Life Extension Magazine June 2012
As We See It
The Testosterone Controversy
By William Faloon
Despite compelling findings of efficacy, conventional doctors still question the value of testosterone replacement in maturing men. This oversight is causing needless heart attacks and strokes.
Low testosterone is associated with excess abdominal fat,1-4 loss of insulin sensitivity,5,6 and atherosclerosis.7,8
A critically important role of testosterone is to enable HDL to remove excess cholesterol from the arterial wall and transport it to the liver for disposal. This effect of enhancing HDL is termed “reverse cholesterol transport” and is vital to preventing arterial occlusion.9,10
Cardiologists routinely prescribe statin drugs to lower LDL, a lipoprotein that transports cholesterol from the liver to the arteries. These same doctors, however, fail to maintain sufficient testosterone levels in their patients to enable HDL to remove cholesterol buildup in the arteries. This is one reason why statin drugs have not always been shown to work in older men, who require functional HDL to keep arterial linings free of excess cholesterol. 11,12
Numerous studies document the vital role that testosterone plays in maintaining youthful metabolic processes throughout the body.6,7,13-21 A large new study confirms the deadly impact of low testosterone in older men.22
What’s scary are clinical trials designed by doctors who have no idea how to achieve youthful hormone levels. Men who enroll in these studies are subjected to lethal dangers because testosterone and estrogen blood levels are not properly balanced.
Cells throughout a man’s body are laden with receptor sites that are activated by the hormone testosterone. When testosterone is available to bind to these receptor sites, good things happen such as elevated mood and improved cognition in response to plentiful testosterone being available to the brain.23-25
Be it muscle, bone, vascular, or nerve tissue, testosterone provides critical command signals for your cells to behave in a youthful manner.8,26-33 As testosterone levels diminish, degenerative processes set in.
New Published Study Confirms Testosterone’s Benefits
Of considerable interest is the relationship between testosterone blood levels and cardiovascular events such as heart attack and stroke. In a revealing new study, researchers identified 2,416 men (aged 69-81 years) who were not on any kind of testosterone- affecting treatment. These men were subjected to a battery of blood tests that included total testosterone and estradiol (estrogen).
The first observation was that men with increasing levels of testosterone had a decreased prevalence of diabetes, hypertension, and body fat mass. Compared to men with the highest testosterone levels, those with low testosterone were twice as likely to have a history of cardiovascular disease. It was also observed that men with the highest testosterone levels were the most physically active.17
This large group of men was followed for an average of 5.1 years. Men in the highest quartile of total testosterone (above 550 ng/dL) had a 30% lower risk of cardiovascular events. Any level of total testosterone below 550 ng/dL resulted in significant increased risk, thus helping to establish a minimal baseline as to where total testosterone should be to guard against heart attack or stroke.
Estradiol levels measured in this group appeared to be mostly in safe ranges and did not impact incidence of cardiovascular events.
Data was tabulated based on hospital reports and/or death certificates for heart attack, stroke, unstable angina, bypass surgery, or stenting.
The four quartiles of total testosterone in this large group of older men were:
Quartile 1: Total testosterone below 340 ng/dL.
Quartile 2: Total testosterone be-tween 341-438 ng/dL.
Quartile 3: Total testosterone be-tween 439-549 ng/dL.
Quartile 4: Total testosterone above 550 ng/dL.
Of interest was the finding that Quartiles 1, 2, and 3 had about the same risk of cardiac adverse events. It was only in Quartile 4 (when total testosterone exceeded 550 ng/dL) that the 30% reduction in cardiovascular events occurred.
This finding showed that it did not matter if these men’s total testosterone was very low (below 340 ng/dL) or moderately low (up to 549 ng/dL)…they all had a similar increased risk for suffering a cardiovascular event. Only when total testosterone exceeded 550 ng/dL did cardiovascular risk plummet.
This finding remained consistent for cerebrovascular disease incidence, where men with the highest total testosterone (Quartile 4) had a 24% reduced risk of transient ischemic attack or full-blown stroke. The researchers noted this association with reduced cerebrovascular risk remained after adjustment for traditional risk factors.
The conclusions by the researchers who conducted this study were:
“Higher serum testosterone levels are associated with a reduced risk of fatal and non-fatal cardiovascular events in community dwelling elderly men.” 17
Mainstream Doctors Know Nothing About Hormone Balance
If you ever wonder why so many deaths are directly caused by medical errors, look no further than the obvious mistakes made by doctors who design human clinical trials.34-36
It has long been known that aging men are at risk for having excess activity of an enzyme called aromatase. The effect of surplus aromatase is that too much testosterone is converted to estrogen.37,38
Aging men have a propensity to develop dangerously high levels of estrogen combined with woefully inadequate testosterone, though many aging men suffer both low testosterone and estrogen.39,40
Elevated estrogen can sharply increase heart attack risk by promoting platelet aggregation and coagulation in coronary arteries.41,42 Higher estrogen in men also increases inflammation which can cause unstable plaque to rupture and occlude a coronary artery, thus creating a sudden heart attack.43-45
Now just imagine designing a study where a huge dose of testosterone cream is applied to dilapidated men with a high prevalence of obesity, hypertension, diabetes, and elevated LDL. These men (average age 74) all suffered limited mobility and many had known cardiovascular disease. All these physically impaired men had very low total testosterone levels (mean 243 ng/dL) at baseline, but the doctors never bothered to check their estrogen levels.
The study was stopped after six to twelve months because the decrepit men receiving testosterone (at a dose more than twice what is typically prescribed) showed a 4.6-fold increase in adverse cardiovascular events.46
The purpose of the study was to see if high-dose testosterone cream could improve strength and mobility in these degenerated men. Early results showed it to be effective in improving muscle strength, but the study had to be stopped because too many cardiovascular events occurred.
The study authors admitted that the testosterone cream may have converted to estrogen and caused these cardiac problems. My question is why they failed to test estrogen levels in the beginning and monitor estrogen after administering high-dose testosterone cream?
Obesity alone causes estrogen levels in men to spike.38 The reason overweight men grow breasts is that abdominal fat tissue synthesizes huge amounts of aromatase, which converts their testosterone to estrogen. Obese men with elevated estradiol are strongly advised to take aromatase-inhibiting agents.
By applying high doses of testosterone cream, estrogen levels would be expected to spiral upward in many of these unhealthy men, thus predisposing them to cardiovascular events inflicted by abnormal arterial blood clotting (thrombosis) and inflammation.
Despite these obvious flaws, this negative study was widely circulated in the medical mainstream and used as a basis to advice doctors to prescribe testosterone cream with caution.
This is unfortunate as the preponderance of data shows significant protective effects when testosterone and estrogen are in a youthful state of balance. Most published studies fail to look at estrogen levels in men, despite a massive body of evidence showing significant increases in mortality when estrogen levels are too high or too low.47-52
Unpublished Study Associates Testosterone With Greater Heart Risk
In August 2010, an unpublished report was circulated in the media that contradicted numerous published studies showing higher levels of testosterone protect against heart attack.53
This negative report was based on a study of less than 700 men (aged 65 and older) and claimed that men with higher testosterone doubled their risk of a heart attack or other cardiac events.
While even the author of this study admitted the findings were preliminary and had not been peer-reviewed, one striking discrepancy was that it defined high total testosterone as being greater than 495 ng/dL. Recall that in the much larger (2,416 men) published study (described at the beginning of this article) that a 30% reduction in cardiovascular events did not occur until total testosterone levels exceeded 550 ng/dL.
As is typical of so many of these studies, estrogen levels do not appear to have been measured, so we have no idea if any of these men in this negative study had the youthful balance of testosterone and estrogen required to protect against cardiovascular disease. (Estrogen was measured in the study showing reduction in cardiovascular events in men with the highest testosterone level.)
How Testosterone Protects Against Heart Attacks
Most people know that higher blood levels of HDL protect against atherosclerosis and subsequent heart attack. What few understand is the critical role that testosterone plays in enabling HDL to remove built-up cholesterol from the arterial wall.
HDL removes cholesterol from the arterial wall and returns it to the liver for safe disposal via a process known as reverse cholesterol transport. Testosterone enhances HDL-induced reverse cholesterol transport from the arterial wall.9 That is one of testosterone’s unique and lifesaving anti-atherosclerotic effects.
While a person can reduce their arterial wall exposure to cholesterol through healthier diets and by taking certain drugs, the average person still synthesizes about 750 mg every day of cholesterol in their peripheral tissues (outside of the liver). If there is any distortion in the HDL-mediated removal of cholesterol (i.e. reverse cholesterol transport) from the arterial wall, the consequence is atherosclerosis.54
Said differently, testosterone is required for optimal transport of excess cholesterol from our tissues and blood vessels to our liver for processing and disposal. In the testosterone-deficient state, reverse cholesterol transport is compromised, and excess cholesterol cannot be removed from the arterial wall.55-57
HDL and testosterone levels often plummet in aging humans.59,60 The combination of low HDL and low testosterone virtually guarantees an explosion in demand for vascular stents and drugs that earn tens of billions of dollars in profits each year for pharmaceutical behemoths.
Under optimal circumstances, HDL efficiently removes cholesterol from arterial walls and then transports it (via reverse cholesterol transport) to the liver for elimination (mostly through the bile duct into the intestines). When there is a deficiency of testosterone, HDL is less efficient in removing debris from the arterial wall and the liver is less efficient in breaking down cholesterol- laden HDL from the blood- stream.
Armed with this knowledge, you can now see past the charade perpetrated by the medical establishment that still questions the value of testosterone supplementation.
Numerous well-controlled human studies show that higher testosterone levels play a critical role in maintaining healthy blood flow throughout the body by accelerating reverse cholesterol transport—thereby helping to prevent atherosclerosis.61,62
Low Testosterone Sharply Increases Coronary Artery Disease Risk
The relationship between low testosterone and increased coronary artery disease incidence has been the featured topic of several covers of Life Extension Magazine® over the past two decades.
One study evaluated men under age 45 who presented with coronary artery disease compared with an age-matched control group. The findings revealed that even moderately reduced free testosterone blood levels (below 17.3 pg/mL of blood) in these younger men resulted in a 3.3-fold greater risk of developing premature coronary artery disease compared with men who had values above 17.3 pg/mL.70
To put this testosterone blood reading in perspective, aging men who don’t use testosterone-boosting nutrients or drugs often have very low free testosterone blood levels (less than 10 pg/mL of blood). These same men often have low HDL blood test readings in the danger zone (less than 40-50 mg/dL).
More recent studies confirm low blood levels of free testosterone increase cardiovascular mortality in men.71,72
Is it any wonder that despite aggressive use of statin drugs and other advances in cardiac medicine, heart attack and stroke are still today’s leading killers?
Testosterone for Chronic Heart Failure
Chronic heart failure is a disabling condition characterized by exercise intolerance and shortness of breath. The disease arises from prolonged inflammatory cytokine activation that also causes severe muscle wasting. Testosterone increases anabolic function, improves arterial dilation, augments cardiac output, and is known to have anti-inflammatory activities. Low testosterone is a common characteristic in men suffering from heart failure.
In an interesting report, 20 men with an average age of 62 took part in a randomized study in which testosterone or placebo was injected every two weeks for 12 weeks. Compared to the placebo group, men receiving testosterone could walk 3.5 times farther.73 Mean symptom scores and a critical blood measurement of heart function (brain natriuretic peptide) improved in men receiving testosterone, but not in the placebo group.
A trend toward improved mood scores was noted in the testosterone group, which is important because men with chronic heart failure have high rates of depression. The doctors concluded that 12 weeks of testosterone treatment led to significant improvements in physical capacity and symptoms.73
Testosterone and Stroke Risk
One way to evaluate one’s risk for a stroke is to undergo an ultrasound test to measure carotid artery thickness. When excess occlusion is detected, a risky surgical procedure (carotid endarterectomy) is performed to restore blood flow to the brain.
In a study published by the American Heart Association in April 2004, ultrasounds were used to measure the carotid intima-media thickness in 195 independently living elderly men in 1996 and again in 2000. The researchers also measured blood levels of free testosterone in these men.
The results showed that men with low testosterone had a 3.57 times greater progression of carotid intima-media thickening than those with higher testosterone levels. These associations were independent of body mass index, waist-to-hip ratio, hypertension, diabetes, smoking, and serum cholesterol levels. The doctors concluded:
“Low free testosterone levels were related to intima-media thickening of the common carotid artery in elderly men independently of cardiovascular risk factors.” 21