Test effects on the heart.

[Deacon]

Effects of Testosterone on Coronary Vasomotor Regulation in Men With Coronary Heart D

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Effects of Testosterone on Coronary Vasomotor Regulation in Men With Coronary Heart Disease
Carolyn M. Webb, PhD; John G. McNeill, DCRR; Christopher S. Hayward, MB, BS, FRACP; Dominique de Zeigler, MD; Peter Collins, MD, FRCP
From Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, and Royal Brompton Hospital, London, UK (C.M.W., J.G.M., C.S.H., P.C.), and Columbia Laboratories, Paris, France (D.d.Z).

Correspondence to Dr Peter Collins, Cardiac Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY, UK. E-mail peter.collins@ic.ac.uk

Background—The increased incidence of coronary artery disease in men compared with premenopausal women suggests a detrimental role of male hormones on the cardiovascular system. However, testosterone has direct relaxing effects on coronary arteries in animals, as shown both in vitro and in vivo. The effect of testosterone on the human coronary circulation remains unknown.

Methods and Results—We studied 13 men (aged 61±11 years) with coronary artery disease. They underwent measurement of coronary artery diameter and blood flow after a 3-minute intracoronary infusion of vehicle control (ethanol) followed by 2-minute intracoronary infusions of acetylcholine (10-7 to 10-5 mol/L) until peak velocity response. A dose-response curve to 3-minute infusions of testosterone (10-10 to 10-7 mol/L) was then determined, and the acetylcholine infusions were repeated. Finally, an intracoronary bolus of isosorbide dinitrate (1000 µg) was given. Coronary blood flow was calculated from measurements of blood flow velocity using intracoronary Doppler and coronary artery diameter using quantitative coronary angiography. Testosterone significantly increased coronary artery diameter compared with baseline (2.78±0.74 mm versus 2.86±0.72 mm [P=0.05], 2.87±0.71 mm [P=0.038], and 2.90±0.75 mm [P=0.005] for baseline versus testosterone 10-9 to 10-7 mol/L, respectively). A significant increase in coronary blood flow occurred at all concentrations of testosterone compared with baseline (geometric mean [95% CI]: 32 [25, 42] versus 36.3 [27, 48] {P=0.006}, 35.3 [26, 47] {P=0.029}, 36.8 [28, 49] {P=0.002}, and 37 [28, 48] {P=0.002} mL/min for baseline versus testosterone 10-10 to 10-7 mol/L, respectively). No differences existed in coronary diameter or blood flow responses to acetylcholine before versus after testosterone.

Conclusions—Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.
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[Mr.X]

Conclusions—Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.

something I'd like to research further

[mega12]

There are also some interesting studies on the thickening of the center wall of the heart, (not sure of all the medical terms)... which can lead to heart problems down the road. 100% of AAS users tested had the condition to some degree, however something like 60-70% of non-using PL and strength athaletes also had the condition. I thought it was interesting...
mega

[Hard Gainer]

Heart disease runs in my family (supposed to hit me hard, I shouldn't live past 40 or 50) so I've read up on this a little bit. When you do cardio, long use of the heart, the heart cavity itself increases in size. This allows more blood to fill and be pushed out of the heart with each contraction. When you lift, short bursts of energy, the heart walls thicken. With the heart walls thicker this creates a smaller area inside the heart itself. The heart is then not able to fill up with as much blood on each contraction. IE...less blood pushed out. When you use AS every muscle in your body increases in size. This holds true with the heart as well. The walls of your heart will thicken when you do a cycle. However, with that being said research has shown when the cycle is stopped, most of this will go away. Again, most of it, not all of it. Like mega said though, almost all lifters have this condition. The recommendation is that you do at least 30min of cardio 3 times a week, expecially when "on". This is so while your heart walls will thicken your heart cavity will expand as well, sort of a balancing effect.

[Janus]

Great read. Thanks...

[liftsiron]

Testosterone: a natural tonic for the failing heart?
P.J. Pugh, K.M. English, T.H. Jones1 and K.S. Channer
From the Department of Cardiology, Royal Hallamshire Hospital 1 Department of Human Metabolism and Clinical Biochemistry, University of Sheffield, Sheffield, UK

Introduction

Chronic congestive heart failure (CHF) remains a significant cause of mortality and morbidity in the UK, accounting for 5% of acute hospital admissions and 1% of the total NHS budget.1 Coronary artery disease (CAD) and hypertension are the most commonly associated conditions. The condition is characterized by left ventricular dysfunction, impaired vascular tone and skeletal muscle abnormalities, producing breathlessness and fatigue. Neuro-hormonal and cytokine activation are self-perpetuating maladaptive responses to the failing heart, which cause further deterioration in cardiac function and increased catabolism.

The mainstay of current therapy includes diuretics and neuro-hormonal manipulation; ACE inhibitors are well established as the most important intervention for improving prognosis, and angiotensin II receptor antagonists offer a good alternative.2 More recently, reduced mortality has been demonstrated from the use of both beta-blockers and the aldosterone receptor antagonist spironolactone.3,4 Vasodilators may also provide symptomatic and prognostic benefit. However, the only therapy offering long-term survival is cardiac transplantation, which remains limited by lack of donors and recipient suitability.

There remains, therefore, a need for therapies which alleviate the suffering associated with CHF, as well as reducing mortality. Potential strategies under evaluation include anti-cytokine therapy and inhibitors of neutral endopeptidases, which prevent breakdown of natriuretic peptides. Testosterone therapy has also been proposed as a useful add-on treatment for men with CHF, although there are currently no clinical data to support this.6 In this article, we review the cardiovascular and neuro-hormonal actions of testosterone, and discuss how androgen therapy may be of benefit to men with chronic heart failure.

Gonadal function in men with CHF

No studies have sought specifically to determine gonadal function in men with heart failure. However, several small studies suggest that these patients may have relatively low androgen levels. A study of 53 men with CHF found that dehydroepiandrosterone (DHEA) levels were significantly lower than in healthy controls.7 In 17 men with non-ischaemic cardiomyopathy, testosterone levels correlated with cardiac index, and five men with severe left ventricular dysfunction had markedly reduced plasma testosterone, which normalized 2 months after implantation of a ventricular assist device.8,9 In an animal model of heart failure, hamsters with cardiomyopathy were found to have very low testosterone levels.10

These findings are perhaps to be expected given the effect of chronic disease on gonadal function. However, there is also a link between hypotestosteronaemia and stable CAD. Epidemiological data suggest that men with ischaemic heart disease have low androgen levels, and men with proven coronary atheroma have lower testosterone levels than healthy controls.11,12 In animals, castration promotes atherosclerosis while androgen therapy retards it.13 Similarly, hypertensive men have relatively low androgen levels, which show an inverse correlation with blood pressure.11 Men with CHF, therefore, are likely to have low testosterone levels, potentially exacerbating the catabolic imbalance.

Effects on cardiovascular function

There are no clinical trial data concerning the effects of testosterone on left ventricular function. In rats, androgen therapy improves coronary blood flow and increases both fractional shortening and peak myocardial oxygen consumption, thereby improving cardiac function.14 Castration results in reduced ejection fraction and diastolic dysfunction, with alteration of the isoenzyme composition of the myosin heavy chain.14

Testosterone therapy has been used to treat men with angina; the beneficial effects on both ischaemia and exercise tolerance have been demonstrated in several studies (see Table 1).




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Table 1 Studies of testosterone therapy for men with angina




Numerous reports from animal studies have demonstrated the vasodilator properties of androgens in several vascular beds, both in vitro and in vivo (see Table 2). In humans, testosterone reduces blood pressure and enhances relaxation of brachial arteries; direct injection into coronary arteries produces dilatation and increased coronary blood flow.39–41 Low circulating levels of testosterone may therefore contribute to the generalized increase in vascular tone found in patients with CHF. A vasodilator effect could be important in relieving pulmonary congestion and improving peripheral perfusion. Androgen therapy could therefore also improve cardiac function by reducing pre-load and after-load and by increasing coronary blood flow.



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Table 2 Animal studies of effects of androgens on vascular tone






Skeletal muscle and strength

Fatigue and poor exercise tolerance are central features of the symptoms of heart failure, and may be out of proportion to the degree of left ventricular dysfunction. Patients with CHF suffer loss of skeletal muscle mass with reduced muscle strength and endurance. Muscle fibre type and mitochondrial structure are altered, with reduction in the enzymes of the Krebs cycle and oxidative chain.42 These features may arise from the catabolic effects of neuro-hormonal and cytokine activity. Also, endothelial function is impaired in CHF, resulting in reduced peripheral vasodilator capacity and muscle hypoperfusion.

Testosterone may counter these deleterious effects both by its vasodilator action and by promoting protein synthesis and blocking the catabolic action of glucocorticoids.6 The anabolic effects of androgens are well described in healthy men, producing skeletal muscle hypertrophy and increased muscle bulk and strength.43

There have been no studies of the effects of androgen therapy on strength and endurance in heart failure. However, several small studies have evaluated testosterone therapy in elderly men; these showed improvement in grip and leg strength as well as an increase in lean body mass.44–46

Testosterone deficiency is likely to contribute to the weakness and fatigue of CHF which constitute a major aspect of the morbidity. Androgen therapy could potentially improve patient well-being by combating this.

Neuro-hormonal activity

In recent years, advances in our understanding of the role hormones play in the progression, morbidity and mortality of CHF have directed modern therapy at reducing hormonal activity. Patients have varying degrees of hormonal activation which results in a catabolic/anabolic imbalance, ranging from a rise in the cortisol/DHEA ratio to elevation of circulating catecholamines, cortisol, aldosterone and plasma renin activity.7 Levels of anabolic factors, including testosterone and insulin-like growth factor-1 (IGF-1), are depressed, and insulin resistance may develop.47,48

Although the effects of androgens on hormonal activation in CHF have not been studied, it would seem logical to oppose excess catabolism with anabolism. Testosterone has been found to increase IGF-1 levels and reduce hyperinsulinaemia and insulin resistance.39,49 In addition, in animal experiments, the increased release of atrial natriuretic peptide (ANP) which results from cardiac overload is reduced by testosterone, an effect which may have positive prognostic implications.50

Cytokine activation

It is now recognized that cytokine activation is likely to play an important role in the progression of cardiac failure. The ‘cytokine hypothesis’ of heart failure is perhaps a natural progression of the neurohumoral theory and is based on the known actions of several cytokines.51 Circulating levels of tumour necrosis factor (TNF) and interleukin-6 (Il-6) are elevated in CHF and independently predict mortality.52 The levels correlate adversely with several prognostic markers, including NYHA class, exercise tolerance and myocardial oxygen consumption, as well as plasma levels of ANP, catecholamines, endothelin-1 and angiotensin II.52–54

TNF is produced mainly by macrophages, but also by the myocardium in CHF. It impairs synthesis and promotes catabolism of skeletal muscle, and reduces testosterone production. It causes endothelial dysfunction and impairs production of NO by endothelium.55 Administration causes left ventricular dysfunction and heart failure in humans; anti-TNF therapy may improve cardiac function.56,57 Cytokines therefore appear to mediate many of the pathophysiological processes of heart failure.

The immune-modulatory properties of androgens have been well described. In various disease models (though not in heart failure), androgens have been found to significantly suppress macrophage production of cytokines both in vitro and in vivo (see Table 3). In man, androgen levels correlate negatively with plasma cytokine levels and gonadotropin therapy suppresses the high level seen in hypogonadal men.72




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Table 3 Effects of androgens on cytokine activity




These findings suggest another important mechanism by which androgen therapy could improve outcome in men with CHF.

Conclusion

Patients with chronic heart failure suffer considerable morbidity as well as early mortality. They exhibit altered structure and function of cardiac and skeletal muscle and excessive activation of catabolic hormones and inflammatory cytokines. Men with CHF have relatively low androgen levels, which may contribute to the pathophysiological process. Androgen replacement therapy could potentially ameliorate symptoms by improving cardiac and vascular function and increasing strength and endurance. It may also redress the catabolic/anabolic imbalance of chronic CHF and suppress the cytokine activation which leads to progression of the disease. Clinical trials are needed to evaluate the effects of androgen therapy for chronic congestive heart failure.


Notes

Address correspondence to Dr K.S. Channer, Room 131, M Floor, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF. e-mail: kevin.channer@csuh.nhs.uk

References

1. Cowie MR. The epidemiology of heart failure—an epidemic in progress. In: Coats A, ed. Controversies in the management of heart failure. London, Churchill Livingstone, 1997:11–24.

2. Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, Konstam MA, Riegger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II. Lancet2000; 355:1582–7.[Medline]

3. The Cardiac Insufficiency Bisoprolol Study II (CIBIS II): a randomised trial. Lancet1999; 353:9–13.[Medline]

4. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomised aldactone evaluation study investigators. N Engl J Med1999; 341:709–17.[Abstract/Free Full Text]

5. Cohn JN, Archibald DG, Ziesche S, Franciosa JA, Harston WE, Tristani FE, Dunkman WB, Jacobs W, Francis GS, Flohr KH. Effect of vasodilator therapy on mortality in chronic congestive heart failure: results of a Veterans Administration Cooperative Study. N Engl J Med1986; 314:1547–52.[Abstract]

6. Shapiro J, Christiana J, Frishman WH. Testosterone and other anabolic steroids as cardiovascular drugs. Am J Ther1999; 6:167–74.[Medline]

7. Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, Poole-Wilson PA, Coats AJS. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation1997; 96:526–34.[Abstract/Free Full Text]

8. Tappler B, Katz M. Pituitary-gonadal dysfunction in low-output cardiac failure. Clin Endocrinol1979; 10:219–26.[Medline]

9. Noirhomme P, Jaquet L, Underwood M, El Khoury G, Goenen M, Dion R. The effect of chronic mechanical circulatory support on neuroendocrine activation in patients with end-stage heart failure. Eur J Cardiothorac Surg1999; 16:63–7.[Abstract/Free Full Text]

10. Otenweller JE, Tapp WN, Creighton D, Natelson BH. Aging, stress and chronic disease interact to suppress plasma testosterone in Syrian hamsters. J Gerontol1988; 43:M175–80.[Medline]

11. English KM, Steeds R, Jones TH, Channer KS. Testosterone and coronary heart disease: is there a link? Q J Med1997; 90:787–91.[Medline]

12. English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J2000; 21:890–4.[Medline]

13. Alexandersen P, Haarbo J, Byrjalsen I, Lawaetz H, Christiansen C. Natural androgens inhibit male atherosclerosis. A study in castrated, cholesterol-fed rabbits. Circ Res1999; 84:813–19.[Abstract/Free Full Text]

14. Scheuer J, Malhotra A, Schaible TF, Capasso J. Effects of gonadectomy and hormonal replacement on rat hearts. Circ Res1987; 61:12–19.[Abstract]

15. Hamm L. Testosterone propionate in the treatment of angina pectoris. J Clin Endocrinol1942; 2:325–8.

16. Walker TC. Use of testosterone propionate and estrogenic substance in treatment of essential hypertension, angina pectoris and peripheral vascular disease. J Clin Endocrinol1942; 2:560–8.

17. Levine SA, Likoff WB. The therapeutic value of testosterone propionate in angina pectoris. N Engl J Med1943; 229:770–2.

18. Sigler LH, Tulgan J. Treatment of angina pectoris by testosterone propionate. N Y State J Med1943; 43:1424–8.

19. Lesser MA. Testosterone propionate therapy in one hundred cases of angina pectoris. J Clin Endocrinol1946; 6:549–57.

20. Jaffe MD. Effect of testosterone cypionate on postexercise ST segment depression. Br Heart J1977; 39:1217–22.[Abstract]

21. Wu S-Z, Weng X-Z. Therapeutic effects of an androgenic preparation on myocardial ischemia and cardiac function in 62 elderly male coronary heart disease patients. Chin Med J1993; 106:415–18.[Medline]

22. Rosano GMC, Leonardo F, Pagnotta P, Pelliccia F, Panina G, Cerquetani E, Della Monica PL, Bonfigli B, Volpe M, Chierchia SL. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation1999; 99:1666–70.[Abstract/Free Full Text]

23. Webb CM, Adamson DL, De Zeigler D, Collins P. Effect of acute testosterone on myocardial ischaemia in men with coronary artery disease. Am J Cardiol1999; 83:437–9.[Medline]

24. English KM, Steeds RP, Jones TH, Diver MJ, Channer KS. Low dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina. Circulation2000: in press.

25. Greenberg S, George WR, Kadowitz PJ, Wilson WR. Androgen-induced enhancement of vascular reactivity. Can J Physiol Pharmacol1974; 52:14–22.[Medline]

26. Mosnarova A, Stecova A, Huzulakova I, Motesicka M. The influence of one month sex hormones administration on the isolated rabbit vessels reactivity. Acta Physiol Hung1994; 82:251–6.[Medline]

27. Schror K, Morinelli TA, Masuda A, Mathur R, Halushka PV, Matsuda K. Testosterone treatment enhances thromboxane A2 mimetic induced coronary artery vasoconstriction in guinea pigs. Eur J Clin Invest1994; 24:50–2.

28. Adams MR, Williams JK, Kaplan JR. Effects of androgens on coronary artery atherosclerosis and atherosclerosis related impairment of vascular responsiveness. Arterioscler Thromb Vasc Biol1995; 15:562–70.[Abstract/Free Full Text]

29. Farhat MY, Wolfe R, Vargas R, Foegh ML, Ramwell PW. Effect of testosterone treatment on vasoconstrictor response of left anterior descending artery in male and female pigs. J Cardiovasc Pharmacol1995; 25:495–500.[Medline]

30. Yue P, Chatterjee K, Beale C, Poole-Wilson PA, Collins P. Testosterone relaxes rabbit coronary arteries and aorta. Circulation1995; 91:1154–60.[Abstract/Free Full Text]

31. Perusquia M, Hernandez R, Morales MA, Campos MG, Villalon CM. Role of endothelium in the vasodilating effect of progestins and androgens on the rat thoracic aorta. Gen Pharmacol1996; 27:181–5.[Medline]

32. Costarella CE, Stallone JN, Rutecki GW, Whittier FC. Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Exp Ther1996; 277:34–9.[Abstract]

33. Chou TM, Sudhir K, Hutchison SJ, Ko E, Amidon TM, Collins P, Chatterjee K. Testosterone induces dilation of canine conductance and resistance arteries in vivo. Circulation1996; 94:2614–19.[Abstract/Free Full Text]

34. Hutchison SJ, Sudhir K, Chou TM, Sievers RE, Zhu BO, Sun YP, Deedwania PC, Glantz SA, Parmley WW, Chatterjee K. Testosterone worsens endothelial dysfunction associated with hypercholesterolaemia and environmental tobacco smoke exposure in male rabbit aorta. J Am Coll Cardiol1997; 29:800–7.[Medline]

35. Farrukh IS, Peng W, Orlinska U, Hoidal JR. Effect of dehydroepiandrosterone on hypoxic pulmonary vasoconstriction: a Ca2+ activated K+ channel opener. Am J Physiol1998;274:L186–95.[Abstract/Free Full Text]

36. Honda H, Unemoto T, Kogo H. Different mechanisms for testosterone-induced relaxation of aorta between normotensive and spontaneously hypertensive rats. Hypertension1999; 34:1232–6.[Abstract/Free Full Text]

37. Teoh H, Quan A, Leung SWS, Man RY. Different effects of 17beta-estradiol and testosterone on the contractile responses of porcine coronary arteries. Br J Pharmacol2000;129:1301–8.[Abstract/Free Full Text]

38. Crews JK, Khalil RA. Antagonistic effects of 17ß-estradiol, progesterone and testosterone on Ca2+ entry mechanisms of coronary vasoconstriction. Arterioscler Thromb Vasc Biol1999; 19:1034–40.[Abstract/Free Full Text]

39. Marin P, Holmang S, Jonsson L, Sjostrom L, Kvist H, Holm G, Lindstedt G, Bjorntorp P. The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes1992; 16:991–7.

40. Ong PJL, Patrizi G, Chong WCF, Webb CM, Hayward CS, Collins P. Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease. Am J Cardiol 2000, 85:269–72.

41. Webb CM, McNeill JG, Hayward CS, De Zeigler D, Collins P. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation1999; 100:1690–6.[Abstract/Free Full Text]

42. Drexler H, Riede U, Munzel T, Konig H, Funke E, Just H. Alterations of skeletal muscle in chronic heart failure. Circulation1992; 85:1751–9.[Abstract]

43. Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi R, Casaburi R. The effects of supraphysiological doses of testosterone on muscle size and strength in normal men. N Engl J Med1996; 335:1–7.[Abstract/Free Full Text]

44. Sih R, Morley JE, Kaiser FE, Perry HM, Pareick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomised controlled trial. J Clin Endocrinol1997; 82:1661–7.[Abstract/Free Full Text]

45. Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, Ferrando A. Testosterone administration to older men increases skeletal muscle strength and protein synthesis. Am J Physiol1995;269:E820–6.[Abstract/Free Full Text]

46. Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab1992; 75:1092–8.[Abstract]

47. Niebauer J, Pflaum C-D, Clark AL, Strasburger CJ, Hooper J, Poole-Wilson PA, Coats AJS, Anker SD. Deficient insulin-like growth factor 1 in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation. J Am Coll Cardiol1998; 32:393–7.[Medline]

48. Swan JW, Walton C, Godsland IF, Clark AL, Coats AJS, Oliver MF. Insulin resistance in chronic heart failure. Eur Heart J1994; 15:1528–32.[Medline]

49. Hobbs CJ, Plymate SR, Rosen CJ, Adler RA. Testosterone administration increases insulin-like growth factor-1 levels in normal men. J Clin Endocrinol Metab1993; 77:776–9.[Abstract]

50. Deng Y, Kaufman S. The influence of reproductive hormones on ANF release by rat atria. Life Sci1993; 53:689–96.[Medline]

51. Seta Y, Shan K, Bozkurt B, Oral H, Mann DL. Basic mechanisms in heart failure: the cytokine hypothesis. J Card Fail1996; 2:243–9.[Medline]

52. Tsutamoto T, Hisanaga T, Wada A, Maeda K, Ohnishi M, Fukai D, Mabuchi N, Sawaki M, Kinoshita M. Interleukin-6 spillover in the peripheral circulation increases with the severity of heart failure, and the high plasma level of interleukin-6 is an important prognostic predictor in patients with congestive heart failure. J Am Coll Cardiol1998; 31:391–8.[Medline]

53. Anker SD, Clark AL, Kemp M, Salsbury C, Teixera MM, Hellewell PG, Coats AJS. Tumour necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting. J Am Coll Cardiol1997; 30:997–1001.[Medline]

54. Torre-Amione G, Kapadia S, Benedict C, Oral H, Young JB, Mann DL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol1996; 27:1201–6.[Medline]

55. Yoshizumi M, Perrella MA, Burnett JCJ, Lee M-E. Tumor necrosis factor downregulates endothelial nitric oxide synthase mRNA by shortening its half-life. Circ Res1993; 73:205–9.[Abstract]

56. Hegewisch S, Weh H-J, Hossfeld DK. Tumour necrosis factor-induced cardiomyopathy. (Letter) Lancet1990;335:294–5.[Medline]

57. Deswal A, Bozkurt B, Seta Y, Parilti-Eiswirth S, Hayes FA, Blosch C, Mann DL. Safety and efficacy of a soluble P75 tumor necrosis factor receptor (Enbrel, etanercept) in patients with advanced heart failure. Circulation1999; 99:3224–6.[Abstract/Free Full Text]

58. Chao T-C, Van Alten PJ, Greager JA, Walter RJ. Steroid sex hormones regulate the release of tumor necrosis factor by macrophages. Cell Immunol1995; 160:43–9.[Medline]

59. D'Agostino P, Milano S, Barbera C, Di Bella G, La Rosa M, Ferlazzo V, Farruggio R, Miceli DM, Miele M, Castagnetta L, Cillari E. Sex hormones modulate inflammatory mediators produced by macrophages. Ann N Y Acad Sci1999; 876:426–9.[Free Full Text]

60. Kanda N, Tsuchida T, Tamaki K. Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells. Clin Exp Immunol1996; 106:410–15.[Medline]

61. Kanda N, Tsuchida T, Tamaki K. Testosterone suppresses anti-DNA antibody production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum1997; 40:1703–11.[Medline]

62. 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 Rheumatol1993; 11:157–62.[Medline]

63. Gornstein RA, Lapp CA, Bustos-Valdes SM, Zamorano P. Androgens modulate interleukin-6 production by gingival fibroblasts in vitro. J Periodontol1999; 70:604–9.[Medline]

64. Hofbauer LC, Ten RM, Khosla S. The anti-androgen hydroxyflutamide and androgens inhibit interleukin-6 production by an androgen-responsive human osteoblastic cell line. J Bone Miner Res1999; 14:1330–7.[Medline]

65. Araneo BA, Dowell T, Diegel M, Daynes RA. Dihydrotestosterone exerts a depressive influence on the production of interleukin-4 (Il-4), Il-5 and -interferon, but not Il-2 by activated murine T cells. Blood1991; 3:688–99.

66. 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 Immunol1997; 159:3–6.[Abstract]

67. Kimura M, Tanaka S-I, Yamada Y, Kiuchi Y, Yamakawa T, Sekihara H. Dehydroepiandrosterone decreases serum tumor necrosis factor- and restores insulin sensitivity: independent effect from secondary weight reduction in genetically obese Zucker fatty rats. Endocrinology1998; 139:3249–53.[Abstract/Free Full Text]

68. Ben-Nathan D, Padgett DA, Loria RM. Androstenediol and dehydroepiandrosterone protect mice against lethal bacterial infections and lipopolysaccharide toxicity. J Med Microbiol1999; 48:425–31.[Abstract]

69. Padgett DA, Loria RM. Endocrine regulation of murine macrophage function: effects of dehydroepiandrosterone, androstenediol, and androstenetriol. J Neuroimmunol1998; 84:61–8.[Medline]

70. Straub RH, Konecna L, Hrach S, Rothe G, Kreutz M, Scholmerich J, Falk W, Lang B. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (Il-6) and DHEA inhibits Il-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab1998; 83:2012–17.[Abstract/Free Full Text]

71. Spinedi E, Suescun MO, Hadid R, Daneva T, Gaillard RC. Effects of gonadectomy and sex hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism. Endocrinology1992; 131:2430–6.[Abstract]

72. Yesilova Z, Ozata M, Kocar IH, Turan M, Pekel A, Sengul A, Ozdemir IC. The effects of gonadotropin treatment on the immunological features of male patients with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab2000; 85:66–70.[Abstract/Free Full Text]

[liftsiron]

Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms.

English KM, Mandour O, Steeds RP, Diver MJ, Jones TH, Channer KS.

Department of Cardiology, Royal Hallamshire Hospital, Sheffield, U.K.

AIMS: High androgen levels are presumed by many to explain the male predisposition to coronary artery disease. However, natural androgens inhibit male atherosclerosis(1). Our aim was to determine whether levels of androgens differ between men with and without coronary artery disease. METHODS AND RESULTS: Ninety male subjects (60 with positive, and 30 with negative coronary angiograms) were recruited. Early morning, fasting blood samples were taken from each patient and free, total and bioavailable testosterone, sex hormone binding globulin, oestradiol, and lipids were measured. Bioavailable testosterone was assayed using a modified technique. Free androgen index was calculated. Men with coronary artery disease had significantly lower levels of free testosterone (mean (standard deviation)); 47.95 (13.77) vs 59.87 (26. 05) pmol. l(-1), P=0.027), bioavailable testosterone; 2.55 (0.77) vs 3.26 (1.18) nmol. l(-1), P=0.005 and free androgen index; 37.8 (10. 4) vs 48.47 (18.3), P=0.005, than controls. After controlling for differences in age and body mass index the differences in free androgen index and bioavailable testosterone remained statistically significant (P=0.008 and P=0.013, respectively). CONCLUSION: Men with coronary artery disease have significantly lower levels of androgens than normal controls, challenging the preconception that physiologically high levels of androgens in men account for their increased relative risk for coronary artery disease. Copyright 2000 The European Society of Cardiology.

PMID: 10806012 [PubMed - indexed for MEDLINE]

[liftsiron]

Origanlly posted by Severed Ties


The Positive Effects of Testosterone on the Heart
by Doug Kalman MS, RD




Steroids will cause your kidneys to implode, your heart to blow a ventricle, and your liver to squirt out of your arse, fly across the room, and knock the cat off the futon. We read it on the Internet and saw an after school special about it, so it must be true, right?

Actually, the more you learn about steroids, the more you come to realize that, like all drugs, there's a difference between their intelligent use and outright abuse. In this article, Doug Kalman takes a look at the effects of Testosterone on the heart. What he found may surprise you.


Over the years we've all heard the repeated mantra that anabolic steroids are bad for the heart. Some physicians will tell you that gear raises your risk of heart disease by lowering your good cholesterol (HDL) and raising your bad cholesterol (LDL). In fact, as some docs will tell you, steroids are known to even induce cardiac hypertrophy (enlargement of the heart). And since you can't flex your heart in an effort to woo women, who'd want that?

But, as in every story, there's more than one side. In fact, let it be said, the dangers of steroids are overstated and, hold onto your seats, may even be good for the heart. Let's examine some of the scientific studies on the positive effects of Testosterone on the heart.


What are the cardiovascular effects of steroids?

Cardiologists at the Royal Prince Alfred Hospital in Australia recruited both juicing and non-juicing bodybuilders for a study. Each bodybuilder had various aspects of the heart measured (carotid intima-media thickness, arterial reactivity, left ventricular dimensions, etc.). These measurements indicate whether bodybuilding, steroid usage or both affect the function, size, shape and activity of the heart.

The doctors found some obvious and not so obvious results. Predictably, those bodybuilders who used steroids were physically stronger than those who didn't. What was surprising was that the use of steroids was not found to cause any significant changes or abnormalities of arterial structure or function.

In essence, when the bodybuilders (both groups) were compared with sedentary controls, any changes in heart function were common to bodybuilders. The take home message from this study is that bodybuilding itself can alter (not impair) arterial structure/function and that steroids do not appear to impair cardiac function. (1)


Does MRFIT need a T boost?

A famous cardiac study was published about 10 years ago. It soon became on ongoing study known as the Multiple Risk Factor Intervention Trial (MRFIT). The present study examined changes in Testosterone over 13 years in 66 men aged 41 to 61 years. The researchers determined if changes in total Testosterone are related to cardiovascular disease risk factors.

The average Testosterone levels at the beginning of the study were 751 ng/dl and decreased by 41 ng/dl. Men who smoked or exhibited Type A behavior were found to have even greater decreases in T levels. The change in Testosterone was also associated with an increase in triglyceride levels and a decrease in the good cholesterol (HDL).

The authors concluded that decreases in Testosterone levels as observed in men over time are associated with unfavorable heart disease risk. (2) Sounds to me like a good reason to get T support/replacement therapy in the middle age years!

In a similar study, researchers in Poland examined if Testosterone replacement therapy in aging men positively effected heart disease risk factors. Twenty-two men with low T levels received 200 mg of Testosterone enanthate every other week for one year. Throughout treatment, Testosterone, estradiol, total cholesterol, HDL and LDL were measured.

The researchers determined that T replacement returned both Testosterone and estradiol levels back to normal and acceptable levels. They also found that T replacement lowered cholesterol and LDL (the bad cholesterol) without altering HDL (the good cholesterol). Furthermore, there was no change in prostate function or size.

The take home message from this study is that T replacement doesn't appear to raise heart disease risk and it may actually lower your risk. (3) It appears that more physicians should be prescribing low dose Testosterone to middle age and aging men for both libido, muscle tone and for cardiac reasons.


What about younger men?

It's been long established that men have a higher risk of heart disease. One of the risk factors implicated is Testosterone. Reportedly, the recreational use of Testosterone can alter lipoprotein levels and, in fact, case reports exist describing bodybuilders who've abused steroids and have experienced heart disease or even sudden death. But the question remains, is the causal association one of truth or just an association?

To answer this, researchers at the University of North Texas recruited twelve competitive bodybuilders for a comprehensive evaluation of the cardiovascular effects of steroids. Six heavyweight steroid-using bodybuilders were compared with six heavyweight drug-free bodybuilders.

As expected, the heavy steroid users had lower total cholesterol and HDL levels as compared to the drug-free athletes. What was unexpected was that the steroid users also had significantly lower LDL (the bad cholesterol) and triglyceride levels as compared to the non-steroid users. In addition, the juicers also had lower apolipoprotein B levels (a marker for heart disease risk). Thus, the authors concluded that androgens do not appear to raise the risk of cardiovascular disease. (4) The take home message from this study is that the negative cardiac side effects of steroids are most likely overstated.

In a little more progressive study, researchers at the Albert Einstein College of Medicine in the Boogie Down Bronx (the BDB to those in the know) examined Testosterone as a possible therapy for cardiovascular disease. (5) The researchers note that T can be given in oral, injectable, pellet and transdermal delivery forms. It's noted that injections of Testosterone (100 to 200 mg every two weeks) in men with low levels of T will decrease total cholesterol and LDL while raising the HDL.

In fact, Testosterone therapy has been found to have antianginal effects (reduces chest pain). Low levels of Testosterone are also correlated with high blood pressure, specifically high systolic pressure. The researchers determined that returning T levels back to normal and even high-normal levels have positive cardiovascular effects and should be considered as an adjunctive treatment for maintaining muscle mass when someone has congestive heart failure.


Putting it all together

Strong research demonstrates that the risks of negative cardiovascular effects of steroids are overstated. In fact, a recent paper published in the Canadian Journal of Applied Physiology questioned the whole risk of using steroids. (6) Joey Antonio, Ph.D. and Chris Street MS, CSCS published strong data showing that the risks of steroid use are largely exaggerated, much like scare tactics used by your parents while you were a kid. Of course, it goes unsaid that abuse of anything will lead to unwanted consequences.

We know that as we age, circulating Testosterone levels naturally decrease. For most people the Testosterone decrease goes from high-normal to mid to low normal. Data shows that there's an inverse relationship between T levels and blood pressure as well as abdominal obesity (that paunch we see on so many middle age males).

Testosterone replacement lowers abdominal obesity and restores Testosterone back to normal levels. Restored Testosterone is correlated with better mood, better muscle tone, stronger sex drive, lower cardiovascular disease risks, stronger bones and better memory. It's important to note that while conservative use gives a pronounced positive health benefit, higher doses may not necessarily lead to further health benefits.


What to do

If you see your body composition changing (your gut starts looking like your Uncle Lester's), your strength or muscle tone diminishing despite your hard training and good diet, and your sex drive not matching up to TC's columns, have your Testosterone levels checked. The acceptable normal range for Testosterone to physicians is 300 mg/dl to 1100 mg/dl. Yes, that's a pretty wide range.

In the clinic, we see people with the complaints consistent with "andropause" (a term for male menopause) and/or increased cardiovascular risk having Testosterone levels between 300 mg/dl and 550 mg/dl. Bringing it up to the mid to high-normal level is what gives the health and "youthful" benefits. Traditionally 200 mg/dl of supplemental Testosterone given every one to two weeks improves body composition, lowers total cholesterol and LDL, while raising HDL.

It appears that supplemental T is a healthier and safer way to go than many of the drugs used to treat poor lipid profiles. The data presented in this article applies for males over 35, not those who are 18. If you think that you can benefit from Testosterone therapy look for physicians who market themselves as "anti-aging" or "longevity physicians" as well as the more progressive endocrinologists or cardiologists.

Long story short, used intelligently, Testosterone is good medicine!


About the author: Douglas S. Kalman MS, RD is a Director for Miami Research Associates (MiamiResearch.com) a leading pharmaceutical and nutrition research organization in Miami, Florida. Doug is also a national spokesperson for the American College of Sports Medicine and according to his latest test has high T levels. Doug can be reached at dknole@hotmail.com.

References:

1) Sader MA, Griffiths KA, McCredie RJ, et al. Androgenic anabolic steroids and arterial structure and function in male bodybuilders. J Am Coll Cardiol 2001;37(1):224-230.

2) Zmuda JM, Cauley JA, Kriska A, et al. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle aged men. A 13 year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997;146(8):609-617.

3) Zgliczynski S, Ossowski M, Slowinska-Srednicka J, et al. Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Atherosclerosis 1996;121(1):35-43.

4) Diekerman RD, McConathy WJ, Zachariah NY. Testosterone, sex hormone-binding globulin, lipoproteins and vascular disease risk. J Cardiovasc Risk 1997;4(5-6):363-366.

5) Shapiro J, Christiana J, Frishman WH. Testosterone and other anabolic steroids as cardiovascular drugs. Am J Ther 1999;6(3):167-174.

6) Antonio J, Street C. Androgen use by athletes: A reevaluation of the health risks. Can J Appl Physiol 1996;21(6):421-440.
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[Deacon]

thanks for the added posts LI - all good information

[Scott]

MOST of that's true, you get what they call eccentric growth of the heart-specifically the left ventrical, w/cardio and concentric w/weights, juice, and chronic high blood pressure... so when you rip out a heart of a cadavre, a weight trainer's heart will look like a heart of someone w/high blood pressure... HOWEVER, the perfomance, the function of the left ventricle is totally different in these two hearts (weight trainer vs. high blood pressure). The weight trained heart, though atrophied, tends to perform as good as, or slightly better than, the sedentary heart.

Heart disease runs in my family (supposed to hit me hard, I shouldn't live past 40 or 50) so I've read up on this a little bit. When you do cardio, long use of the heart, the heart cavity itself increases in size. This allows more blood to fill and be pushed out of the heart with each contraction. When you lift, short bursts of energy, the heart walls thicken. With the heart walls thicker this creates a smaller area inside the heart itself. The heart is then not able to fill up with as much blood on each contraction. IE...less blood pushed out. When you use AS every muscle in your body increases in size. This holds true with the heart as well. The walls of your heart will thicken when you do a cycle. However, with that being said research has shown when the cycle is stopped, most of this will go away. Again, most of it, not all of it. Like mega said though, almost all lifters have this condition. The recommendation is that you do at least 30min of cardio 3 times a week, expecially when "on". This is so while your heart walls will thicken your heart cavity will expand as well, sort of a balancing effect.