Testosterone levels and increased risk of CHD

this is some recent opinion on the same subject:

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Coron Artery Dis. 2007 May;18(3):159-162.The association between androgen levels and premature coronary artery disease in men.Turhan S, Tulunay C, Gulec S, Ozdol C, Kilickap M, Altn T, Gerede M, Erol C.
Department of Cardiology, Ankara University School of Medicine, Ankara, Turkey.

OBJECTIVE: The relationship between androgens and the risk of development of coronary artery disease has not been clarified well. This study was planned to determine the relationship between serum androgen levels and premature development of coronary artery disease in men. METHODS: Sixty-nine men below 45 years of age with documented coronary artery disease (mean age 41.0+/-4.7) constituted the study group. Control group consisted of 56 men with similar age and normal coronary angiograms (mean age 41.3+/-3.8). Total and free testosterone, estradiol, and fasting plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol, and triglyceride levels were measured, and compared between the two groups. RESULTS: Mean age, body mass index, and the frequency of hypertension were similar between the two groups; however, diabetes mellitus, smoking, hyperlipidemia, and family history of coronary artery disease were more frequent in the coronary artery disease group. Total and free testosterone levels of the patients with coronary artery disease were significantly lower than those of controls, whereas estradiol levels did not differ. Multivariate logistic regression analysis revealed that free testosterone levels (P=0.014; odds ratio=0.90; 95% confidence interval=0.87-0.99), hyperlipidemia (P<0.001; odds ratio=8.2; 95% confidence interval=3.17-21.0), and smoking (P=0.026; odds ratio=3.12; 95% confidence interval=1.15-8.48) were independent predictors of premature coronary artery disease. Moreover, using receiver operating characteristic analysis, patients with free testosterone levels below the cut-off value of 17.3 pg/ml had an adjusted 3.3-fold risk of developing premature coronary artery disease compared to those with free testosterone levels above the cut-off level (odds ratio=3.3; 95% confidence interval=1.57-6.87). CONCLUSION: A low level of free testosterone may be related to the development of premature coronary artery disease.

One of the things that I have learned here is that is not a good idea to have a high % of body fat.

More:

Low Male Hormones: Hypogonadism in the Aging Adult Male
by Abraham Kryger, M.D.

Menopause has generated a large population of women who have excessive rates of bone fracture and CHD due to hypogonadism - low hormone levels. Andropause, which refers to sexual regression touches all men sooner or later over 40. The word appeared in the literature in 1952 and is defined at the '"'natural cessation of the sexual function older men.'"' Low hormone levels have detrimental influences on mood and mental abilities with decline of memory as well as affecting sexual functioning. The sexual aging process causes organic impotence, ejaculatory and urination problems, decreased sexual motivation and deterioration of the general condition.

Endocrinologically, the difference between the irreversibly hypogonadal man and the post-menopausal hypogonadal woman is not very great. (1) Neither has adequate levels of androgens or estrogens and they both can be expected to show similar tendencies; i.e. hypogonadal men also tend to have frequent MI's and bone fractures. There is some evidence of a protective effect of testosterone against heart attacks and bone fracture.

Testosterone is the hormone which regulates the structure of all body proteins and assures the development and integrity of the genitals in males. The testicles normally produce about 7-10mg of testosterone daily. A deficiency below this level causes only modest changes initially such as an increase in weight, progressive aging of the face, muscular weakening, weakening of bone tissue sometimes followed by rheumatism and arthritis of the vertebrae. Slow transformation of the body organs causes the failing of memory, irritability, general fatigue, the development of arteriosclerosis, varicose veins, hemorrhoids, atrophy of the skin, hypertension and increased cholesterol and body fat.

Androgens and estrogens have similar metabolic effects in the liver where testosterone is enzymatically converted into estradiol. This hormone causes breast enlargement in men as well as all the female changes that occur in women. During menopause, women typically experience hot flashes, but no similar consistent signal seems to appear in aging men as they develop hypogonadism. However, most men do experience hot flashes when hypogonadism is abruptly induced by pharmacological agents that rapidly abolish lutenizing hormone (LH). The absence of obvious symptoms and the slow course and unpredictability of the development of hypogonadism contribute to its lack of recognition and attribution to "normal aging". The loss of sexual drive and "the impotence experienced by hypogonadal men tends to be accompanied not by frustrated sexual urges or corresponding complaints of frustration but rather by passivity" according to Dr. Swartz in his article on Low Serum Testosterone. More than half of the healthy men over age 70 that he surveyed showed morning serum testosterone levels at or below 300ng/dl, the customary threshold of hypogonadism. One of the earliest signs of impending impotence is ejaculation without full erection. Men who notice that they masturbate and ejaculate without full erection should be seen by their physician.

One of the major causes of impotence is heavy drinking which is common in 25% of American men at some time during their adulthood. The relationship between alcohol consumption and testosterone secretion has both reversible and irreversible components. Serum testosterone abruptly rises to normal levels when high alcohol intake is discontinued but moderate alcohol intake does not substantially affect its level in men less than 60 years of age. However, the very low serum testosterone level --under 300ng.--was found in 62% of long abstinent ex-alcoholic men over the age of 60 and in only 15% of nonalcoholic men of the same age, indicating that past heavy drinking is associated with a reduction of the current morning serum testosterone level by an average of 122ng/dl. Therefore, alcohol induced hypogonadism is common and may affect many men over the age of 60. A moderate amount of alcohol is the equivalent of 1-2 ounces per day or 2-4 beers or glasses of wine or 2 shots of hard liquor. Women are much more sensitive to alcohol's effects and no more than three drinks a week are recommended to reduce breast cancer risk.

The best-known consequences of hypogonadism in men are impotence and dwindling libido, but melancholia and psychiatric disturbances can also occur in association with testosterone deficiency. Perhaps the most dangerous consequence of hypogonadism in men is myocardial infarction (MI). Serum testosterone levels were about 90 ng/dl lower in patients who had suffered MI than in those who had not. Results also suggested that low testosterone levels predispose to MI and are lower in men with severe coronary artery atherosclerotic disease than in controls. Very high blood levels of testosterone might protect against atherosclerosis especially in men over age 60.

Testosterone is not the only androgen that appears to protect again MI. Dehydroepiandrosterone (DHEA) is a precursor of testosterone which has digitalis like effects and strengthens the heart muscle. Both testosterone and DHEA prevent the death of CNS nerve cells and suggest that there are beneficial systemic effects in maintaining blood levels of androgens similarly to the benefits of maintaining normal thyroid hormone levels. Testosterone has been found to inhibit clot formation and hardening of the arteries by increasing HDL and decreasing serum triglycerides. It also strengthens muscles beyond normal limits and in cardiac tissue, testosterone is the androgen of greatest concentration. Testosterone can make heart muscle more resistant to death during ischemia through improved maintenance of cardiac output as well as generating feeling of well-being, greater strength and return of libido.

There are health problems in aging men associated with testosterone administration. Enlargement of the prostate, accelerated progression of undiagnosed prostate cancer, increased hematocrit and a variety of liver lesions can occur. Administering testosterone by intramuscular injection tends to avoid the liver toxicity seen with oral preparations. Administration of Testosterone Cypionate reduced HDL and synthetic androgen also increase total serum cholesterol. Synthetic androgens are not preferable to preparations of testosterone itself.

Natural testosterone has been available for over 60 years. Most of the anabolic (tissue building) steroids are synthetic analogs of natural Testosterone, the male hormone. Usually they are taken orally in large quantities which are dangerous and can cause serious liver diseases as well as organ failure; examples such as Stanozolol or winstrol and Android or methyltestosterone, are used by bodybuilders. Injections of nandrolone deconate, or Durabolin, have been available for over ten years. It is a synthetic hormone which transforms to produce both testosterone and excess estradiol which can cause gynecomastia (breast enlargement) in men. Testosterone's action on the muscles has been observed by young male athletes who try to bulk up and recover faster.

These hormones cause increased incorporation of new amino acids which increase protein synthesis and result in growth or hypertrophy of the muscle. They are used to treat breast cancer, anemia, hypogonadism and replacement therapy in deficient males.

Natural Testosterone can be used safely in large doses by men who are deficient . Physiologic doses present no apparent health risks. A novel method of administration through a skin delivery system is now available pharmaceutically. (2) Testoderm(c) is a patch delivery system of natural testosterone. It delivers 4-6mg of testosterone daily and is applied to the shaved scrotum. Since the normal pattern is to have higher levels in the morning, the patch is applied each morning and results in a surge of hormone within a few hours of application. Self-administration by this technique is safe but awkward. A Dihydroxytestosterone gel and a natural testosterone cream, in various doses up to 100mg., are also available for hormone replacement in men. These are prescription items and need to be applied twice daily due to their short duration of action. The hormone testosterone is naturally derived and is identical to that secreted by the testicles. Testosterone pellets , containing 25mg., can be inserted beneath the skin to deliver testosterone over 4-months.

It does not take much hormone to exceed the recommended physiologic dosage. Monitoring by a physician and regular blood tests are important. A study is now underway in this office using the testosterone cream. Depot or longer lasting injectable preparations are synthetic steroid supplements and should only be give intramuscularly by injection under physician supervision. These synthetic products do have various potentially dangerous side effects. It is also extremely dangerous for women to take steroids since they can become masculinized and grow facial hair among other problems they may develop. However testosterone does convert to progesterone in the female and it has been used successfully as an implant in a low dose, for women with decreased sex drive due to menopause.

The testosterone cream is a prescription item and requires an early morning blood test to check the serum level before starting on the hormone therapy. It is also recommended that the PSA (prostate surface antigen) and a DRE ( digital rectal exam) be done prior to hormone treatments.

Testosterone cream costs about $20.00 per month depending on the dose used and is applied directly to the scrotum or penis twice a day. Monthly testing must be performed initially to check your hormone response levels and should be covered by your insurance. Please keep your appointments and report your results to the doctor.

References:

1. Low Serum Testosterone: a Cardiovascular Risk in Elderly Men. Conrad Swartz, Geriatric Medicine today/Vol 7. No 12/Dec. 1988.

2. Transdermal testosterone Substitution Therapy for male hypogonadism. Bals-Pratsch,M, Yoo YD, Knuth VA, Nieschlag E , 1986 . Lancet 4/943-946.

3. Transdermal delivery of Testosterone. Findlay JC, Place V, Snyder PJ, 1989. J. Clinical Endocrinolology Metab. 64; 266-268.
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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).

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.

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

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: [email protected]

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All good papers lifts, congrats.