Testosterone Replacement Therapy Repairs Heart Attack Damage

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Testosterone Replacement Therapy Repairs Heart Attack Damage

By: William LLewellyn

April 13, 2012


The potential health benefits of testosterone replacement therapy in men suffering from low testosterone levels are mounting in the medical literature. This latest study examined the potential effects of TRT after a heart attack, or myocardial infarction (1). During the investigation, castrated rats were subject to ligation of the left anterior descending coronary, which is used as a model for myocardial infarction. Some were then given doses of testosterone to replace normal physiological levels. The two groups (HRT treated and untreated) were followed for 4 weeks, and then compared to see how well each recovered from the myocardial infarction.

Rats that had untreated hypogonadism (low testosterone due to castration) noticed reduced capillary density, cardiac function that was more notably impaired, and a greater level of heart tissue damage 28 days post-infarction. When the hypogonadal rats were given testosterone, however, these negative cardiac effects were reversed. In this study, testosterone administration (replacement) promoted a greater level of angiogenesis (formation of new blood vessels). This pro-angiogenesis effect was also associated with an enhanced expression of HIF-1a (hypoxia-inducible factor 1a), SDF-1a (stromal cell-derived factor 1a) and VEGF (vascular endothelium growth factor). While more research is needed, this study suggests testosterone replacement may be beneficial for men following heart attack.


(1) Eur J Pharmacol. 2012 Mar 30. [Epub ahead of print]

Testosterone Treatment Cuts Mortality Rate in Half

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Testosterone Treatment Cuts Mortality Rate in Half

APRIL 21, 2012
By: William Llewellyn

There is an abundance of studies in the medical literature associating low testosterone levels with negative health outcomes such as cardiovascular disease, metabolic syndrome, diabetes and increased mortality. We also find no shortage of papers linking testosterone replacement therapy with improvements in related short-term health markers such as blood lipids, adiposity, insulin and blood sugar levels. However, there are as of yet a limited number of long-term large-population-based studies examining the overall changes in mortality rates when men are given hormone replacement therapy. A new paper in the Journal or Clinical Endocrinology and Metabolism expands our knowledge in this needed area of study.

The paper concerns the recent study of 1,031 male veterans over the age of 40. Each of the men began the study with testosterone levels below 250 ng/dL, regarded as the very low limit of the “normal” range for testosterone (they had clinical hypogonadism). Approximately 400 of the men were then given testosterone medications to correct the hypogonadism. The two groups (treated and untreated) were followed for at least 3 years, during which time health and mortality were assessed. The results were quite startling. Testosterone treatment cut the mortality rate in half (20.7% vs. 10.3%). After assessing other factors such as age, diabetes, and CVD status, only a strong association remained between testosterone treatment status and reduced death rate.

This study further underlines what we’ve been finding with short-term health markers, and long-term studies of hypogonadism; low testosterone appears to be a strong risk factor for increased mortality. In this case, which examined a substantial population of men; treatment had a remarkable influence over mortality. More research in this area is sorely needed. However, this positive trend seems to be gaining in strength. Common TRT drugs such as AndroGel, Testim, or Axiron may be much more important to men than for just treating physical (muscle, strength) or sexual (erectile dysfunction, low libido) issues. These medicines may turn out to be some of the most effective ways to protect our health when our levels of natural testosterone drop.


Hormonal Body Fat Signatures

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Have you ever wondered why people respond differently to diets?  Why is it that one person can eat all they want and never gain and inch while someone else gains weight just looking at food? Can we really say this is all about genetics?  After all, the collective genetics of our society didn’t just drastically change in the last fifty years.  We have roughly the same genetics as our grandmothers and grandfathers yet they did not have the same struggles with weight. These questions have confused and frustrated dieters and health care practitioners for decades.  But why are we so confused?  Doesn’t it go without saying that every person is unique and therefore requires a different approach to food?  While this may seem like common sense, it is not common practice.  In fact, the very people who claim to be the experts on diet and nutrition have been pushing a one-size fit all approach for years and it is not working.

People come in all shapes and sizes.  We have all come to appreciate the unique appearance of individuals.  It is actually pretty amazing to think that of the close to 7 billion people on the planet not one is physically identical. Even twins can vary in shape, behavior, likes and dislikes, etc.  The fact is we are as different on the inside as we are on the outside.  We each have a unique biochemistry that sets us apart from everyone else.  While we all undoubtedly share common traits and overlapping metabolic tendencies, to assume we will all derive equal benefit from the same diet is a bit short-sighted.

Hormones and Diet

When most people think of dieting they imagine calories and weight loss.  This way of thinking is not the most beneficial way to think for a couple of very important reasons. First, there are different types of calories you can eat. There are calories from fat, carbohydrates, and protein and these calories may come with varying micro-nutrient content. And all these calories are not equal as far as the body is concerned.  It is no longer accurate to treat all calories as the same because calories from different sources affect the body differently.  Likewise, there are different calories that can be burned.  When talking about diet most people desire to lose fat and therefore seek to burn fat calories.  Speaking of calories and weight loss in general terms is not useful because it treats all calories from any source as the same and ignores the individual nature in which people burn fat.  What is needed is a new conceptualization of the calorie/weight loss model.

The hormone model of weight loss is a much more useful way of thinking about nutrition because it explains the variations people see in outcome from different diets.  Every time a person eats they release hormones into the body.  The type of calories consumed directly determine the hormones released.  For instance starch or sugar is a major stimulant of insulin while protein also stimulates insulin but is a major stimulant of a hormone called glucagon as well. This is a hugely powerful piece of information because insulin is a fat storing hormone while glucagon is a fat burning hormone.  Both protein and carbohydrates supply calories, but these calories affect hormonal biochemistry differently.  The choice of the type or quality of food eaten determines a great deal related to body composition.

So does this mean we should only eat protein and stay away from starch?  Not exactly, and this is where things start to get a little complicated.  When you eat a food it is not just the food that determines what happens to your body, but also the natural metabolic tendencies your body was born with.  Remember, we are all different.  Our genetics and metabolic actions play a large role in our response to food.  Some people have naturally high levels of insulin because it is there natural physiological state.  Others have naturally low levels.  The combination of your inherent hormonal state coupled with the diet you choose is the real determinant of dietary success.  But how can you determine your own unique hormonal makeup without expensive tests?

Hormones and Body Shape

Wouldn’t it be nice if there were a way to look in the mirror and have a clue of your individual needs and which diet may be right for you?  To a degree you can. We have all heard of “apples” and “pears”.  These terms are a reference to different fat storage patterns on the body.  “Apples” store their fat in the belly or midsection, while “pears” store it lower down.  There are also other types of fat storage. Some people tend to have large fat deposits on their sides below their armpits, and on the back of their arms.  Some people store fat as love handles, and some more in the front of the belly.  Others store in the backs of their legs or sides of their hips.  Still others store fat mostly in their upper back.  And of course some people store fat all over.  Most likely you already know where you tend to store your fat.  But what is responsible for this site-specific fat storage?

Hormones not only tell the body how to use the fuel it consumes, but they also play a role in where on the body fat is stored.  This is a complicated matter and we caution you not to think of hormones in an all-or-nothing fashion.  Hormones behave differently depending on their ratios with other hormones.  For instance, the ratio of insulin to glucagon is a major determinant of fat storage.  If insulin is elevated along with glucagon, there is less fat storage.  Excess fat storage becomes an issue when insulin levels rise unopposed by glucagon.  With the fat burning action of glucagons absent, the fat storing effects of insulin go unchecked.  It is impossible to know the effects of one hormone without understanding the impact of others.

This is why labeling one point on the body with a particular hormone may not be the best approach. For example, testosterone is largely regarded as a hormone that reduces fat storage around the middle. We can also see it in action by studying transgender population. Females undergoing hormone therapy to become more “male” take large doses of testosterone and will see their breast shrink and become more like pecs and will also see there arms and legs tighten. This has to do with testosterone’s relationship to estrogen and progesterone and not just testosterone’s action alone.  A man who begins to develop “man boobs” could be low in testosterone, have too much estrogen, be dealing with a high prolactin level or be suffering from hypothyroid. Not understanding how all these hormones can impact that one area (the pecs) may leave you confused.  So, it is not enough to know how one hormone acts by itself, but you also need to know how it interacts with other hormones to pinpoint the issue.

Despite the complexity of hormones there are some generalities that can be made and these can be directly observed by body shape and where on the body fat is stored.  Insulin and cortisol levels in higher amounts tend to result in fat accumulation in the middle of the body.  Fat storage in the lower body may signal decreased levels of insulin and cortisol with higher levels of estrogen and progesterone (estrogen opposes the action of insulin and cortisol and progesterone opposes the action of cortisol).  Fat deposits on the back of the arm or leg may signal a reduction in growth hormone or testosterone, while fat storage in the breasts and hips are may provide an indication of excess estrogen.

Food and Hormones

Hopefully you are beginning to see the problem.  We each have a unique hormonal makeup in the body.  Some of us have higher insulin and lower glucagon.  Some of us are more estrogen dominant.  Others have high testosterone levels.  Now couple the unique nature of people hormonally with the known hormonal effects of food and things are impacted even more. A new study published this year in the May 16th issue of the Journal of the American Medical Association shows what we have always known.  People respond differently to diets based on their individual nature.  This study was interesting because it showed the determining factor for success or failure with a diet was hormonal responses in the body.  The goal was to use two different diets that affected insulin differently and see how these diets performed in people with varying insulin responses.

The diets compared were a low carbohydrate diet (40 % carbohydrate and 35% fat) and a low fat diet (55% carbohydrate and 20% fat).  In this study “apples” (individuals who store fat primarily in the midsection) were compared to “pears” (people who tend to store fat in the hips and thighs). Apples secrete more insulin after meals and pears secrete less. The apples lost more weight on the low carbohydrate diet and were able to maintain that weight loss for 18 months. The pears lost weight on both diets as long as the calories were reduced.  Pears lost weight more slowly and tended to regain weight more quickly.  What this study showed is that body shape and hormonal influence play a role in responses to dietary interventions.

Taking it one step further

Analysis of the above study shows that it is not just calories that matter when it comes to weight loss.  We must understand our individual nature and act accordingly.  The shape of the body provides direct insight into the hormonal situation we find ourselves in.  Apple types who are strong insulin secreters should avoid foods that cause large rises in insulin.  The natural tendency to produce excess insulin in response to a meal along with a higher insulin level in the body is a recipe for fat gain.  Pears are less insulin responsive and are less affected by changes in carbohydrate intake.  Instead, they should focus on lifestyle changes that address their unique hormonal makeup.  Excess storage of fat in the lower body is primarily a result of estrogen and growth hormone levels.  Avoiding exogenous estrogen sources like plastics, soy, and coffee along with human growth hormone producing exercise is a smart strategy.

Other areas to address are high cortisol to progesterone or estrogen ratios.  Excess cortisol is characterized by a round face and stomach along with a puffy appearance on the body.  As cortisol rises and progesterone falls women in particular will begin to develop fat storage at the belly.  Working to lower stress by engaging in cortisol lowering exercise like yoga, Tai Chi, and meditation will help as will high intensity shorter duration cardio and weight training.  For issues with thyroid look for swelling in the neck and fat deposition under the armpits as well as thinning hair and general fatigue.  A strategy that addresses the cause of the thyroid dysfunction may take you beyond exercise into the realm of nutrition, stress management, micronutrition and toxin exposure.

The back of the arms and upper chest are a window into the testosterone to estrogen ratio.  As men begin to develop fat deposits around the pecs, it is a sure sign their testosterone levels are falling and/or the estrogen levels are rising. As stated before this can also be due to other hormonal influences like prolactin.  Heavy weight training and good quality protein sources can help reverse this trend. As can the use of aromatase inhibiting herbs and supplements.  Women with loose and sagging triceps are also suffering from a lack of relative testosterone & HGH, but this may also be due to thyroid or excess cortisol issues.  In order to reverse this trend, they must make heavy weight training a priority.

As you can see, when you are dealing with the hormonal influences on body fat it is best to view hormones in the context of the full hormone interactions. It is also useful to know other clinical signs that come along with these dysfunctions.  Low libido and depression may bolster your suspicion of low testosterone. A round face, fat storage in the upper back and neck and decreased muscle mass/flabby body may confirm issues with cortisol.  Thin hair, brittle nails, constipation and fatigue along with fat storage around the neck, underarms and triceps may confirm suspicion of thyroid hormone issues.  And of course blood labs can be extremely valuable to get measures of these hormones. It is important to realize however you will often see these fat distribution effects occur first before labs show any dysfunction.

Final thoughts

The individual nature of humans is evident.  This intuitive understanding must be translated to the world of diets and exercise instruction.  The shape of the body is a window into the hormonal make up of an individual.  Apple shapes and Pear shapes are two popular examples of body types and their relationship to diets.  The JAMA article cited in this paper points to the effect individual nature combined with dietary practices has on the body’s ability to respond to any given diet.  This is an important concept that can be developed even further when one understands the hormonal effects on body shape. The one size fits all approach to diet and exercise is no longer appropriate.  Pay attention to your individual body shape and you will have greater insight in to the diet and lifestyle that is appropriate for you.

-Article By: Metabolic Effect

Male Hormone Restoration

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Male Hormone Restoration

Originally Published by Life Extension Magazine

Life Extension Magazine reports that new studies show the benefits of testosterone therapy reach far beyond sexual health. 

The significance of testosterone for male sexual function is obvious to most. New insights, however, underscore the critical role testosterone plays in maintaining youthful neurological structure, alleviating depression, as well as inducing fat loss in those who are unable to reduce body weight regardless of diet and exercise.

Recent studies have demonstrated that low testosterone in men is strongly associated with metabolic syndrome, type 2 diabetes, cardiovascular disease (Miner and Seftel 2007), and an almost 50% increase in mortality over a seven year period (Malkin et al 2010).

Restoring testosterone to youthful ranges in middle–aged, obese men resulted in an increase in insulin sensitivity as well as a reduction in total cholesterol, fat mass, waist circumference and pro–inflammatory cytokines associated with atherosclerosis, diabetes, and the metabolic syndrome (Kapoor et al 2006, Malkin et al 2004, Heufelder et al 2009). Testosterone therapy also significantly improved erectile function (Fukui 2007) and improved functional capacity, or the ability to perform physical activity without severe duress, in men with heart failure (Malkin et al 2007).

Factors That Affect Testosterone Levels in Men 

DHEA: Dehydroepiandrosterone (DHEA) is a hormone produced from cholesterol that then follows one of two pathways, both involving two–step enzymatic conversions, to yield either estrogens or testosterone. Thus, levels of DHEA can have a role in determining levels of estrogen and testosterone, though DHEA alone is seldom enough to sufficiently restore testosterone levels in aging men.

Aromatase: One of the most important factors that affect testosterone levels and the ratio between testosterone and estrogen is the aromatase enzyme. Aromatase converts testosterone to estrogen, further depleting free testosterone levels and increasing estrogen levels.

Obesity: Obesity and associated hyperinsulinemia suppress the action of luteinizing hormone (LH) in the testis, which can significantly reduce circulating testosterone levels (Mah and Wittert 2010), even in men under the age of 40 (Goncharov et al 2009). In addition, increased belly fat mass has been correlated with increased aromatase levels (Kalyani and Dobs 2007).

The vicious circle of low testosterone and obesity has been described as the hypogonadal/obesity cycle. In this cycle a low testosterone level results in increased abdominal fat, which in turn leads to increased aromatase activity. This enhances the conversion of testosterone to estrogens, which further reduces testosterone and increases the tendency toward abdominal fat (Cohen 1999, Tishova and Kalinchenko 2009).

Sex hormone–binding globulin (SHBG): Most testosterone circulating in the bloodstream is bound to either sex hormone–binding globulin (SHBG) (60%) or albumin (38%). Only a small fraction (2%) is unbound, or “free”. (Morales et al 2010).

Testosterone binds more tightly to SHBG than to albumin (Henry et al 2002). Consequently, only albumin–bound testosterone and free testosterone constitute the bioavailable forms of testosterone, which are accessible to target tissues and carry out the actions of the essential hormone (Morales et al 2010). Thus the bioavailability of testosterone is influenced by the level of SHBG.

Aging men experience both an increase in aromatase activity and an elevation in SHBG production. The net result is an increase in the ratio of estrogen to testosterone and a decrease in total and free testosterone levels (Lapauw et al 2008). As will be discussed below, it is crucial that this skewed ratio be balanced. 

Liver Function: The liver is responsible for removing excess estrogen and SHBG, and any decrease in liver function could exacerbate hormonal imbalances and compromise healthy testosterone levels. Thus it is important that aging men also strive for optimal liver function.

Effects of Age–Related Decline in Testosterone Levels and Testosterone Therapy 

The exact cause of the age–related reduction in testosterone levels is not known; it is probably the result of a combination of factors, including:

  • Increasing body fat (especially belly fat, and therefore increasing aromatase activity)
  • Oxidative damage to tissues responsible for the production of testosterone
  • Reduction in testicular testosterone synthesis
  • Declining levels of precursor molecules, such as DHEA
  • Nutritional status and liver function

The consequences of declining testosterone levels are striking. 

Body Composition: Testosterone affects fat cell metabolism and fat loss in several ways: inhibiting fat storage by blocking a key enzyme called lipoprotein lipase that is necessary for the uptake of fat into the body’s fat cells; stimulating fat burning by increasing the number of specific receptors on the fat–cell membrane that release stored fat; increasing insulin sensitivity; enhancing growth of muscle fibers; and decreasing fat deposits. All of these effects promote lean body mass and reduce fat mass (Naharci et al 2007, Saad et al 2007).Placebo–controlled trials have demonstrated both significant increases in lean body mass and decreases in fat mass after varying courses of testosterone treatment in older men. In these studies, the greatest favorable changes in body composition were seen in participants with low baseline testosterone levels who received testosterone therapy for 12 months or longer (Allen et al 2007).

Musculoskeletal system: Bone integrity rests upon a balance between bone formation and bone resorption, which is controlled by multiple factors – including levels of estrogen and testosterone (Tok et al 2004, Valimaki et al 2004). In a clinical trial, testosterone increased bone mineral density in elderly men (Kenny et al 2010). Testosterone supplementation also has a positive effect on muscle metabolism and strength (Herbst 2004). This positive effect is undiminished with age.

Central Nervous System (CNS): Key to aging well is an optimistic outlook on life and the ability to engage in social and physical activity. However, low levels of testosterone have been associated with depression and other psychological disorders (Almeida et al 2008). To make matters worse for aging men, many conventional antidepressant medications suppress libido. Some experts suggest that testosterone therapy might reduce the need for the antidepressant medications entirely (Morley 2003, Carnhan and Perry 2004).Furthermore, testosterone treatment often increases feelings of well–being (Orengo et al 2004).

Cognition and alertness are also governed, in part, by testosterone’s effects on the CNS (Cherrier et al 2004). Low testosterone levels have been shown to correlate with lower scores on various psychometric tests (Moffat et al 2002), and similar effects have been reported in men undergoing androgen-deprivation therapy for prostate cancer (Salminen et al 2004).

Testosterone also acts as an endogenous neuroprotective agent, able to support neuron integrity against a variety of toxic insults, including oxidative stress (Ahlbom et al 2001, Pike et al 2009). In addition, testosterone has been shown to reduce β–amyloid accumulation, an important pathophysiologic factor in Alzheimer’s disease (Zhang et al 2004, Rosario and Pike 2008).

Testosterone improves neuron survival in brain regions vulnerable to neurodegenerative disease. This may explain the association of low testosterone levels in men with neurodegenerative diseases (Hogervorst et al 2004, Ready et al 2004). Studies demonstrate testosterone loss occurred 5 to 10 years prior to Alzheimer’s disease diagnosis. This suggests low testosterone is an important risk factor for Alzheimer’s disease (Moffat et al 2005; Rosario et al 2004). In a clinical study of 36 men recently diagnosed with Alzheimer’s disease, intramuscular testosterone treatment with 200mg every two weeks for up to one year was associated with improvement in both overall cognitive ability as well as critical visual–spatial function (Tan and Pu 2003). 

Glucose and Lipid Metabolism: Testosterone also has been linked to metabolic function in the body. Specifically, studies have found inverse associations between the severity of metabolic syndrome, a condition characterized by excess abdominal fat, high cholesterol and high blood pressure that predisposes one for cardiovascular disease, and low plasma testosterone (Allan et al 2007, Saad et al 2008). A clinical study demonstrated that men with low testosterone levels are twice as insulin resistant as their counterparts with normal testosterone levels, and 90% met the criteria for the metabolic syndrome (Pitteloud et al 2005). 

There also appears to be an inverse relationship between low testosterone levels and diabetes in men (Saad and Gooren 2009). Men with diabetes have lower testosterone levels compared to men without a history of diabetes (Stanworth and Jones 2009). The Third National Health and Nutrition survey of 1,413 men showed that men initially ranked in the lowest one–third with respect to either free or bioavailable testosterone were approximately four times more likely to have prevalent diabetes compared to those ranked in the top one–third, after researchers adjusted the results for age, race/ethnicity, and adiposity (Selvin et al 2007).

Cardiovascular Health: While conventional thought has been that because more men die from heart attacks than women, the disparity must have something to do with testosterone. However, research is pointing out that, in fact, the opposite may be true. Low levels of testosterone appear to be correlated with several cardiovascular risk factors, including atherogenic lipid profiles, insulin resistance, obesity, and a propensity to clot (Jones et al 2005). In addition, recent research is showing a clear relationship between low testosterone levels and increased incidence of cardiovascular disease and mortality in men (Malkin et al 2010).

Prostate health: Compared to younger men, older males have much more estradiol (a potent form of estrogen) than free testosterone circulating in the body. These rising estrogen and declining androgen levels are even more sharply defined in the prostate gland.

Estrogen levels increase significantly in the prostate with age, and estrogen levels in prostate gland tissues rise even higher in men who have BPH (Shibata Y et al 2000; Gann PH et al 1995; Krieg M et al 1993).

An important study indicates that testosterone is beneficial for the prostate gland in the vast majority of cases. In this study researchers looked at multiple parameters, including prostate volume, prostate–specific antigen (PSA) levels, and lower urinary tract symptoms in a group of men with low or low-normal testosterone levels (Pechersky et al 2002). Of the 207 men studied, 187 responded favorably to testosterone treatment.
The Importance of Hormone Testing 

Millions of aging men have the dual conditions of low testosterone and high cholesterol. Conventional physicians prescribe cholesterol–lowering drugs to reduce cholesterol, when, in fact, the age–related rise in cholesterol might simply be the body’s way of increasing hormone levels by supplying the raw materials necessary to make hormones (Dzugan et al 2002). Researchers at the Life Extension Foundation have successfully treated high cholesterol levels through a program of bioidentical hormone replacement therapy.

Comprehensive tests, along with a careful physical examination, are essential in detecting hormonal imbalances in aging men.

The so-called “normal” levels of testosterone in older men reflect population averages.  Most aging men would prefer not to accept the loss of youthful vigor as normal. Instead, we suggest that a more valid optimal level for all men would be in the upper one–third of the reference range used for men aged 21 to 49 years, and that any supplementation should aim to restore hormone levels to that range. The current optimal level of free testosterone is 20-25pg/mL.

When measuring testosterone levels, it is critical to determine the levels of both free and total testosterone to understand the cause of any observed symptoms of deficiency (Khosla et al 2008). 

Because of difficulties with equipment standardization and inter–laboratory variability, it is recommended that physicians consistently use the same local laboratories and gain familiarity with the accuracy, precision and definition of normal values for the assays offered in their communities (Morales et al 2010).

It is also important to remember that blood levels of both free and total testosterone vary widely among individuals, making it difficult to establish a general baseline on which to prescribe a standardized treatment protocol. However, levels are quite consistent within individuals, and thus it is important that men have multiple tests over time to determine trends and individual thresholds for treatment.

Finally, during the initial testing, it is also imperative to test estrogen levels. Many of the unwanted effects of male hormone imbalance are actually caused by an elevated estrogen level relative to low testosterone levels (the estrogen/testosterone ratio). The optimal level of estrogen (measured as estradiol) for aging men is 20-30pg/mL.

A study published in the Journal of the American Medical Association (JAMA) measured blood estradiol in 501 men with chronic heart failure. Compared to men in the balanced estrogen quintile, men in the highest quintile (serum estradiol levels of 37.40 pg/mL or greater) were significantly (133%) more likely to die. Those in the lowest estradiol quintile (serum estradiol levels under 12.90 pg/mL) had a 317% increased death rate compared to the balanced group. The men in the balanced quintile–with the fewest deaths–had serum estradiol levels between 21.80 and 30.11 pg/mL (Ewa et al 2009). This is the ideal range that THARC has long recommended male members strive for.

An epidemic problem we observe in aging male members is insufficient free testosterone, i.e., less than 20 – 25 pg/mL of serum. When accompanied by excess estradiol (over 30 pg/mL of serum), this can signal excess aromatase enzyme activity.

Testosterone Replacement Therapies 

Optimal testosterone treatment usually requires a physician’s prescription. Integrative physicians typically prescribe bioidentical testosterone creams (available from compounding pharmacies). Conventional physicians are more likely to prescribe prepackaged, testosterone patches and/or gels from pharmaceutical companies that have sought FDA approval for the mass commercialization of their products.

All forms of bioidentical testosterone have the same molecular structure and will increase free and total testosterone in the blood. The major difference is that prepackaged versions could cost up to 10 times more per dose than compounded versions. Furthermore, prepackaged testosterone gels are sold only in a limited number of doses, whereas compounded testosterone can be formulated at virtually any dose the physician feels is clinically necessary and useful.

If a man opts for testosterone therapy (available orally or as an injection, subcutaneous implant, topical cream, gel, or skin patch), he should keep several facts and precautions in mind (Schaeffer et al 2004, Cunningham and Toma 2010):

  • Hormone replacement should not be initiated without comprehensive testing.
  • The patterns and trends over time of multiple hormone levels, (for instance free testosterone, total testosterone, and estrogen), determine the specific hormone replacements required.
  • It may not be safe to use large amounts of testosterone in any form without also using aromatase–inhibiting supplements or medications.
  • Because of the risk of worsening prostate cancer, careful screening, including a digital rectal examination and prostate specific antigen (PSA) screening, must be done before starting any hormone replacement program. However, recent research indicates that low endogenous testosterone levels may present a greater risk for prostate cancer than higher levels (Morgantaler 2006, Rodman et al 2008). If a man already has prostate cancer, however, testosterone replacement should be delayed until the underlying cancer is eradicated.
  • A man contemplating hormone replacement, whether through a prescription or supplements, should work closely with a qualified physician to plan a rational treatment approach that includes continued monitoring and screening.
  • There is no “one size fits all” treatment. Individuals vary, and hormone replacement can be a simple or complex process and often requires careful attention to signs and symptoms, as well as laboratory testing.

Testosterone and Prostate Cancer: The Myth 

For more than 6 decades, the medical establishment erroneously conjectured that testosterone replacement therapy increases one’s risk of developing prostate cancer. This fear has made it standard practice for physicians to deprive hypogonadal male patients of testosterone replacement that could otherwise provide them with a world of cardiovascular, musculoskeletal, cognitive, metabolic and other health benefits, as discussed above.

Remarkably, though, it appears that, in most cases, the opposite is true–lower levels of endogenous testosterone present a greater risk of prostate cancer than higher levels (Morgentaler 2009). A review of data from the National Institutes of Health revealed that, in men of advancing age, “high testosterone levels are not associated with an increased risk of prostate cancer, nor are low testosterone levels protective against prostate cancer” (Morgentaler 2006).

A collaborative review of 18 prospective studies compared serum concentrations of androgen and estrogen in 3,886 men with prostate cancer with those in 6,438 healthy controls. The results showed no significant associations between the risk of prostate cancer and sex hormone levels (Roddam et al 2008). 

In more than 500 men diagnosed with prostate cancer (followed over a mean of 8.7 years), high androgen levels were actually associated with a decreased risk of aggressive prostate disease, compared with no change in the risk of non–aggressive disease. Overall, levels of any steroid hormones (except estradiol) were not correlated with the risk of aggressive prostate cancer (Severi et al 2006).

Dr. Abraham Morgentaler, an associate clinical professor at the Harvard Medical School, in his book Testosterone for Life, convincingly makes the case for the benefits and safety of high testosterone vs. the dangers of low testosterone. He also goes back to the original 1941 Nobel Prize–winning research (Huggins et al 1941) about testosterone and shows how these data have been misinterpreted and unquestioned for over 70 years. 


It is critical that men undergo comprehensive medical testing before embarking on a hormone modulation program. First, a baseline blood PSA must be taken to rule out existing prostate cancer (for more information, please see the chapter on prostate cancer). Then, free and total testosterone and estradiol tests are needed to make sure that testosterone is not being excessively converted into estrogen. If estrogen levels are too high, the use of aromatase inhibitors can reduce the rate at which testosterone converts to estrogen in the body. Follow–up testing for estrogen, testosterone, and PSA levels are needed to rule out prostate cancer and fine–tune your program. Additional tests that should be considered include:

  • Complete blood cell count and chemistry profile, including liver and kidney function, glucose, minerals, lipids and thyroid–stimulating hormone (TSH)
  • DHEA
  • Luteinizing hormone (LH) (optional)
  • SHBG (optional)
  • Dihydrotestosterone (optional)

Blood for these tests may be drawn at your physician’s office or directly at a laboratory in your area. These tests will yield crucial information that can help you design a program tailored to your unique situation.


Free testosterone:  Direct testing for free testosterone is the best way to test for testosterone activity, as free testosterone is the active form of the hormone and comprises only about 2% of total testosterone.

It is recommended that men strive for a free testosterone level that is in the upper one–third range for men aged 21 to 49 years. The range of free testosterone serum level is 20 to 25 picograms per milliliter (pg/mL), using our current testing methodology.

There are five reasons that free testosterone levels may be low:

  1. Too much testosterone is being converted to estrogen through the activity of aromatase.
  2. Too much free testosterone is being bound by SHBG. This would be especially apparent if a man’s total testosterone level is in the high normal range but his free testosterone level is low.
  3. The pituitary gland, which controls testosterone production through the production of luteinizing hormone (LH), is not secreting enough LH to stimulate gonadal production of testosterone. In this case, total testosterone would be low.
  4. The testicles (gonads) have lost their ability to produce testosterone, despite adequate amounts of LH. In this case, the level of LH would be high despite a low testosterone level.
  5. DHEA level is abnormally low.

Estrogen: Measured as estradiol, should be kept in a range of 20 to 30 pg/ml. If a man’s estrogen level is elevated, it could be associated with:

  • Increased aromatase activity, often caused by increased abdominal fat.
  • The liver is failing to remove excess estrogen, possibly because of heavy alcohol intake. In men, heavy alcohol intake has been shown to boost estrogen levels within the liver (Colantoni et al 2002).

If a man’s estradiol level is higher than 30 pg/mL, it should be reduced by using aromatase–inhibiting drugs or nutrients. (Optimal estradiol levels are between 20–30 pg/mL.)


Ultimately, the ideal program will depend on the results of various tests. Below are some common scenarios and solutions to correct hormone imbalances.

Low Free Testosterone, High Estradiol, Mid Total Testosterone: This situation suggests excessive aromatase activity, which converts free testosterone to estrogen. Inhibition of aromatase and reduction in aromatase–containing tissue (fat) is indicated. Suggestions include:

  • Lose weight to reduce aromatase activity.
  • Reduce or eliminate alcohol intake to enable excess estrogen removal by the liver.
  • Review all current medications to see if they might be interfering with healthy liver function. Common medications that affect liver function are nonsteroidal anti–inflammatory drugs (NSAIDs) (e.g., naproxen, ibuprofen, acetaminophen, and aspirin); the statin class of cholesterol–lowering drugs (e.g., simvastatin, atorvastatin); some heart medications; some blood pressure–lowering medications; and some antidepressants. Drugs being prescribed to treat the symptoms of testosterone deficiency (such as the statins and certain antidepressants) may actually aggravate the testosterone deficit, thus making the cholesterol problem or depression worse. However, do not discontinue any prescription medicine without consulting your physician
  • If all of the above fail to increase free testosterone and lower excess estradiol, consider discussing with your physician the use of the aromatase inhibitor anastrozole (Arimidex) at the very low dose of 0.5 mg twice per week.

Low Free Testosterone, Low Estrogen, High Total Testosterone: This situation suggests excessive SHBG levels, making sufficient testosterone unavailable to target tissues. The elevation of SHBG explains why some older men who are on testosterone replacement therapy do not report a long–term beneficial effect, that is, the administered testosterone becomes bound by SHBG and is not bioavailable to cellular receptor sites where it would normally produce an effect. Suggestions include:

  • Inhibit aromatase by following some of the recommendations in the previous section, since low testosterone and high estrogen are involved in excess SHBG activity.
  • Take the following supplements:
    • Chrysin—1500 mg/day
    • Nettle root extract—240 mg/day
    • Pygeum extract—100 mg/day
    • Cruciferous vegetable extract (I3C)—400 mg/day
    • Fish oil—2000mg/day (at least 700mg EPA, 500mg DHA)
    • DHEA—15 to 75 mg/day, followed by blood tests in 3 to 6 weeks

Low Free Testosterone, Low Estrogen, Low Testosterone: This situation suggests low production of testosterone, with resultant low conversion to estrogen. Suggestions include:

  • Use testosterone patches or creams. Do not use testosterone injections or tablets. If tests reveal low levels of LH, ask your physician about the possibility of using human chorionic gonadotropin (HCG). HCG functions in a manner similar to that of LH and can restart gonadal production of LH.
  • Take DHEA—15 to 75 mg/day.
  • Tribulus fruit extract (40% saponins)—450mg/day


A number of nutrients have been studied for their ability to boost testosterone and/or treat conditions such as erectile dysfunction and loss of libido. This nutrient group includes antioxidants, which may function by reducing oxidative damage to testosterone–producing tissues.

  • Selenium—200 micrograms (mcg)/day
  • Vitamin E—400 IU/day with at least 200 mg of gamma–tocopherol
  • Vitamin D (Wehr et al 2010)—5000 to 10,000 IU/day
  • Protein Powder—10–20g/day
  • Maca Powdered Extract—1500–3000mg/day

Male Hormone Restoration Safety Caveats 

An aggressive program of dietary supplementation should not be launched without the supervision of a qualified physician. Several of the nutrients suggested in this protocol may have adverse effects. These nutrients include:


  • For some people, L–carnitine, especially acetyl–L–carnitine, may have a stimulating effect. Therefore, it may be unwise to take it in the evening.


  • Do not take chrysin if you have prostate cancer. Chrysin can also increase the effects of aromatase inhibitors, such as aminoglutethimide, anastrozole, and letrozole.


  • Do not take DHEA if you have prostate cancer. DHEA can also cause androgenic effects, such as acne, deepening of the voice, and facial hair growth.


  • This can inhibit such drugs as propranolol, theophylline, phenytoin, sulfadiazine, rifampicin, isoniazid, ethambutol, pyrazinamide, and dapsone, all of which are metabolized by cytochrome P450 enzymes in the liver.


  • Supplemental zinc can inhibit the absorption and availability of copper. If more than 50 mg of supplemental zinc is taken daily, 2 mg of supplemental copper should also be taken to prevent deficiency. Chronic ingestion of more than 100 mg of zinc daily may be toxic.
  • Testosterone, the chief male hormone, is essential for libido and erectile function, and plays a crucial role in mood, energy, bone health, and body composition.
  • Testosterone levels decline with age, usually beginning in a man’s mid–30s. Diminishing testosterone levels have been linked with disorders such as depression, fatigue, obesity and cognitive decline.
  • Low testosterone in men is strongly associated with metabolic syndrome, and may be a risk factor for type 2 diabetes and cardiovascular disease.
  • Restoring testosterone to youthful levels offers men a wealth of health benefits, including benefits for heart health, body composition, mood, and memory.
  • Bioidentical testosterone has not been found to have adverse effects on the healthy prostate gland–in fact, it may help improve prostate symptoms in men with low–normal testosterone levels. Testosterone therapy is contraindicated in men with prostate cancer.
  • Regular blood testing can help you and your physician decide if testosterone therapy is right for you. Optimizing testosterone levels requires a multi–pronged approach that includes optimal diet, proper nutrition, nutritional supplements, exercise, and bioidentical testosterone.