Hormone Replacement Therapy (HRT) – Part 1

You say you want some information about test therapy and it’s benefits? You say you haven’t found any articles or studies? Well bunky this is your lucky day. Boy did you come to the right place or what. As men age past year 40, hormonal changes occur that perceptibly inhibit physical, sexual, and cognitive function. The outward appearance of a typical middle-age 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.(94-97,271 )

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

A remarkable amount of data has been compiled that indicates that many of the diseases that middle-aged men begin experiencing, including depression, abdominal weight gain, 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 patient’s 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 21-year- old.

Few physicians know what hormone blood tests to order for men, nor do they have the experience to properly adjust hormones 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 precipitously increase. Through a variety of mechanisms, as men grow older, they suffer 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. (1-12,28)

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 is higher than those of the average 59-year-old women. (1,5,13-18, 48)

The reason that testosterone repla***ent therapy by itself does not work 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 repla***ent 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. (4,8,9,17,22-25,27,29-32)

Estrogen is a necessary hormone for men, but too much 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. (39-43, 261-270) High levels of estrogen have been implicated as a cause of benign prostatic hypertrophy (BPH) (35-44,46,47 ) and one mechanism by which nettle extract works is to block the binding of growth-stimulating estrogen to prostate cells .(42-44,48,49,50)

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 common loss of libido so common in aging men. (94,99,259)

High serum levels of estrogen also trick the brain into thinking that enough testosterone is being produced, thereby slowing down 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. (1,54,271-276,277)

One further complication of excess estrogen is that it increases the body’s production of sex hormone-binding globulin (SHBG). (280) SHBG binds free testosterone in the blood and makes it unavailable to cell receptor sites. (51-52,55,56)

Based on the multiple deleterious effects of excess estrogen in men, aggressive actions 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. (60, 180) Youthful protein synthesis for maintaining muscle mass and bone formation requires testosterone. (59,61-74, 87-90,261-264,287) Testosterone improves oxygen uptake throughout the body, helps control blood sugar, (68,75-78-80) regulate cholesterol, (67,69,81) and maintain immune surveillance. (82,83) The body requires testosterone to maintain youthful cardiac output and neurological function. (58, 65 ) Testosterone is a critical hormone in the maintenance of healthy bone density, (59, 66,67,84-86 ) muscle mass, (65-67,87-90,287 ) and red blood cell production. (67,69,92,93,98)

Of critical concern to psychiatrists are studies showing that men suffering from depression have lower levels of testosterone than control subjects. (94-98 ) For some men, elevating free testosterone levels could prove to be an effective anti-depressant therapy. There is a basis for free testosterone levels being measured in men suffering from depression and repla***ent therapy initiated if free testosterone levels are low normal or below normal.

One of the most misunderstood hormones is testosterone. 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 repla***ent therapy because of an erroneous concern that testosterone causes prostate cancer. As we will later show, fear of prostate cancer is not a scientific reason to avoid testosterone modulation therapy.

Another concern skeptical doctors have about prescribing testosterone repla***ent 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 their outlook on life, i.e., alleviate depression.(261-270)

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 fail to produce sufficient amounts of LH, thus preventing a healthy pair of testes from secreting testosterone. Blood testing can determine if sufficient amounts of LH are being secreted by the pituitary gland and help determine the proper 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 safely restore testosterone 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 excessive conversion of testosterone to estrogen. Again, specific therapies will be discussed later about how to suppress excess estrogen and boost free testosterone back to youthful physiologic levels.

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 impacted and the genitals atrophy. When free testosterone is restored, positive changes in structure and function of the sex organs can be expected. (It should be noted that sexual dysfunction can be caused by other factors unrelated to hormone balance such as 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. (98) 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, this 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 non-active “bound testosterone”. Bound testosterone is not able to be 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 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 .(99-102)

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, at some point their heart just stops beating.

Testosterone is a muscle-building hormone and there are many testosterone-receptor sites in the heart. (57) The weakening of the heart muscle can sometimes be attributed to testosterone deficiency. (103-108) Testosterone is not only responsible for maintaining heart muscle protein synthesis, but it is a promoter of coronary artery dilation (109-113) and helps to maintain healthy cholesterol levels. (81,114)

There is an ever-increasing number of studies indicating an association between high testosterone and low cardiovascular disease rates in men. (81) 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 . (9) In China, doctors are successfully treating angina with testosterone therapy. (9,115,116)

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 heart attack risk)

Those with cardiovascular disease should have their blood tested for free testosterone and estrogen. Some men (with full cooperation from their physician) 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 and/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. (9,30,31,77,93,111-113,115,116,261-270)

Testosterone and the Prostate Gland

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

As readers of Life Extension Magazine learned in late 1997, estrogen has been identified as a primary culprit in the development of BPH. (117-119) Estrogen has been shown to bind to SHBG in the prostate gland and cause the proliferation of epithelial cells in the prostate. (124, 182-184) 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. (8,36,41,117-137)

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 to not 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 the perception is so strong that any augmentation of testosterone can increase the risk of prostate cancer, we 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. The score was therefore:

21 studies indicating testosterone does not cause prostate cancer


5 studies indicating testosterone causes prostate cancer

(and one study that did not produce significant results)

Before anyone starts a testosterone repla***ent program, they 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 30-45 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 with non-surgical 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 will likely sharply boost PSA 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 of men who take lycopene, selenium, and vitamins A and E. (135-144) Nor did they factor in possible prostate disease preventives such as saw palmetto, nettle, soy, and pygeum. (42-44,145-170,172)

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 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 cautiously approach testosterone repla***ent. It would be prudent for those with BPH who are taking testosterone repla***ent therapy to also use the drug Proscar (finasteride) to inhibit 5- alpha-reductase levels, thereby suppressing the formation of dihydrotestosterone (DHT). (171-182) DHT is ten times more potent than testosterone in promoting 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 the enzyme 3-ketosteroid (that 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 to 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. (8,41,117-134,182-217,236) Some studies show elevated estrogen is associated with increased prostate cancer risk while other studies contradict this. For more information on testosterone, estrogen and the prostate gland, refer to the February 1999 issue of Life Extension Magazine. (182-217)

Testosterone and Depression

A consistent finding in the scientific literature is that testosterone repla***ent 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.(94-97,272)

A common side-effect of prescription anti-depressant drugs is the suppression of libido. Those suffering with depression either accept this drug-induced reduction in quality of life, or get off the anti-depressant drugs so they can at least have a somewhat normal sex life. If more psychiatrists tested their patients blood 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 repla***ent often enhances libido which has the opposite effect of most prescription anti-depressants.

One study showed that patients with major depression experienced improvement that was equal to that achieved with standard antidepressant drugs. (97)

Androderm is one of several natural testosterone repla***ent therapies that can be prescribed by doctors. A 12- month clinical trial on this FDA-approved drug resulted in a statistically significant reduction in the depression score (6.9 before vs 3.9 after). Also noted were highly significant decreases in fatigue from 79% before the patch to only 10% after 12 months. (218)

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
Great timidity
Feeling weak
Inner unrest
Loss of ability to concentrate
Memory failure
Reduced intellectual agility
Passive attitudes
General tiredness
Reduced interest in surroundings
The above feelings can all be clinical symptoms of depression, and testosterone repla***ent 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.(58,219)

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 such as immune dysfunction, brain cell injury, arterial wall damage, etc.

A group of scientists conducted two double-blind studies where 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. These scientists then 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. (289)

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 De***ber 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 that appeared in the March 1999 issue of Life Extension Magazine:

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. (220-223) Secondly, testosterone functions also as a prohormone. (99) Local tissue conversion to estrogens, dihydrotestosterone (DHT), or other active 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. (201,205,224-229) While fear of prostate cancer keeps many men from testosterone repla***ent, 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. (76,80,230)

Another myth is that testosterone is bad for the heart. Actually, low testosterone correlates with heart disease more reliably than high cholesterol. (231) 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. (232) Testosterone lowers LDL cholesterol and total cholesterol, (69,81,111) and improves every cardiac risk factor. It has been shown to improve or eliminate arrhythmia and angina. (9,106,113-115,233,266 ) A Testosterone repla***ent is the most underutilized important treatment for heart disease.

Testosterone shines as a blood thinner, preventing blood clots. 32 Testosterone also helps prevent colon cancer. (235-236)

Previous research on testosterone used the wrong form of repla***ent. Injections result in initial excess of testosterone, with excess conversion 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 and the delicate balance between androgens (testosterone) and estrogens. Each individual has his or her own pattern of hormone balance; this indicates that hormone repla***ent should be individualized and carefully monitored.

Dr. Shippen’s book, The Testosterone Syndrome retails for $21.95. Foundation members can purchase it for $15.00 by calling 1-800-544-4440. The book 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.