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DOI: 10.1055/s-0035-1564070
The Effect of Metformin and Metformin-Testosterone Combination on Cardiometabolic Risk Factors in Men with Late-onset Hypogonadism and Impaired Glucose Tolerance
Autoren
Publikationsverlauf
received 15. April 2015
first decision 27. Juli 2015
accepted 20. August 2015
Publikationsdatum:
24. November 2015 (online)
Abstract
No previous study has investigated the effect of metformin, administered alone or together with testosterone, on cardiometabolic risk factors in men with hypogonadism. The study included 30 men with late-onset hypogonadism (LOH) and impaired glucose tolerance (IGT) who had been complying with lifestyle intervention. After 12 weeks of metformin treatment (1.7 g daily), the participants were allocated to one of 2 groups treated for the following 12 weeks with oral testosterone undecanoate (120 mg daily, n=15) or not receiving androgen therapy (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 and 24 weeks of therapy with the final dose of metformin. Patients with LOH and IGT had higher levels of hsCRP, homocysteine and fibrinogen than subjects with only LOH (n=12) or only IGT (n=15). Metformin administered alone improved insulin sensitivity, as well as reduced 2-h postchallenge plasma glucose and triglycerides. Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone. The effect of this combination therapy on testosterone, insulin sensitivity, hsCRP, homocysteine and fibrinogen was stronger than that of metformin alone. The obtained results indicate that IGT men with LOH receiving metformin may gain extra benefits if they are concomitantly treated with oral testosterone.
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References
- 1 Rato L, Alves MG, Duarte AI et al. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells. Int J Biochem Cell Biol 2015; pii: S1357-2725(15)00178-8
- 2 Costanzo PR, Suárez SM, Scaglia HE et al. Evaluation of the hypothalamic-pituitary-gonadal axis in eugonadal men with type 2 diabetes mellitus. Andrology 2014; 2: 117-124
- 3 Corona G, Monami M, Rastrelli G et al. Type 2 diabetes mellitus and testosterone: a meta-analysis study. Int J Androl 2011; 34: 528-540
- 4 Rabijewski M, Papierska L, Piątkiewicz P. Late-onset hypogonadism among old and middle-aged males with prediabetes in Polish population. Aging Male 2015; 18: 16-21
- 5 Casulari LA, Caldas AD, Domingues Casulari Motta L et al. Effects of metformin and short-term lifestyle modification on the improvement of male hypogonadism associated with metabolic syndrome. Minerva Endocrinol 2010; 35: 145-151
- 6 Ozata M, Oktenli C, Bingol N et al. The effects of metformin and diet on plasma testosterone and leptin levels in obese men. Obes Res 2001; 9: 662-667
- 7 Miles JM, Rule AD, Borlaug BA. Use of metformin in diseases of aging. Curr Diab Rep 2014; 14: 490
- 8 Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab 2013; 27: 557-579
- 9 Yeap BB. Androgens and cardiovascular disease. Curr Opin Endocrinol Diabetes Obes 2010; 17: 269-276
- 10 Basaria S. Reproductive aging in men. Endocrinol Metab Clin North Am 2013; 42: 255-270
- 11 Huhtaniemi I. Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment. Asian J Androl 2014; 16: 192-202
- 12 Feldman HA, Longcope C, Derby CA et al. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 2002; 87: 589-598
- 13 Nieschlag E, Swerdloff R, Behre HM et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male 2005; 8: 56-58
- 14 Burch JB, Augustine AD, Frieden LA et al. Advances in geroscience: impact on healthspan and chronic disease. J Gerontol A Biol Sci Med Sci 2014; 69 (Suppl. 01) S1-S3
- 15 Kalyani RR, Egan JM. Diabetes and altered glucose metabolism with aging. Endocrinol Metab Clin North Am 2013; 42: 333-347
- 16 Ridker PM. Inflammatory biomarkers and risks of myocardial infarction, stroke, diabetes, and total mortality: implications for longevity. Nutr Rev 2007; 65 (12 Pt 2) S253-S259
- 17 Kinlay S, Egido J. Inflammatory biomarkers in stable atherosclerosis. Am J Cardiol 2006; 98: 2P-8P
- 18 Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med 2008; 359: 1811-1821
- 19 McCully KS. Homocysteine, vitamins, and vascular disease prevention. Am J Clin Nutr 2007; 86: 1563S-1568S
- 20 Krysiak R, Okopien B, Herman Z. Effects of HMG-CoA reductase inhibitors on coagulation and fibrinolysis processes. Drugs 2003; 63: 1821-1885
- 21 Diabetes Prevention Program Research Group . Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403
- 22 Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male 2003; 6: 1-7
- 23 Krysiak R, Gilowski W, Okopien B. The effect of testosterone and fenofibrate, administered alone or in combination, on cardiometabolic risk factors in men with late-onset hypogonadism and atherogenic dyslipidemia. Cardiovasc Ther 2015;
- 24 Krentz AJ. UKPDS and beyond: into the next millennium. United Kingdom Prospective Diabetes Study. Diabetes Obes Metab 1999; 1: 13-22
- 25 Pruski M, Krysiak R, Okopien B. Pleiotropic action of short-term metformin and fenofibrate treatment, combined with lifestyle intervention, in type 2 diabetic patients with mixed dyslipidemia. Diabetes Care 2009; 32: 1421-1424
- 26 Krysiak R, Gdula-Dymek A, Okopien B. Effect of simvastatin and fenofibrate on cytokine release and systemic inflammation in type 2 diabetes mellitus with mixed dyslipidemia. Am J Cardiol 2011; 107: 1010-1018
- 27 Natarajan P, Ray KK, Cannon CP. High-density lipoprotein and coronary heart disease: current and future therapies. J Am Coll Cardiol 2010; 55: 1283-1299
- 28 Wittert GA, Chapman IM, Haren MT et al. Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. J Gerontol A Biol Sci Med Sci 2003; 58: 618-625
- 29 Jockenhövel F, Bullmann C, Schubert M et al. Influence of various modes of androgen substitution on serum lipids and lipoproteins in hypogonadal men. Metabolism 1999; 48: 590-596
- 30 Webb CM, Elkington AG, Kraidly MM et al. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease. Am J Cardiol 2008; 101: 618-624
- 31 Petersen JL, McGuire DK. Impaired glucose tolerance and impaired fasting glucose - a review of diagnosis, clinical implications and management. Diab Vasc Dis Res 2005; 2: 9-15
- 32 Nelson RH. Hyperlipidemia as a risk factor for cardiovascular disease. Prim Care 2013; 40: 195-211
- 33 Ginsberg HN, Maccallum PR. The obesity, metabolic syndrome, and type 2 diabetes mellitus pandemic: II. Therapeutic management of atherogenic dyslipidemia. J Clin Hypertens (Greenwich) 2009; 11: 520-527
- 34 Li SN, Wang X, Zeng QT et al. Metformin inhibits nuclear factor kappaB activation and decreases serum high-sensitivity C-reactive protein level in experimental atherogenesis of rabbits. Heart Vessels 2009; 24: 446-453
- 35 Li S, Guo Y, Zhu P et al. Role of Ox-LDL/LOX-1/NF-κB signaling pathway in regulation of atherosclerotic plaque growth by testosterone in male rabbits. Vascul Pharmacol 2013; 59: 131-137
- 36 Kelly DM, Jones TH. Testosterone: a vascular hormone in health and disease. J Endocrinol 2013; 217: R47-R71
- 37 Mitsuhashi K, Senmaru T, Fukuda T et al. Testosterone stimulates glucose uptake and GLUT4 translocation through LKB1/AMPK signaling in 3T3-L1 adipocytes. Endocrine 2015;
- 38 Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights?. Diabetologia 2013; 56: 1898-1906
