Male Hormone Restoration
A Word about Testosterone and Prostate Disease

For more than 50 years, it has been thought that men should avoid testosterone replacement therapy because testosterone increases the risk of prostate disease, including BPH and prostate cancer. A look at the published literature, however, reveals that this long-standing belief is actually a myth.

In fact, a review of studies on the National Institutes of Health database reveals that high testosterone levels are not associated with increased risk of prostate cancer and, conversely, that low testosterone levels are not protective against prostate cancer (Morgentaler A 2006). In one study (with a 7-year follow-up) of more than 500 men, high levels of androgens were associated with a decreased risk of aggressive prostate cancer, while there was no change in the risk of nonaggressive prostate cancer. Overall, levels of any steroid hormones (except estrogen) had no correlation to the risk of prostate cancer (Severi G et al 2006).

Elevated estrogen levels, however, are frequently associated with BPH. As readers of Life Extension magazine learned in late 1997, estrogen has been identified as a factor behind the enlargement of the prostate gland that affects so many older men. Compared to younger males, older males have much more estradiol (a potent form of estrogen) than free testosterone because of aromatase activity. These rising estrogen and declining androgen levels are even more sharply defined in the prostate gland. With aging, estrogen levels increase significantly in the prostate gland. Estrogen levels in prostate gland tissues rise even higher in men who have BPH (Shibata Y et al 2000; Gann PH et al 1995; Krieg M et al 1993).

Based on research, high levels of testosterone are not implicated in an increased risk of developing either prostate cancer or BPH. However, among men who already have these conditions, testosterone replacement therapy will likely cause increased disease activity. For these reasons, it is important that men who are considering hormone replacement therapy undergo frequent screening for prostate cancer (with PSA testing and digital rectal exams). If cancerous cells are present in the prostate, testosterone therapy will likely produce a spike in PSA levels that will lead to a diagnosis of prostate cancer.

Once a man actually has prostate cancer, testosterone therapy cannot be recommended because most prostate cancer cells use testosterone to promote the growth of the cancerous cells. Similarly, men with BPH should approach testosterone replacement cautiously. It may be prudent for men with BPH who are undergoing testosterone replacement therapy to also use a 5-alpha-reductase inhibitor (such as finasteride or dutasteride). These drugs inhibit the synthesis of dihydrotestosterone (DHT), a metabolite of testosterone that causes BPH. 5-Alpha-reductase inhibitors are a standard part of prescription therapy for BPH. For more information on natural ways to suppress BPH, please see the chapter on Benign Prostatic Hyperplasia.

Recommendations

Hormone therapy for aging men can be a complicated topic. While many books talk about the dangers of low testosterone levels, there are few sources that can help men safely embark on a program of testosterone replacement therapy. The Life Extension Foundation offers a step-by-step program to safely restore youthful hormone levels in aging men.

Step One: Testing

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

Complete blood cell count and chemistry profile to include liver and kidney function, glucose, minerals, lipids, and thyroid-stimulating hormone (TSH)

DHEA
Homocysteine
Luteinizing hormone (LH) (optional)
SHBG (optional)
Blood for these tests may be drawn at your physician's office or directly at a laboratory in your area. Information about ordering these tests on your own may be obtained by calling 1-800-208-3444. These tests will yield crucial information that can help you design a program tailored to your unique situation.

Step Two: Interpreting the Results

Free testosterone. Most conventional physicians accept testosterone levels that are far too low. Normal ranges usually reflect population averages among men of a particular age. This assumes, however, that decreasing hormone levels are acceptable and normal. The Life Extension Foundation recommends that men strive for a free testosterone level that is in the upper one-third range for men aged 21 to 49 years. These ranges can be found in the Blood Testing appendix at the back of this book.

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

• Too much testosterone is being converted to estrogen through the activity of aromatase, and/or the liver is failing to remove excess estrogen, possibly because of heavy alcohol intake.
  
• Too much free testosterone is being bound by SHBG. This would be especially apparent if a man’s total testosterone level is in the high normal range but his free testosterone level is low.
  
• The pituitary gland, which controls testosterone production through the production of LH, is not secreting enough LH to stimulate gonadal production of testosterone. In this case, total testosterone would be low.
  
• The testicles (gonads) have lost their ability to produce testosterone, despite adequate amounts of LH. In this case, the level of LH would be high despite a low testosterone level.
  
• DHEA level is abnormally low.
  

Estrogen. Estrogen (measured as estradiol) should be kept at 30 picograms per milliliter (pg/mL) or lower. If a man’s estrogen level is more than 30 pg/mL, it should be reduced by using aromatase-inhibiting drugs or nutrients. If a man’s estrogen level is elevated, it could be associated with:

• Increased aromatase activity, often caused by increased abdominal fat.
  
• Heavy alcohol intake. An animal study has shown that high alcohol intake results in increased aromatization and decreases the ability of the liver to clear excess estrogen (Purohit V 2000). In men, heavy alcohol intake has been shown to boost estrogen levels within the liver, possibly as a protective mechanism, resulting in the “feminization” of the liver (Colantoni A et al 2002).
  

Total testosterone. The Life Extension Foundation believes that direct testing for free testosterone is the best way to test for testosterone activity, as free testosterone is active testosterone and consists of only 1 to 2 percent of total testosterone. However, some men have their total testosterone measured also.

Step Three: Correcting Abnormal Levels

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

Low Free Testosterone, High Estradiol, Mid Total Testosterone

This situation suggests excessive aromatase activity, which converts free testosterone to estrogen. Inhibition of aromatase and reduction in aromatase-containing tissue (fat) is indicated. Suggestions include:

Take the following supplements:

• Zinc—50 milligrams (mg)/day
  
• Acetyl-L-carnitine—1000 to 2000 mg/day
  
• Muira puama—850 mg/day
  
• Chrysin—1500 mg/day
  
• Piperine—10 mg/day to enhance absorption of chrysin
  
• Quercetin—500 to 1000 mg/day
  

Lose weight to reduce aromatase activity.

Reduce or eliminate alcohol to enable the liver to better remove excess estrogen.

Review all current medications to see if they are interfering with healthy liver function. Common medications that affect liver function are nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen, ibuprofen, acetaminophen, and aspirin; the statin class of cholesterol-lowering drugs; some heart medications; some blood pressure–lowering medications; and some antidepressants. Drugs being prescribed to treat the symptoms of testosterone deficiency (such as the statins and certain antidepressants) may actually aggravate the testosterone deficit, thus making the cholesterol problem or depression worse. However, do not discontinue any prescription medicine without consulting your physician.

If all of the above fail to increase free testosterone and lower excess estradiol, consider discussing with your physician the use of the aromatase inhibitor anastrozole at the very low dose of 0.5 mg twice per week.

Low Free Testosterone, Low Estrogen, High Total Testosterone

This situation suggests excessive SHBG levels, making testosterone unavailable to target tissues. Suggestions include:

Inhibit aromatase by following some of the recommendations in the previous section. Many of the same factors are involved in excess SHBG activity.

Take the following supplements:

• Saw palmetto extract—320 mg/day
  
• Nettle root extract—240 mg/day
  
• Cruciferous vegetable extract—400 mg/day
  
• DHEA—15 to 75 mg/day, followed by blood tests in 3 to 6 weeks
  

Low Free Testosterone, Low Estrogen, Low Testosterone

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

Use testosterone patches, pellets, or cream. Do not use testosterone injections or tablets. If tests reveal low levels of LH, ask your physician about the possibility of using human chorionic gonadotropin (HCG). HCG function is similar to LH function, and HCG can restart gonadal production of LH.

Take 15 to 75 mg/day of DHEA.

General Nutrients to Boost Testosterone

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

• Selenium—200 micrograms (mcg)/day
  
• Vitamin A—5000 International Units (IU)/day
  
• Vitamin E—400 IU/day with at least 200 mg of gamma-tocopherol
  

Male Hormone Restoration Safety Caveats

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

Acetyl-L-Carnitine
Acetyl-L-carnitine can cause gastrointestinal symptoms such as nausea and diarrhea.

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

DHEA
(1) Do not take DHEA if you could be pregnant, are breastfeeding, or could have prostate, breast, uterine, or ovarian cancer.
(2) DHEA can cause androgenic effects in woman such as acne, deepening of the voice, facial hair growth and hair loss.

Piperine
(1) Piperine can inhibit drugs such as: propanolol, theophylline, phenytoin, sulfadiazene, rifampicin, isoniazid, ethambutol, pyrazinamide and dapsone that are metabolized by cytochrome P450 enzymes.

Quercetin
(1) Quercetin can cause headache, mild tingling of the extremities, and gastrointestinal symptoms such as nausea.

Saw Palmetto
(1) Consult your doctor before taking saw palmetto if you have any form of cancer that is stimulated by hormones.

Selenium
(1) High doses of selenium (1000 micrograms or more daily) for prolonged periods may cause adverse reactions.
(2) High doses of selenium taken for prolonged periods may cause chronic selenium poisoning. Symptoms include loss of hair and nails or brittle hair and nails.
(3) Selenium can cause rash, breath that smells like garlic, fatigue, irritability, and nausea and vomiting.

Vitamin A
(1) Do not take vitamin A if you have hypervitaminosis A.
(2) Do not take vitamin A if you take retinoids or retinoid analogues (such as acitretin, all-trans-retinoic acid, bexarotene, etretinate, and isotretinoin). Vitamin A can add to the toxicity of these drugs.
(3) Do not take large amounts of vitamin A. Taking large amounts of vitamin A may cause acute or chronic toxicity. Early signs and symptoms of chronic toxicity include dry, rough skin; cracked lips; sparse, coarse hair; and loss of hair from the eyebrows. Later signs and symptoms of toxicity include irritability, headache, pseudotumor cerebri (benign intracranial hypertension), elevated serum liver enzymes, reversible noncirrhotic portal high blood pressure, fibrosis and cirrhosis of the liver, and death from liver failure.

Vitamin E
(1) Consult your doctor before taking vitamin E if you take warfarin (Coumadin).
(2) Consult your doctor before taking high doses of vitamin E if you have a vitamin K deficiency or a history of liver failure.
(3) Consult your doctor before taking vitamin E if you have a history of any bleeding disorder such as peptic ulcers, hemorrhagic stroke, or hemophilia.
(4) Discontinue using vitamin E 1 month before any surgical procedure.

Zinc
(1) High doses of zinc (above 30 milligrams daily) can cause adverse reactions.
(2) Zinc can cause a metallic taste, headache, drowsiness, and gastrointestinal symptoms such as nausea and diarrhea.
(3) High doses of zinc can lead to copper deficiency and hypochromic microcytic anemia secondary to zinc-induced copper deficiency.
(4) High doses of zinc may suppress the immune system.