Testosterone undecanoate effects on cardiovascular risk factors in men with metabolic syndrome

Aim. To study testosterone undecanoate effects on some modifiable cardiovascular risk factors in men with metabolic syndrome (MS).
Material and methods. Androgen status screening (anthropometry, total and free testosterone level measurement) was performed in 35-75-year-old men with cardiovascular disease (CVD). In 50 MS patients, a double-blind, randomized, placebo-controlled trial of testosterone undecanoate was performed, focusing on hypogonadism clinics, erectile function (EF), quality of life (QoL), lipid profile (LP), inflammatory markers: C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6).
Results. In men with CVD, clinical and laboratory androgen deficiency was observed in 67,8%, more often in those with visceral obesity. By Week 30 of testosterone treatment, androgen deficiency became less manifested clinically; EF, QoL, and LP also improved. Baseline levels of inflammatory markers pointed to elevated CVD risk. Testosterone undecanoate therapy was associated with significant, 2-fold reduction in CRP concentration, and 1.2-fold decrease in TNF-alpha and IL-6 levels.
Conclusion. In men with CVD, hypogonadism was widely prevalent; testosterone level was age-independent in combined pathology. Testosterone level normalization facilitated improvements in LP and QoL. Testosterone undecanoate therapy was safe and well-tolerated.

1. Gruen G and Connor B-. A prospective study of sex hormonebinding globulin and fatal cardiovascular disease in Rancho Bernardo men and women. J Clin Endocrinol Metab 1996; 81: 2999–3003.

2. Cesari M, Penninx BWJH, Newman AB, et al. Inflammatory Markers and Onset of Cardiovascular Events Results From the Health ABC Study. Circulation 2003; 108 (19): 2317–22.

3. Sullivan JM. Estrogens, menopause, and coronary artery disease. Cardiol Clin 1996; 14(1): 105–16.

4. Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb 1994; 14(5): 701–5.

5. English KM, Steeds RP, et al. Low dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina. Circulation 2000; 102: 1906–11.

6. Верткин А.Л., Лоран О.Б., Тополянский А.В. и др. Эректильная дисфункция у кардиологических и терапевтических пациентов. РМЖ 2002; 10: 28–33.

7. Gray A, Feldman HA, McKinley JB, Longcope C. Age, disease and changing sex hormone levels in middle-aged men. Results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991; 72(5): 1016–25.

8. Simon D, Charles MA, Nahoul K, et al. Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: The Telecom Study. J Clin Endocrinol Metab 1997; 82(2): 682–5.

9. Chen RY, Wittert GA, Andrews GR. Relative androgen deficiency in relation to obesity and metabolic status in older men. Diabetes Obes Metab 2006; 8(4): 429–35.

10. Muller M, van den Beld AW, Bots ML, et al. Endogenous Sex Hormones and Progression of Carotid Atherosclerosis in Elderly Men. Circulation 2004; 109: 2074–9.

11. Vermeulen A, Kaufman JM. Aging of the hypothalamo-pituitarytesticular axis in men. Horm Res 1995; 43: 25–31.

12. Barud W, Palusinski R, Piotrowska-Swirszcz A, et al. Sex hormones, HDL cholesterol and other lipoproteins in older males. Pol Merkuriusz Lek 2005; 18(105): 295–7.

13. Bogdanski P, Kujawska-Luczak M, Lacki J, Pupek-Musialik D. Evaluation of selected interleukins, tumor necrosis factor, insulin and leptin in obese patients with hypertension. Pol Merkuriusz Lek 2003; 15(88): 347–9; discussion 349–51.

14. Bruun JM, Verdich C, Toubro S, et al. Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men. Eur J Endocrinol 2003; 148(5): 535–42.

15. Aronson D, Bartha P, Zinder O, et al. Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome. Int J Obes Relat Metab Disord 2004; 28(5): 674–9.

16. Florez H, Castillo-Florez S, Mendez A, et al. C-reactive protein is elevated in obese patients with the metabolic syndrome. Diabetes Res Clin Pract 2006; 71(1): 92–100.

17. Araneo BA, Dowell T, Diegel M, Daynes RA. Dihydrotestosterone exerts a depressive influence on the production of interleukin-4 (IL-4), IL-5, and gamma-interferon, but not IL-2 by activated murine T cells. Blood 1991; 78(3): 688–99.

18. Li ZG, Danis VA, Brooks PM. Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. Clin Exp Rheumatol 1993; 11(2): 157–62.

19. Chao TC, Van Alten PJ, Greager JA, Walter RJ. Steroid sex hormones regulate the release of tumor necrosis factor by macrophages. Cell Immunol 1995; 160(1): 43–9.

20. Dalal M, Kim S, Voskuhl RR. Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response. J Immunol 1997; 159(1): 3–6.

21. Gornstein RA, Lapp CA, Bustos-Valdes SM, Zamorano P. Androgens modulate interleukin-6 production by gingival fibroblasts in vitro. J Periodontol 1999; 70(6): 604–9.

22. Hatakeyama H, Nishizawa M, Nakagawa A, et al. Testosterone inhibits tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression in human aortic endothelial cells. FEBS Lett 2002; 530(1–3): 129–32.

23. Carson CC. Oral and injectable Medications for the Treatment of Erectile Dysfunction. Cur Urol Rep 2000; 1: 307–12.

24. Hutley L, Prins JB. Fat as an endocrine organ: relationship to the metabolic syndrome. Am J Med Sci 2005; 330(6): 280–9.

25. Malik S, Wong ND, Franklin S, et al. Cardiovascular disease in U.S. patients with metabolic syndrome, diabetes, and elevated C-reactive protein. Diabetes Care 2005; 28(7): 1833–4.

26. Gillum R, Mussolino M, Madans J. Body fat distribution, obesity, overweight and stroke incidence in women and men: the NHANES I Epidemic Follow-up Study. Int J Obes Relat Metab Disord 2001; 25: 628–38.