tracz M.J., Sideras K., Boloña E.R. et al. Testosterone use in men and its effects on bone health. A systematic review and metaanalysis of randomized placebo-controlled trials. J Clin Endocrinol Metab 2006;91(6):2011–6.
16. Jockenhovel F. Male hypogonadism. Practical aspect of androgen therapy. Bremen: Uni-Med Verga, 2004. Pp. 117–34.
17. Morgentaler A. Male impotence. Lancet 1999;354(9191):1713–8.
18. Jain P., Rademaker A.W., McVary K.T. Testosterone supplementation for erectile dysfunction: results of meta-analysis. J Urol 2000;164(2):371–5.
19. Kalinchenko S.Y., Kozlov G.I., Gontcharov N.P., Katsiya G.V. Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone. Aging Male 2003;6(2):94–9.
20. Lakshman K.M., Basaria S. Safety and efficacy of testosterone gel in the treatment of male hypogonadism. Clin Interv Aging 2009;4:397–412.
21. Boyanov M.A., Boneva Z., Christov V.G. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003;6(1):1–7.
22. Moffat A.D., Zonderman A.B., Metter E.J. et al. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab 2002;87(11):5001–7.
23. Alexander J.M. Swerdloff R.S., Wang C. et al. Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and response to auditory sexual stimuli. Horm Behav 1997;31(2):110–9.
24. Jockenovel F., Gerhardts S. Erkrankungen von hypotalamus und hypophyse. Bremen: Uni-Med Verlag, 2002.
25. Isidori A.M., Giannetta E., Greco E.A. et al. Effects of testosterone on body composition, body metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf) 2005;63(3):280–93.
26. Kapoor D., Goodwin E., Channer K.S., Jones T.H. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006;154(6):899–906.
27. Stattin P., Lumme S., Tenkanen L. et al. High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. Int J Cancer 2004;108(3):418–24.
28. Fernández-Balsells M.M., Murad M.H., Lane M. et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010;95(6):2560–75.
29. Haddad R.M., Kennedy C.C., Caples S.M. et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebocontrolled trials. Mayo Clin Proc 2007;82(1):29–39.
30. Saad F., Aversa A., Isidori A.M. et al. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol 2011;165(5):675–85.
31. Еuropean Association of Urology Guidelines 2014. Pp. 788–815.
Andrology and Genital Surgery. 2015; 16: 95-101
Late-onset hypogonadism: etiology, clinical features, diagnostics, treatment
https://doi.org/10.17650/2070-9781-2015-1-95-101Abstract
In a critical review of the literature current data concerning etiology, clinical features, diagnostics, treatment of late-onset hypogonadism (LOH) are given. LOH is a multidisciplinary problem, because a patient with LOH can have osteoporosis, anemia, depression, obesity, diabetes mellitus, erectile dysfunction. Sometimes it is hard to realize that all this complaints are symptoms of LOH. LOH has a negative impact on a patient,s quality of life and it,s impossible to help without androgen replacement therapy. Furthermore doctors often have doubts about testosterone replacement therapy safety because of lack of accurate information. In a convenient for medical practitioners form clinical and laboratory diagnostic criteria of LOH are presented together with formulas for conversion from one measurement unit of main sex hormones into another. Based on latest ISSAM guidelines (International Society for the Study of the Aging Male) modern treatment options of LOH are summarized, full information about available testosterone preparations (oral, transdermal, injectable) with comparative analysis of advantages and disadvantages of each is given. A full description of indications and contraindications for androgen replacement treatment is presented, also treatment regimen and medical supervision algorithm during treatment are described.
References
1. Bhasin S., Buckwater J.G. Testosterone supplementation in older men: a rational idea whose time has not yet come. J Androl 2001;22(5):718–31.
2. Feldman H.A., Longcope C., Derby C.A. et al. Age trends in the level of serum testosterone and other hormones in middleaged men: longitudinal results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2002;87(2):589–98.
3. Harman S.M., Metter E.J., Tobin J.D. et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86(2):724–31.
4. Mitchell R., Hollis S., Rothwell C., Robertson W.R. Age related changes in the pituitary-testicular axis in normal men; lower serum testosterone results from decreased bioactive LH drive. Clin Endocrinol (Oxf) 1995;42(5):501–7.
5. Wu F.C., Tajar A., Pye S.R. et al. Hypothalamic-pituitary-testicular axis disruptions in older man are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 2008;93(7):2737–45.
6. Wang C., Nieschlag E., Swerdloff R. et al.; International Society of Andrology; International Society for the Study of Aging Male; European Association of Urology; European Academy of Andrology; American Society of Andrology. Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur Urol 2009;55(1):121–30.
7. Gray A., Berlin J.A., McKinlay J.B., Longcope C. An examination of research design effects on the association of testosterone and male aging: results of meta-analysis. J Clin Epidemiol 1991;44(7):671–84.
8. Gray A., Feldman H.A., McKinlay J.B., Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991;73(5):1016–25.
9. Kaufman J.M., Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005;26(6):833–76.
10. Nieschlag E., Behre H., Nieschlag S. Testosterone: action, deficiency, substitution. Cambridge: Cambridge University Press, 2004.
11. Bross B., Javanbahkit M., Bhasin S. Anabolic interventions for agingassociated sarcopenia. J Clin Endocrinol Metab 1999;84(10):3420–30.
12. Wu F.C., Tajar A., Beynon J.M. et al.; EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010;363(2):123–35.
13. Khat K.T., Barret-Connor E. Lower endogenous androgens predict central adiposity in men. Ann Epidemiol 1992;2(5):675–82.
14. Ringe J., Dorst A. Osteoporose bei Mannern. Dtsch Med Wochenschr 1994;119:943–7.
15. Tracz M.J., Sideras K., Boloña E.R. et al. Testosterone use in men and its effects on bone health. A systematic review and metaanalysis of randomized placebo-controlled trials. J Clin Endocrinol Metab 2006;91(6):2011–6.
16. Jockenhovel F. Male hypogonadism. Practical aspect of androgen therapy. Bremen: Uni-Med Verga, 2004. Pp. 117–34.
17. Morgentaler A. Male impotence. Lancet 1999;354(9191):1713–8.
18. Jain P., Rademaker A.W., McVary K.T. Testosterone supplementation for erectile dysfunction: results of meta-analysis. J Urol 2000;164(2):371–5.
19. Kalinchenko S.Y., Kozlov G.I., Gontcharov N.P., Katsiya G.V. Oral testosterone undecanoate reverses erectile dysfunction associated with diabetes mellitus in patients failing on sildenafil citrate therapy alone. Aging Male 2003;6(2):94–9.
20. Lakshman K.M., Basaria S. Safety and efficacy of testosterone gel in the treatment of male hypogonadism. Clin Interv Aging 2009;4:397–412.
21. Boyanov M.A., Boneva Z., Christov V.G. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003;6(1):1–7.
22. Moffat A.D., Zonderman A.B., Metter E.J. et al. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metab 2002;87(11):5001–7.
23. Alexander J.M. Swerdloff R.S., Wang C. et al. Androgen-behavior correlations in hypogonadal men and eugonadal men. I. Mood and response to auditory sexual stimuli. Horm Behav 1997;31(2):110–9.
24. Jockenovel F., Gerhardts S. Erkrankungen von hypotalamus und hypophyse. Bremen: Uni-Med Verlag, 2002.
25. Isidori A.M., Giannetta E., Greco E.A. et al. Effects of testosterone on body composition, body metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf) 2005;63(3):280–93.
26. Kapoor D., Goodwin E., Channer K.S., Jones T.H. Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006;154(6):899–906.
27. Stattin P., Lumme S., Tenkanen L. et al. High levels of circulating testosterone are not associated with increased prostate cancer risk: a pooled prospective study. Int J Cancer 2004;108(3):418–24.
28. Fernández-Balsells M.M., Murad M.H., Lane M. et al. Clinical review 1: Adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2010;95(6):2560–75.
29. Haddad R.M., Kennedy C.C., Caples S.M. et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebocontrolled trials. Mayo Clin Proc 2007;82(1):29–39.
30. Saad F., Aversa A., Isidori A.M. et al. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol 2011;165(5):675–85.
31. European Association of Urology Guidelines 2014. Pp. 788–815.
