Андрология и генитальная хирургия. 2013; 14: 7-10
Метаболический синдром и мужское бесплодие (обзор литературы)
https://doi.org/10.17650/2070-9781-2013-2-7-10Аннотация
Литературный обзор посвящен одной из наиболее актуальных проблем современной андрологии – патогенетической связи компонентов метаболического синдрома и мужского бесплодия. В настоящее время в мировой популяции мужчин наблюдается неуклонный рост частоты заболеваемости метаболическим синдромом, что сопровождается прогрессирующим ухудшением у них показателей фертильности. На основе современных клинико-эпидемиологических и экспериментальных данных показано негативное влияние ключевых компонентов метаболического синдрома – ожирения и инсулинорезистентности – на репродуктивную функцию мужчин, а также описаны известные патофизиологические механизмы этого влияния. Индуцируемые метаболическим синдромом оксидативный стресс сперматозоидов, нейропатия и андрогенный дефицит являются наиболее значимыми механизмами реализации его нейроэндокринных и репродуктивных последствий. Показана настоятельная необходимость раннего выявления и фармакологической коррекции ожирения и инсулинорезистентности у всех пациентов с мужским бесплодием, так как они являются курабельными причинами инфертильности. Однако в рутинной клинической практике они редко выявляются и еще реже корректируются в силу недостаточной информированности урологов и андрологов об этих системных гормонально-метаболических факторах, роль которых в патогенезе мужского бесплодия в условиях мировой эпидемии метаболического синдрома будет только увеличиваться.
Список литературы
1. Божедомов В.А., Ушакова И.В., Спори ш Е.А. и др. Роль гиперпродукции активных форм кислорода в мужском бесплодии и возможности антиоксидантной терапии (обзор литературы). Consilium Medicum 2012;7:51–5.
2. Божедомов В.А., Громенко Д.С., Ушаков а И.В. и др. Причины оксидативного стресса cперматозоидов. Пробл репродукции 2008;6:67–73.
3. Божедомов В.А., Громенко Д.С., Ушаков а И.В. и др. Оксидативный стресс сперматозоидов в патогенезе мужского бесплодия. Урология 2009;2:51–6.
4. Fujii J., Tsunoda S. Redox regulation of fertilisation and the spermatogenic process. Asian J Androl 2011;13(3):420–3.
5. Sheriff D.S, Ali E.F. Perspective on plasma membrane cholesterol efflux and spermatozoa function. J Hum Reprod Sci 2010;3(2):68–75.
6. Villegas J., Schulz M., Soto L. et al. Influence of reactive oxygen species produced by activated leukocytes at the level of apoptosis in mature human spermatozoa. Fertil Steril 2005;83(3):808–10.
7. Zorn B., Vidmar G., Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl 2003;26:279–85.
8. Koppers A.J., Mitchell L.A., Wang P. et al. Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa. Biochem J 2011; 436(3):687–98.
9. Kemal Duru N., Morshedi M., Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril 2000;74(6):1200–7.
10. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update 2008;14(3):243–58.
11. Garrido N., Meseguer M., Alvarez J. et al. Relationship among standard semen parameters, glutathione peroxidase/ glutathione reductase activity, and mRNA expression and reduced glutathione content in ejaculated spermatozoa from fertile and infertile men. Fertil Steril 2004; 82(Suppl 3):1059–66.
12. Henkel R., Kierspel E., Stalf T. et al. Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients. Fertil Steril 2005;83(3):635–42.
13. Sarkar O., Bahrainwala J., Chandrasekaran S. et al. Impact of inflammation on male fertility. Front Biosci (Elite Ed) 2011;3:89–95.
14. Eisenberg M.L., Lipshultz L.I. Varicocele-induced infertility: Newer insights into its pathophysiology. Indian J Urol 2011;27(1):58–64.
15. Perez-Crespo M., Pintado B., Gutierrez-Adan A. Scrotal heat stress effects on sperm viability, sperm DNA integrity, and the offspring sex ratio in mice. Mol Reprod Dev 2008;75(1):40–7.
16. WHO laboratory manual for the examination and processing of human semen. 5th ed., 2010; pp. 142–6.
17. Аляев Ю.Г., Алленов С.Н., Кулаков а Е.В. и др. Стресс и инфертильность: психологические аспекты бесплодия. Материалы IV Конгресса «Мужское здоровье». М., 2008. С. 198–9.
18. Божедомов В.А., Громенко Д.С., Ушаков а И.В. и др. Причины оксидативного стресса сперматозоидов. Материалы IV Конгресса «Мужское здоровье». М., 2008. С. 209.
19. Макрушин Г.А., Кузнецова Н.Н., Шами н М.В. и др. Зависимость фертильных свойств эякулята от уровня лейкоспермии. Материалы VI Конгресса «Мужское здоровье». М., 2010. С. 205–6.
20. Gorbachinsky I., Akpinar H., Assimos D.G. Metabolic syndrome and urologic diseases. Rev Urol 2010;12(4):e157–80.
21. Knowler W.C., Barrett-Connor E., Fowler S.E.; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346(6):393–403.
22. Flegal K.M., Carroll M.D., Ogden C.L., Johnson C.L. Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002;288(14):1723–7.
23. Geiss L.S., Pan L., Cadwell B. Changes in incidence of diabetes in U.S. adults, 1997–2003. Am J Prev Меd 2006;30(5):371–7.
24. Kalyani R.R., Dobs A.S. Androgen deficiency, diabetes and the metabolic syndrome in men. Curr Opin Endocrinol Diabetes Obes 2007;14(3):226–34.
25. Kupelian V., Hayes F.J., Link C.L. et al. Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab 2008;93(9):3403–10.
26. Alberti G. Introduction to the metabolic syndrome. Eur Heart J 2005; 7(Suppl D):D3–5.
27. Huang P.L. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009;2(5–6):231–7.
28. Dohle G.R., Diemer T., Giwercman A. et al. Male Infertility Guideline. EAU, 2012. 68 р.
29. Тюзиков И.А., Бажина О.В. Некоторые аспекты эндокринного бесплодия у мужчин. Заочные электронные конференции РАЕ. URL: http://article4728 (дата обращения 13.10. 2010).
30. Тюзиков И.А. К вопросу о нарушении сперматогенной функции яичек. Сб. материалов Пленума Российского общества урологов. Краснодар, 2010. С. 217–8.
31. Тюзиков И.А. Скрытые нарушения метаболизма как возможная причина мужской ифертильности. Актуальные вопросы урологии и андрологии: Сборник материалов международной научнопрактической конференции, посвященной 100-летию кафедры урологии
32. и андрологии СПбМАПО. СПб., 2011. С. 227–30.
33. Тюзиков И.А. Возможности метаболической терапии бесплодия у молодых мужчин с ожирением. Материалы VII Всероссийского конгресса «Мужское здоровье». Ростов-на-Дону, 2011. С. 288–90.
34. Gustafson B., Hammarstedt А., Andersson C.X., Smith U. Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol 2007;27(11):2276–83.
35. Trayhurn P., Wood I.S. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004;92(3):347–55.
36. Sánchez-Lara K., Morales-Graf L., Green D. et al. Cancer and obesity. Gac Med Mex 2010;146(5):326–31.
37. Ройтберг Г.Е. Метаболический синдром. М.: МЕДпресс-информ, 2007. 224 с.
38. Lee M.J., Fried S.K. Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion. Am J Physiol Endocrinol Metab 2009;296(6):E1230–8.
39. Kapoor D., Clarke S., Stanworth R. et al. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2007;156(5):595–602.
40. Svartberg J., von Möhlen D., Schirmer H. et al. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. Eur J Endocrinol 2004;150(1):65–71.
41. Schaffer J.E. Lipotoxicity: when tissues overeat. Curr Opin Lipidol 2003;14(3):281–7.
42. Weinberg J.M. Lipotoxicity. Kidney Int 2006;70(9):1560–6.
43. Aitken R.J., Krausz C. Oxidative stress, DNA damage and the Y chromosome. Reproduction 2001;122(4):497–506.
44. Nguyen R.H., Wilcox A.J., Skaerven R., Baird D.D. Men’s body mass index and infertility. Hum Reprod 2007;22(9):2488–93.
45. Ohwaki K., Endo F., Yano E. Relationship between body mass index and infertility in healthy male Japanese workers: a pilot study. Andrologia 2009;41(2):100–4.
46. Bener A., Al-Ansari A.A., Zirie M., Al-Hamaq A.O. Is male fertility associated with type 2 diabetes mellitus? Int Urol Nephrol 2009;41(4):777–84.
47. Stewart T.M., Liu D.Y., Garrett C. et al. Associations between andrological measures, hormones and semen quality in fertile Australian men: inverse relationship between obesity and sperm output. Hum Reprod 2009;24(7):1561–8.
48. Chavarro J.E., Toth T.L., Wright D.L. et al. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril 2010;93(7):2222–31.
49. Hammoud A.O., Wilde N., Gibson M. et al. Male obesity and alteration in sperm parameters. Fertil Steril 2008;90(6):2222–5.
50. Kort H.I., Massey J.B., Elsner C.W. et al. Impact of body mass index values on sperm quantity and quality. J Androl 2006;27(3):450–52.
51. Fejes I., Koloszár S., Szöllosi J. et al. Is semen quality affected by male body fat distribution? Andrologia 2005;37(5):155–9.
52. Ali S.T., Shaikh R.N., Siddiqi A.N., Siddiqi P.Q. Semen analysis in insulindependent/ noninsulin-dependent diabetic men with/without neuropathy. Arch Androl 1993;30(1):47–54.
53. Vinik A.I., Maser R.E., Mitchell B.D., Freeman R. Diabetic autonomic neuropathy. Diabetes Care 2003;26(5):1553–79.
54. Gilja I., Parazajder J., Radej M. et al. Retrograde ejaculation and loss of emission: possibilities of conservative treatment. Eur Urol 1994;25(3):226–8.
55. el-Rufaie O.E., Bener A., Abuzeid M.S., Ali T.A. Sexual dysfunction among type II diabetic men: a controlled study. J Psychosom Res 1997;43(6):605–12.
56. El-Sakka A.I. Premature ejaculation in non-insulin-dependent diabetic patients. Int J Androl 2003;26(6):329–34.
57. Kasturi S.S., Tannir J., Brannigan R.E. The metabolic syndrome and male infertility. J Androl 2008;29(3):251–9.
58. Тюзиков И.А., Греков Е.А. Новая метаболическая концепция патогенеза идиопатического мужского бесплодия. Здравоохр Таджикистана 2011;3:392–4.
59. Тюзиков И.А. Системная метаболическая терапия мужского бесплодия, ассоциированного с ожирением и инсулинорезистентностью. Материалы Пленума Российского общества урологов. Кисловодск, 2011. С. 415–6.
60. Тюзиков И.А., Калинченко С.Ю., Марто в А.Г. Роль коррекции метаболического статуса при репродуктивных нарушениях у мужчин. Материалы X Всероссийского Форума с международным
61. участием «Мужское здоровье и долголетие». М., 2012. С. 95–6.
62. Shiraishi K., Takihara H., Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol 2010;28(3):359–64.
63. Tsao C.W., Hsu C.Y., Chou Y.C. et al. The relationship between varicoceles and obesity in a young adult population. Int J Androl 2009;32(4):385–90.
64. Handel L.N., Shetty R., Sigman M. The relationship between varicoceles and obesity. J Urol 2006;176(5):2138–40.
65. Shafik A., Olfat S. Scrotal lipomatosis. Br J Urol 1981;53(1):50–4.
66. Shafik A., Olfat S. Lipectomy in the treatment of scrotal lipomatosis. Br J Urol 1981;53:55–61.
67. Brannian J.D. Obesity and fertility. S D Med 2011;64(7):251–4.
68. Goulis D.G., Tarlatzis B.C. Metabolic syndrome and reproduction: I. testicular function. Gynecol Endocrinol 2008;24(1):33–9.
69. Pasquali R., Patton L., Gambineri A. Obesity and infertility. Curr Opin Endocrinol Diabetes Obes 2007;14(6):482–7.
70. Mah P.M., Wittert G.A. Obesity and testicular function. Mol Cell Endocrinol 2010;316(2):180–6.
71. Бернштейн Л.М. Антидиабетический бигуанид метформин и онкологическая заболеваемость. Сах диабет 2010;3:3–6.
72. Baron A.D. Insulin resistance and vascular function. J Diabetes Complications 2002;16(1):92–102.
73. Srikanthan P., Karlamangla A.S. Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab 2011;96(9):2898–903.
74. McVary K.T., Rademaker A., Lloyd G.L. et al. Autonomic nervous system overactivity in men with lower
75. urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174(4 Pt 1):1327–33.
76. Brüning J.C., Gautam D., Burks D.J. et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000;289(5487):2122–5.
77. Palmer N.O., Bakos H.W., Owens J.A. et al. Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Am J Physiol Endocrinol Metab 2012;302(7):768–80.
78. Sankhla M., Sharma T.K., Mathur K. et al. Relationship of oxidative stress with obesity and its role in obesity induced metabolic syndrome. Clin Lab 2012; 58(5–6):385–92.
79. La Vignera S., Condorelli R., Vicari E. et al. Diabetes mellitus and sperm parameters. J Androl 2012;33(2):145–53.
80. Yassin A.A., Saad F., Gooren L.J. Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone. Andrologia 2008;40(4):259–64.
81. Mallidis C., Czerwiec A., Filippi S. et al. Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism. Reproduction 2011;142(1):63–71.
82. Тюзиков И.А. Патология мужских половых органов как маркер сахарного диабета. Материалы Пленума Российского общества урологов. Краснодар, 2010. С. 292.
83. Тюзиков И.А., Калинченко С.Ю., Мартов А.Г. Диагностическое и прогностическое значение нейропатии в протоколе андрологического обследования. Материалы I Конгресса урологов Сибири. Кемерово, 2012. С. 325–8.
84. Morgante G., Tosti C., Orvieto R. et al. Metformin improves semen characteristics of oligo-teratoasthenozoospermic men with metabolic syndrome. Fertil Steril 2011;95(6):2150–2.
85. Тюзиков И.А. Инсулинорезистентность и мужское бесплодие: диагностика и возможности медикаментозной коррекции. Материалы Всероссийской научно-практической конференции с международным участием «Рациональная фармакотерапия в урологии-2011». М., 2011. С. 148–9.
86. Тюзиков И.А. Идиопатическое мужское бесплодие: есть ли «свет в конце туннеля» современной стандартной диагностики? Материалы Региональной научной конференции «Мужское здоровье в Сибири». Томск, 2011. С. 100–3.
Andrology and Genital Surgery. 2013; 14: 7-10
Metabolic syndrome and male infertility (review)
https://doi.org/10.17650/2070-9781-2013-2-7-10Abstract
The literary review is devoted to one of the most actual problems of modern andrology – pathogenetic communication of metabolic syndrome components and male infertility. Now a steady growth of metabolic syndrome frequency in world men population is observed, and that is accompanied by progressing deterioration of fertility parameters at them. Negative influence of key metabolic syndrome components – obesity and insulin resistance – at male reproductive function is shown on the basis of modern clinical, epidemiological and experimental data, and known pathophysiological mechanisms of this influence are described also. Induced by a metabolic syndrome oxidative stress of spermatozoas, neuropathy and androgen deficiency are the most significant mechanisms of neuro-endocrinological and reproductive consequences realization. The imperative necessity of early revealing and pharmacological correction of obesity and insulin resistance in all infertility men is shown, as well as they are curable reasons of male infertility . However, they seldom come to light and even less often corrected in routine clinical practice owing to insufficient knowledge of urologists and andrologists about these system hormonal-metabolic factors of male infertility, which role in male infertility pathogenesis will increase only in the conditions of world epidemic of a metabolic syndrome.
References
1. Bozhedomov V.A., Ushakova I.V., Spori sh E.A. i dr. Rol' giperproduktsii aktivnykh form kisloroda v muzhskom besplodii i vozmozhnosti antioksidantnoi terapii (obzor literatury). Consilium Medicum 2012;7:51–5.
2. Bozhedomov V.A., Gromenko D.S., Ushakov a I.V. i dr. Prichiny oksidativnogo stressa cpermatozoidov. Probl reproduktsii 2008;6:67–73.
3. Bozhedomov V.A., Gromenko D.S., Ushakov a I.V. i dr. Oksidativnyi stress spermatozoidov v patogeneze muzhskogo besplodiya. Urologiya 2009;2:51–6.
4. Fujii J., Tsunoda S. Redox regulation of fertilisation and the spermatogenic process. Asian J Androl 2011;13(3):420–3.
5. Sheriff D.S, Ali E.F. Perspective on plasma membrane cholesterol efflux and spermatozoa function. J Hum Reprod Sci 2010;3(2):68–75.
6. Villegas J., Schulz M., Soto L. et al. Influence of reactive oxygen species produced by activated leukocytes at the level of apoptosis in mature human spermatozoa. Fertil Steril 2005;83(3):808–10.
7. Zorn B., Vidmar G., Meden-Vrtovec H. Seminal reactive oxygen species as predictors of fertilization, embryo quality and pregnancy rates after conventional in vitro fertilization and intracytoplasmic sperm injection. Int J Androl 2003;26:279–85.
8. Koppers A.J., Mitchell L.A., Wang P. et al. Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa. Biochem J 2011; 436(3):687–98.
9. Kemal Duru N., Morshedi M., Oehninger S. Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil Steril 2000;74(6):1200–7.
10. Tremellen K. Oxidative stress and male infertility – a clinical perspective. Hum Reprod Update 2008;14(3):243–58.
11. Garrido N., Meseguer M., Alvarez J. et al. Relationship among standard semen parameters, glutathione peroxidase/ glutathione reductase activity, and mRNA expression and reduced glutathione content in ejaculated spermatozoa from fertile and infertile men. Fertil Steril 2004; 82(Suppl 3):1059–66.
12. Henkel R., Kierspel E., Stalf T. et al. Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients. Fertil Steril 2005;83(3):635–42.
13. Sarkar O., Bahrainwala J., Chandrasekaran S. et al. Impact of inflammation on male fertility. Front Biosci (Elite Ed) 2011;3:89–95.
14. Eisenberg M.L., Lipshultz L.I. Varicocele-induced infertility: Newer insights into its pathophysiology. Indian J Urol 2011;27(1):58–64.
15. Perez-Crespo M., Pintado B., Gutierrez-Adan A. Scrotal heat stress effects on sperm viability, sperm DNA integrity, and the offspring sex ratio in mice. Mol Reprod Dev 2008;75(1):40–7.
16. WHO laboratory manual for the examination and processing of human semen. 5th ed., 2010; pp. 142–6.
17. Alyaev Yu.G., Allenov S.N., Kulakov a E.V. i dr. Stress i infertil'nost': psikhologicheskie aspekty besplodiya. Materialy IV Kongressa «Muzhskoe zdorov'e». M., 2008. S. 198–9.
18. Bozhedomov V.A., Gromenko D.S., Ushakov a I.V. i dr. Prichiny oksidativnogo stressa spermatozoidov. Materialy IV Kongressa «Muzhskoe zdorov'e». M., 2008. S. 209.
19. Makrushin G.A., Kuznetsova N.N., Shami n M.V. i dr. Zavisimost' fertil'nykh svoistv eyakulyata ot urovnya leikospermii. Materialy VI Kongressa «Muzhskoe zdorov'e». M., 2010. S. 205–6.
20. Gorbachinsky I., Akpinar H., Assimos D.G. Metabolic syndrome and urologic diseases. Rev Urol 2010;12(4):e157–80.
21. Knowler W.C., Barrett-Connor E., Fowler S.E.; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346(6):393–403.
22. Flegal K.M., Carroll M.D., Ogden C.L., Johnson C.L. Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002;288(14):1723–7.
23. Geiss L.S., Pan L., Cadwell B. Changes in incidence of diabetes in U.S. adults, 1997–2003. Am J Prev Med 2006;30(5):371–7.
24. Kalyani R.R., Dobs A.S. Androgen deficiency, diabetes and the metabolic syndrome in men. Curr Opin Endocrinol Diabetes Obes 2007;14(3):226–34.
25. Kupelian V., Hayes F.J., Link C.L. et al. Inverse association of testosterone and the metabolic syndrome in men is consistent across race and ethnic groups. J Clin Endocrinol Metab 2008;93(9):3403–10.
26. Alberti G. Introduction to the metabolic syndrome. Eur Heart J 2005; 7(Suppl D):D3–5.
27. Huang P.L. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009;2(5–6):231–7.
28. Dohle G.R., Diemer T., Giwercman A. et al. Male Infertility Guideline. EAU, 2012. 68 r.
29. Tyuzikov I.A., Bazhina O.V. Nekotorye aspekty endokrinnogo besplodiya u muzhchin. Zaochnye elektronnye konferentsii RAE. URL: http://article4728 (data obrashcheniya 13.10. 2010).
30. Tyuzikov I.A. K voprosu o narushenii spermatogennoi funktsii yaichek. Sb. materialov Plenuma Rossiiskogo obshchestva urologov. Krasnodar, 2010. S. 217–8.
31. Tyuzikov I.A. Skrytye narusheniya metabolizma kak vozmozhnaya prichina muzhskoi ifertil'nosti. Aktual'nye voprosy urologii i andrologii: Sbornik materialov mezhdunarodnoi nauchnoprakticheskoi konferentsii, posvyashchennoi 100-letiyu kafedry urologii
32. i andrologii SPbMAPO. SPb., 2011. S. 227–30.
33. Tyuzikov I.A. Vozmozhnosti metabolicheskoi terapii besplodiya u molodykh muzhchin s ozhireniem. Materialy VII Vserossiiskogo kongressa «Muzhskoe zdorov'e». Rostov-na-Donu, 2011. S. 288–90.
34. Gustafson B., Hammarstedt A., Andersson C.X., Smith U. Inflamed adipose tissue: a culprit underlying the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol 2007;27(11):2276–83.
35. Trayhurn P., Wood I.S. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004;92(3):347–55.
36. Sánchez-Lara K., Morales-Graf L., Green D. et al. Cancer and obesity. Gac Med Mex 2010;146(5):326–31.
37. Roitberg G.E. Metabolicheskii sindrom. M.: MEDpress-inform, 2007. 224 s.
38. Lee M.J., Fried S.K. Integration of hormonal and nutrient signals that regulate leptin synthesis and secretion. Am J Physiol Endocrinol Metab 2009;296(6):E1230–8.
39. Kapoor D., Clarke S., Stanworth R. et al. The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2007;156(5):595–602.
40. Svartberg J., von Möhlen D., Schirmer H. et al. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromsø Study. Eur J Endocrinol 2004;150(1):65–71.
41. Schaffer J.E. Lipotoxicity: when tissues overeat. Curr Opin Lipidol 2003;14(3):281–7.
42. Weinberg J.M. Lipotoxicity. Kidney Int 2006;70(9):1560–6.
43. Aitken R.J., Krausz C. Oxidative stress, DNA damage and the Y chromosome. Reproduction 2001;122(4):497–506.
44. Nguyen R.H., Wilcox A.J., Skaerven R., Baird D.D. Men’s body mass index and infertility. Hum Reprod 2007;22(9):2488–93.
45. Ohwaki K., Endo F., Yano E. Relationship between body mass index and infertility in healthy male Japanese workers: a pilot study. Andrologia 2009;41(2):100–4.
46. Bener A., Al-Ansari A.A., Zirie M., Al-Hamaq A.O. Is male fertility associated with type 2 diabetes mellitus? Int Urol Nephrol 2009;41(4):777–84.
47. Stewart T.M., Liu D.Y., Garrett C. et al. Associations between andrological measures, hormones and semen quality in fertile Australian men: inverse relationship between obesity and sperm output. Hum Reprod 2009;24(7):1561–8.
48. Chavarro J.E., Toth T.L., Wright D.L. et al. Body mass index in relation to semen quality, sperm DNA integrity, and serum reproductive hormone levels among men attending an infertility clinic. Fertil Steril 2010;93(7):2222–31.
49. Hammoud A.O., Wilde N., Gibson M. et al. Male obesity and alteration in sperm parameters. Fertil Steril 2008;90(6):2222–5.
50. Kort H.I., Massey J.B., Elsner C.W. et al. Impact of body mass index values on sperm quantity and quality. J Androl 2006;27(3):450–52.
51. Fejes I., Koloszár S., Szöllosi J. et al. Is semen quality affected by male body fat distribution? Andrologia 2005;37(5):155–9.
52. Ali S.T., Shaikh R.N., Siddiqi A.N., Siddiqi P.Q. Semen analysis in insulindependent/ noninsulin-dependent diabetic men with/without neuropathy. Arch Androl 1993;30(1):47–54.
53. Vinik A.I., Maser R.E., Mitchell B.D., Freeman R. Diabetic autonomic neuropathy. Diabetes Care 2003;26(5):1553–79.
54. Gilja I., Parazajder J., Radej M. et al. Retrograde ejaculation and loss of emission: possibilities of conservative treatment. Eur Urol 1994;25(3):226–8.
55. el-Rufaie O.E., Bener A., Abuzeid M.S., Ali T.A. Sexual dysfunction among type II diabetic men: a controlled study. J Psychosom Res 1997;43(6):605–12.
56. El-Sakka A.I. Premature ejaculation in non-insulin-dependent diabetic patients. Int J Androl 2003;26(6):329–34.
57. Kasturi S.S., Tannir J., Brannigan R.E. The metabolic syndrome and male infertility. J Androl 2008;29(3):251–9.
58. Tyuzikov I.A., Grekov E.A. Novaya metabolicheskaya kontseptsiya patogeneza idiopaticheskogo muzhskogo besplodiya. Zdravookhr Tadzhikistana 2011;3:392–4.
59. Tyuzikov I.A. Sistemnaya metabolicheskaya terapiya muzhskogo besplodiya, assotsiirovannogo s ozhireniem i insulinorezistentnost'yu. Materialy Plenuma Rossiiskogo obshchestva urologov. Kislovodsk, 2011. S. 415–6.
60. Tyuzikov I.A., Kalinchenko S.Yu., Marto v A.G. Rol' korrektsii metabolicheskogo statusa pri reproduktivnykh narusheniyakh u muzhchin. Materialy X Vserossiiskogo Foruma s mezhdunarodnym
61. uchastiem «Muzhskoe zdorov'e i dolgoletie». M., 2012. S. 95–6.
62. Shiraishi K., Takihara H., Matsuyama H. Elevated scrotal temperature, but not varicocele grade, reflects testicular oxidative stress-mediated apoptosis. World J Urol 2010;28(3):359–64.
63. Tsao C.W., Hsu C.Y., Chou Y.C. et al. The relationship between varicoceles and obesity in a young adult population. Int J Androl 2009;32(4):385–90.
64. Handel L.N., Shetty R., Sigman M. The relationship between varicoceles and obesity. J Urol 2006;176(5):2138–40.
65. Shafik A., Olfat S. Scrotal lipomatosis. Br J Urol 1981;53(1):50–4.
66. Shafik A., Olfat S. Lipectomy in the treatment of scrotal lipomatosis. Br J Urol 1981;53:55–61.
67. Brannian J.D. Obesity and fertility. S D Med 2011;64(7):251–4.
68. Goulis D.G., Tarlatzis B.C. Metabolic syndrome and reproduction: I. testicular function. Gynecol Endocrinol 2008;24(1):33–9.
69. Pasquali R., Patton L., Gambineri A. Obesity and infertility. Curr Opin Endocrinol Diabetes Obes 2007;14(6):482–7.
70. Mah P.M., Wittert G.A. Obesity and testicular function. Mol Cell Endocrinol 2010;316(2):180–6.
71. Bernshtein L.M. Antidiabeticheskii biguanid metformin i onkologicheskaya zabolevaemost'. Sakh diabet 2010;3:3–6.
72. Baron A.D. Insulin resistance and vascular function. J Diabetes Complications 2002;16(1):92–102.
73. Srikanthan P., Karlamangla A.S. Relative muscle mass is inversely associated with insulin resistance and prediabetes. Findings from the third National Health and Nutrition Examination Survey. J Clin Endocrinol Metab 2011;96(9):2898–903.
74. McVary K.T., Rademaker A., Lloyd G.L. et al. Autonomic nervous system overactivity in men with lower
75. urinary tract symptoms secondary to benign prostatic hyperplasia. J Urol 2005;174(4 Pt 1):1327–33.
76. Brüning J.C., Gautam D., Burks D.J. et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000;289(5487):2122–5.
77. Palmer N.O., Bakos H.W., Owens J.A. et al. Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Am J Physiol Endocrinol Metab 2012;302(7):768–80.
78. Sankhla M., Sharma T.K., Mathur K. et al. Relationship of oxidative stress with obesity and its role in obesity induced metabolic syndrome. Clin Lab 2012; 58(5–6):385–92.
79. La Vignera S., Condorelli R., Vicari E. et al. Diabetes mellitus and sperm parameters. J Androl 2012;33(2):145–53.
80. Yassin A.A., Saad F., Gooren L.J. Metabolic syndrome, testosterone deficiency and erectile dysfunction never come alone. Andrologia 2008;40(4):259–64.
81. Mallidis C., Czerwiec A., Filippi S. et al. Spermatogenic and sperm quality differences in an experimental model of metabolic syndrome and hypogonadal hypogonadism. Reproduction 2011;142(1):63–71.
82. Tyuzikov I.A. Patologiya muzhskikh polovykh organov kak marker sakharnogo diabeta. Materialy Plenuma Rossiiskogo obshchestva urologov. Krasnodar, 2010. S. 292.
83. Tyuzikov I.A., Kalinchenko S.Yu., Martov A.G. Diagnosticheskoe i prognosticheskoe znachenie neiropatii v protokole andrologicheskogo obsledovaniya. Materialy I Kongressa urologov Sibiri. Kemerovo, 2012. S. 325–8.
84. Morgante G., Tosti C., Orvieto R. et al. Metformin improves semen characteristics of oligo-teratoasthenozoospermic men with metabolic syndrome. Fertil Steril 2011;95(6):2150–2.
85. Tyuzikov I.A. Insulinorezistentnost' i muzhskoe besplodie: diagnostika i vozmozhnosti medikamentoznoi korrektsii. Materialy Vserossiiskoi nauchno-prakticheskoi konferentsii s mezhdunarodnym uchastiem «Ratsional'naya farmakoterapiya v urologii-2011». M., 2011. S. 148–9.
86. Tyuzikov I.A. Idiopaticheskoe muzhskoe besplodie: est' li «svet v kontse tunnelya» sovremennoi standartnoi diagnostiki? Materialy Regional'noi nauchnoi konferentsii «Muzhskoe zdorov'e v Sibiri». Tomsk, 2011. S. 100–3.
