Serum sex hormone-binding globulin and testosterone in relation to cardiovascular disease risk factors in young men: A population-based study

European Journal of Endocrinology

Volumn 170, Issue 6, 2014, Pages 863-872

  Canoy, D ^a   Barber, T M ^b   Pouta, A ^b   Hartikainen, A L ^d   McCarthy, M I ^a,e   Franks, S ^f   Jarvelin M R ^c,d,f,g   Tapanainen, J S ^d,h   Ruokonen, A ^d,g   Huhtaniemi, I T ^f   Martikainen, H ^d  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b UNIVERSITY OF WARWICK   (United Kingdom)

^c NATIONAL PUBLIC HEALTH INSTITUTE   (Finland)

^d OULU UNIVERSITY HOSPITAL   (Finland)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f IMPERIAL COLLEGE LONDON   (United Kingdom)

^g UNIVERSITY OF OULU   (Finland)

^h HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

C REACTIVE PROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; SEX HORMONE BINDING GLOBULIN; TESTOSTERONE; TRIACYLGLYCEROL;

ANTHROPOMETRY; ARTICLE; BLOOD PRESSURE MEASUREMENT; BLOOD SAMPLING; BODY MASS; CARDIOVASCULAR DISEASE; CONTROLLED STUDY; CROSS-SECTIONAL STUDY; DIASTOLIC BLOOD PRESSURE; DISEASE ASSOCIATION; EDUCATION; FINLAND; HUMAN; LIPID ANALYSIS; MALE; METABOLIC SYNDROME X; OBESITY; OBSERVATIONAL STUDY; PHYSICAL ACTIVITY; POPULATION RESEARCH; PRIORITY JOURNAL; RISK FACTOR; SMOKING; SYSTOLIC BLOOD PRESSURE; WAIST CIRCUMFERENCE;

ADULT; CARDIOVASCULAR DISEASES; COHORT STUDIES; FINLAND; HUMANS; MALE; METABOLIC SYNDROME X; RISK FACTORS; SEX HORMONE-BINDING GLOBULIN; TESTOSTERONE;

EID: 84902578977     PISSN: 08044643     EISSN: 1479683X     Source Type: Journal    
DOI: 10.1530/EJE-13-1046     Document Type: Article

References (59)

1. Pearlman WH & Crepy O. Steroid-protein interaction with particular reference to testosterone binding by human serum. Journal of Biological Chemistry 1967 242 182-189.
2. Kahn SM, Hryb DJ, Nakhla AM, Romas NA & Rosner W. Sex hormone-binding globulin is synthesized in target cells. Journal of Endocrinology 2002 175 113-120. (doi:10.1677/joe.0.1750113)
3. Rosner W. Plasma steroid-binding proteins. Endocrinology and Metabolism Clinics of North America 1991 20 697-720.
4. Rajala UM, Keinanen-Kiukaanniemi SM, Hirsso PK, Jokelainen JJ, Laakso MA, Hiltunen LA, Ruokonen AO, Harkonen PK & Timonen MJ. Associations of total testosterone and sex hormone-binding globulin levels with insulin sensitivity in middle-aged Finnish men. Diabetes Care 2007 30 e13. (doi:10.2337/dc06-1979)
5. Rosner W, Hryb DJ, Khan MS, Nakhla AM & Romas NA. Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane. Journal of Steroid Biochemistry and Molecular Biology 1999 69 481-485. (doi:10.1016/S0960-0760(99)00070-9)
6. Rosner W, Hryb DJ, Khan MS, Nakhla AM & Romas NA. Androgen and estrogen signaling at the cell membrane via G-proteins and cyclic adenosine monophosphate. Steroids 1999 64 100-106. (doi:10.1016/S0039-128X(98)00108-1)
7. Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ & McKinlay JB. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. Journal of Clinical Endocrinology and Metabolism 2006 91 843-850. (doi:10.1210/jc.2005-1326)
8. Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R & Salonen JT. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 2004 27 1036-1041. (doi:10.2337/diacare.27.5.1036)
9. Ding EL, Song Y, Malik VS & Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. Journal of the American Medical Association 2006 295 1288-1299. (doi:10.1001/jama.295.11.1288)
10. Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N, Buring JE, Gaziano JM & Liu S. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. New England Journal of Medicine 2009 361 1152-1163. (doi:10.1056/NEJMoa0804381)
11. Vikan T, Schirmer H, Njolstad I & Svartberg J. Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. European Journal of Endocrinology 2010 162 747-754. (doi:10.1530/EJE-09-0943)
12. Haring R, Volzke H, Spielhagen C, Nauck M & Wallaschofski H. The role of sex hormone-binding globulin and testosterone in the risk of incident metabolic syndrome. European Journal of Preventive Cardiology 2012 20 1061-1068. (doi:10.1177/2047487312452965)
13. Bhasin S, Jasjua GK, Pencina M, D'Agostino R Sr, Coviello AD, Vasan RS & Travison TG. Sex hormone-binding globulin, but not testosterone, is associated prospectively and independently with incident metabolic syndrome in men: the framingham heart study. Diabetes Care 2011 34 2464-2470. (doi:10.2337/dc11-0888)
14. Li C, Ford ES, Li B, Giles WH & Liu S. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insulin resistance in men. Diabetes Care 2010 33 1618-1624. (doi:10.2337/dc09-1788)
15. Hong D, Kim YS, Son ES, Kim KN, Kim BT, Lee DJ & Kim KM. Total testosterone and sex hormone-binding globulin are associated with metabolic syndrome independent of age and body mass index in Korean men. Maturitas 2013 74 148-153. (doi:10.1016/j.maturitas.2012.10.016)
16. Pugeat M, Moulin P, Cousin P, Fimbel S, Nicolas MH, Crave JC & Lejeune H. Interrelations between sex hormone-binding globulin (SHBG), plasma lipoproteins and cardiovascular risk. Journal of Steroid Biochemistry and Molecular Biology 1995 53 567-572. (doi:10.1016/0960-0760(95)00102-6)
17. Gyllenborg J, Rasmussen SL, Borch-Johnsen K, Heitmann BL, Skakkebaek NE & Juul A. Cardiovascular risk factors in men: the role of gonadal steroids and sex hormone-binding globulin. Metabolism: Clinical and Experimental 2001 50 882-888. (doi:10.1053/meta.2001.24916)
18. Bataille V, Perret B, Evans A, Amouyel P, Arveiler D, Ducimetiere P, Bard JM & Ferrieres J. Sex hormone-binding globulin is a major determinant of the lipid profile: the PRIME study. Atherosclerosis 2005 179 369-373. (doi:10.1016/j.atherosclerosis.2004.10.029)
19. Haffner SM & Valdez RA. Endogenous sex hormones: impact on lipids, lipoproteins, and insulin. American Journal of Medicine 1995 98 40S-47S. (doi:10.1016/S0002-9343(99)80058-8)
20. Haffner SM, Newcomb PA, Marcus PM, Klein BE & Klein R. Relation of sex hormones and dehydroepiandrosterone sulfate (DHEA-SO4) to cardiovascular risk factors in postmenopausal women. American Journal of Epidemiology 1995 142 925-934.
21. Birkeland KI, Hanssen KF, Torjesen PA & Vaaler S. Level of sex hormone-binding globulin is positively correlated with insulin sensitivity in men with type 2 diabetes. Journal of Clinical Endocrinology and Metabolism 1993 76 275-278.
22. Nestler JE & Strauss JF. Insulin as an effector of human ovarian and adrenal steroid metabolism. Endocrinology and Metabolism Clinics of North America 1991 20 807-823.
23. Reaven GM & Laws A. Insulin resistance, compensatory hyperinsulinaemia, and coronary heart disease. Diabetologia 1994 37 948-952. (doi:10.1007/BF00400953)
24. Xun P, Wu Y, He Q & He K. Fasting insulin concentrations and incidence of hypertension, stroke, and coronary heart disease: a meta-analysis of prospective cohort studies. American Journal of Clinical Nutrition 2013 98 1543-1554. (doi:10.3945/ajcn.113.065565)
25. Plymate SR, Leonard JM, Paulsen CA, Fariss BL & Karpas AE. Sex hormone-binding globulin changes with androgen replacement. Journal of Clinical Endocrinology and Metabolism 1983 57 645-648. (doi:10.1210/jcem-57-3-645)
26. Longcope C, Goldfield SR, Brambilla DJ & McKinlay J. Androgens, estrogens, and sex hormone-binding globulin in middle-aged men. Journal of Clinical Endocrinology and Metabolism 1990 71 1442-1446. (doi:10.1210/jcem-71-6- 1442)
27. Yeap BB. Androgens and cardiovascular disease. Current Opinion in Endocrinology, Diabetes, and Obesity 2010 17 269-276. (doi:10.1097/MED. 0b013e3283383031)
28. Chubb SA, Hyde Z, Almeida OP, Flicker L, Norman PE, Jamrozik K, Hankey GJ & Yeap BB. Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study. European Journal of Endocrinology 2008 158 785-792. (doi:10.1530/EJE-07-0893)
29. Muller M, van den Beld AW, Bots ML, Grobbee DE, Lamberts SW & van der Schouw YT. Endogenous sex hormones and progression of carotid atherosclerosis in elderly men. Circulation 2004 109 2074-2079. (doi:10.1161/01.CIR.0000125854. 51637.06)
30. Rantakallio P. The longitudinal study of the northern Finland birth cohort of 1966. Paediatric and Perinatal Epidemiology 1988 2 59-88. (doi:10.1111/j.1365-3016.1988.tb00180.x)
31. Vartiainen E, Jousilahti P, Alfthan G, Sundvall J, Pietinen P & Puska P. Cardiovascular risk factor changes in Finland, 1972-1997. International Journal of Epidemiology 2000 29 49-56. (doi:10.1093/ije/29.1.49)
32. Vermeulen A, Verdonck L & Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. Journal of Clinical Endocrinology and Metabolism 1999 84 3666-3672. (doi:10.1210/jcem.84.10.6079)
33. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM & Smith SC. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009 120 1640-1645. (doi:10.1161/CIRCULATIONAHA.109.192644)
34. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF & Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985 28 412-419. (doi:10.1007/BF00280883)
35. Firtser S, Juonala M, Magnussen CG, Jula A, Loo BM, Marniemi J, Viikari JS, Toppari J, Perheentupa A, Hutri-Kahonen N et al. Relation of total and free testosterone and sex hormone-binding globulin with cardiovascular risk factors in men aged 24-45 years. The Cardiovascular Risk in Young Finns Study. Atherosclerosis 2012 222 257-262. (doi:10.1016/j.atherosclerosis.2012.02.020)
36. Daka B, Rosen T, Jansson PA, Larsson CA, Rastam L & Lindblad U. Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population. BMC Cardiovascular Disorders 2013 13 30. (doi:10.1186/1471-2261-13-30)
37. Kweon SS, Shin MH, Nam HS, Jeong SK, Park KS, Choi JS & Lee YH. Sex differences in the associations of testosterone and sex hormone-binding globulin with metabolic syndrome in middle-aged and elderly Koreans: the Namwon study. Circulation Journal 2013 77 734-740. (doi:10.1253/circj.CJ-12-0613)
38. Matsumoto AM & Bremner WJ. Serum testosterone assays - accuracy matters. Journal of Clinical Endocrinology and Metabolism 2004 89 520-524. (doi:10.1210/jc.2003-032175)
39. Sartorius G, Ly LP, Sikaris K, McLachlan R & Handelsman DJ. Predictive accuracy and sources of variability in calculated free testosterone estimates. Annals of Clinical Biochemistry 2009 46 137-143. (doi:10.1258/acb. 2008.008171)
40. Coviello AD, Haring R, Wellons M, Vaidya D, Lehtimaki T, Keildson S, Lunetta KL, He C, Fornage M, Lagou V et al. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation. PLoS Genetics 2012 8 e1002805. (doi:10.1371/journal.pgen.1002805)
41. Wu FC & von Eckardstein A. Androgens and coronary artery disease. Endocrine Reviews 2003 24 183-217. (doi:10.1210/er.2001-0025)
42. Sorva R, Kuusi T, Dunkel L & Taskinen MR. Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes. Journal of Clinical Endocrinology and Metabolism 1988 66 408-413. (doi:10.1210/jcem-66- 2-408)
43. Desmeules A, Couillard C, Tchernof A, Bergeron J, Rankinen T, Leon AS, Rao DC, Skinner JS, Wilmore JH, Despres JP et al. Post-heparin lipolytic enzyme activities, sex hormones and sex hormone-binding globulin (SHBG) in men and women: the HERITAGE Family Study. Atherosclerosis 2003 171 343-350. (doi:10.1016/j.atherosclerosis.2003.08.018)
44. Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS & Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. Journal of Clinical Endocrinology and Metabolism 2004 89 3313-3318. (doi:10.1210/jc.2003-031069)
45. Kienitz T & Quinkler M. Testosterone and blood pressure regulation. Kidney & Blood Pressure Research 2008 31 71-79. (doi:10.1159/000119417)
46. Malkin CJ, Pugh PJ, Jones RD, Jones TH & Channer KS. Testosterone as a protective factor against atherosclerosis - immunomodulation and influence upon plaque development and stability. Journal of Endocrinology 2003 178 373-380. (doi:10.1677/joe.0.1780373)
47. Pugh PJ, Channer KS, Parry H, Downes T & Jone TH. Bio-available testosterone levels fall acutely following myocardial infarction in men: association with fibrinolytic factors. Endocrine Research 2002 28 161-173. (doi:10.1081/ERC-120015055)
48. Ruige JB, Mahmoud AM, De Bacquer D & Kaufman JM. Endogenous testosterone and cardiovascular disease in healthy men: a meta-analysis. Heart 2011 97 870-875. (doi:10.1136/hrt.2010.210757)
49. Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, Mellstrom D & Tivesten A. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. Journal of the American College of Cardiology 2011 58 1674-1681. (doi:10.1016/j.jacc.2011.07.019)
50. Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A et al. Adverse events associated with testosterone administration. New England Journal of Medicine 2010 363 109-122. (doi:10.1056/NEJMoa1000485)
51. Haring R, Teumer A, Volker U, Dorr M, Nauck M, Biffar R, Volzke H, Baumeister SE & Wallaschofski H. Mendelian randomization suggests non-causal associations of testosterone with cardiometabolic risk factors and mortality. Andrology 2013 1 17-23. (doi:10.1111/j.2047-2927.2012.00002.x)
52. Tajar A, Forti G, O'Neill TW, Lee DM, Silman AJ, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. Journal of Clinical Endocrinology and Metabolism 2010 95 1810-1818. (doi:10.1210/jc.2009-1796)
53. Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H, Dalrymple SA, Murray R & Manolagas SC. Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens. The role of the androgen receptor. Journal of Clinical Investigation 1995 95 2886-2895. (doi:10.1172/JCI117995)
54. Ohlsson C, Wallaschofski H, Lunetta KL, Stolk L, Perry JR, Koster A, Petersen AK, Eriksson J, Lehtimaki T, Huhtaniemi IT et al. Genetic determinants of serum testosterone concentrations in men. PLoS Genetics 2011 7 e1002313. (doi:10.1371/journal.pgen.1002313)
55. Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ & McKinlay JB. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. Journal of Clinical Endocrinology and Metabolism 2002 87 589-598. (doi:10.1210/jcem.87.2.8201)
56. Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K & Flicker L. In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study. European Journal of Endocrinology 2007 156 585-594. (doi:10.1530/EJE-06-0714)
57. Vermeulen A, Kaufman JM & Giagulli VA. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. Journal of Clinical Endocrinology and Metabolism 1996 81 1821-1826. (doi:10.1210/jcem.81.5.8626841)
58. Assmann G, Cullen P, Jossa F, Lewis B & Mancini M. Coronary heart disease: reducing the risk: the scientific background to primary and secondary prevention of coronary heart disease. A worldwide view. International Task force for the Prevention of Coronary Heart disease. Arteriosclerosis, Thrombosis, and Vascular Biology 1999 19 1819-1824. (doi:10.1161/01.ATV.19.8.1819)
59. Lawlor DA, Harbord RM, Sterne JA, Timpson N & Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Statistics in Medicine 2008 27 1133-1163. (doi:10.1002/sim. 3034)