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DHEA - precautions

precautions

In 1981 the Life Extension Foundation introduced DHEA (dehydroepiandrosterone) through an article that described the multiple antiaging effects this hormone might produce. The general public learned about DHEA in 1996, as the benefits of DHEA were touted by the news media and in several popular books.

DHEA obtained credibility in the medical establishment when the New York Academy of Sciences published a book entitled DHEA and Aging and summarized in their journal, Aging (Dec. 29, 1995, 774:1-350). This highly technical book provided scientific validation for the many life extension effects of DHEA replacement therapy.

DHEA has been shown to improve neurological function (including memory, mood enhancement, and EEG readings), immune surveillance, and stress disorders. DHEA replacement therapy has become popular as an antiaging regimen and offers aging patients help in preventing diseases such as osteoporosis, fatigue, depression, atherosclerosis, and cancer.

DHEA replacement therapy involves the supplementation of the hormone to restore serum levels to those of a 21-year-old. DHEA is a precursor building block that allows our bodies to more easily create hormones that may be in decline because of age, disease, prescription medications, or other factors. Hormones such as testosterone and estrogen as well as serum DHEA levels begin to decline between 25 and 30 years of age and may be reduced by 95% of youthful peak levels by age 85.

The most remarkable finding about DHEA came from a human study by S. S. C. Yen and associates at the University of California, San Diego, in which 50 mg a day of DHEA over a 6-month period restored youthful serum levels of DHEA in both men and women. Dr. Yen showed that DHEA replacement was associated with an increase in perceived physical and psychological well-being for both men (67%) and women (84%). Increases in lean body mass and muscle strength were reported in men taking 100 mg a day, but this dose appeared to be excessive in women.

DHEA (50 or 100 mg a day) was also shown to significantly elevate insulin growth factor (IGF). Aging causes a decline in IGF levels that contributes to the loss of lean body mass, as well as to excess fat accumulation, neurological impairment, and age-associated immune dysfunction.

DHEA has been shown to protect against heart disease and atherosclerosis. A study using coronary artery angiography showed that low DHEA levels predispose people to more significant coronary artery blockage. Another study showed that DHEA inhibits abnormal blood platelet aggregation, a factor in the development of sudden heart attack and stroke. In contrast, some studies on DHEA do not show the cardiovascular disease protection.

In the journal Drugs and Aging (Oct. 1996), an analysis of previous studies on DHEA showed that

• In both humans and animals, the decline of DHEA production with aging is associated with immune depression, increased risk of several different cancers, loss of sleep, decreased feelings of well-being, and increased mortality.
  
• DHEA replacement in aged mice significantly improved immune function to a more youthful state.
  
• DHEA replacement has shown a favorable effect on osteoclasts and lymphoid cells, an effect that may delay osteoporosis. (Editor's note: DHEA has been shown in other studies to promote the activity of bone-forming osteoblasts.)
  
• Low levels of DHEA inhibit energy metabolism, thus increasing the risk of heart disease and diabetes mellitus.
  
• Studies in humans show essentially no toxicity at doses that restore DHEA to youthful levels.
  
• DHEA deficiency may expedite the development of some diseases that are common in the elderly.

Depression is a broad term for a host of unpleasant feelings, including emotional numbness, lack of energy, lack of motivation, feeling like a failure, and feeling undesirable. These feelings frequently show up for the first time in middle-aged people who feel like they're "over the hill." Elderly people, too, frequently get depressed, and they are particularly at risk of suicide. Depression is a growing problem among teenagers as well.

Doctors have long known that giving estrogen to women and testosterone to men during midlife can avert symptoms of depression, although the effects have never been phenomenal. Reports are stacking up that DHEA works better. DHEA turns into both estrogen and testosterone. And it just so happens that it goes south about the time people start thinking about being "over the hill."

DHEA is definitely a brain chemical. It's not only utilized by the brain, it's manufactured by it. Although researchers don't know what it's supposed to do yet, they do know that giving a person 500 mg of DHEA will cause them to have more REM (dream) sleep. This indicates a major role in brain chemistry.

DHEA is the only hormone besides cortisol that has consistently been linked with depression. It was studied as far back as the 1950s as an antidepressant. Back then, researchers reported that it gave people energy and confidence, and made them less depressed. While it seemed to work great, no one followed up on the studies.

DHEA emerged on the scene again in the 1980s when interest in antiaging hormones geared up. It was noted then that antidepressant activity was part of DHEA's overall antiaging benefits. Then, in 1996, a report suggested that DHEA's antidepressant effects might be direct, and not just a result of its antiaging benefits in older people. Researchers at Cambridge University discovered that young kids with major depression have abnormally low levels of DHEA (and abnormally high levels of cortisol).

In the late 1990s, this phenomenon was confirmed in a larger study. Researchers at the University of California at San Diego went back and analyzed old data from a large study that had been done on 699 older women living in Rancho Bernardo, California. That analysis is the largest study ever done on the association between levels of DHEA and depression. Nine different hormones had been measured during the study, which took place during the 1970s and 1980s. Included in the measurements were such things as bioavailable testosterone and sex-hormone-binding globulin. When the results were in, of all the hormones, only DHEA was associated with depression. (Low testosterone levels have been correlated with depression in men.)

Women at the lowest end of DHEA were far more likely to be depressed. This coincides with an earlier study where the percentage of women with depression was 21.7% if they had no detectable DHEA, versus 4.6% if DHEA could be detected in their blood. Interestingly, levels of DHEA in the Rancho study correlate with mood even within the normal range. In other words, the lower the DHEA, the worse the mood got. And DHEA correlated with mood irrespective of whether a person was taking antidepressants or not.

A group at the University of California, San Francisco went at the DHEA/depression question another way. They decided to give DHEA to people with depression and see if it would help. In the first double-blind, placebo-controlled study on DHEA's potential as an antidepressant, 11 patients with major depression were given up to 90 mg/day of DHEA for 6 weeks, and 11 were given a placebo. One week before the study actually began, all patients were given a placebo to weed out people who would respond to a sugar pill. people getting the real McCoy received 30 mg a day of DHEA for the first 2 weeks, 60 mg the second 2 weeks, and 90 mg the last 2 weeks. The idea of the graduated dose was to bring patients up to the DHEA levels they had when they were 20 to 30 years old (DHEA declines with age). Although the amount of DHEA wasn't adjusted individually, as it could have been, the graduated dose approximates what it takes to reach a "youthful" level in most people, according to Dr. Owen Wolkowitz, principle investigator on the study. Some of the participants were taking antidepressants. For these people, the antidepressants were either working partially, or not working at all. Only people who had been on the same antidepressant for at least 6 weeks without changing were allowed in the study, and no changes could be made in anyone's medication during the study.

After 6 weeks, psychological tests indicated that about half the participants responded to DHEA therapy, with an overall enhancement of mood scores by 30.5%. This is close to the response rate of antidepressant drugs.

An even better response was seen in another study conducted by researchers at the National Institute of Mental Health. In this study, participants were middle-aged people with dysthymia, a chronic, low-grade depression. They were given 90 mg of DHEA a day for 3 weeks, then 450 mg a day for 3 weeks more. Batteries of psychological tests were administered, including the Hamilton Depression Rating Scale, the Beck Depression Inventory, a visual analogue scale, and the Cornell Dysthymia Scale. (In addition, a day's worth of cognitive function tests was given, but DHEA didn't show a significant effect on cognition in this study. However, the researchers note a trend towards better cognition that could have played out if the study had lasted longer). None of the patients were taking any prescription drugs whatsoever except one man who was taking a hypertension drug. The study was set up in a very rigorous way; all participants got the drug or the placebo for 6 weeks, and then they were all secretly switched. All people involved in the study were blind to who was getting what. DHEA significantly alleviated the participants' depression. Seven symptoms in particular got much better: lack of pleasure, low energy, low motivation, emotional numbness, sadness, inability to cope, and excessive worry. DHEA worked for most people within 10 days. If the supplement was stopped, the symptoms came back. Overall, the response rate was 60%, which is better than what antidepressants usually do for dysthymia. Ninety milligrams a day was sufficient. No extra benefit was provided by the 450 mg dose.

Researchers have different theories about how DHEA alleviates depression. Both DHEA and DHEA-s can cross the blood-brain barrier and interact with the brain directly. DHEA can affect serotonin, GABA receptors, and other brain factors. A recent study indicates it might modulate the serotonin signaling pathway. In addition, DHEA is the precursor for estrogen and testosterone which have been reported to enhance mood.

DHEA also has antistress effects that may be part of its antidepressant action. Research shows that cortisol, the stress hormone, is elevated in major depression. DHEA counteracts cortisol. Calmness appears to be associated with higher levels of DHEA. people who practice transcendental meditation have higher levels of DHEA than those who don't. people who took part in a stress reduction program were able to increase their DHEA by 100%. At the same time, they reduced their stress hormone by 23%.

Exercise has been reported to enhance mood. This mood-enhancing effect may be due to DHEA. Exercise raises levels of DHEA, which also positively affects the heart. In a study published in the American Journal of Cardiology , depression and heart attack went together: women with depression are at greater risk of heart attack, and vice-versa. Exercise elevates DHEA, which, in turn, benefits the heart.

DHEA Inhibits Cancer Cell proliferation

DHEA may be effective in preventing and treating cancer. In one study, DHEA inhibited tumor proliferation of rat liver cells by blocking the cancer cell promoting enzyme glucose 6-phosphate dehydrogenase (G6pDH). The human equivalent dose of 600 mg a day suppressed breast tumors in mice by 70%, yet these scientists showed that even human equivalent doses of 25 to 120 mg showed striking cancer prevention benefits, with no evidence of toxicity.

DHEA has been shown to inhibit chemically induced cancers in the colon, lung, breast, and skin. When DHEA is applied directly to the skin, DHEA prevented chemically induced skin cancer. DHEA had this effect by blocking the binding of carcinogens to skin cells and by inhibiting the enzyme G6pDH.

One study showed that patients with adult T-cell leukemia (ATL) had significantly decreased levels of DHEA compared to healthy controls. This has led some doctors to speculate that DHEA might be beneficial in treating this form of leukemia since DHEA has already been shown effective in treating hairy cell leukemia. Other cancer studies show DHEA inhibits cancer cell thymidine incorporation needed for cellular propagation and disrupts the oxidizing effects of chemical carcinogens. Scientists point out that DHEA functions not as an antioxidant, but as a modulator of the effects of chemical carcinogens on cells ( American Journal of Hematology , 1996, 533).

DHEA protects against Brain Aging

Acetylcholine is a neurotransmitter that transmits nerve impulses from one brain cell to another. Acetylcholine is crucial for short-term memory and to protect brain cells against age-associated atrophy. Aging causes a decline in the release of acetylcholine into regions of the brain where it is needed for learning and memory.

In a study in Brain Research (Sept. 16, 1996), DHEA was administered to rats in order to measure the effect it produced on acetylcholine release into the hippocampus region of the brain. DHEA significantly increased acetylcholine release above pretreatment levels in all doses tested. At the highest dose, DHEA caused a fourfold increase in the release of acetylcholine compared to the control group. The scientists concluded that this was the first study to demonstrate a direct effect of DHEA in promoting the release of acetylcholine from brain cells in the hippocampus (a critical area for the storage of memory).

In a study published in Behavioral Brain Research (1997, 831-2), DHEA interacted with certain neuronal receptors involved in short-and long-term memory storage. The results showed an improvement in memory in the Y-maze spatial leaning test that measures short-term memory and the step-down passive avoidance test that measures long-term memory in mice.

A study in Life Sciences (Oct. 4, 1996) showed that DHEA could protect against the precursor changes in brain cells that result in the pathological alterations associated with Alzheimer's disease.

DHEA Saves Skin

DHEA has powerful skin protective effects. A study published in the Journal of Surgical Research demonstrates that topically applied DHEA protects the skin's delicate blood vessels. Researchers found that if DHEA was applied after a serious burn, the blood vessels underlying the burned area were protected. protecting the blood vessels saves the skin. Skin and blood vessels that would otherwise die and peel off can be saved by DHEA. No one knows for sure how DHEA saves skin this way, but its anti-inflammatory action no doubt has something to do with it. DHEA prevents destructive white blood cells and their biochemical cousins from gearing up. In particular, DHEA affects the blood vessel killer known as tumor necrosis factor (TNF). At the same time it's inhibiting the destructive process, it appears to be prolonging the healing process: DHEA causes edema (swelling) to last longer. This apparently helps save tissue.

Estrogen's skin-enhancing effects are well-known. It provokes collagen and a moisture factor known as hyaluronic acid. Aging decreases both estrogen and collagen. Enzymes that convert DHEA to estrogen also decline. Not surprisingly, women who take synthetic estrogen have scientifically proven thicker skin. Women who take both estrogen and testosterone have really thick skin-48% thicker than women who don't take either hormone. DHEA is converted to both estrogen and testosterone, providing the benefits of both hormones. DHEA is converted into estrogen and androgen-type metabolites found only in skin.

Studies show that DHEA is absorbed by skin when applied topically. A study from CHul Research Center (in Canada) shows that the skin activity of DHEA applied topically is 85 to 90% greater than when taken orally (at least in rodents). No special carriers are needed to get DHEA into skin. A properly formulated topical preparation of DHEA will contain just enough hormone to benefit skin without providing enough to escape into circulation. It makes sense to apply the hormones directly to the skin if skin protection is the goal, since ingested hormones may end up everywhere but the skin.

DHEA has action against everyday insults as well. By maintaining skin immunity, DHEA preserves the ability of skin to react to cancer-causing, skin-destroying pollutants in air, food, and water. DHEA also has antioxidant action against peroxyl and superoxide free radicals.

Immune Function and DHEA

DHEA levels decline 80 to 90% by age 70 or later. DHEA has demonstrated a striking ability to maintain immune system synchronization. Oral supplementation with low doses of DHEA in aged animals restored immunocompetence to a reasonable level within days of administration. DHEA supplementation in aged rodents resulted in almost complete restoration of immune function.

DHEA has been shown in numerous animal studies to boost immune function via several different mechanisms. Only limited human studies have been done to measure DHEA's effect on the immune system.

In one study, scientists proposed that the oral administration of DHEA to elderly men would result in activation of their immune system. Nine healthy men averaging 63 years of age were treated with a placebo for 2 weeks followed by 20 weeks of DHEA (50 mg/day). After 2 weeks on oral DHEA, serum DHEA levels increased by three to four times. These levels were sustained throughout the study. Compared to the placebo, DHEA administration resulted in:

• An increase of 20% in IGF-1. Many people are taking expensive growth hormone injections for the purpose of boosting IGF levels. IGF stands for insulin-like growth factor and is thought to be responsible for some of the antiaging, anabolic effects that DHEA has produced in previous human studies.
  
• An increase of 35% in the number of monocyte immune cells.
  
• An increase of 29% in the number of B immune cells and a 62% increase in B-cell activity.
  
• A 40% increase in T-cell activity even though the total number of T-cells was not affected.
  
• An increase of 50% in interleukin-2.
  
• An increase of 22 to 37% in natural killer cells (NK) number and an increase of 45% in NK cell activity.
  
• No adverse effects noted with DHEA administration.

The scientists' conclusion: "While extended studies are required, our findings suggest potential therapeutic benefits of DHEA in immunodeficient states." ( Journals of Gerontology , Series A, 1997, 521)

A study in the Journal of Clinical Endocrine Metabolism (June 1998) showed that when old female mice were treated with DHEA, melatonin, or DHEA + melatonin, splenocytes (macrophages) were significantly higher as compared to young mice. B-cell proliferation in young and in old mice significantly increased. DHEA, melatonin, and DHEA + melatonin helped to regulate immune function in aged female mice by significantly increasing cytokines, interleukin-2, and interferon-gamma and significantly decreasing cytokines, interleukin-6, and interleukin-10, thus regulating cytokine production.

Interleukin-6 (IL-6) is one of the pathogenic elements in inflammatory and age-related diseases such as rheumatoid arthritis, osteoporosis, atherosclerosis, and late-onset B-cell neoplasia. "Higher circulating levels of IL-6 predict disability onset in older persons," according to the report in the June 1999 issue of the Journal of the American Geriatrics Society (47:639-46, 755-56). The authors suggest that IL-6 may cause a reduction in muscle strength or contribute to specific diseases such as congestive heart failure, osteoporosis, arthritis, and dementia, which cause disability.

DHEA has consistently been shown to boost beneficial interleukin-2 and suppress damaging interleukin-6 levels. Interleukin-6 is overproduced in the aged, which contributes to autoimmune disease, immune dysfunction, osteoporosis, depressions in healing, breast cancer, B-cell lymphoma, and anemia. Chronic DHEA administration maintained immunocompetence in aged animals (by boosting interleukin-2 and other beneficial immune components and suppressing interleukin-6 and other detrimental immune components). Suppression of interleukin-6 with 200 mg a day of DHEA was shown to be effective against systemic lupus erythematosus ( J. Rheumatol. , Feb. 1998, 252:285-89).

Researchers compared levels of IL-6 in 283 subjects with a mobility or functional disability with IL-6 levels in 350 adults without a disability. The investigators found that adults in the highest third of values of IL-6 had a 76% higher rate for mobility disabilities and a 62% higher rate for inability to perform daily activities than subjects in the lowest third of values. "These data suggest that IL-6 is a global marker of impending deterioration in health status in older adults," wrote a team led by Dr. Luigi Ferrucci at the National Institute on Aging in Bethesda, Maryland.

In a study in the proceedings of the Society for Experimental Biology and Medicine (May 1998; 2181:76-82), DHEA has been shown to restore normal cytokine production in immune system dysfunction induced by aging by suppressing the excessive production of cytokines (IL-6) by 75%, while increasing IL-2 secretion by nearly 50%, during a leukemia virus infection in old mice.

Another study in normal healthy individuals over the age of 40 found an opposite relationship between plasma DHEA levels and the presence of detectable levels of IL-6. Studies also revealed that low doses of DHEA and DHEA-s inhibited the production of IL-6 in unstimulated human spleen cell suspension cultures while enhancing its release by cultures transferred from organs of the same tissue ( Mech. Ageing Dev. , Feb. 1997, 93:1-3, 15-24).

The age-related increase in circulating IL-6 levels in humans which has been attributed to decline in DHEA production by the adrenal gland is currently attracting attention because of its possible relevance to the aetiology and management of a number of age-related clinical disorders. The potential importance of these observations and suggestions has prompted us to perform more detailed studies on the relationship between IL-6 and DHEA. Using immunoassay techniques we have found in normal healthy individuals over the age of 40 an inverse relationship between plasma DHEA levels and the presence of detectable levels of IL-6 (more than 1 pg/ml). In vitro, studies also revealed that low dose (10(-6)-10(-8) M) of DHEA and DHEA-s inhibited the production of IL-6 in unstimulated human spleen cell suspension cultures whilst enhancing its release by explant cultures of the same tissue. In contrast they had no effect on immunoglobulin production. These studies suggest that there is a real, but complex relationship between IL-6 production and DHEA levels which warrants further investigation.

DHEA Dosing and Safety precautions

properly managed DHEA therapy can be useful for most older men and women to increase energy, vitality and to foster an overall youthful feeling. However, there are guidelines that should be followed for safe long-term use of DHEA.

When taking oral supplements of DHEA, it is important that antioxidants are available to the liver because DHEA can promote free radicals in liver cells. Animal studies have shown that extremely high doses (from 2000 to 10,000 mg DHEA daily in human terms) caused liver damage in mice and rats. When antioxidants were given along with the DHEA, liver damage did not occur despite the massive doses of DHEA being administered to these animals. It should be noted that the amount of DHEA shown to cause liver damage is 20 times more than is necessary to produce anti-aging benefits. Alpha lipoic acid, vitamin E and N-acetyl- cysteine (NAC) are antioxidants that have been shown to be especially effective in suppressing free radicals in the liver.

The Life Extension Foundation has evaluated thousands of DHEA blood tests to determine the ideal dose of DHEA for both men and women. The Foundation's findings indicate that the optimal dosage range for DHEA varies considerably among individuals. prior recommendations to take DHEA three times a day are now being replaced with a general recommendation that men and women should consider taking a total of 15 mg to 75 mg a day in one to three divided doses. Most human studies use a daily dose of 50 mg, and this is the typical daily dose the majority of people use to restore serum DHEA to youthful levels. DHEA can be taken with or without food, though some believe that fat helps DHEA to assimilate better. Some people absorb DHEA better by taking it 20 to 30 minutes before meals.
A DHEA-s blood test should be taken three to six weeks after beginning DHEA therapy to help determine optimal dosing. Some people neglect to test their blood levels of DHEA and wind up chronically taking the wrong dose. When having your blood tested for DHEA, blood should be drawn three to four hours after the last dose. DHEA testing can save you money if it shows that you can take less DHEA to maintain youthful DHEA serum levels.
The standard blood test to evaluate DHEA status is one that measures DHEA-s (sulfate). The DHEA-s is calculated in micrograms per deciliter (mcg/dL) of blood.

people over age 40 who do not supplement with DHEA usually have serum levels below 200, and many are way below 100. Chronic DHEA deficiency is a risk factor for developing the degenerative diseases of aging according to the preponderance of evidence existing in the scientific literature.

Some people obtain a baseline DHEA-s blood test before beginning DHEA replacement therapy. However, based upon numerous DHEA blood tests evaluated by the Life Extension Foundation, anyone over age 40 who does not supplement DHEA is already deficient in serum DHEA. Therefore, it may be more economical to have the first DHEA blood test three to six weeks after initiating DHEA replacement therapy. There are precautions that should be observed that are different for men and women.

Men

Before initiating DHEA therapy, men should know their serum pSA (prostate specific antigen) level and have passed a digital rectal exam.

We have previously recommended that men with prostate cancer should avoid DHEA. Our concern is that in some men, DHEA may convert into testosterone and other growth factors that could cause existing prostate cancer cells to propagate. In some men, however, DHEA will mildly elevate estrogen levels, which would theoretically be good for those with prostate cancer since estrogen is known to help suppress prostate cancer cell growth. At the end of this article is a diagram showing the different endocrine pathways that DHEA can transform to in the body.

The preponderance of the published literature shows that higher DHEA blood levels do not cause prostate cancer. In fact, recent studies indicate that DHEA may confer a protective effect against prostate cancer. While some doctors still express theoretical concern that DHEA could cause prostate cancer, this theory loses credibility upon reading scientific studies showing that DHEA may protect against the development of prostate cancer.

Most prostate cancers develop in aged men that have extremely low levels of DHEA compared to when they were young. DHEA levels decline with age, yet prostate gland enlargement and cancers increase with age. Is it possible that DHEA, being a weak androgen, can actually attach to and block testosterone or DHT receptors on prostate tissue, thus preventing the influence by more powerful androgens We do not fully know the answer to this question, which is why we advise prostate cancer patients to proceed cautiously in considering whether or not to use low-dose DHEA.

Those with existing prostate cancer have a difficult decision to make in deciding whether or not to supplement with DHEA. On one side are the studies showing DHEA to be critically important to just about every part of the body. A substantial body of evidence indicates that DHEA protects against and alleviates many age-related diseases and improves quality of life scores. Therefore, asking a prostate cancer patient to forgo the systemic benefits of partial DHEA restoration therapy could mean that prostate cancer patient will suffer other serious diseases related to DHEA deficiency. On the other hand is the risk that higher DHEA levels could cause increased propagation of prostate cancer cells.

If prostate cancer patients are going to supplement with DHEA, we would suggest a dose not higher than 15 mg to 25 mg every day or every other day. Most men (without prostate cancer) take 50 mg to 75 mg of supplemental DHEA every day to fully restore serum DHEA to youthful ranges. It may therefore be possible for a prostate cancer patient to enjoy some of the benefits of DHEA without risking a pSA elevation by taking a lower dose of DHEA, but we dont know this for sure at this time. One problem with prostate cancer patients taking DHEA are the contradicting studies in published literature and the fact that no definitive studies exist to confirm if low-dose DHEA is safe.

prostate cancer patients who choose to experiment with low-dose DHEA replacement are advised to know their baseline pSA (prostate specific antigen) before initiating supplementation with DHEA. Another blood test that helps to determine prostate cancer activity in addition to the pSA is the pAp (prostate acid phosphatase). Monthly pSA (and pAp) tests are recommended, along with physician supervision, if a prostate cancer patient is going to take even low dose DHEA. Low-dose DHEA is defined as 15 mg to 25 mg every day or every other day. Any clinical indication or blood test reading that DHEA may be causing increased prostate cancer cell propagation means that DHEA supplementation should be discontinued immediately.

Before any prostate cancer patient takes supplemental DHEA, they should read the related scientific abstracts posted at the Foundations website. These abstracts point to the risks that are known at this time, so that those with prostate cancer can make an informed choice as to whether or not to consider any form of DHEA replacement therapy. You can also access the full text papers of these abstracts at www.lef.orgjust look under DHEA Replacement Therapy and click on to these papers. For those who are fortunate enough to have a cooperative physician, sharing these scientific papers with their doctors could assist in making a choice as to whether or not to consider any form of DHEA replacement therapy.

To reduce the risk that hormone modulation with DHEA could contribute to a prostate problem, men taking DHEA are also advised to take:
Vitamin E 400 to 800 IU a day
Selenium 200 to 600 mcg a day
Mega Soy Extract one to two capsules per day (40% isoflavone extract)
Lycopene Extract 20 to 40 mg a day
Saw palmetto Extract 160 mg, 2 times a day
pygeum Extract 50 mg, 2 times a day
Nettle Extract 120 mg, 2 times a day
Gamma Tocopherol 210 mg

We have previously recommended that men with severe benign prostate hypertrophy (BpH) avoid DHEA since DHEA may convert into estrogen and/or dihydrotestosterone(DHT), which could worsen the problem. Based on the newly identified benefits of DHEA, those with benign prostate disease may be able take low doses of DHEA if they also take an aromatase inhibitor such as the drug Arimidex (0.5 mg once or twice a week) only if estrogen levels are high and the drug proscar (5 mg a day) to suppress excess DHT. A dietary supplement that functions as a mild aromatase inhibitor is the flavonoid chrysin (found in the Super Mira Forte formula). Saw palmetto can block DHT activity on prostate cell receptor sites and nettle extract can block estrogen receptor sites on prostate cells. Life Extension members obtain saw palmetto and nettle extracts in the popular Natural prostate Formula or Super Saw palmetto/Nettle Root Formula. Men taking DHEA should refer to the Male Hormone Modulation protocol (or in the book Disease prevention and Treatment) for additional hormone balance testing that can be done at when serum DHEA and pSA are being tested.

Healthy men over 40 should consider checking their pSA and DHEA-s serum levels every 6 to 12 months. Men should also periodically check their blood levels for free testosterone and estrogen to make sure that DHEA is following a youthful metabolic pathway.

Women

DHEA can increase serum estrogen levels in women and eliminate the need for estrogen replacement therapy in some women. To help protect cells (especially breast cells) from excessive proliferation in response to estrogen, women taking DHEA should also take additional supplements. (See box below.)

Women taking DHEA are also advised to take:
Melatonin 500 mcg to 3 mg every night
Vitamin E Succinate 400 to 800 IU a day
Mega Soy Extract 135 mg, twice a day
(40% isoflavone extract)
Indole-3-Carbinol 200 mg, twice a day
Vitamin D3 1000 to 1400 IU a day
Gamma Tocopherol 210 mg

Women should consider estrogen and testosterone testing when they take their DHEA blood test in order to evaluate DHEAs effect on their blood levels of estrogens.

Women who have been diagnosed with an estrogen-dependent cancer should consult their physicians before beginning DHEA therapy. Some studies indicate that higher serum DHEA protects against breast cancer, but no adequate studies have been done to evaluate the effects of DHEA in breast cancer patients. If DHEA were to elevate estrogen too much, this could theoretically increase the risk of breast cancer. (Women taking DHEA should refer to the Female Hormone Replacement protocol for information about restoring youthful hormone balance.)

Liver disease

Men or women with existing liver disease (such as viral hepatitis or cirrhosis) should consider taking DHEA sublingually (under your tongue) or using a topical DHEA cream to reduce the amount of DHEA entering the liver. DHEA is converted by the liver into DHEA-s (dehydroepiandrosterone sulfate). Those with liver disease should carefully monitor liver enzyme levels to make sure that DHEA therapy is not making existing liver disease worse.

DHEA is best taken early in the day or possible insomnia could result. DHEA is normally produced by the adrenal glands early in the day and then converted by the liver to DHEA-s by midday when the DHEA/DHEA-s ratio is usually stabilized (10% DHEA/90% DHEA-s).

We again recommend that those taking DHEA have a DHEA blood test to make sure they are taking the precise dose to suit their individual biochemistry. Some people only need to take a small amount of DHEA in order to restore blood levels to that of a 21-year-old, while others need to take higher levels of DHEA. Those with existing prostate or breast cancers should not take DHEA unless closely supervised by a knowledgeable physician who understands DHEAs metabolic pathways.

Some people supplement with the hormone pregnenolone in lieu of, or in addition to DHEA. Since pregnenolone naturally converts into many of the same hormones as DHEA, some of the precautions we advise for DHEA may apply to pregnenolone.

DHEA tests often cost more than $100 at local laboratories, but the Life Extension Foundation offers low-cost DHEA-s and pSA (prostate-specific antigen) testing to members by mail order. For complete information about the availability of discount blood testing in your area, refer to the Medical Testing protocols or call (800) 208-3444.

If DHEA replacement sounds complicated, it is, compared to other preventive supplement programs. We suggest weighing the documented antiaging benefits of maintaining youthful serum DHEA levels when deciding whether to embark on a DHEA replacement regimen. Or stated differently, review the degenerative effects of chronic DHEA deficiency to decide whether this program is worth your time and money.

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