Андрология и генитальная хирургия. 2016; 17: 59-67
Влияние терапии тестостероном (1 % трансдермальный гель) на качество жизни мужчин с андрогенодефицитом в условиях рутинной клинической практики: 6-месячное наблюдательное исследование
https://doi.org/10.17650/2070-9781-2016-17-4-59-67Аннотация
Материалы и методы. Данное исследование являлось открытым многоцентровым наблюдательным неинтервенционным у мужчин с дефицитом тестостерона, применявших ежедневно 1 % гель тестостерона (Андрогель®) в дозе 50 или 100 мг (с возможностью титрации) в условиях рутинной клинической практики. Первичной конечной точкой являлось качество жизни, связанное с состоянием здоровья, оцениваемое при заполнении опросника симптомов старения мужчин (Aging Males’ Symptoms, AMS). Вторичными конечными точками были изменения общего балла шкалы Международного индекса эректильной функции (МИЭФ) и его доменов, изменения показателей индекса массы тела (ИМТ) и окружности талии, корреляция изменений в показателях качества жизни, определяемая с помощью опросника AMS, с лабораторными показателями уровней тестостерона и данными по шкале МИЭФ, демографические характеристики, а также исходные характеристики пациентов, анамнез диагностических и терапевтических процедур, причины прекращения лечения и любые нежелательные явления, возникшие в ходе лечения препаратом Андрогель®.
Результаты. Данные о 196 из 202 включенных в исследование пациентов были доступны для обработки после 6 мес наблюдения. Средние значения уровня общего тестостерона в начале исследования составили 10,8 ± 0,3 (95 % доверительный интервал (ДИ) 10,2–11,4) нмоль/л, после 6 мес терапии – 21,1 ± 0,4 (95 % ДИ 20,4–21,9) нмоль/л. Значимые изменения были отмечены по шкале AMS, средний балл на 1-м визите составил 47,4 ± 1,0 (95 % ДИ 45,5–49,4), а на 4-м – 27,5 ± 0,8 (95 % ДИ 25,9–29,1); по шкале МИЭФ на 1-м визите – 33,0 ± 1,0 (95 % ДИ 31,0–35,0), на 4-м – 54,0 ± 1,0 (95 % ДИ 52,0–57,0). Дополнительные положительные эффекты отмечены в отношении ИМТ и окружности талии – уменьшение показателей на 1,2 кг/м2 и 5 см соответственно.
Выводы. В ходе исследования отмечено достоверное уменьшение выраженности симптомов дефицита тестостерона, улучшение показателей качества жизни и сексуальной функции. За 6 мес наблюдения клинически значимых нежелательных явлений не выявлено.
Список литературы
1. Morgentaller A., Zitzmann M., Traish A. M. et al. Mayo Clin Proc 2016;91(7):881–96. DOI: 10.1016/j.mayocp.2016.04.007.
2. Lunenfeld B., Mskhalaya G., Zitzmann M. et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male 2015, Ahead of Print: Pp. 1–11.
3. Trinick T. R., Feneley M. R., Welford H., Carruthers M. International web survey shows highprevalence of symptomatic testosterone deficiency in men. Aging Male 2011;14(1):10–5. DOI: 10.3109/13685538.2010.511325.
4. Traish A. M., Miner M. M., Morgentaler A., Zitzmann M. Testosterone deficiency. Am J Med 2011;124(7):578–87. DOI: 10.1016/j.amjmed.2010.12.027.
5. Bhasin S., Basaria S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab 2011;25(2):251–70. DOI: 10.1016/j.beem.2010.12.002.
6. Giagulli V. A., Triggiani V., Corona G. et al. Evidence-based medicine update on testosterone replacement therapy (TRT) in male hypogonadism: focus on new formulations. Curr Pharm Des 2011;17(15):1500–11.
7. Thwaites J. H. Practical aspects of drug treatment in elderly patients with mobility problems. Drugs Aging 1999;14(2):105–14.
8. Bhasin S., Cunningham G. R., Hayes F. J. et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95(6): 2536–59. DOI: 10.1210/jc.2009-2354.
9. Nieschlag E., Swerdloff R., Behre H. M. et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J Androl 2006;27(2):135–7.
10. Petak S. M., Nankin H. R., Spark R. F. et al. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients – 2002 update. Endocr Pract 2002;8(6):440–56.
11. Aversa A., Bruzziches R., Francomano D. et al. Effects of longacting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study. Aging Male 2012;15(2):96–102. DOI: 10.3109/13685538.2011.631230.
12. Ho C. C., Tong S. F., Low W. Y. et al. A randomized, double-blind, placebocontrolled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale. BJU Int 2012;110:260–5.
13. Khera M., Bhattacharya R. K., Blick G. et al. Improved sexual function with testosterone replacement therapy in hypogonadal men: real-world data from the Testim Registry in the United States (TRiUS). J Sex Med 2011;8:3204–13.
14. Miner M. M., Bhattacharya R. K., Blick G. et al. 12-Month observation of testosterone replacement effectiveness in a general population of men. Postgrad Med 2013;125:8–18.
15. Snyder P. J., Peachey H., Hannoush P. et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999;84:1966–72.
16. Wang C., Cunningham G., Dobs A. et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004;89:2085–98.
17. Wang C., Swerdloff R. S., Iranmanesh A., et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 2000;85:2839–53.
18. Shores M. M., Smith N. L., Forsberg C. W. et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012;97:2050–8.
19. Wang C., Alexander G., Berman N. et al. Testosterone replacement therapy improves mood in hypogonadal men – a clinical research center study. J Clin Endocrinol Metab 1996;81:3578–83.
20. URL: http://www.grls.rosminzdrav.ru.
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24. Pexman-Fieth C., Behre H. M., Morales A. et al. A 6-month observational study of energy, sexual desire, and body proportions in hypogonadal men treated with a testosterone 1 % gel. Aging Male 2014;17(1):1–11.
25. Heinemann L. A., Moore C., Dinger J. C., Stoehr D. Sensitivity as outcome measure of androgen replacement: the AMS scale. Health Qual Life Outcomes 2006;4:23–9.
26. Chiang H. S., Hwang T. I., Hsui Y. S. et al. Transdermal testosterone gel increases serum testosterone levels in hypogonadal men in Taiwan with improvements in sexual function. Int J Impot Res 2007;19:411–7.
27. McNicholas T. A., Dean J. D., Mulder H. et al. A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function. BJU Int 2003;91:69–74.
28. Steidle C., Schwartz S., Jacoby K. et al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 2003;88:2673–81.
29. Shabsigh R., Kaufman J. M., Steidle C., Padma-Nathan H. Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2004;172:658–63.
30. Srinivas-Shankar U., Roberts S. A., Connolly M. J. et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebocontrolled study. J ClinEndocrinol Metab 2010;95:639–50.
31. Camacho E. M., Huhtaniemi I. T., O’Neill T. W. et al. Age-associated changes in hypothalamic-pituitary-testicular functionin middleaged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol 2013;168:445–55.
32. Gates M. A., Mekary R. A., Chiu G. R. et al. Sex steroid hormone levels and body composition in men. J Clin Endocrinol Metab 2013;98:2442–50.
33. Saboor Aftab S. A., Kumar S., Barber T. M. The role of obesity and type 2 diabetes mellitus in the development of male obesityassociated secondary hypogonadism. Clin Endocrinol (Oxf) 2013;78:330–47.
34. Swerdloff R. S., Wang C., Cunningham G. et al. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000;85:4500– 10.
35. Wang C., Berman N., Longstreth J. A. et al. Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. J Clin Endocrinol Metab 2000; 85:964–9.
Andrology and Genital Surgery. 2016; 17: 59-67
Influence of the testosterone therapy (1 % transdermal gel) on the life quality of men of androgen deficiency in terms of routing clinical practice: 6 months monitoring test
https://doi.org/10.17650/2070-9781-2016-17-4-59-67Abstract
Маterials and methods. The study hereunder was an open multicenter surveillance non-intervention study at men with testosterone deficiency, apllying daily 1 % testosterone gel (Аndrogel®) in the dosage of 50 or 100 mg (with possible titration) in terms of routine clinical practice. The initial end point was the life quality, referred to the health status, evaluated at the filling of the questionnaire on Aging Males’ Symptoms (AMS). As secondary end points served changes of the total score of the International Erectile Function Index (IEFE) and its domains, changes of body weight index (BWI) and of the waist circumference, correlation of changes in life quality indices, determined with AMS questionnaire, with laboratory indices of the testosterone level and of the data by the IEFE scale, demographic features, as well as original characteristics of patients, anamnesis of diagnostic and therapeutic procedures, reason for the treatment termination and any adverse effects, arising in the course of treatment with Androgel®.
Results. The data on 196 of 202 patients, included in studies, was available for processing after 6 months of monitoring. Average values of the total testosterone level in beginning of studies were 10.8 ± 0.3 (95 % confidence interval (CI) 10.2–11.4) nmol/l after 6 months of therapy – 21.1 ± 0.4 (95 % CI 20.4–21.9) nmol/l. Significant changes were marked on the AMS scale, the average point at the 1st visit was 47.4 ± 1.0 (95 % CI 45.5–49.4), аnd at the 4th – 27.5 ± 0.8 (95 % CI 25.9–29.1); by IEFE scale at the 1st visit – 33.0 ± 1.0 (95 % CI 31.0–35.0), at the 4th – 54.0 ± 1.0 (95 % CI 52.0–57.0). Additional positive effects were marked as to BWI and the waist circumference – decrease of indices by 1,2 kg/m2 and 5 сm accordingly.
Conclusion. Studies have shown the authentic reduction of expressed symptoms of testosterone deficiency, improvement of the life quality indices and of the sexual function. During 6 months of monitoring no clinically significant adverse effects were revealed.
References
1. Morgentaller A., Zitzmann M., Traish A. M. et al. Mayo Clin Proc 2016;91(7):881–96. DOI: 10.1016/j.mayocp.2016.04.007.
2. Lunenfeld B., Mskhalaya G., Zitzmann M. et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male 2015, Ahead of Print: Pp. 1–11.
3. Trinick T. R., Feneley M. R., Welford H., Carruthers M. International web survey shows highprevalence of symptomatic testosterone deficiency in men. Aging Male 2011;14(1):10–5. DOI: 10.3109/13685538.2010.511325.
4. Traish A. M., Miner M. M., Morgentaler A., Zitzmann M. Testosterone deficiency. Am J Med 2011;124(7):578–87. DOI: 10.1016/j.amjmed.2010.12.027.
5. Bhasin S., Basaria S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab 2011;25(2):251–70. DOI: 10.1016/j.beem.2010.12.002.
6. Giagulli V. A., Triggiani V., Corona G. et al. Evidence-based medicine update on testosterone replacement therapy (TRT) in male hypogonadism: focus on new formulations. Curr Pharm Des 2011;17(15):1500–11.
7. Thwaites J. H. Practical aspects of drug treatment in elderly patients with mobility problems. Drugs Aging 1999;14(2):105–14.
8. Bhasin S., Cunningham G. R., Hayes F. J. et al. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95(6): 2536–59. DOI: 10.1210/jc.2009-2354.
9. Nieschlag E., Swerdloff R., Behre H. M. et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. J Androl 2006;27(2):135–7.
10. Petak S. M., Nankin H. R., Spark R. F. et al. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients – 2002 update. Endocr Pract 2002;8(6):440–56.
11. Aversa A., Bruzziches R., Francomano D. et al. Effects of longacting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study. Aging Male 2012;15(2):96–102. DOI: 10.3109/13685538.2011.631230.
12. Ho C. C., Tong S. F., Low W. Y. et al. A randomized, double-blind, placebocontrolled trial on the effect of long-acting testosterone treatment as assessed by the Aging Male Symptoms scale. BJU Int 2012;110:260–5.
13. Khera M., Bhattacharya R. K., Blick G. et al. Improved sexual function with testosterone replacement therapy in hypogonadal men: real-world data from the Testim Registry in the United States (TRiUS). J Sex Med 2011;8:3204–13.
14. Miner M. M., Bhattacharya R. K., Blick G. et al. 12-Month observation of testosterone replacement effectiveness in a general population of men. Postgrad Med 2013;125:8–18.
15. Snyder P. J., Peachey H., Hannoush P. et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999;84:1966–72.
16. Wang C., Cunningham G., Dobs A. et al. Long-term testosterone gel (AndroGel) treatment maintains beneficial effects on sexual function and mood, lean and fat mass, and bone mineral density in hypogonadal men. J Clin Endocrinol Metab 2004;89:2085–98.
17. Wang C., Swerdloff R. S., Iranmanesh A., et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 2000;85:2839–53.
18. Shores M. M., Smith N. L., Forsberg C. W. et al. Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 2012;97:2050–8.
19. Wang C., Alexander G., Berman N. et al. Testosterone replacement therapy improves mood in hypogonadal men – a clinical research center study. J Clin Endocrinol Metab 1996;81:3578–83.
20. URL: http://www.grls.rosminzdrav.ru.
21. Rosen R. C. Cappelleri J. C., Gendrano N. The International Index of Erectile Function (IIEF): a state-of-the-science review. Int J Impot Res 2002;14:226–44.
22. URL: https://uroweb.org/guideline/male-hypogonadism.
23. Dedov I. I., Mel'nichenko G. A., Rozhivanov R. V., Kurbatov D. G. Rekomendatsii po diagnostike i lecheniyu gipogonadizma (defitsita testosterona) u muzhchin. Proekt. Problemy Endokrinologii. 2015;61(5):60–71. [Dedov I. I., Melnichenko G. A., Rozhivanov R. V., Kurbatov D. G. Recommendations on the diagnostics and treatment of hypogenitalism (testosterone deficiency) at men. Project. Problemy endokrinologii = Problems of Endocrinology. 2015;61(5):60– 71. (In Russ.)].
24. Pexman-Fieth C., Behre H. M., Morales A. et al. A 6-month observational study of energy, sexual desire, and body proportions in hypogonadal men treated with a testosterone 1 % gel. Aging Male 2014;17(1):1–11.
25. Heinemann L. A., Moore C., Dinger J. C., Stoehr D. Sensitivity as outcome measure of androgen replacement: the AMS scale. Health Qual Life Outcomes 2006;4:23–9.
26. Chiang H. S., Hwang T. I., Hsui Y. S. et al. Transdermal testosterone gel increases serum testosterone levels in hypogonadal men in Taiwan with improvements in sexual function. Int J Impot Res 2007;19:411–7.
27. McNicholas T. A., Dean J. D., Mulder H. et al. A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function. BJU Int 2003;91:69–74.
28. Steidle C., Schwartz S., Jacoby K. et al. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab 2003;88:2673–81.
29. Shabsigh R., Kaufman J. M., Steidle C., Padma-Nathan H. Randomized study of testosterone gel as adjunctive therapy to sildenafil in hypogonadal men with erectile dysfunction who do not respond to sildenafil alone. J Urol 2004;172:658–63.
30. Srinivas-Shankar U., Roberts S. A., Connolly M. J. et al. Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebocontrolled study. J ClinEndocrinol Metab 2010;95:639–50.
31. Camacho E. M., Huhtaniemi I. T., O’Neill T. W. et al. Age-associated changes in hypothalamic-pituitary-testicular functionin middleaged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Eur J Endocrinol 2013;168:445–55.
32. Gates M. A., Mekary R. A., Chiu G. R. et al. Sex steroid hormone levels and body composition in men. J Clin Endocrinol Metab 2013;98:2442–50.
33. Saboor Aftab S. A., Kumar S., Barber T. M. The role of obesity and type 2 diabetes mellitus in the development of male obesityassociated secondary hypogonadism. Clin Endocrinol (Oxf) 2013;78:330–47.
34. Swerdloff R. S., Wang C., Cunningham G. et al. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000;85:4500– 10.
35. Wang C., Berman N., Longstreth J. A. et al. Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. J Clin Endocrinol Metab 2000; 85:964–9.
