Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population

BMC Cardiovascular Disorders

Ulf Lindblad³  Lennart Råstam¹  Charlotte A Larsson¹  Per Anders Jansson²  Thord Rosen⁴  Bledar Daka³ 

[1] Department of Clinical Sciences, Malmö, Social Medicine and Global Health, CRC 28-12, Lund University, Jan Waldenströms gata 35, Malmö 205 02, Sweden;Department of Internal Medicine, University of Gothenburg, PO Box 454, Gothenburg SE-405 30, Sweden;Department of Primary Health Care, Institute of Medicine, Gothenburg, Sweden;Department of Endocrinology, Gothenburg, Sweden

关键词: BMI;    Hypertension;    Gender;    Testosterone;    Sex hormone binding globulin (SHBG);   

Others  :  857728
DOI  :  10.1186/1471-2261-13-30

 received in 2012-09-19, accepted in 2013-03-17,  发布年份 2013

【 摘 要 】

Background

The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population.

Methods

The study is based on a random sample of a Swedish population of men and women aged 30–74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7.

Results

In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: β=−0.143 p<0.001) and systolic blood pressure (systolic blood pressure β=−0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: β=−0.113 p<0.001; systolic blood pressure β=−0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=−0.024 p<0.001) and women (B=−0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=−0.014, p=0.008).

Conclusion

In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure.

【 授权许可】

   
2013 Daka et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Dandona P, Dhindsa S, Chaudhuri A, Bhatia V, Topiwala S: Hypogonadotrophic hypogonadism in type 2 diabetes. Aging Male 2008, 11(3):107-117.
• [2]Haffner SM: Sex hormone-binding protein, hyperinsulinemia, insulin resistance and noninsulin-dependent diabetes. Horm Res 1996, 45(3–5):233-237.
• [3]Oh JY, Barrett-Connor E, Wedick NM, Wingard DL: Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diabetes Care 2002, 25(1):55-60.
• [4]Haffner SM: Sex hormones, obesity, fat distribution, type 2 diabetes and insulin resistance: epidemiological and clinical correlation. Int J Obes Relat Metab Disord 2000, 24(Suppl 2):S56-58.
• [5]Khaw KT, Barrett-Connor E: Blood pressure and endogenous testosterone in men: an inverse relationship. J Hypertens 1988, 6(4):329-332.
• [6]Kienitz T, Quinkler M: Testosterone and blood pressure regulation. Kidney Blood Press Res 2008, 31(2):71-79.
• [7]Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P: Testosterone relaxes rabbit coronary arteries and aorta. Circulation 1995, 91(4):1154-1160.
• [8]Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P: Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 1999, 100(16):1690-1696.
• [9]Barrett-Connor E: Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann Intern Med 1992, 117(10):807-811.
• [10]Barrett-Connor E, Khaw KT: Endogenous sex hormones and cardiovascular disease in men. A prospective population-based study. Circulation 1988, 78(3):539-545.
• [11]Barud W, Palusinski R, Beltowski J, Wojcicka G: Inverse relationship between total testosterone and anti-oxidized low density lipoprotein antibody levels in ageing males. Atherosclerosis 2002, 164(2):283-288.
• [12]Kapoor D, Clarke S, Stanworth R, Channer KS, Jones TH: 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.
• [13]Simon D, Charles MA, Nahoul K, Orssaud G, Kremski J, Hully V, Joubert E, Papoz L, Eschwege E: Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: The Telecom Study. J Clin Endocrinol Metab 1997, 82(2):682-685.
• [14]Guler N, Batyraliev T, Dulger H, Ozkara C, Tuncer M, Aslan S, Okut H, Agirbasli M: The effects of short term (3 weeks) testosterone treatment on serum inflammatory markers in men undergoing coronary artery stenting. Int J Cardiol 2006, 109(3):339-343.
• [15]Musabak U, Bolu E, Ozata M, Oktenli C, Sengul A, Inal A, Yesilova Z, Kilciler G, Ozdemir IC, Kocar IH: Gonadotropin treatment restores in vitro interleukin-1beta and tumour necrosis factor-alpha production by stimulated peripheral blood mononuclear cells from patients with idiopathic hypogonadotropic hypogonadism. Clin Exp Immunol 2003, 132(2):265-270.
• [16]Sullivan ML, Martinez CM, Gennis P, Gallagher EJ: The cardiac toxicity of anabolic steroids. Prog Cardiovasc Dis 1998, 41(1):1-15.
• [17]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. N Engl J Med 2009, 361(12):1152-1163.
• [18]Lakshman KM, Bhasin S, Araujo AB: Sex hormone-binding globulin as an independent predictor of incident type 2 diabetes mellitus in men. J Gerontol A Biol Sci Med Sci 2010, 65(5):503-509.
• [19]Nyholm M, Gullberg B, Haglund B, Rastam L, Lindblad U: Higher education and more physical activity limit the development of obesity in a Swedish rural population. The Skaraborg Project. Int J Obes (Lond) 2008, 32(3):533-540.
• [20]Booth ML, Owen N, Bauman A, Gore CJ: Relationship between a 14-day recall measure of leisure-time physical activity and a submaximal test of physical work capacity in a population sample of Australian adults. Res Q Exerc Sport 1996, 67(2):221-227.
• [21]Goransson M, Hanson BS: How much can data on days with heavy drinking decrease the underestimation of true alcohol consumption? J Stud Alcohol 1994, 55(6):695-700.
• [22]Kamal S: Radioimmunoassay and related techniques. J Pak Med Assoc 1993, 43(11):224-225.
• [23]Morris PD, Malkin CJ, Channer KS, Jones TH: A mathematical comparison of techniques to predict biologically available testosterone in a cohort of 1072 men. Eur J Endocrinol 2004, 151(2):241-249.
• [24]Alberti KG, Zimmet PZ: Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998, 15(7):539-553.
• [25]World Health Organization and International Society of Hypertension: Guidelines for the Management of Hypertension. J Hypertens 1999, 17:151-183.
• [26]Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985, 28(7):412-419.
• [27]Svartberg J, von Muhlen D, Schirmer H, Barrett-Connor E, Sundfjord J, Jorde R: Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromso Study. Eur J Endocrinol 2004, 150(1):65-71.
• [28]Wang L, Szklo M, Folsom AR, Cook NR, Gapstur SM, Ouyang P: Endogenous sex hormones, blood pressure change, and risk of hypertension in postmenopausal women: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis 2012, 224(1):228-234.
• [29]Krupenko SA, Krupenko NI, Danzo BJ: Interaction of sex hormone-binding globulin with plasma membranes from the rat epididymis and other tissues. J Steroid Biochem Mol Biol 1994, 51(1–2):115-124.
• [30]Phillips GB, Jing TY, Laragh JH, Sealey JE: Serum sex hormone levels and renin-sodium profile in men with hypertension. Am J Hypertens 1995, 8(6):626-629.
• [31]Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR: 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):724-731.
• [32]Maggio M, Lauretani F, Basaria S, Ceda GP, Bandinelli S, Metter EJ, Bos AJ, Ruggiero C, Ceresini G, Paolisso G: Sex hormone binding globulin levels across the adult lifespan in women–the role of body mass index and fasting insulin. J Endocrinol Invest 2008, 31(7):597-601.
• [33]de Ronde W, van der Schouw YT, Muller M, Grobbee DE, Gooren LJ, Pols HA, de Jong FH: Associations of sex-hormone-binding globulin (SHBG) with non-SHBG-bound levels of testosterone and estradiol in independently living men. J Clin Endocrinol Metab 2005, 90(1):157-162.
• [34]Jansen SC, Temme EH, Schouten EG: Lifetime estrogen exposure versus age at menopause as mortality predictor. Maturitas 2002, 43(2):105-112.
• [35]de Kleijn MJ, van der Schouw YT, Verbeek AL, Peeters PH, Banga JD, van der Graaf Y: Endogenous estrogen exposure and cardiovascular mortality risk in postmenopausal women. Am J Epidemiol 2002, 155(4):339-345.
• [36]Rosner W, Vesper H: Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab 2010, 95(10):4542-4548.
• [37]Plymate SR, Tenover JS, Bremner WJ: Circadian variation in testosterone, sex hormone-binding globulin, and calculated non-sex hormone-binding globulin bound testosterone in healthy young and elderly men. J Androl 1989, 10(5):366-371.