NOTE: Some of this information is from THE LIFE EXTENSION FOUNDATION. Their web site is found at the end of this article.

Male Hormones and Aging

As men age past year 40, hormonal changes occur that perceptibly inhibit physical, sexual, and cognitive function. The outward appearance of a typical middle aged male shows increased abdominal fat and shrinkage of muscle mass, a hallmark effect of hormone imbalance. A loss of feeling of well being, sometimes manifesting as depression, is a common psychological complication of hormone imbalance.

Until recently, these changes were attributed to “growing old,” and men were expected to accept the fact that their bodies were entering into a long degenerative process that would someday result in death.

A remarkable amount of data has been compiled indicating that many of the diseases that middle aged men begin experiencing, including depression, abdominal weight gain, and prostate and heart disease, are directly related to hormone imbalances that are correctable with currently available drug and nutrient therapies. To the patient’s detriment, conventional doctors are increasingly prescribing drugs to treat depression, elevated cholesterol, angina, and a host of other diseases that may be caused by an underlying hormone imbalance.

If doctors checked their male patients’ blood levels of estrogen, testosterone, thyroid, and DHEA (instead of prescribing drugs to treat symptoms), they might be surprised to learn that many problems could be eliminated by adjusting hormone levels to fit the profile of a healthy 25-year-old.

Few physicians know what hormone blood tests to order for men, nor do they have the experience to adjust hormones properly to reverse the degenerative changes that begin in mid-life.

This protocol will provide the patient and physician with the information necessary to safely modulate hormone levels for the purpose of preventing and treating many of the common diseases associated with growing older.

Too Much Estrogen

The most significant hormone imbalance in aging men is a decrease in free testosterone, while estrogen levels remain the same or increase precipitously. As men grow older, they suffer through a variety of mechanisms from the dual effects of having too little testosterone and excess estrogen. The result is a testosterone-estrogen imbalance that directly causes many of the debilitating health problems associated with normal aging.

One cause of hormone imbalance in men is that their testosterone is increasingly converted to estrogen. One report showed that estrogen levels of the average 54-year-old man are higher than those of the average 59-year-old woman.

The reason that testosterone replacement therapy does not work by itself for many men is that exogenously administered testosterone may convert (aromatize) into even more estrogen, thus potentially worsening the hormone imbalance problem in aging males (i.e., too much estrogen and not enough free testosterone). While there are studies showing that testosterone replacement therapy does not increase estrogen beyond normal reference ranges, we are going to show later how the standard laboratory reference ranges do not adequately address the issue of estrogen overload.

Testosterone Metabolic Pathways

Estrogen is an essential hormone for men, but too much of it causes a wide range of health problems. The most dangerous acute effect of excess estrogen and too little testosterone is an increased risk of heart attack or stroke. High levels of estrogen have been implicated as a cause of benign prostatic hypertrophy (BPH). One mechanism by which nettle extract works is to block the binding of growth-stimulating estrogen to prostate cells.

When there is too little testosterone present, estrogen attaches to testosterone cell receptor sites throughout the body and creates many problems in aging men. In youth, low amounts of estrogen are used to turn off the powerful cell-stimulating effects of testosterone. As estrogen levels increase with age, testosterone cell stimulation may be locked in the “off” position, thus reducing sexual arousal and sensation and causing the loss of libido so common in aging men.

High serum levels of estrogen also trick the brain into thinking that enough testosterone is being produced, further slowing the natural production of testosterone. This happens when estrogen saturates testosterone receptors in the hypothalamus region of the brain. The saturated hypothalamus then stops sending out a hormone to the pituitary gland to stimulate secretion of luteinizing hormone, which the gonads require to produce testosterone. High estrogen can thus shut down the normal testicular production of testosterone.

One further complication of excess estrogen is that it increases the body’s production of sex hormone-binding globulin (SHBG). SHBG binds free testosterone in the blood and makes it unavailable to cell receptor sites.

Based on the multiple deleterious effects of excess estrogen in men, aggressive action should be taken to reduce estrogen to a safe range if a blood test reveals elevated levels. We will discuss the appropriate blood tests and steps that can be taken to lower estrogen levels later in this protocol.

The Critical Importance of Free Testosterone

Testosterone is much more than a sex hormone. There are testosterone receptor sites in cells throughout the body, most notably in the brain and heart. Youthful protein synthesis for maintaining muscle mass and bone formation requires testosterone. Testosterone improves oxygen uptake throughout the body, helps control blood sugar, regulate cholesterol and maintain immune surveillance. The body requires testosterone to maintain youthful cardiac output and neurological function. Testosterone is also a critical hormone in the maintenance of healthy bone density, muscle mass, and red blood cell production.

Of critical concern to psychiatrists are studies showing that men suffering from depression have lower levels of testosterone than do control subjects. For some men, elevating free testosterone levels could prove to be an effective antidepressant therapy. There is a basis for free testosterone levels being measured in men suffering from depression and for replacement therapy being initiated if free testosterone levels are low normal or below normal.

Testosterone is one of the most misunderstood hormones. Body builders tarnished the reputation of testosterone by putting large amounts of synthetic testosterone drugs into their young bodies. Synthetic testosterone abuse can produce detrimental effects, but this has nothing to do with the benefits a man over age 40 can enjoy by properly restoring his natural testosterone to a youthful level.

Conventional doctors have not recommended testosterone replacement therapy because of an erroneous concern that testosterone causes prostate cancer. As we will later show, fear of prostate cancer is not a scientifically valid reason to avoid testosterone modulation therapy.

Another concern skeptical doctors have about prescribing testosterone replacement therapy is that some poorly conducted studies showed it to be ineffective in the long-term treatment of aging. These studies indicate anti-aging benefits when testosterone is given, but the effects often wear off. What doctors fail to appreciate is that exogenously administered testosterone can convert to estrogen in the body. The higher estrogen levels may negate the benefits of the exogenously administered testosterone. The solution to the estrogen-overload problem is to block the conversion of testosterone to estrogen in the body. Numerous studies show that maintaining youthful levels of free testosterone can enable the aging man to restore strength, stamina, cognition, heart function, sexuality, and outlook on life, i.e., to alleviate depression.

Why Testosterone Levels Decline

Testosterone production begins in the brain. When the hypothalamus detects a deficiency of testosterone in the blood, it secretes a hormone called gonadotrophin-releasing hormone to the pituitary gland. This prompts the pituitary to secrete luteinizing hormone (LH), which then prompts the Leydig cells in the testes to produce testosterone.

In some men, the testes lose their ability to produce testosterone, no matter how much LH is being produced. This type of testosterone deficiency is diagnosed when blood tests show high levels of LH and low levels of testosterone. In other words, the pituitary gland is telling the testes (by secreting LH) to produce testosterone, but the testes have lost their functional ability, so the pituitary gland vainly continues to secrete LH because there is not enough testosterone in the blood to provide a feedback mechanism that would tell the pituitary to shut down. In other cases, the hypothalamus, or pituitary gland, fails to produce sufficient amounts of LH, thus preventing healthy testes from secreting testosterone. Blood testing can determine whether sufficient amounts of LH are being secreted by the pituitary gland and help determine the appropriate therapeutic approach.

If serum (blood) testosterone levels are very low, it is important to diagnose the cause, but no matter what the underlying problem, therapies exist today to restore testosterone safely to youthful levels in any man (who does not already have prostate cancer).

As indicated earlier in this article, a major problem aging men face is not low production of testosterone, but conversion of testosterone to estrogen. Specific therapies to suppress excess estrogen and boost free testosterone back to youthful physiological levels will be discussed later.

Aging men sometimes convert testosterone to estrogen. Testosterone receptor sites in cells throughout the body then take up the estrogen. When an estrogen molecule occupies a testosterone receptor site on a cell membrane, it blocks the ability of serum testosterone to induce a healthy hormonal signal. It does not matter how much serum free testosterone is available if excess estrogen is competing for the same cellular receptor sites.

SHBG – Sex Hormone-Binding Globulin

Testosterone is a hormone responsible for sex drives in both men and women. For testosterone to promote youthful sexual interest, satisfaction and performance, it must be freely available to cell receptor sites in the brain, the nerves, muscles and genitals. Sex Hormone-Binding Globulin (SHBG) attaches to testosterone as does a certain percentage to Albumin as well. This is how how testosterone is transported throughout our bodies. Once the testosterone-SHBG complex reaches a point in the body that needs the testosterone, the SHBG releases the “bound testosterone” to become “free” testosterone where in can readily enter the body’s cells and bind to the testosterone receptor sites so it can perform its function as an anabolic hormone. The problem comes when testosterone is bound to serum globulin and is not available to the cell receptor sites were it is needed to initiate sex stimulating centers in the brain, etc. This can occur because there may be too little testosterone initially or there may be an excessive amount of SHBG. Excess estrogen can increase the production of SHBG and block testosterone receptor sites. This means there are two mechanisms by which excess estrogen interferes with sex dive in aging males.

For testosterone to produce long-lasting libido enhancing effects, it must be in the “free” form in the bloodstream. Bound testosterone is not able to be picked up by testosterone receptors on cell membranes. For aging men, it is desirable to suppress excess levels of SHBG and estrogen while boosting free testosterone to the level of a young man. There is now a natural way of modulating testosterone and estrogen levels in aging men that does not require expensive prescription drugs.

Restoring youthful hormone balance can have a significant impact on one’s sexuality. To reiterate, the hormone modulation objectives that most aging men need to facilitate sexual rejuvenation involves an increase in “free” testosterone coupled by a decrease in both estrogen and SHBG levels.

For many men, a safe and easy way to increase free testosterone is to prevent it from being converted (aromatized) into excess estrogen. Too much estrogen plays havoc with a man’s sex life by binding to testosterone receptor sites and may contribute to the over-production of SHBG. Too much SHBG that binds testosterone in a way that makes it unavailable to receptor sites in the brain, nerves and genitals.

Estrogen overload can be a common and serious problem in aging men. One report showed that estrogen levels of the average 54-year-old man are higher than those of the average 59-year-old woman. Estrogen is a necessary hormone for men, but too much cause a wide range of health problems. High serum levels of estrogen also trick the brain into thinking that enough testosterone is being produced, thereby slowing the natural production of testosterone.

Based on the multiple deleterious effects of excess estrogen in men, aggressive actions should be taken to reduce estrogen to a safe range. To determine if estrogen levels are too high, men are encouraged to have their blood tested for estradiol. If the blood test results show estradiol levels are greater than 30 pg/mL, men should consider radical lifestyle changes, and/or taking an aromatase-inhibiting nutrient or drug.

A numerical example of the effects of a nutritional aromatase inhibitor can be seen on one of the subjects in the pilot studies whose initial serum estradiol level was a high 54 and free testosterone a moderately low 14.4. After only 30 days on a nutritional aromatase inhibitor, estradiol levels fell to 36 (from 54) and free testosterone levels increased to 22.5 (from 14.4). In this pilot study, funded by The Life Extension Foundation, 9 of 10 test subjects showed a significant decline in excess estrogen levels when several herbal extracts were combined. These kinds of results show how some men reduce excess estrogen while boosting free testosterone.

The Effects of Testosterone on Libido

Sexual stimulation and erection begin in the brain when neuronal testosterone-receptor sites are prompted to ignite a cascade of biochemical events that involve testosterone-receptor sites in the nerves, blood vessels, and muscles. Free testosterone promotes sexual desire and then facilitates performance, sensation, and the ultimate degree of fulfillment.

Without adequate levels of free testosterone, the quality of a man’s sex life is adversely affected and the genitals can atrophy. When free testosterone is restored, positive changes can be expected in the structure and function of the sex organs. (It should be noted that sexual dysfunction can be caused by other factors unrelated to hormone imbalance. An example of such a factor is arteriosclerotic blockage of the penile arteries.)

The genital-pelvic region is packed with testosterone receptors that are ultra-sensitive to free testosterone-induced sexual stimulation. Clinical studies using testosterone injections, creams, or patches have often failed to provide a long-lasting, libido-enhancing effect in aging men. We now know why. The testosterone can be converted to estrogen. The estrogen is then taken up by testosterone receptor sites in cells throughout the body. When an estrogen molecule occupies a testosterone receptor site on a cell membrane, it blocks the ability of serum testosterone to induce a healthy hormonal signal. It does not matter how much serum free testosterone is available if excess estrogen is competing for the same cellular receptor sites.

Estrogen can also increase the production of sex hormone-binding globulin (SHBG), which binds the active free testosterone into a nonactive “bound testosterone.” Bound testosterone is picked up by testosterone receptors on cell membranes. For testosterone to produce long-lasting, libido-enhancing effects, it must be kept in the “free” form (not bound excessively to SHBG) in the bloodstream. It is also necessary to suppress excess estrogen, as this hormone can compete for testosterone receptor sites in the sex centers of the brain and the genitals.

Restoring youthful hormone balance can have a significant impact on male sexuality.

Testosterone and the Heart

Normal aging results in the gradual weakening of the heart, even in the absence of significant coronary artery disease. If nothing else kills the elderly male, at some point his heart just stops beating.

Testosterone is a muscle-building, anabolic hormone, and there are many testosterone-receptor sites in the heart. The weakening of the heart muscle can sometimes be attributed to testosterone deficiency. Testosterone is not only responsible for maintaining heart muscle protein synthesis, it is also a promoter of coronary artery dilation and helps to maintain healthy cholesterol levels.

There are an ever-increasing number of studies indicating an association between high testosterone and low cardiovascular disease rates in men. In the majority of patients, symptoms and EKG measurements improve when low testosterone levels are corrected. One study showed that blood flow to the heart improved 68.8% in those receiving testosterone therapy. In China, doctors also are successfully treating angina with testosterone therapy.

The following list represents the effects of low testosterone on cardiovascular disease:

* Cholesterol, fibrinogen, triglycerides, and insulin levels increase (30-33).
* Coronary artery elasticity diminishes.
* Blood pressure rises.
* Human growth hormone (HGH) declines (weakening heart muscle).
* Abdominal fat increases (increasing the risk of heart attack).

Those with cardiovascular disease should have their blood tested for free testosterone and estrogen. Some men (with full cooperation from their physicians) may be able to stop taking expensive drugs to stimulate cardiac output, lower cholesterol, and keep blood pressure under control, if they correct a testosterone deficit or a testosterone-estrogen imbalance.

Despite numerous studies substantiating the beneficial effects of testosterone therapy in treating heart disease, conventional cardiologists continue to overlook the important role this hormone plays in keeping their cardiac patients alive.

Testosterone and the Prostate Gland

Many doctors will tell you that testosterone causes prostate disease. The published scientific literature indicates otherwise.

Estrogen has been identified as a primary culprit in the development of BPH. Estrogen has been shown to bind to SHBG in the prostate gland and cause the proliferation of epithelial cells in the prostate. This is corroborated by the fact that as men develop benign prostate enlargement, their levels of free testosterone are plummeting, while their estrogen levels remain the same or are rising. As previously discussed, aging men tend to convert their testosterone into estrogen. The published evidence shows that serum levels of testosterone are not a risk factor for developing benign prostate disease.

The major concern that has kept men from restoring their testosterone to youthful levels is fear of prostate cancer. The theory is that since most prostate cancer cell lines need testosterone to proliferate, it is better not to replace the testosterone that is lost with aging. The problem with this theory is that most men who contract prostate cancer have low levels of testosterone, and the majority of published studies show that serum testosterone levels do not affect one’s risk for contracting prostate cancer.

Since there is such a strong perception that any use of testosterone can increase the incidence of prostate cancer, we (Life Extension Foundation) did a MEDLINE search on all the published studies relating to serum testosterone and prostate cancer. The appendix at the end of this article provides quotations from the published literature as it relates to the issue of whether testosterone causes prostate disease. Out of 27 MEDLINE studies we found, five indicated that men with higher testosterone levels had a greater incidence of prostate cancer, whereas 21 studies showed that testosterone was not a risk factor. One study was considered neutral.

Before anyone starts a testosterone replacement program, he should have a serum PSA test and a digital rectal exam to rule out prostate cancer. Nothing is risk free. A small minority of men with low testosterone and prostate cancer will not have an elevated PSA or palpable lesion detectable by digital rectal exam. If these men use supplemental testosterone, they risk an acute flare-up in their disease state. That is why PSA monitoring is so important every 30 to 45 days during the first 6 months of any type of testosterone augmentation therapy. If an underlying prostate cancer is detected because of testosterone therapy, it is usually treatable by nonsurgical means.

Please remember that testosterone does not cause acute prostate cancer, but if you have existing prostate cancer and don’t know it, testosterone administration is likely to boost PSA sharply and provide your doctor with a quick diagnosis of prostate cancer (and an opportunity for very early treatment). We acknowledge that some aging men will not want to take this risk.

As stated above, the MEDLINE score was 21 to 5 against the theory that testosterone plays a role in the development of prostate cancer. None of these studies took into account the prostate cancer prevention effects for men who take lycopene, selenium, and vitamins A and E, nor did they factor in possible prostate disease preventives such as saw palmetto, nettle, soy, and pygeum.

In Dr. Jonathan Wright’s book, Maximize Your Vitality and Potency, a persuasive case is made that testosterone and DHEA actually protect against the development of both benign and malignant prostate disease. Dr. Wright also points out that natural therapies such as saw palmetto, nettle, and pygeum provide a considerable degree of protection against the alleged negative effects that higher levels of testosterone might have on the prostate gland.

We eagerly await the results of more studies, but the fear of developing prostate cancer in the future should not be a reason to deprive your body today of the life-saving and life-enhancing benefits of restoring a youthful hormone balance.

Once a man has prostate cancer, testosterone therapy cannot be recommended because most prostate cancer cells use testosterone as a growth promoter. This, regrettably, denies prostate cancer patients the wonderful benefits of testosterone therapy. Men with severe BPH should approach testosterone replacement cautiously. It would be prudent for those with BPH who are taking testosterone replacement therapy to also use the drug Proscar (finasteride) to inhibit 5-alpha-reductase levels, thereby suppressing the formation of dihydrotestosterone. DHT is 10 times more potent than testosterone in promoting abnormal prostate growth, and suppressing DHT is a proven therapy in treating benign prostate enlargement. Saw palmetto extract suppresses some DHT in the prostate gland, but its effectiveness in alleviating symptoms of BPH probably has more to do with:

* Its blocking of alpha-adrenergic receptor sites on the sphincter muscle surrounding the urethra. (This is how the drug Hytrin? works.)
* Its inhibition of estrogen binding to prostate cells (like nettle).
* Its inhibition of the enzyme 3-ketosteroid (which causes the binding of DHT to prostate cells).
* Its anti-inflammatory effect on the prostate.

It is unfortunate that many people still think that restoring testosterone to youthful levels will increase the risk of prostate disease. This misconception has kept many men from availing themselves of this life-enhancing and life-saving hormone.

While it is clear that excess estrogen causes benign prostate enlargement, the evidence for excess estrogen’s role in the development of prostate cancer is uncertain. Some studies show that elevated estrogen is associated with increased prostate cancer risk, while other studies contradict this finding.

Testosterone and Depression

A consistent finding in the scientific literature is that testosterone replacement therapy produces an increased feeling of well-being. As stated earlier, newly published studies show that low testosterone correlates with symptoms of depression and other psychological disorders.

A common side effect of prescription antidepressant drugs is also the possible suppression of one’s libido. Those suffering with depression either accept this drug induced reduction in quality of life, or get one can off the antidepressant drugs so they can at least have a somewhat normal sex life. If more psychiatrists tested their patients’ blood levels for free testosterone and prescribed natural testosterone therapies to those with low free testosterone, the need for libido-suppressing anti-depressant drugs could be reduced or eliminated. As previously described, testosterone replacement often enhances libido, which is the opposite effect of most prescription antidepressants.

One study showed that patients with major depression experienced improvement that was equal to that achieved with standard antidepressant drugs.

Androderm? is one of several natural testosterone-replacement therapies that can be prescribed by doctors. A 12-month clinical trial using this FDA-approved drug resulted in a statistically significant reduction in the depression score (6.9 before versus 3.9 after). Also noted were highly significant decreases in fatigue from 79% before the patch to only 10% after 12 months.

According to Jonathan Wright, M.D., author of the book, Maximize Your Vitality & Potency, the following effects have been reported in response to low testosterone levels:

* Loss of ability to concentrate
* Moodiness and emotionality
* Touchiness and irritability
* Great timidity
* Feeling weak
* Inner unrest
* Memory failure
* Reduced intellectual agility
* Passive attitudes
* General tiredness
* Reduced interest in surroundings
* Hypochondria

The above feelings can all be clinical symptoms of depression, and testosterone replacement therapy has been shown to alleviate these conditions. Testosterone thus has exciting therapeutic potential in the treatment of depression in men.Testosterone and Aging

We know that many of the degenerative diseases of aging in men such as Type II diabetes, osteoporosis, and cardiovascular disease are related to a testosterone deficiency. We also know that common characteristics of middle age and older age such as depression, abdominal fat deposition, muscle atrophy, low energy, and cognitive decline are also associated with less than optimal levels of free testosterone.

A consistent pattern that deals with fundamental aging shows that low testosterone causes excess production of a dangerous hormone called cortisol. Some anti-aging experts call cortisol a “death hormone” because of the multiple degenerative effects it produces. That, however, is a little dramatic. Cortisol is in our body for a reason or the good Lord would not have put it there in the first place. Some of these effects can be immune dysfunction, brain cell injury, and arterial wall damage, if cortisol is in excessive amounts for prolonged periods of time due to various stresses the body is experiencing.

A group of scientists conducted two double-blind studies in which they administered supplemental testosterone to groups of aging men and observed the typical responses of lower levels of cholesterol, glucose, and triglycerides, reductions in blood pressure, and decreased abdominal fat mass. The scientists showed that excess cortisol suppressed Testosterone and Growth Hormone production and that the administration of testosterone acted as a “shield” against the over-production of cortisol in the adrenal gland.

It is important to point out that testosterone is an anabolic (or protein building) hormone while cortisol is a catabolic hormone that breaks down proteins in the body. Normal aging consists of a progressive decrease in free testosterone with a marked increase in cortisol. As men age past 40, cortisol begins to dominate, and the catabolic effects associated with growing older begin to dominate.

These findings have significant implications in the battle to maintain youthful hormone balance for the purpose of staving off normal aging and its associated degenerative diseases.

The Testosterone Doctor

Eugene Shippen, M.D., authored a book in 1998 called The Testosterone Syndrome. He was a speaker at the American Academy of Anti-Aging Medicine Conference held in December 1998, where he provided extensive evidence documenting the pathology of the testosterone deficiency syndrome in men. Here are some excerpts from Dr. Shippen’s presentation:

“First, Testosterone is not just a “sex hormone.” It should be seen as a “total body hormone,” affecting every cell in the body. The changes seen in aging, such as the loss of lean body mass, the decline in energy, strength, and stamina, unexplained depression, and decrease in sexual sensation and performance, are all directly related to testosterone deficiency. Degenerative diseases such as heart disease, stroke, diabetes, arthritis, osteoporosis, and hypertension are all directly or indirectly linked to testosterone decline. Secondly, testosterone also functions as a prohormone. Local tissue conversion to estrogens, dihydrotestosterone (DHT), and other tissue metabolites plays an important part in cellular physiology.

Excess estrogen seems to be the culprit in prostate enlargement. Low testosterone levels are in fact associated with more aggressive prostate cancer. While fear of prostate cancer keeps many men from testosterone replacement, it is in fact testosterone deficiency that leads to the pathology that favors the development of prostate cancer.

Testosterone improves cellular bioenergetics. It acts as a cellular energizer. Since testosterone increases the metabolic rate and aerobic metabolism, it also dramatically improves glucose metabolism and lowers insulin resistance.

Another myth is that testosterone is bad for the heart. Actually, low testosterone correlates with heart disease more reliably than does high cholesterol. Testosterone is the most powerful cardiovascular protector for men. Testosterone strengthens the heart muscle; there are more testosterone receptors in the heart than in any other muscle. Testosterone lowers LDL cholesterol and total cholesterol, and improves every cardiac risk factor. It has been shown to improve or eliminate arrhythmia and angina. “Testosterone replacement is the most underutilized important treatment for heart disease.”

Testosterone shines as a blood thinner, preventing blood clots. Testosterone also helps prevent colon cancer.

Interestingly enough, is the fact that young men whose testosterone levels are normal have fewer heart problems, are not depressed and do not get prostate cancer. Maybe this a coincidence, you know, because “they are young”. But I think not. Studies are showing the same results in older men whose testosterone levels have been restored close to those levels in younger men.

Previous research on testosterone used the wrong form of testosterone replacement. Testosterone injections result in initial excess of testosterone, with conversion of the excess being converted to estrogens. Likewise, total testosterone is often measured instead of free testosterone, the bioavailable form. Some studies do not last long enough to show improvement. For instance, it may take six months to a year before the genital tissue fully recovers from atrophy caused by testosterone deficiency and potency is restored.

Physicians urgently need to be educated about the benefits of testosterone therapy and the delicate balance between androgens (testosterone) and estrogens. Each individual has his or her own pattern of hormone balance; this indicates that hormone replacement should be individualized and carefully monitored.”

Dr. Shippen’s book, The Testosterone Syndrome, provides a persuasive argument in favor of hormone modulation in the aged male, and contains many interesting case histories. Dr. Wright’s and Dr. Ullis’s books on this subject are also available.

Obesity and Hormone Imbalance

A consistent finding in the scientific literature is that obese men have low testosterone and very high estrogen levels. Central or visceral obesity (pot belly) is recognized as a risk factor for cardiovascular disease and type II diabetes. New findings have shed light on subtle hormone imbalances of borderline character in obese men and often fall within the normal laboratory reference range. Boosting testosterone levels seems to decrease the abdominal fat mass, reverse glucose intolerance, and reduce lipoprotein abnormalities in the serum. Further analysis has also disclosed a regulatory role for testosterone in counteracting visceral fat accumulation. Longitudinal epidemiological data demonstrate that relatively low testosterone levels are a risk factor for development of visceral obesity.

One study showed that serum estrone and estradiol were elevated twofold in one group of morbidly obese men. Fat cells synthesize the aromatase enzyme, causing male hormones to convert to estrogens. Fat tissues, especially in the abdomen, have been shown to literally “aromatize” testosterone and its precursor hormones into potent estrogens.

Eating high-fat foods may reduce free testosterone levels according to one study that measured serum levels of sex steroid hormones after ingestion of different types of food. High-protein and high-carbohydrate meals had no effect on serum hormone levels, but a fat-containing meal reduced free testosterone levels soci4 hours.

Obese men suffer from testosterone deficiency caused by the production of excess aromatase enzyme in fat cells and also from the fat they consume in their diet. The resulting hormone imbalance (too much estrogen and not enough free testosterone) in obese men partially explains why so many are impotent, and suffer from a wide range of premature degenerative diseases.

Factors Causing the Estrogen-Testosterone Imbalance in Men

If your blood tests reveal high estrogen and low testosterone, here are the common factors involved:

Excess “aromatase” enzyme. As men age, they produce larger quantities of an enzyme called aromatase. The aromatase enzyme converts testosterone into estrogen in the body. Inhibiting the aromatase enzyme results in a significant decline in estrogen levels while often boosting free testosterone to youthful levels. Therefore, an agent designated as an “aromatase inhibitor” may be of special value to aging men who have excess estrogen.

Liver enzymatic activity. A healthy liver eliminates surplus estrogen and sex hormone-binding globulin. Aging, alcohol, and certain drugs impair liver functionand can be a major cause of hormone imbalance in aging men. Heavy alcohol intake increases estrogen in men and women.

Obesity. Fat cells create aromatase enzyme and especially contribute to the buildup of abdominal fat. Low testosterone allows the formation of abdominal fat, which then causes more aromatase enzyme formation and thus even lower levels of testosterone and higher estrogen (by aromatizing testosterone into estrogen). It is especially important for overweight men to consider hormone modulation therapy.

Zinc deficiency. Zinc is a natural aromatase enzyme inhibitor. Since most people do not consume adequate amounts of zinc (30 to 90 mg a day), elevated estrogen can often be cyourd by this fble r.

Lifestyle changes (such as reducing alcohol intake) can produce a dramatic improvement in the testosterone-estrogen balance, but many people need to use aromatase-inhibiting agents to lower estrogen and to improve their liver function to remove excess SHBG. Aromtase enzyme converts testosterone into estrogen and can indirectly increase SHBG. Excess SHBG binds to free testosterone and can prevent it from exerting its biochemical effects in the body.

Correcting a Hormone Imbalance

A male hormone imbalance can be detected through use of the proper blood tests and can be corrected using available drugs and nutrients. The following represents a step-by-step program to safely restore youthful hormone balance in aging men:

Step 1: Blood testing

The following initial blood tests are recommended for any man over age 40:

* Complete blood count and chemistry profile to include liver-kidney function, glucose, minerals, lipids, and thyroid (TSH)
* Free and Total Testosterone
* Estradiol (estrogen)
* Progesterone
* Luteinizing hormone (LH)

Step 2: Interpretation of estrogen (estradiol)- free testosterone ratio

One of the difficulties in offering standardized interpretations at this time is that blood testing laboratories are using varying test methodologies and reference ranges for testosterone and other hormones.
The following guidelines should be followed when interpreting serum testosterone-estrogen (estradiol) levels:

Free testosterone should be at the high-normal reference range. We define high-normal range as the upper one-third of the highest number on the reference range. Under no circumstances should free or total testosterone be above the high- normal range.

Estrogen (estradiol) should be in the mid-to lower-normal range. If estradiol levels are in the upper-third of the normal reference range, or above the normal reference range, this excessive level of estrogen should be reduced.

There are five possible reasons why free testosterone levels may be low-normal (below the upper third of the highest number of the reference range):

* Too much testosterone is being converted to estradiol by excess aromatase enzyme and/or the liver is failing to adequately detoxify surplus estrogen. Excess aromatase enzyme and/ or liver dysfunction is likely the cause if estradiol levels are over 35. Remember, aromatase converts testosterone into estradiol, which can cause estrogen overload and testosterone deficiency.

* Too much free testosterone is being bound by excessive SHBG (sex hormone-binding globulin). This would be especially apparent if total testosterone levels were in the high normal range, while free testosterone was below the upper one-third range.

* The pituitary gland fails to secrete adequate amounts of luteinizing hormone (LH) to stimulate testicular production of testosterone. Total testosterone in this case would be in the bottom one-third to one-half range.

* The testes have lost their ability to produce testosterone, despite adequate amounts of the testicular-stimulating luteinizing hormone. In this case, LH would be above normal, and total testosterone would in very low normal or below normal ranges.

* Inadequate amounts of DHEA are being produced in the body. (DHEA is a precursor hormone to testosterone and estrogen).

Step 3: What to do when results are less than optimal

If estradiol levels are high (above 35), total testosterone is mid-to high-normal and free testosterone levels are low or low-normal (at the bottom one-third of the highest number on the reference range), you should:

* Make sure you are getting 80 to 90 mg a day of zinc. (Zinc functions as an aromatase inhibitor for some men.)

* Reduce or eliminate alcohol consumption to enable your liver to better remove excess estrogens.

* Review all drugs you are regularly taking to see if they may be interfering with healthy liver function. Common drugs that affect liver function are the NSAIDs: ibuprofen, acetaminophen, aspirin, the “statin” class of cholesterol-lowering drugs, some heart and blood pressure medications, and some antidepressants. It is interesting to note that drugs being prescribed to treat the symptoms of so-called high cholesterol such as the statin drugs and certain antidepressants may actually aggravate a testosterone deficit, thus making the cholesterol problem or depression worse.

* Lose weight. Fat cells, especially in the abdominal region, produce aromatase enzyme, which converts testosterone into estrogen.

* If all of the above fail to increase free testosterone and lower excess estradiol, ask your medical doctor to prescribe the potent aromatase inhibiting drug Arimidex? (anastrozole) in the very low dose of one-half mg (0.5 mg), twice a week. Arimidex? is prescribed to breast cancer patients at the dose of 1 to 10 mg a day. Even at the higher dose prescribed to cancer patients, side effects are rare. In the minute dose of 0.5 mg twice a week, a man will see an immediate drop in estradiol levels and should experience a rise in free testosterone to the optimal range. Oftentimes, you can reduce the dosage of Arimidex? to once weekly or even to only twice monthly. You can determine this when you see what your estradiol levels are after getting your blood tests.

If free testosterone levels are in the lower two-thirds of the highest number in the reference range, but total testosterone is high-normal, and estradiol levels are not over 30, you should:

* Consider following some of the recommendations in the previous section to inhibit aromatase, since many of the same factors are involved in excess SHBG activity.

* Take 320 mg a day of the super-critical extract of saw palmetto and 240 mg a day of the methanolic extract of nettle (Urtica dioica). Nettle may specifically inhibit SHGB, while saw palmetto may reduce the effects of excess estrogen by blocking the nuclear estrogen receptor sites in prostate cells, which in turn activate the cell-stimulating effects of testosterone and dihydrotestosterone. Saw palmetto also has the effect of blocking the oxidation of testosterone to androstenedione, a potent androgen that has been implicated in the development of prostate disease.

If total testosterone is in the lower one-third of the reference range or below normal, and free testosterone is low, you should:

* See if your luteinizing hormone (LH) is below normal. If LH is low, your doctor can prescribe an individual dose of chorionic gonadotropin (HCG) hormone for injection. Chorionic gonadotropic hormone functions similarly to LH and can re-start testicular production of testosterone. Your doctor can instruct you on how to use tiny 30-gauge needles to inject yourself 2 to 3 times a week. (Editor’s note: Some scientists think HCG may cause cancer. If this concerns you, consider using a testosterone patch, cream, or pellet.)

* After one month on chorionic gonadotropic hormone, a blood test can determine whether total testosterone levels are significantly increasing. You may also see your testicles growing larger. If total testosterone levels are restored, monitor blood levels of estradiol and free testosterone every 30 to 45 days for the first 5 months to make sure the exogenous testosterone you are putting into your body is following a healthy metabolic pathway, i.e., is raising your levels of free testosterone, but not increasing estradiol levels beyond about 35.

If total testosterone remains low in spite of several months of chorionic gonadotropic hormone therapy, this indicates that your testicles are not capable of producing testosterone. In that case, initiate therapy with the testosterone patch, pellet, or cream. Try not to use testosterone injections or tablets.

Before initiating testosterone replacement therapy, have a PSA blood test and a digital rectal exam to rule out detectable prostate cancer. Once total testosterone levels are restored to a high-normal range, monitor blood levels of estradiol, free testosterone, and PSA every 30 to 45 days for the first 6 months to make sure the exogenous testosterone you are putting into your body is following a healthy metabolic pathway and not causing a flare up of an underlying prostate cancer. The objective is to raise your levels of free testosterone to the upper third of the reference range, but to not increase estradiol levels beyond about 35.

Excess estrogen (estradiol) blocks the production and effect of testosterone throughout the body, dampens sexuality, and increases the risk of prostate and cardiovascular disease. Once you have established the proper ratio of free testosterone (upper one-third of the highest number in the reference range) and estradiol (not more than 35), make sure your blood is tested every 30 to 45 days for the first 5 months. Test every 6 months thereafter for free testosterone, estradiol, and PSA. For men in their 40s to 50s, correcting the excess level of estradiol is often all that has to be done. Men over 60 sometimes need the chorionic gonadotropin injection, and may need to use a testosterone patch, cream, or pellet later in life.

The Testosterone Patch and PSA

An oncologist affiliated with the Life Extension Foundation reports that some men on the testosterone patch will show an elevated PSA that then drops upon cessation of the exogenously administered testosterone. There are published studies that contradict this finding. Elevation of PSA could be caused by the conversion of exogenous testosterone to estrogen or DHT.

Therapies have been discussed that can prevent testosterone from cascading into estrogen and DHT. This oncologist noteete at prostate cancer patients with low testosterone levels have a more aggressive disease, most likely related to the development of tumor cells that are androgen independent, and thus more resistant to therapy. This observation is substantiated by the published literature.

“Andro” Supplements

Androstenedione is a precursor to both testosterone and estrogen. Early studies showed that “andro” supplements could markedly increase testosterone levels, but more recent studies cast doubt on this concept. A study in the Journal of the American Medical Association (JAMA) reported on an 8-week study showing that androstenedione supplements increased estrogen levels in 30 men. No increase in strength, muscle mass, or testosterone levels was observed. Perhaps combining androstenedione with an aromatase inhibitor that would prevent it from converting to estrogen would make this precursor hormone work better in men. In the meantime, we suggest avoiding androstenedione until more definitive research is published.

Testosterone Drugs

Synthetic testosterone “steroid” drugs are chemically different from the testosterone your body makes and do not provide the same effect as natural testosterone. Here is a listing of some of the synthetic testosterone drugs that should be avoided, especially on a long-term basis: Methyltestosterone, Danazol, Oxandrolone, Testosterone propionate, cypionate, or enanthate.

The fact that testosterone is marketed as a “drug” does not mean it is not the same natural hormone your body produced. Scientists learned decades ago how to make the same identical testosterone that our body produces, but, since natural testosterone could not be patented, drug companies developed all kinds of synthetic testosterone analogs, for various reasons, such as, they could be patented and then get approved by the FDA as new drugs. Here is a listing of currently available recommended natural testosterone drugs:

* Androderm? Transdermal System (Smith Kline Beecham’s testosterone patch)

* Testoderm? Transdermal System (Alza’s testosterone patch)

* Testosterone creams, pellets, and sublingual tablets (available from compounding pharmacies)

NOTE: Natural testosterone used in creams are about one-third the cost of the prepared patches. Contact the International Academy of Compounding Pharmacists at to find a compounding pharmacy nearest you.

Both synthetic and natural testosterone drugs require a prescription, and a prescription should be written only after blood or saliva tests reveal a testosterone deficiency.

Alternative physicians usually prescribe testosterone creams and other types made at compounding pharmacies, whereas conventional doctors are more likely to prescribe a box of ready-made, FDA-approved testosterone patches. All forms of natural testosterone are the same and all will markedly increase free testosterone in the blood or saliva.

If you interact with children, you may want to avoid testosterone creams. There is a report of a young male child going through pre-mature puberty after he made contact with the testosterone cream on his father’s body and on weightlifting equipment in the home. This is unique case, but is a testament to the powerful effects that testosterone exerts in the body.


THE STANDARD DOSAGE FOR TESTOSTERONE CREAM PER DAY IS: 100MG/ML. 1/2 ML IS TO BE APPLIED TO THE SKIN (transdermally) TWICE DAILY, UPON ARISING AND AGAIN AT BEDTIME NOTE: Vary the application sites by not using the same place on your skin repeatedly. For example, one dose on the tummy below the belly button, the next dose on the tummy above the belly button. Then use the inside of your forearms or your thighs. After 30 days repeat the following blood tests:

1. PSA

2. Free testosterone

3. Total testosterone

4. Estradiol (only if your Estradiol levels were elevated

NOTE: You are attempting to get your FREE TESTOSTERONE-ESTRADIOL ratio to that of a 25 year old which is a ratio of 4 : 1. NOTE: This is a general ratio depending on the results you get from the various labs. FOR THE MOST PART try to get your lab results to be right in the middle to the upper one-third of the upper & lower limits of the values from whatever lab you use.

Continue this protocol for another 30 days and repeat the above 4 blood tests to insure everything is OK. Thereafter, blood tests can be performed every 6 months to one year, always moderating how you feel also.

What’s the difference between injectable and cream based Testosterone?

These synthetic derivatives are patentable by the pharmaceutical manufacturers, while naturally occurring hormones are not. These patentable synthetic hormones are then marketed to the medical profession as somehow better than their naturally occurring parent hormone. An example of this is Provera, a synthetic derivative of progesterone. This drug is widely used by Gynecologists and Family Doctors for treatment of menstrual and menopausal bleeding disorders and combined with synthetic estrogens for postmenopausal hormone replacement therapy. There is actually no reason for this drug to be prescribed. Testosterone is a steroid hormone with anabolic properties as is estrogen and progesterone. These hormones are known as fat-soluble (as opposed to water soluble). Fat-soluble hormones will penetrate the skin, water-soluble generally will not, which means that they are particularly suited to transdermal administration. Virtually any drug or supplement that is taken by mouth must first pass through the liver to gain access to the rest of the body. This “first pass” as it is known in pharmacology is responsible for a large amount of the substance being metabolized (degraded or altered). Virtually any hormone that can be absorbed through the skin (fat soluble) is preferably administered transdermally (through the skin), allowing use of smaller doses and minimizing the production of undesirable metabolic by-products that result from the “first pass” phenomenon. In addition, it is very easy to adjust the dosage by varying the amount of the cream you apply. No need for cutting pills in half, etc.

The greatest advantage of creams over injections, however is that it reproduces the natural daily cycle that exists in young healthy individuals. Testosterone levels are highest in the morning and decline through the day. This natural cycle exists because of the burst of Leutenizing Hormone from the pituitary gland that occurs during sleep. This LH stimulates the testicles to increase their production of testosterone. Testosterone injections, on the other hand, maintain a constant level of testosterone throughout the day and night, which cause constant feedback suppression of the nighttime LH burst. This is why testosterone injections cause such severe testicular atrophy (shrinkage). This atrophy of the testicles can be very dramatic, as is found in many body builders and other athletes that have a history of anabolic steroid use.

Another very important advantage is that daily cream administration results in consistent day-to-day blood levels, while the injections have very high blood levels for the first few days after the injection and very low levels for the last few days before the next injection. The blood levels are only “normal” for the few days in the middle. This is also explains why injectable steroid users may get gynecomastia, which is overgrowth of the breast tissue. During the first days after injection, when testosterone levels are way above normal, some of it is converted into estrogen, which then causes the breast tissue (usually dormant in males) to develop.

Does testosterone replacement stop a man’s own production of testosterone?

Some forms of testosterone replacement such as injections of long acting synthetic testosterone derivatives will virtually stop an individual’s own testosterone production at the same time causing severe testicular atrophy that, after as short a time as six months, is only partially reversible. However, daily cream administration of testosterone will cause only partial suppression of the testicular production, which is reversible on cessation of treatment.


About 10 years ago progressive physicians noted that men and women who use bio-identical hormone replacement creams transdermally (through the skin) began showing lowered or non-responses to hormone replacement. They called this condition “DERMAL FATIGUE”. They said that to remedy this problem these creams should be used transmucosally (through mucosal tissue). Women should use vaginal/intravaginal or rectal application and men should use rectal application. This is because the mucosal tissues are very thin and the hormones will be absorbed more easily into the blood stream. Also, with transmucosal application these doctors found that hormone levels will not diminish as is possible with transdermal applications.

So, as in my own personal case, I was quite fortunate that transdermal application kept my hormones levels in the optimum ranges for about 15 years. Then in March of 2013 my blood test revealed my levels were half of what they were supposed to be. So I decided to double the dose of my testosterone cream. A month later another blood test showed my hormones levels had not moved at all.

Consequently, I now use the transmucosal route for my Testosterone, Progesterone and DHEA hormone creams. Now, about 6 weeks later, I just had a blood test to see where my hormone levels are. The results in about one week.

RECOMMENDATION: Use transdermal application for your hormone cream for as long as your hormone blood levels are in the optimum range. However, when your next periodic blood test shows your hormone levels have diminished, then switch application sites to the above-notes areas and re-test in about 4 to 6 weeks. At that time you will have enough information to adjust your hormone dosages to obtain the optimum ranges.

CAUTION: Do not use testosterone replacement if you have prostate cancer.

Men with existing prostate cancer should follow an opposite approach as it relates to testosterone. Prostate cancer patients are normally prescribed testosterone ablation therapy (using a drug that blocks the pituitary release of LH and another drug that blocks testosterone-receptor sites on the cells). Early state prostate cancer cells can often be controlled by totally suppressing testosterone in the body. Late-stage prostate cancer patients are sometimes given drugs that produce estrogenic effects to suppress prostate cancer cells that no longer depend on testosterone for growth. Regrettably, prostate cancer patients put on testosterone ablation therapy often temporarily suffer many of the unpleasant effects of low testosterone that have been described in this article. Before initiating a therapy that boosts your free testosterone level, a blood PSA (prostate specific antigen) test and digital rectal exam are recommended for men over age 40. While restoring free testosterone to healthy physiological levels does not cause prostate cancer, it can induce existing prostate cancer cells to proliferate faster.

Mandatory Testing

When embarking on a hormone modulation program, medical testing is critical. First, a baseline blood PSA must be taken to rule out existing prostate cancer. Then free testosterone and estradiol tests are needed to make sure that too much testosterone is not being converted into estradiol (estrogen). If estrogen levels are too high, the use of aromatase inhibitors can keep testosterone from converting (aromatizing) into estrogen in the body. Follow-up testing for estrogen, testosterone, and PSA are needed to rule out occult prostate cancer est to fine tune your program. It’s possible that testosterone patches and creams can increase testosterone levels too much. In that case, blood testing could save you money by allowing you to use less of the testosterone drug.

There are now natural dietary supplements in development that boost free testosterone levels and suppress excess estrogen. Even when these supplements become available, PSA testing is still mandatory, since any substance that increases testosterone should be avoided by most prostate cancer patients.

More Information

Over the last year, three new books have been written about testosterone replacement therapy. The best place to read about actual case histories of men who successfully used hormone modulation is Dr. Eugene Shippen’s book The Testosterone Syndrome. Dr. Shippen’s book provides many interesting details that could not be covered in this concise protocol. Dr. Jonathan Wright’s book, Maximize Your Vitality and Potency, contains historical and more technical data about the benefits of testosterone that again, could not be fit into this concise protocol. Dr. Karlis Ullis’s book, Super T, deals primarily with dietary and supplement modifications related to testosterone deficiency.

You can contact LIFE EXTENSION FOUNDATION at for updated information on this and other subjects on health and aging.