Testosterone for Rejuvenation | Too Late Schmart

THE DISCOVERY OF TESTOSTERONE

The strong, healthy, vigorous, sexually-driven young man inevitably evolves into the aging old man whose characteristics include loss of sexual ability (memories are the last to go), loss of muscle mass, sagging skin, rising blood pressure, decreased energy, chronic illness, and a flabby appearance. These characteristics are related to a general decline in body systems as one approaches the end of life. Can anything be done to improve the quality and length of life during the decline? The answer is "YES" with a high degree of certainty. How do we know?

The story goes back to the ancient times in Rome, the Middle East, India and China when strong men were made into eunuchs by castration (cutting off the testicles - the medical term is "orchiectomy"). The eunuchs then could be trusted to protect the women in harems without the possibility of the eunuchs becoming sexually involved with the women. So, it was known from early times that male virility was associated with the testicles (also known as "testes").

In 1889 in France at age 72, a physician named Charles Brown-Sequard, a pioneer of endocrinology, injected ground-up dog testicles into himself and then reported sexual rejuvenation - although it was short-lived. Initially, other physicians laughed at his work. That was a normal response to the situation given the lack of knowledge of hormones and their physiology.

By the 1920s in America, it was discovered that the testes contained very little testosterone and that the production of testosterone was controlled by the brain. That knowledge provided the incentive for the chemical synthesis of testosterone. In 1935 in Zurich, a Yugoslavian chemist named Leopold Ruzicka synthesized testosterone from cholesterol. For that feat, he was awarded the Nobel Prize.

The pharmaceutical companies jumped on this one! They embarked on research to develop testosterone-related chemicals that had more powerful and enduring physiological effects than natural testosterone. Their main incentive for following that path has its roots in the U.S. patent system which says that you cannot patent a natural substance. Their research led to the development of anabolic steroids which were not natural (not identical to testosterone) but were decidedly patentable and therefore, potentially very profitable.

By the 1960s, the anabolic steroids (mainly methyltestosterone) were injected by body-builders, weight-lifters and other athletes at supraphysiological doses to induce a rapid anabolic response. The results were astounding in terms of achieving muscle mass and strength. However, the lack of endocrine knowledge at the time resulted in many cases of liver diseases (the liver was desperately trying to detoxify large doses of unnatural hormone-like chemicals to maintain balance), liver cancer and many deaths. That experience with "testosterone" provided a reinforcement to the fear by the medical practice that testosterone supplementation was extremely dangerous. Earlier (in 1941), it was found that orchiectomy slowed the progression of prostate cancer. Therefore, it was assumed that testosterone suppression had slowed the cancer and testosterone was to be feared. Those assumptions proved to be correct, and today (2001), an Important part of prostate cancer protocol is to suppress testosterone.

It is only recently (>1998) that the causes of prostate, breast and endometrial cancers have been biochemically traced to carcinogenic metabolites of estrogens which can be produced in the body from testosterone.

RECENT ADVANCES IN THE BIOCHEMISTRY OF TESTOSTERONE METABOLISM

Testosterone can be converted to:

* Dihydrotestosterone (DHT) by reduction catalyzed by the 5-alpha reductase enzyme.
* Androstenedione (Andro) by oxidation.
* Estradiol (E2) by oxidation and aromatization - catalyzed by the aromatase enzyme.

* Testosterone (T) by reduction.
* Estrone (E1) by oxidation and aromatization - catalyzed by the aromatase enzyme.

* Estrone by oxidation.
* Estratriol (E3) by oxidation.
* 2-Hydroxyestradiol (protective) by oxidation.
* 4-Hydroxyestradiol (carcinogenic) by oxidation.

* Estradiol by reduction.
* 2-Hydroxyestrone (protective) by oxidation.
* 4-Hydroxyestrone (carcinogenic) by oxidation.
* 16 alpha-Hydroxyestrone (carcinogenic) by oxidation.

The recent advances in analytical capabilities are directing attention to the oxidized metabolites of the estrogens (E1, E2, and E3) as the sources of carcinogenic chemicals that lead to cancers of the breast, prostate, endometrium and probably others not yet known. Although unfavorable metabolic processes can convert testosterone to the estrogens and then to carcinogenic metabolites, testosterone itself has not been found to be carcinogenic. To the contrary, testosterone has been found to be protective against cancer. The case against testosterone is without understanding of how the past prejudices evolved and the knowledge of how the diet and chronic stress affects the metabolism of steroid hormones. Further complicating the situation is the intake of chemicals that mimic the estrogens and are carcinogenic.

INHIBITING THE CONVERSION OF TESTOSTERONE TO CARCINOGENS

The recent gains in understanding the biochemistry of testosterone metabolism allow men to inhibit both the conversion of testosterone to estrogens and their subsequent conversion to carcinogenic metabolites. The primary strategy is to inhibit the aromatization of the androgens (testosterone and androstenedione) to the estrogens and to inhibit the oxidation of estrogens. At this point, the effectiveness is empirical and the biochemical explanations are not known. Furthermore, the effect of diet, state of stress, vitamin supplementation and other factors are different for each person. Nevertheless...

* Urtica Dioica (Stinging Nettle root extract)
* Chrysin
* Soy Isoflavones
* Zinc
* Pygeum extract
* Bioflavonoids
* Anastrazole (brand name "Arimidex")

Since 1990, or earlier, the conversion of testosterone to dihydrotestosterone, using the 5 alpha-reductase enzyme, has been thought to be the cause of benign prostate enlargement. However, in 1997, the binding of estradiol to sex hormone binding globulin in the prostate gland was identified as the primary cause of
proliferation of epithelial cells in the prostate. However, saw palmetto extract blocks estrogen receptors in the prostate, and thus minimizes the growth-stimulating effects of estradiol. However, excessive use of 5 alpha-reductase inhibitors to prevent the conversion of testosterone to dihydrotestosterone forces the testosterone down the pathway to estradiol via aromatase. The bottom line is to find the balance that allows the long-term use of saw palmetto berry extract.

* Vitamin E (alpha, beta, gamma, delta) and related tocotrienols are especially important because they and the steroid hormones are both fat - soluble.
* Coenzyme Q10 (fat-soluble)
* Carotenes (fat-soluble)
* Lycopene (fat-soluble)
* Lutein (fat-soluble)
* Selenium
* Green Tea polyphenols
* Vitamin C
* Glutathione (glutamic acid, cysteine, glycine)
* Alpha Lipoic Acid
* Grape Seed and Skin extract (proanthocyanidins)
* Bilberry extract (anthocyanidins)

Indole 3-Carbinol (13C) or its dimer Diindolyl- methane (DIM) preferentially oxidize estrone to 2-hydroxyestrone (protective) and estradiol to 2-hydroxyestradiol (protective).

* B vitamins (all of them)
* Minerals (all of them)
* Cod Liver (it contains the components to make superior cell membranes which enhances cellular communications - it promotes the positive physiological effects and inhibits the negatives of cellular hormones - vital for health)

A PERSONAL EPISODE

In 1995 (age 66), I had my first PSA (prostate specific antigen) test which came in at 5.6 ng/ml. At the HMO (health maintenance organization), anything over 4.0 shunted me to the urologist for a biopsy examination of the prostate. He took six slivers of flesh (each about 3/4" long and a pencil point in diameter) out of the prostate without anesthesia. It was not only extremely painful, but it was also terrifying. I thought this must be something like being in a Nazi death camp. Because three slivers on each side of the prostate is like stabbing in the dark for accuracy, current practice is to take eighteen shots at the prostate. I saw blood in the ejaculate for about a month.

After keeping me waiting for over a month for the results of the biopsy (during which time the sympathetic nervous system carried my blood pressure to 190/110 [normally 120/70]), I was told that I did not have cancer in the six slivers of tissue. I did have a prostate that was 50% larger (60cc) than normal (40cc). I swore I would never have another biopsy.

In mid-1998 (age 69) a saliva test showed my testosterone was 60 pg/ml which was about normal for an 80 year old man. My diminished sexual function had already told me that. I really longed for the pleasures of the past.

I began to supplement with testosterone cream (5% testosterone) by rubbing a small amount under my arm where it could spend all day being absorbed. I did not use the palms of my hands because I washed my hands frequently during the day. I was well aware of the dangers of enlarging the prostate further or getting prostate cancer by the conversion of testosterone to estrogens. Those threats caused me to supplement with an array of antioxidants and inhibitors of aromatization and an inhibitor of testosterone to DHT. The program also included a wide array of nutrients for metabolic support and detoxication.

In early 1999, about nine months after beginning testosterone supplementation, a saliva test (measures "free" [immediately active] hormones) showed testosterone at 880 pg/ml (pg/ml = parts per trillion) and estradiol at 0.5 pg/ml (the low limit of the test). This saliva test indicated that the testosterone supplementation worked well - perhaps too well, and the efforts to prevent conversion to E2 were successful. The beneficial physiological effects of testosterone were evident not only in sexual function, but also in strength, hair growth and a feeling of well-being. Nevertheless, I decided to use much less testosterone in the coming months because of the dangers of high concentrations. I estimated that testosterone in the saliva of a 20-year old would have been about 600 pg/ml. My aim was to reduce the 880 to the 400-600 range.
In late 1999, another saliva test showed testosterone at only 100 pg/ml. I then adjusted the amount of testosterone applied to 1-2 mg every other day. The saliva level then rose to 550 pg/ml. Estradiol continued at 0.5 pg/ml (the lowest measurable level). Estrone was reported at 1.1 pg/ml.

In 2000, I had an MRI (magnetic resonance imaging) with spectroscopic analysis of the prostate. It showed no detectable cancer throughout the entire prostate (much better than a biopsy!). This gave me courage for my next action. I decided to experiment with my regimen to limit estradiol and estrone. I stopped taking the enzyme inhibitors, but I continued the full set of antioxidants.

After about four months (November 2000), the saliva test showed testosterone at 550 pg/ml, E2 at 0.5 pg/ml and E1 at 1.9 pg/ml. I was pleasantly surprised that E2 had not risen at all, and E1 had risen by only a small amount. This experiment indicated that the oxidation reactions of testosterone to E2 and androstenedione to E3 were inhibited by the array of antioxidants. Furthermore, the oxidation of testosterone to androstenedione was probably inhibited, thus contributing to a higher testosterone concentration.

My current protocol (Fall 2001) emphasizes antioxidants, but, to be more secure, I also take the aromatization inhibitors and the 5 alpha reductase inhibitor. In addition, I have stepped up the use of detoxication nutrients because of the unprecedented dangers of estrogenic chemicals in our food and environment.

WHAT IF CANCER ALREADY EXISTS?

In 1994 in Finland, a sharply breaking curve ball was thrown at the antioxidant theory. Long-term heavy smokers who took beta-carotene or vitamin E or both were more likely to die of lung cancer than those who took a placebo. This result was confirmed in a 1996 study in the US named "Carotene and Retinol Efficacy Trial" (CARET). Lung cancer mortality was 28% higher in the vitamin group than in those who took a placebo. The media reacted by describing how beta- carotene could give you cancer. They were like a dog with bone! What was happening?

As cells accumulate carcinogens (cancer precursors) and cancer develops, the cells and the immune system initiate oxidation reactions aimed at cell death or suicide (apoptosis) to cut off the growth of cancer. Radiation treatments to kill cancer also rely on oxidation reactions. The antioxidants interfere with the apoptotic process causing the cells to live and allowing the cancer to spread by using the resources of the cell. This explanation confirms that antioxidants are effective in hindering or stopping oxidation reactions - even though they are beneficial.

Therefore, a man with prostate cancer should not supplement with testosterone because the intake of antioxidants required to prevent conversion to estrogens would work against the body's attempts to kill the cancer by apoptosis.

COMPREHENDING PARTS PER TRIlLION

Steroid hormones in the human body are circulating in parts per trillion (measured as picograms per milliliter [pg/ml]). A pico-anything is
1 x10 -12. Those units of measurement defy comprehension. One way to get some idea of how small a trillionth is, is to make some ratios with things we can comprehend. Incidentally, the potency of steroid hormones at these infinitesimal concentrations explains how homeopathic medicines can be effective. The following are parts per trillion comparisons:

* One person in 160 world populations
* One second in 32,000 years
* One drop in 660 tank cars (a train 6 miles long)
* The distance light travels in 30 millionths of a second (6 miles) compared to the distance traveled in one year (6 trillion miles)
* The diameter of a red blood cell (8 micrometers) compared to the distance traveled on 1000 round-trips from the earth to the moon.

DETOXICATION

To maintain a strong, healthy body, especially when supplementing with testosterone, it is necessary to continuously detoxicate normal metabolic poisons including harmful hormonal metabolites. Furthermore, it is absolutely necessary to minimize the accumulation of environmental chemicals that are poisoning us. Environmental estrogen mimics are the leading cause of the rising rates of prostate cancer in men and breast cancer in women.
A great many of these harmful chemical can be detoxicated at the cellular level and by the liver for excretion in urine, feces and sweat using the following array of chemical supplements:

* Sulfation: glutathione precursors (glutamic acid, cysteine and glycine), methyl sulfonyl methane (MSM), dimethyl sulfoxide (DMSO).
* Methylation: dimethylglycine (DMG), trimethylglycine (TMG), dimethylaminoethanol (DMAE), dimethyl sulfoxide (DMSO), choline (trimethylaminoethanol)
* Glucuronidation: glucose, calcium-D-glucarate.
* Acetylation: acetic acid (vinegar).
* Acylation: glycine, glutamine, taurine.

BENEFITS OF EXTRA TESTOSTERONE

Testosterone is the premier anabolic hormone. It has the potential of producing diverse beneficial physiological effects on elderly men that essentially affect the entire body. Effects include the following:

* Enhances the feeling of well-being
* Enhances strength and energy
* Rebuilds aging muscles and bones
* Enhances sexual function and pleasure
* Protects the cardiovascular system
* Prevents degenerative diseases
* Maintains red blood cell mass
* Increases oxygen uptake
* Helps maintain a strong immune system
* Helps mental concentration

* Use testosterone cream transdermally (under the arm for me) daily or every other day to supply 1 mg/d of testosterone. This provides a steady low dose that is readily metabolized and is very effective. Do not use large weekly doses that will shift the equilibrium to the estrogens. At the same time, use 10 mg/d of progesterone cream transdermally. Progesterone "opposes" any estrogen that may be formed.
* Hypothalamic sensitivity (necessary for all hormone production) is powered by cyclic adenosine monophosphate (cyclic AMP) which is under eicosanoid control. The hormone, glucagon, promotes positive eicosanoids, while excess insulin produces negative eicosanoids. The control of glucagon and insulin is in your diet. This knowledge is known and understood by very few people. Understanding this is a prime requisite for safe testosterone supplementation. The main factors that promote glucagon dominance are:
o Hypocaloric diet (eat slightly less calories than used - calorie restriction)
o Diet should be 30% protein (mainly fish), 30% fat (cod liver oil and olive oil) and 40% complex carbohydrates - no sugar or high gylcemic foods - no hydrogenated oils including margarine - lots of fiber to slow the digestion process and to promote detoxication.

Diet that is high in carbohydrates, high in sugar, high in other glycemic foods (simple carbohydrates), and low in fiber.
* Avoid environmental estrogen mimics (pesticides, crops sprayed with insecticides, insecticides used in homes and gardens and sprayed on pets, plastic (especially heated), cleaning agents, solvents, adhesives and hot polystyrene cups.
* Take a wide range of antioxidants especially those that are fat soluble. Use aromatization and 5 alpha reductase inhibitors.
* Monitor saliva concentrations of testosterone, progesterone, estrone and estradiol - once every 6 months until a steady state is reached - then once a year.
* Get plenty of regular exercise to build your body. The hormones, diet and supplemental nutrients will let you do it.
* Maintain a continual detox program to rid yourself of toxic estrogen metabolites and environmental estrogen mimics.

Diet Probability of extended longevity is improved at a Body Mass Index of 20-25. BMI = (weight in pounds)(703)/(height in inches)² Weight loss to achieve a BMI of 20 should be constrained to 4% per year to maintain homeostatic balance and to allow the body to adjust its biochemistry.	Controlled eating - 5 small meals per day Complex carbohydrates (grains, vegetables, nuts, seeds) Very low sugar Very low saturated fats- use mainly olive oil Cod liver oil every day Protein mainly from cold water ocean fish; some chicken, but no animal (mammal) meat
Water Drinking pure water is a means of delivering nutrients to cells and removing wastes for excretion in the urine (detoxication). Water makes the blood less viscous and easier for the heart to pump.	Home drinking water purifier is mandatory. It should have a UV light to kill pathogens. A magnitude higher in obtaining biologically beneficial water is the use of a mild electrolysis of the purified water to obtain an antioxidant (contains excess electrons) alkaline water.
Exercise Moderate exercise is decidedly beneficial, whereas strenuous exercise can be destructive (felt the most by older people).	Moderate exercise keeps the body in good condition. The heart, lungs and muscles benefit. In addition, the sweat generated from exercise is a means of detoxication. Sweating in a sauna is a very important way to detoxify.
Supplemental Nutrients	The body needs a great variety of supplemental nutrients to support the numerous intertwined biological pathways. The Recommended Dietary Allowance (RDA) for vitamins is unbelievably inadequate. Enhanced health requires a high vitamin intake with a wide coverage.
Mindset Learning to relax (yoga, meditation, listening to calming music) can reset the autonomic nervous system so that you will have a more muted reaction to stress when it arises.	Stress is destructive. Develop the ability to deal with stress. Do something athletic. Relax in the sun. Go walking in the woods. Be honest, reliable, trustworthy, friendly and humorous. Those traits benefit everyone, especially you.
Brain Enhancers and Hormones	The decline of key hormones is associated with the aging process. Health can be enhanced by judiciously supplementing with hormones such as "triple estrogen" and progesterone for women and testosterone and progesterone for men.
Fresh Air	Allow plenty of fresh air into a house to clear out gases that have accumulated from walls, carpets and gas heaters. Use an air cleaner in the bedroom.
Intentional Intake of Toxics	Eliminate alcohol, caffeine, smoking and prescribed drugs. Those things hinder many important biochemical reactions. Furthermore, the body wastes its nutrient and energy resources to detoxify those things.
Sleep Sleep is the opportunity for the body to rejuvenate itself. The energy system is idling, the immune system is in control and repairs are taking place.	Melatonin assists the pineal gland to induce sleep, especially in the elderly. Arginine dilates blood vessels and causes relaxation. Taurine is an inhibitory (relaxing) neurotransmitter. Valerian is a relaxant. Low dose lithium is pleasantly sedating. Do not use antidepressant drugs because they need to be detoxified, and they can be addictive.

TOO LATE SCHMART is written by Stanford Field (BS chemical engineering, 1951) who has been avidly studying biochemistry and physiology, since 1993, with an aim of staying healthy despite the ever-increasing odds of age-related decline. This publication is written to the best of his ability, and it is intended to document any findings that may be useful to interested readers. The publication has neither profit nor political motives.