HealthWatch

The Truth About TestosteroneBy Mike Clark, MBA, PhD, FAARFM, ABAAHP, Brain Fitness CertificationDirector of Education & Research for Natural Bio Health

Low testosterone levels for men can mean high health risks. After decades of research and hype surrounding female menopause and hormone replacement therapy, men have recently started receiving some attention about their own age-related hormonal decline - andropause. Testosterone Plays an Important Role in Our Health. We have advised our clients for years that the overwhelming scientific evidence is that testosterone is protective of the heart. We have provided our clients (and anyone who asks) with the many studies showing the benefits of testosterone therapy and the science that supports the use of testosterone. Does this mean that everyone taking testosterone is immune from a heart attack or cancer or other disease? Of course not! Although testosterone is a critical part of a males health (and female), it is still only ONE important aspect of health. Healthy eating, regular exercise, regular check-ups (including extensive lab testing), healthy body fat, all are necessary to provide maximum protection against heart disease. Comprehensive testing and monitoring by QUALIFIED medical professionals are required to obtain the maximum and safe benefits of testosterone.

Prevention. Testosterone works best as PREVENTION. It will not magically work overnight to rid the body of pre-existing heart conditions, pre-existing plaque or diseases such as diabetes or cancer that already exists in the body. However, when properly prescribed and monitored by qualified medical persons, it can play a significant role in helping to reverse pre-existing conditions and in making the body stronger while working to lower unhealthy body fat, a major determinant in heart disease. It is recommended for all type II diabetic clients (after testing). Men with low testosterone are at a greater risk. We know that studies show that men with LOW testosterone have a HIGHER incident of heart disease. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population. Study. Circulation. 2007 Dec 4;116(23):2694-701. See all of the studies listed in our 26 page whitepaper on Testosterone. Testosterone and LAWYERS? Some lawyers got excited about a Veterans Administration (VA) study (November 2013) published in the Journal of the American Medical Association (JAMA). The lawyers sat in their offices and thought wow. Lots of men take testosterone. This VA study says men may be 29% [30%] more likely to die, suffer a heart attack or stroke on testosterone therapy. We can make some $ off this.

The problem for the attorneys (they have not figured this out yet) is that the study they quoted was INCORRECTLY calculated. The study showed that men on testosterone did better than those not on testosterone. We explained this in our blog and Dr. Feste wrote JAMA (as did a Harvard Professor) demanding the journal correct this error (they did not). The VA study was contrary to years of positive studies. Regardless of the poor quality of the study, the end result was that when the study numbers are properly calculated, they show a decrease in the risk of heart disease, even in a group of older men with pre-existing conditions.

The misinformed attorneys (good luck on their hoped for big payday) also rely on one other study of 209 men in 2009 (TOM study) conducted by the National Institutes of Health. This study lasted a few months and concluded that there was an increased risk of heart incidents. In this study, the participants had low testosterone levels, mobility limitations, an average age of 74 and high rates of chronic diseases such as diabetes and cardiovascular disease. These men were given a testosterone gel administered daily.

The study was stopped because more men in the testosterone group had cardiovascular-related events included heart attack, heart rhythm disturbances and elevated blood pressure. ONE death was from a suspected heart attack. Of course, nothing was said about the activities of the men taking the testosterone, about whether they started doing things they had not done for years because of increased energy, sex drive, etc. Proper testing was not done as noted by many experts. Further, most of these men were not only older with limited mobility when they started the study, but had chronic pre-existing conditions.

Science: The Academy of Anti-Aging Medicine recently published a White Paper on Testosterone and Heart Disease. I have attached a copy of this paper to our Natural Bio Health Testosterone Handout. The introduction to the paper by Pamela W. Smith, M.D., MPH, MS states as follows (with all case study citations included): Two recent trials suggest that testosterone replacement therapy may increase the risk of heart disease and/or stroke. 1, 2. These were poorly designed studies which conflict with numerous previous medical trials that show the beneficial effects of testosterone on the heart and that low testosterone levels in males are associated with an increased risk in the development of heart disease.The following is a comprehensive review of the medical literature on low testosterone being associated with an increased risk in the development of cardiovascular disease and that testosterone replacement at appropriate levels not only decreases the risk of heart disease but can also be used to treat coronary disease.Low testosterone levels for men can mean high health risks. After decades of research and hype surrounding female menopause and hormone replacement therapy, men have recently started receiving some attention about their own age-related hormonal decline, known as andropause. At NBH Lifetime Health, we have been treating men of all ages for testosterone deficiencies for more than fourteen (14) years. A simple lab test for free and total testosterone will determine if the male is deficient in this primary male hormone. We also test the estradiol level to determine if testosterone is converting to estradiol. Another important test is DHEA. This hormone is often called the bodys repair hormone and master hormone.For males in the 40s and above, we offer tests for the major heart factors including cholesterol, homocysteine, fibrinogen, and CRP. Testosterone is of course a major heart factor in that low levels are associated with heart disease. We have found that most men over 40 have less than optimal levels of free testosterone. More and more, we are finding the younger males can also have these difficulties.

Declining testosterone levels. Declining testosterone levels can lead to the development of numerous symptoms such as a decrease in virility, libido and sexual activity, general sense of well-being, as well as fatigue, depression and sleep disturbances. In addition to problems such as sexual dysfunction or general malaise, low testosterone also translates into decreased muscle mass and strength, as well as a decrease in bone mass and an increase in abdominal fat. Studies show that the latter two pay a role in degenerative diseases such as osteoporosis, cardiovascular disease and diabetes. Moreover, depleted testosterone levels are being linked to the incidence of various lipid disorders and heart disease.

Less bone, more fat. While osteoporosis hasnt always been considered a disease that afflicts males, the rising incidence of bone mass degeneration among aging men points a finger to some age-related cause. As androgen receptors are expressed in osteoblasts (bone-forming cells) researchers now believe that androgens have some direct effect on bone formation and resorption.

Declining Testosterone, Fat Mass and Heart Risk. A growing body of research now suggests that an age-related increase in fat mass, or obesity, can be attributed to a fall in free testosterone and growth hormone levels. Moreover, studies report a connection between abdominal obesity and increased cardiovascular mortality and Type II diabetes mellitus. Recent findings from the University Hospital in Ghent, Belgium illustrate that age is related to a drop in free testosterone levels and free insulin-like growth factor-1, while contributing to an increase in body mass index and fat mass.The Heart: Also note that testosterone concentrations are inversely related to mortality due to cardiovascular disease and all causes. Low testosterone may be a predictive marker for those at high risk of cardiovascular disease. Khaw KT, Dowsett M, Folkerd E, et al. Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population. Study. Circulation. 2007 Dec 4;116(23):2694-701.Studies (there are many studies, these are just a few).

Men with CAD had significantly lower

Total Testosterone

Free Testosterone

Bioavailable Testosterone

English K et al. Men with coronary artery disease have lower levels of androgens than men with normal coronary angiograms. Eur Heart J 2000 Jun;21(11):890-4.Acute administration of high-dose testosterone in men with coronary artery disease improves endothelial function. Ong PJ et al. Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease. Am J Cardiol 2000 Jan 15;85(2):269-72.

Intracoronary injection of T at men with established CAD

Coronary artery dilation

Increased coronary blood flow

Webb CM et al. Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease. Circulation 1999 Oct 19;100(16):1690-6.

One recent study consisting of 372 males aged >20-85, revealed that body mass index and age were independent factors in determining testosterone levels. These decreased by about one quarter when researchers compared the young controls to men in the elderly group, while free testosterone levels fell by almost half with age. Likewise, fat-free mass decreased by 18.9%. In a subgroup of 57 men aged 70-80 years, the lower that testosterone levels dropped, the higher the percentage of body and abdominal fat, as well as plasma insulin levels.Low Testosterone and Increased Risk of Diabetes and Adipose Fat. Other findings indicate that low testosterone levels predisposed men to adipose fat which, in turn, seemed to raise their risk of diabetes mellitus. Researchers at the University of Washingtons Department of Medicine set out to examine the effects of age-related decreasing serum testosterone levels on intra-abdominal fat in a group of 110 second-generation healthy Japanese-American men. Measurements were taken first to establish baseline levels of glucose, body mass index, visceral adiposity, subcutaneous fat, fasting insulin and C-peptide levels, and overall testosterone levels (which were within the normal range relative to the mens age). When the researchers performed follow-up measurements 7.5 years later, their results indicated that intra-abdominal fat had increased by an average of 8.0 centimeters squared. More importantly, though, they found that the change in intra-abdominal fat correlated to baseline total testosterone levels, but they were not significantly related to other measurements such as body mass index, total fat or subcutaneous fat. The study authors concluded that, in their sample, lower baseline total testosterone independently predicts an increase in intra-abdominal fat. This would suggest that by predisposing to an increase in visceral adiposity, low levels of testosterone may increase the risk of type II diabetes mellitus.

Note: Diabetic patients are at a high risk of heart disease and generally die of heart disease.

Low testosterone Levels, Excess Abdominal Fat and Heart Disease. Similarly, another study that analyzed some of the health effects of excess abdominal fat, also referred to as android obesity, reported that individuals exhibiting upper body excess fat distribution tend to have lower levels of plasma testosterone and growth hormone levels, suggesting what the authors describe as complex hormonal abnormalities.Abdominal obesity lends itself to an apple-shaped figure and has been related to a heightened risk of conditions such as cancer, diabetes and heart disease. These researchers believe that, Visceral fat tissue, through its portal drainage, could be an important source for free fatty acids that may exert complex metabolic effects: involvement in hepatic lipogenesis, increase in hepatic neoglucogenic flux, reduction in insulin metabolic clearance and involvement in peripheral insulin resistance through a competition mechanism described by Randle. They conclude that abdominal obesity may be related to diabetes by means of an enhanced fatty acid made available from fat tissues (visceral and subcutaneous) in individuals who are genetically predisposed to type II diabetes. Research has also pointed to the possibility of a link between abdominal obesity and hypercorticism, or elevated cortisol levels. A reason for this, suggest scientists, might be that excess cortisol opposes testosterone and growth hormone production, both of which are regulators of body fat. Moreover, low testosterone levels also seem to encourage cortisol levels to rise and elicit their many aging effects, including immune dysfunction, brain cell injury, arterial wall damage and other assaults.

Hypogonadism (low testosterone) and Heart Trouble. Low testosterone levels have also been implicated in playing a role in the development of chronic diseases such as atherosclerosis and cardiovascular heart disease. One study found that, in assessing a group of men and postmenopausal women over 50 years of age for levels of various hormones as they might relate to health conditions, plasma estradiol levels were highest in hypertensive men and testosterone levels were lowest in men with coronary heart disease. The researchers conclude that perhaps, Decreased testosterone and/or increased estradiol may have an adverse effect on lipid profile in elderly men. Another study conducted among a male population likewise reported that low testosterone may be a risk factor for coronary heart disease, which may relate to lipoprotein metabolism by endogenous testosterone. Results showed that mean plasma testosterone levels among patients with coronary heart disease were significantlyabout 40%lower than in healthy subjects. Moreover, there was a negative association between plasma testosterone levels and plasma triglyceride levels and lipoprotein (a), which translated into higher blood lipid levels relative to lower testosterone levels. Contrarily, a positive association between plasma testosterone levels and high-density lipoprotein cholesterol and high-density lipoprotein 3 cholesterol meant that higher testosterone levels equaled higher good cholesterol levels.

The Natural Aging Factor. It is well documented in research that sex hormones such as testosterone are vital components in the sexual development of pubescent males, as well as contributing to the increase of their muscle and bone mass as they transform from boys into men. Meanwhile, dwindling testosterone levels as a result of metabolic aging trigger the opposite kind of effects, including the loss of body hair and progression of male pattern baldness, loss of muscle and bone mass, and increased fat. Low testosterone levels arent just the prospect of a small segment of the male population but rather, they tend to affect the male population as a whole. Natural aging causes a gradual decline in male hormones, so that by age 70, men have less than a quarter of their optimal testosterone levels. Some figures reveal that free testosterone levels start to fall at the age of 25. At NBH Lifetime Health, we have treated many men in their 30s and even several in their 20s.

While men with normal testosterone levels sometimes exhibit some of the symptoms, which may very well stem from other causes besides hypogonadism, the fact that androgen therapy usually alleviates these symptoms suggests a hormonal deficiency as the root cause of such deterioration in health.

Many study results show a positive role in maintaining adequate testosterone levels in aging males. In terms of overall body composition, for example, research has demonstrated a measurable increase in lean body mass and in mid-arm circumference and the decrease in waist-to-hip ratio in elderly men, after they received androgen replacement therapy to treat their low testosterone levels.

Younger men. Meanwhile, in younger, healthy men (i.e. athletes), testosterone treatment has shown to have a positive effect on increased fat-free mass of about 10% and in muscle size (we do not recommend supplementation unless lab tests show low levels and other causes have been ruled out). More specifically, studies have shown that administering testosterone to older men with low levels can help to ward off atherogenic type diseases. For example, a Polish study of 22 men with baseline serum testosterone concentrations below 3.5 ng/ml reported that intramuscular injections of testosterone enanthate (200 mg) every two weeks for 12 months resulted in decreased total cholesterol and low-density protein cholesterol levels.(10) In addition, no significant decrease in HDL-cholesterol levels or HDL2- and HDL3-cholesterol subfractions was apparent.

As one researcher noted: The adverse effects of low testosterone levels are apparent, bothersome, and serious enough to warrant further examination of how androgen impacts on various aspects of male health, and how androgen replacement therapy can serve as a means to contain age-related hormonal pitfalls. The biggest challenge may conceivably be to restore the reputation of testosterone, which has been cast as a bad steroid for some time. Another task for research will be to continue building a case for the vital role that androgens have with regard to bone, heart, sexual, mental health and general well being. Offering solid proof of testosterones various functions will help to show that, while testosterone therapy may not be appropriate for every man, it would be a shame for other men to miss out on its merits.

Prostate cancer the myth of testosterone causation.A number of studies have tried to relate high testosterone levels with the incidence of prostate cancer, but the evidence shows that maintaining youthful testosterone levels does not affect prostate cancer risk, whereas waning testosterone levels carry their own health threats.

No evidence that testosterone causes prostate cancer in men.We still hear concerns from men (and their physicians) that testosterone can cause prostate cancer. The TRUTH is that There is no clinical evidence that the risk of either prostate cancer or BPH increases with TRT. This quote is from an article published in by a Mayo Clinic Journal. Morley, JE. Testosterone replacement and the physiologic aspects of aging in men. Mayo Clin Proc. 2000 Jan; 75 Suppl:S83-7.Studies show that men with LOW levels of testosterone are more likely to get prostate cancer. There have been 50 year of studies and none have shown a connection between testosterone levels and prostate cancer growth. A 2006 study from Harvard Medical School concluded: there is not now, nor has there ever been a scientific basis for the belief that testosterone causes prostate cancer to grow.

Estrogen: The belief that estrogen, rather than testosterone, is one of the prime hormonal initiators of prostate cancer is based on the fact that while testosterone levels are highest in young men, prostate cancer essentially is never seen in this population. It is only in older men, who have lower levels of testosterone but higher levels of estrogen and its breakdown products, that prostate cancer is a significant health threat. However, young men do have high levels of estradiol so this belief is questionable at best.

Further, high doses of estrogen have been used to treat cancer of the prostate and the GnRh agonist, Lupron, is used to decrease the levels of testosterone as a chemotherapy treatment. However, Lupron would also decrease estrogen. Many men have been treated successfully in the past with DES, diethylstilbestrol, and it controlled prostate cancer.Men can get significant breast enlargement with DES. Estrogen treatment is again being used to treat prostate cancer.

Conventional Studies: The Institute of Medicine report includes some data showing that optimal levels of testosterone do not cause prostate cancer, and in fact may protect against this major killer of elderly men. No study has shown that testosterone causes prostate cancer and we have not had a single male develop prostate cancer on our program.Population-based studies clearly document the relationship between aging and both increases in prostate cancer incidence rates and decreases in circulating [and free] testosterone levels. While this relationship does not equal causality, the findings do raise intriguing hypotheses regarding the influence of testosterone on inhibiting prostate carcino-genesis.

Insurance: Hypogonadism is a medical term. To be diagnosed with hypogonadism, a person must have low levels of testosterone as defined according to expected ranges on blood tests. Many men over the age of 40 (and even younger) would not fall into this medical classification. At NBH Lifetime Health, we strive for optimal levels of free testosterone. Most of our patients cannot be medically defined as suffering from hypogonadism although they suffer from all of the symptoms of low free testosterone. Optimal levels at NBH Lifetime Health means levels expected of young healthy men between the ages of 25 to 30. Insurance generally does not pay for treatment designed for those who merely wish to obtain optimal levels. At NBH Lifetime Health, you are the client, not the insurance company.Low Testosterone Levels and

Risk for Alzheimer's Disease in Men Alzheimer's Disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. In most people with Alzheimer's, symptoms first appear after age 60. In some people, symptoms can appear much earlier. Alzheimer's disease is the most common cause of dementia among older people. Dementia is the loss of cognitive functioning, thinking, remembering, and reasoning, to such an extent that it interferes with a person's daily life and activities. Estimates vary, but experts suggest that as many as 5.1 million Americans may have Alzheimer's. Some experts believe that the extensive use of statin drugs to lower cholesterol may result in an increasing incidence of Alzhemers Disease due to the blocking of cholesterol.

Decreased testosterone levels have been reported in men with Alzheimer's Disease. In a recent study published in the journal Neurology, researchers followed 574 men for 19.1 years. Because serum was used, Free Androgen Index (FAI) levels were monitored. (The Free Androgen Index is a ratio that divides total testosterone by the sex hormone binding globulin level and multiplied by 100 to approximate the amount of free testosterone in the serum.) The researchers state that "the FAI is more highly correlated with bioavailable testosterone."

A significant reduction in the risk for Alzheimer's Disease was associated with a higher FAI (more free testosterone).

Numerous studies have supported the concept that testosterone has a neuroprotective effect on cognitive and brain function. In rat models, testosterone has been shown to decrease -amyloid secretion from rat cortical neurons and reduce -amyloid induced neurotoxicity in cultured hippocampal neurons. In humans, testosterone suppression for management of prostate cancer resulted in a two-fold increase in plasma -amyloid concentrations in elderly men, suggesting that endogenous testosterone might reduce plasma amyloid concentrations in humans. Results of the current study suggest that in aging men, maintenance of free testosterone concentrations in the higher part of the normal range may decrease the risk of developing Alzheimer's Disease.

Testosterone is of course a major heart factor in that low levels are associated with heart disease. At NBH Lifetime Health, we have found that most men over 40 have less than optimal levels of free testosterone. More and more, we are finding the younger males can also have these difficulties. Heart disease is still the No.1 killer of men (and women).

Declining Testosterone, Fat Mass and Heart Risk. A growing body of research suggests that an age-related increase in fat mass, or obesity, can be attributed to a fall in free testosterone and growth hormone levels. Moreover, studies report a connection between abdominal obesity and increased cardiovascular mortality and Type II diabetes mellitus. A study conducted at Harvard University concluded that essentially all type II diabetic males had low levels of testosterone. This is not surprising to us as we have been treating overweight males for years and testing their free and total testosterone levels.

Conclusion: Protect your mind, your heart and your weight with Testosterone.

References: Credit for the Alzheimers section research to Labrix Labs.Alzheimer's Disease Fact Sheet. U.S. National Institutes of Health National Institute in Aging. http://www.nia.nih.gov/Alzheimers/Publications/adfact.htm.Accessed 1/3/2011.

Gandy S, et al. Chemical andropause and amyloid-beta peptide. JAMA 2001;285:2195-2196.

Gouras, G.K. et al. Testosterone reduces neuronal secretion of Alzheimer's beta-amyloid peptides. Proc Natl Acad Sci USA 2000; 97:1202-1205.

Moffat, S.D. et al. Free testosterone and risk for Alzheimer disease in older men. Neurology 2004; 62:188-193. Asian J Androl. 2012 May; 14(3): 428435.

White paper (authoritative report) from A4M. NOTE THAT NATURAL BIO HEALTH AND SOME EXPERTS IN THIS FIELD DO NOT AGREE WITH ALL OF THE FOLLOWING OR AT LEAST WE DISTINGUISH CERTAIN ASPECTS. HOWEVER, IT IS A COMPREHENSIVE REPORT ON THE SCIENCE ASSOCIATED WITH TESTOSTERONE.Testosterone and Heart Disease, By Pamela W. Smith, M.D., MPH, MS

Introduction

Two recent trials suggest that testosterone replacement therapy may increase the risk of heart disease and/or stroke. 1, 2. These were poorly designed studies which conflict with numerous previous medical trials that show the beneficial effects of testosterone on the heart and that low testosterone levels in males are associated with an increased risk in the development of heart disease.

The following is a comprehensive review of the medical literature on low testosterone being associated with an increased risk in the development of cardiovascular disease and that testosterone replacement at appropriate levels not only decreases the risk of heart disease but can also be used to treat coronary disease.

Low Testosterone Levels and Increased Risk of Heart Disease. Men with coronary heart disease had a significantly lower total testosterone, free testosterone, and bioavailable testosterone. 3

Low endogenous testosterone concentrations are related to mortality due to cardiovascular disease and other causes. 4, 5

Study showed a possible correlation between lower testosterone levels, erectile dysfunction and conditions associated with higher cardiovascular risk. 6

Study showed that men with coronary heart disease that were under the age of 45 had total and free testosterone levels significantly lower than controls. 7 Serum free testosterone levels were found to be inversely related to carotid intima-media thickness (IMT) and plaque score. 8

Low testosterone levels have been found to be associated with atherosclerosis in men. 9 Low Testosterone Levels and Increase Risk of Diabetes Type II and Metabolic Syndrome. Low testosterone levels are associated with an increased risk for the development of type II diabetes and metabolic syndrome. 10, 11, 12, 13, 14.

Since low testosterone has been shown to lower blood sugar levels, the Endocrine Society now recommends measurement of testosterone in all male patients with type II diabetes mellitus. 15 Low Testosterone Levels Are Associated with an Increased Risk of Mortality Study showed that low testosterone predicts mortality from cardiovascular disease. 16 Study showed that low testosterone levels were associated with an increased risk of all-cause mortality independent of numerous risk factors. Serum testosterone levels were inversely related to mortality due to cardiovascular disease and cancer. 17

Low endogenous testosterone levels are associated with an increased risk of death from all causes and cardiovascular death. 18 Low Testosterone Levels and Increased Risk of Hypertension. Study showed that low total testosterone concentrations are predictive of hypertension, suggesting total testosterone as a potential biomarker for increased cardiovascular risk. 19 Low Testosterone and Congestive Heart Failure. In males with heart failure, low serum androgens were associated with an adverse prognosis. 20 In men with chronic heart failure, anabolic hormone depletion is common and deficiency of each anabolic hormone is an independent marker of poor prognosis. 21 Testosterone Replacement and Heart Disease.

Study showed that for all-cause mortality, for each increase of six nanomoles of testosterone per liter of serum was associated with an almost fourteen percent drop in the risk of death. 22

Study revealed that testosterone replacement was associated with a decrease in HDL-C and lipoprotein a. 23

The mechanism of testosterone replacement decreasing lipids may be due to testosterones positive effects on abdominal fat and insulin resistance. 24

Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary heart disease. This effect may be related to a direct coronary-relaxing effect of testosterone. 25

Short-term intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and an increase in coronary blood flow in men with established coronary heart disease. 26

Low-dose supplementation with testosterone in men with chronic stable angina reduced exercise-induced myocardial ischemia. 27

Testosterone replacement has been shown to increase coronary blood flow in patients with coronary heart disease. 28, 29

Transdermal testosterone replacement has been shown to improve chronic stable angina by increasing the angina-free exercise tolerance vs. controls that were getting placebos. 30

Another study showed that testosterone replacement reduced exercise induced myocardial ischemia. 31

Testosterone is a coronary vasodilator by functioning as a calcium antagonistic agent. 32

Testosterone replacement therapy in hypogonadism moderates metabolic components associated with cardiovascular risk. 33 Testosterone replacement has been shown to decrease inflammation and lower total cholesterol. 34 Testosterone replacement in patients with congestive heart failure has been shown to improve exercise capacity, improve insulin resistance, and improve muscle performance. 35

Testosterone replacement has been shown to be helpful in patients with severe heart failure. 37

In this review of the medical literature one can see that numerous studies have shown that low testosterone levels are associated with an increased risk of heart disease and that testosterone replacement therapy is associated with a decreased risk of developing heart disease and is even beneficial in patients that already have coronary vascular disease.So why did the two recent studies show that there was an increased risk of developing heart disease in male patients that were prescribed testosterone replacement therapy?

There are five serious flows associated with the two recent trials. [THERE ARE 6 IN THAT THE VA STUDY, WHEN PROPERLY CALCULATED, SHOWED A DECREASE RISK OF HEART ATTACKS AND STROKE. IT SEEMS THAT ONLY NATURAL BIO HEALTH AND ONE HARVARD COLLEGE PROFESSOR CALCULATED CORRECTLY.]

Firstly, estrone and estradiol levels were not measure in the subjects in the studies. High

estrogen levels in males have been found to be associated with an increase risk in the

development of heart disease and stroke. [It is the ratio more than the absolute value]. Estrogen levels may elevate due to an increase in aromatase activity, alteration in liver function, zinc deficiency, obesity, abuse of alcohol, drug induced estrogen imbalance, and ingestion of estrogen-containing foods or environmental estrogens.High Estrogens are Associated with an Increased Risk of Heart Disease and Stroke

Study showed that high estradiol in males was associated with an increased risk of stroke. 38. Study showed that elevated circulating estradiol is a predictor of progression of carotid artery intima media thickness in middle age men. 39 High estradiol levels in men were associated with acute myocardial infarctions. 40 High estrone and low testosterone levels were associated with promoting the development of atherogenic lipid milieu in men with coronary heart disease. 41Low testosterone and elevated estradiol was associated in this study with lower extremity peripheral arterand low testosterone levey disease in older men. 42 Men with myocardial infarction had high estradiol ls. 43 Elevated levels of estradiol in men were associated with an increase incidence of strokes, peripheral vascular disease, and carotid artery stenosis compared to subjects with lower estradiol levels. 44 Elevated levels of estrogen in men are associated with an increased risk of heart disease. 45

[Note that the referenced studies involve the combination of LOW TESTOSTERONE and high estradiol. Estradiol can be protective if you also have optimal levels of testosterone.]

Secondly, having erythrocytosis is associated with an increased risk in the development of heart disease and thrombosis. 46 A major study on the risk and benefits of testosterone replacement suggests that a baseline hematocrit should be checked at three and six months and then every six to twelve months. If the hematocrit is more than fifty-four percent then testosterone therapy should be stopped until the hematocrit is at a safe level. 47 Hematocrit levels were not measure in these two trials.[We disagree to some extent with this paragraph as does the leading expert in the field, Dr. Neal Rouzier. Polycythemia, is a disease state in which the proportion of blood volume that is occupied by red blood cells increases. This is not erythrocytosis. We have not found a problem in this area but advise our clients if high donate blood. Again, we monitor and test.]Thirdly, in both studies not all patients had follow-up testing of testosterone levels. Therefore, dosages of testosterone may have been higher than needed. Supraphysiologial levels of testosterone can induce nitric oxide production and cause oxidative stress which induces endothelial dysfunction. 48Fourthly, some of the men in these trials were using testosterone injections, which are

nonphysiologic since they have peak and trough levels over the weekly or biweekly dosing. This issue was wonderfully discussed by Cappola in her review of Vigens study. 49. [We disagree with this paragraph as does the leading expert in the field, Dr. Neal Rouzier. We have not found a problem with injections in 15 years. We do recommend for some to inject 2 x per week and we always test.]Lastly, testosterone can convert to dihydrotestosterone (DHT) which has been shown to

enhance early atherosclerosis. 50 The conclusion of the author of this trial was that the

findings highlighted a new androgen receptor/nuclear factor-kappaB mediated mechanism for vascular cell adhesion molecule-1 expression and monocyte adhesion operating in male endothelial cells that may represent an important unrecognized mechanism for the male predisposition to atherosclerosis. The higher the dose of testosterone that is prescribed the more it is converted by 5 alpha-reductase into DHT. In these two recent trials that suggest that testosterone replacement increases the risk of heart disease in men, DHT levels were not measured.

Conclusion. Given the plethora of medical studies indicating the beneficial effects of properly prescribed testosterone, one would have to conclude that these two recent medical trials are poorly their conclusion is flawed. Some of the patients did not have repeat testosterone levels measured. Consequently, the patients may have had supraphysiological levels of testosterone. In addition DHT, estrone, estradiol, and HCT levels were not addressed.

Furthermore, the medical literature has shown that hormones in the body are a symphony and This web of interconnection was not considered.References1. Vigen, R., et al., Association of testosterone therapy with mortality, myocardial

infarction, and stroke in men with low testosterone levels, JAMA 2013; 310(17):1829-

36.

2. Finkle, W., et al., Increased risk of non-fatal myocardial infarction following

testosterone therapy prescription in men, PLOS January 29, 2014.

3. English, K., et al., Men with coronary artery disease have lower levels of androgens

than men with normal coronary angiograms, Eur Heart Jour 2000; 21(11):890-4.

4. Vermeulen, A., Androgen replacement therapy in the aging male---a critical

evaluation, Jour Clin Endocrinol Metabol 2001; 86:2380-90.

5. Malkin, C., et al., Low serum testosterone and increased mortality in men with

coronary heart disease, Heart 2010; 96:1821-25.

6. Ma, R., et al., Erectile dysfunction predicts coronary heart disease in type 2 diabetes,

Jour Amer Coll Cardiol 2008; 51:2045-50.

7. Turhan, S., et al., The association between androgen levels and premature coronary

artery disease in men, Coron Artery Dis 2007; 18(3):159-62.

8. Bhasin, S., et al., Serum free testosterone is inversely related to carotid intima-media

thickness (IMT) and plaque score, Diabetes Care 2003; 26:1869-73.

9. Svartberg, J., et al., Low testosterone levels are associated with carotid atherosclerosis

in men, Jour Int Med 2006; 269(6):576-82.

10. Ding, E., et al., Sex differences of endogenous sex hormones and risk of type 2

diabetes: a systematic review and meta-analysis, JAMA 2006; 295:1288-99.

11. Laaksonen, D., et al., Testosterone and sex hormone-binding globulin predict the

metabolic syndrome and diabetes in middle-age men, Diabetes Care 2004; 27:1036-41.

12. Pasquali, R., et al., Effects of acute hyperinsulinemia on testosterone serum

concentrations in adult obese and normal-weight men, Metabolism 1997; 46(5):526-9.

13. Rizza, R., et al., Androgen effect on insulin action and glucose metabolism, Mayo Clin

Proc 2000; 75(Suppl):S61-S64.

14. Stellato, R., et al., Testosterone, sex hormone-binding globulin, and the development of

type 2 diabetes in middle-aged men: prospective results from the Massachusetts male

aging study, Diabetes Care 2000; 23(4):490-94. Rizza, R., et al., Androgen effect on

insulin action and glucose metabolism, Mayo Clin Proc 2000; 75(Suppl):S61-S64.

15. Dardona, P., et al., Update: hypogonadotropic hypogonadism in type 2 diabetes and

obesity, Jour Clin Endo and Met 2011; 96(9):2643.

16. Hyde, Z., et al., Low free testosterone predicts mortality from CVD but not other

causes: The Health in Men Study, Jour of Clin Endocriol and Met 2012; 97(1):179.

17. Haring, R., et al., Low serum testosterone levels are associated with increased risk of

mortality in a population-based cohort of men aged 20-79, European Heart Jour 2010;

31(12):1494-1501.

18. Araujo, A., et al., Endogenous testosterone and mortality in men: a systematic review

and meta-analysis, Jour Clin Endocrinol Metab 2011; 90:3007-19.

19. Torkler, S., et al., Inverse association between total testosterone concentrations,

incident hypertension and blood pressure, Aging Male 2011; 14(3):176-82.

20. Guder, G., et al., Low circulating androgens and mortality risk in heart failure, Heart

2010; 96:504-09.

21. Jankowska, E., et al., Anabolic deficiency in men with chronic heart failure: prevalence

and detrimental impact on survival, Circulation 2006; 114:1829-37.

22. Khaw, K., et al., Endogenous testosterone and mortality due to all causes,

cardiovascular disease, and cancer in men: European Prospective Investigation into

Cancer in Norfolk (EPIC-Norfolk) Prospective Population study, Circulation 2007;

December 4th.

23. Baum, N., et al., Testosterone replacement in elderly men, Geriatrics 207; 62:15-8.

24. Marin, P., et al., Androgen treatment of abdominally obese men, Obes Res 1993;

1:245-48.

25. Rosano, G., et al., Acute anti-ischemic effect of testosterone in men with coronary

artery disease, Circulation 1999; 99:166-70.

26. Webb, C., et al., Effects of testosterone on coronary vasomotor regulation in men with

coronary heart disease, Circulation 1999 100(16):1690-96.

27. English, K., et al., Low dose transdermal testosterone therapy improves angina

threshold in men with chronic stable angina, Circulation 2000; 102:1906-11.

28. Haffner, J., et al., Sex hormones and DHEASO4 in relation to ischemic heart disease in

diabetic subjects, The WESDR Study. Diabetes Care 1996; 19:1045-50.

29. Channer, K., et al., Cardiovascular effects of testosterone: implications of the male

menopause? Heart 2003; 89(2):121-22.

30. Whitsel, E., et al., Intramuscular testosterone esters and plasma lipids in hypogonadal

men: a meta-analysis, Amer Jour Med 2001; 111:261-69.

31. English, K., et al., Low-dose transdermal testosterone therapy improves angina

threshold in men with chronic stable angina: A randomized, double-blind, placebocontrolled

study, Circulation 2000; 102(16):1906-11.

32. English, K., et al., Testosterone acts as a coronary vasodilator by a calcium antagonistic

action, Jour Endocrinol Invest 2002; 25(5):455-58.

33. Corona, G., et al., Hypogonadism as a risk factor for CV mortality in men: a metaanalytic

study, Eur Jour Endocrinol 2011; 165:687-701.

34. Malkin, C., et al., The effect of testosterone replacement on endogenous inflammatory

cytokines and lipid profiles in hypogonadal men, Jour Clin Endocrinol Metab 2004;

89(7):3313-18.

35. Carminiti, G., et al., Effect of long-acting testosterone treatment on functional exercise

capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in

elderly patients with chronic heart failure a double-blind, placebo-controlled,

randomized study, Jour Amer Coll Cardiol 2009; 54(10):919-27.

36. Malkin, C., et al., Testosterone therapy in men with moderate severity heart failure: a

double-blind randomized placebo controlled trial, Eur Hear Jour 2006; 27:57-64.

37. Toma, M., et al., Testosterone supplementation in heart failure, Circulation 2012;

5:315-21.

38. Abbott, R., et al., Serum estradiol and risk of stroke in elderly men, Neurology 2007;

68(8):563-68.

39. Tivesten, A., et al., Circulating estradiol is an independent predictor of progression of

carotid artery intima-media thickness in middle-aged men, Jour Clin Endocrinol Met

2006; 91(11):4433-37.

40. Mohamad, M., Serum levels of sex hormones in men with acute myocardial infarction,

Neuro Endocrinol Lett 2007; 28(2):182-86.

41. Dunajska, K., et al., Evaluation of sex hormone levels and some metabolic factors in

men with coronary atherosclerosis, Aging Male 2004; 7(3):197-204.

42. Tivesten, A., et al., Low serum testosterone and high serum estradiol associated with

lower extremity peripheral arterial disease in elderly men. The MrOS Study in Sweden,

Jour Amer Coll Cardiol 2007; 50(11):1070-76.

43. Tripathi, Y., et al., Serum estradiol and testosterone levels following acute myocardial

infarction in men, Jour Physiol harmacol 1998; 42(2):291-94.

44. Lerchbaum, E., et al., High estradiol levels are associated with an increase in mortality

in older men referred to coronary angiography, Exp Clin Endocrinol Diabetes 2011;

119(8):490-96.

45. Sudhir, K., et al., Cardiovascular actions of estrogens in men, Jour Clin Endocrinol

Metab 1999; 84(10):3411-15.

46. Merchant, S., et al., Erythrocytosis. In Hematopathology. 2nd Ed. His, E., (Ed.)

Philadelphia: Elsevier/Saunders, 2012.

47. Bassil, N., et al., The benefits and risk of testosterone replacement: a review, Ther Clin

Risk Manag 2009: 5:427-48.

48. Skogastiema, C., et al., A supraphysiological dose of testosterone induces nitric oxide

production and oxidative stress, Eur Jour Prev Cariol March 7, 2013.

49. Cappola, A., Testosterone therapy and risk of cardiovascular disease in men, JAMA

2013; 310(17):1805-06.

50. Death, A., et al., DHT promotes vascular cell adhesion molecule-1 expression in male

human endothelial cells via a nuclear factor-kappa-B-dependent pathway,

Endocrinology 2004; 145(4):1889-97.

More studies

Published online 2012 April 23. doi: 10.1038/aja.2012.21PMCID: PMC3720171

Testosterone and cardiovascular disease in men

Paul D Morris and Kevin S ChannerIrrespective of regional variations in the prevalence of coronary heart disease, the burden of coronary disease in men is approximately three times that of women.1 Moreover, men develop coronary disease approximately 10 years ahead of women. Multiple logistic regression analyses have shown that these differences are not explained by simple differences in coronary risk factor profiles.2 The relationship between male gender and the prevalence of coronary heart disease suggests a role for sex hormones in the aetiology of cardiovascular disease. Historically, much attention has been paid to the cardioprotective effects of female sex hormones in women. In women, physiological levels of oestrogen appear protective against atherosclerosis, whereas conditions associated with oestrogen deficiency such as early menopause or bilateral oopherectomy are associated with an increased burden of coronary disease.3, 4, 5The combination of: (i) the male preponderance of coronary disease; (ii) the cardioprotective effects of oestrogens in pre-menopausal women; and (iii) the increased cardiovascular death in men abusing anabolic steroids, have led to the view that testosterone is deleterious to the male heart. Contrary to this view, current evidence suggests that normal and physiological levels of testosterone are not deleterious to the male heart and are, in fact, beneficial. It is hypotestosteronaemia (low testosterone) which is associated with adverse coronary risk profiles and with coronary morbidity and mortality in men. Moreover, androgen replacement therapy has positive effects on coronary risk factor profile and acts as a vasodilator demonstrating potential, because it is an anti-ischaemic agent.

Physiology and decline with age

Testosterone is a steroid hormone synthesized, predominantly, by the testicular Leydig cells under the control of the gonadotrophins, chiefly, luteinizing hormone. Testosterone secretion demonstrates both diurnal and circannual secretion, peaking in the early morning and in the autumn. Once synthesized, it circulates bound to serum proteins with approximately 68% tightly bound to sex hormone binding globulin and 30% bound more loosely to albumin. Only about 2% circulates freely and it is this free portion along with the albumin bound portion that make up the biologically available (bioavailable) testosterone. Testosterone is metabolized by 5- reductase to dihydrotestosterone or by aromatase, in adipose tissue, to oestrogens. Men with increased abdominal fat, therefore, metabolize more testosterone to oestrogen, resulting in gynaecomastia and a reduction in secondary sexual characteristics.

Multiple cross-sectional studies have demonstrated a fall in androgen levels with advancing age.16, 17, 18, 19, 20, 21, 22, 23, 24, 25 However, unlike women, men do not experience the well characterized, sudden and rapid decline in sex hormone levels and cessation of reproductive capability as they age. Contrasting with the female menopause, the male andropause' often results in rather non-specific symptoms, including reduced libido, fatigue, weakness, depression, dry skin and poor concentration, symptoms which are often regarded simply as a natural part of the aging process. Clinical signs can include fine-wrinkled dry skin, low hairline, gynaecomastia and muscle wasting. Due to the non-specific nature of the symptoms, hypogonadism often remains undiagnosed and thus untreated in many cases. In others, it is diagnosed but remains untreated due to a perceived concern regarding adverse iatrogenic effects on the prostate and heart. Harman et al.25 investigated the nature and potential aetiological factors involved in the change in sex hormone levels with age in the Baltimore Longitudinal Study of Aging. They found that in 890 generally healthy men, both total and free testosterone decreased at a constant rate from the third to ninth decade. the fall in free testosterone was more impressive and due, at least in part, to the significant rise of sex hormone binding globulin with age. These observations were independent of obesity, comorbid illnesses, medication, smoking and alcohol consumption.

Testosterone and coronary risk factors

It was previously believed that the higher prevalence of coronary disease in men may be explained by differences in risk factor profiles between genders. It is widely regarded that men display behaviours which are considered, cardiologically, more risky with increased levels of smoking and with diets richer in saturated fats.2 However, multiple logistic regression analysis has shown that differences in behavioural profiles do not account for the excess burden of coronary disease in men.2, 26 The development and progression of coronary atherosclerosis is heavily influenced by the interaction of multiple risk factors. The lipid profile in men is naturally more pro-atherogenic than in women, a difference that has, in the past, been attributed to higher circulating testosterone levels. Irrespective of regional variations in the prevalence of coronary heart disease, the burden of coronary disease in men is approximately three times that of women.1 Moreover, men develop coronary disease approximately 10 years ahead of women. Multiple logistic regression analyses have shown that these differences are not explained by simple differences in coronary risk factor profiles.2 The relationship between male gender and the prevalence of coronary heart disease suggests a role for sex hormones in the aetiology of cardiovascular disease. Historically, much attention has been paid to the cardioprotective effects of female sex hormones in women. In women, physiological levels of oestrogen appear protective against atherosclerosis, whereas conditions associated with oestrogen deficiency such as early menopause or bilateral oopherectomy are associated with an increased burden of coronary disease.3, 4, 5Moreover, there is a negative correlation between the number of components of the metabolic syndrome and the absolute serum testosterone level with a 10-fold increase in the relative risk of frank hypogonadism, if all four of the components of the metabolic syndrome are present.37 In an analysis of data from the Massachusetts Male Aging Study, it was found that, over a 15-year period, in non-obese men, low testosterone at baseline led to a two- to fourfold increased risk of developing metabolic syndrome. The authors concluded that low testosterone may act as an early warning sign for the development of the metabolic syndrome, and provide an opportunity for early (primary) intervention.38Testosterone levels in men with coronary heart disease

Contrary to the notion that higher testosterone levels account for the higher burden of coronary disease in men than women, there is an increasing body of literature indicating that men with coronary artery disease (CAD) have significantly lower testosterone levels than men without CAD. Cross-sectional studies comparing men with and without CAD have repeatedly demonstrated significantly lower levels of both total and bioavailable testosterone in men with CAD than in controls with normal coronary arteries.39 . One study of over 900 men found that both total and bioavailable testosterone were significantly lower in men with coronary artery disease than in those without.42 The magnitude of the difference in testosterone levels between men with coronary artery disease and those without is clinically significant. The same study demonstrated a prevalence of hypogonadism of 24% in men with coronary artery disease, by strict criteria, which is approximately three times higher than the expected background rate.

One question which remains unanswered is whether low testosterone levels accelerate the development of CAD or whether they are simply a consequence of chronic illness?

Cause consequence?

Coronary artery disease is a chronic illness and patients with CAD often have other associated chronic illnesses such as hypertension, diabetes and hypercholesterolaemia. Maybe this is the cause of the lower testosterone levels? Regression analysis has demonstrated that even when the effects of such comorbid conditions are controlled for the relationship between CAD and lower testosterone levels remains.2, 26 Furthermore, if hypogonadism was a consequence of CAD, it might be expected that patients with more severe CAD might have lower testosterone levels than those with milder disease. This hypothesis has not been proven. The prevalence of hypogonadism in men with asymptomatic coronary plaque is similar to the prevalence in men with symptomatic CAD and both groups have lower levels of testosterone than men with normal coronary arteries, supporting a causative role more than a symptomatic consequence (Morris PD, 2001. unpublished data).

Studies in male animals have shown accelerated atherosclerosis after castrationan effect that is abrogated by androgen replacement therapy.43, 44Risk factors for coronary disease such as diabetes are also associated with lower testosterone levels and testosterone supplementation in these men improves their risk factor profile with improvements in glycaemic control, adiposity and lipid profiles.45 . In a study of over seventy thousand men (73 196) treated with androgen suppressive therapy (blocking testosterone) for prostate cancer, there was a 44% increase in the risk of developing diabetes and 16% increase in the risk of cardiovascular death or myocardial infarction, effects which were evident as early as 14 months.13 Similar conclusions were drawn in a study of men treated by orchidectomy, where, over a 10 year period, there was a twofold increase of cardiovascular mortality.50 Androgen suppressive therapy has also been linked with increased central blood pressure, insulin resistance, and hyperglycaemia.51, 52, 53, 54 However, one must be careful to consider the difference in androgen levels between the moderate hypotestosteronaemia associated with aging and the more extreme low testosterone levels associated with androgen suppressive therapy used in prostate cancer treatment.

Vaso-active properties of testosterone

Although some people have suggested that the reported positive effects of androgens in cardiovascular disease may simply reflect non-specific effects on skeletal muscle function and mood, it has been demonstrated that testosterone does have direct vaso-active effects. It is known that testosterone levels inversely correlate with penile artery smooth muscle compliance with men with lower testosterone levels more likely to suffer erectile dysfunction.55 . One study showed that acute intracoronary administration of testosterone, at physiological concentrations, induces coronary artery dilatation and increases coronary blood flow in men with established coronary artery disease.61 Other studies of acute intravenous testosterone therapy have demonstrated increased cardiac output mediated by a reduction in the systemic vascular resistance and increased ischaemic threshold in men with CAD.62, 63 Clinical trials have demonstrated that chronic and physiological dose testosterone supplementation significantly improves anginal symptoms and the time to electrocardiographic ischaemia on exercise treadmill testing,64, 65, 66, 67 an effect which is proposed to be mediated by testosterone's vasodilatory action.

Testosterone levels and mortality

The aforementioned decline in testosterone in some men has previously been regarded by some simply as part of the natural physiology of ageing. However, five recent studies have demonstrated that lower baseline testosterone levels are a significant predictive marker for mortality even after controlling for the effects of comorbid conditions. In 2004, Shores et al.68 reported that hypotestosteronaemia was a marker for mortality in a group of 44 geriatric inpatients within a 6-month period. In a following study, the same group performed a computerized analysis of the Veteran's Affair's clinical database.69 They looked at 850 men over a 4- to 8-year period controlling for comorbid conditions which would affect mortality, e.g. concurrent cancer. They found that men with low testosterone levels had an 88% (20.1% vs. 34.9%, P