DHEA Hormone Replacement Therapy
(dehydroepiandrosterone)
and the Adrenal Gland
by
Edmund Chein, M.D., J.D.

THE FACTS ABOUT DHEA REPLACEMENT THERAPY

Hormone replacement therapy now appears to be one of the most promising ways of slowing aging and reducing our risk of degenerative diseases.  In fact, this type of therapy could provide us with enough life extension and medical breakthroughs to perhaps enable us to achieve an indefinitely extended life span.

As a medical discipline, hormone replacement therapy is complex, but if we wait until scientists perfect it, it could be too late for most of us to receive benefits. Doctors are now able to administer therapy according to each individual's unique levels of hormones already in the blood.

The hormone DHEA (dehydroepiandrosterone) is produced from cholesterol in our adrenal glands and serves a wide variety of functions, providing us with health and longevity benefits. It is a "mother" hormone that the body converts on demand into such hormones as estrogen, progesterone, testosterone, and androstenedione.

DHEA usually begins to appear in the bloodstream at the age of seven and peaks when we are about 25 years old. After that point, the older we are,the less DHEA we have, as the DHEA levels decline with age. Around the ages of 60 to 80, one generally produces only 10 to 20 percent of the DHEA that was produced in the second decade of life. Males generally produce higher levels of DHEA than females, until old-age brings the DHEA in both to comparable levels. Studies have shown a direct relationship between blood levels of DHEA and the inhibition of many diseases, and its decline signals the onset of many of those illnesses that are age-related. DHEA levels in the blood can indicate the present and future status of a person with regards to cancer, immune function, cardiovascular disease, memory disorder, and aging itself.

If you have high levels of DHEA, you are less likely to develop:

* Arteriosclerosis

* A decline in mental function or the onset of Alzheimer's Disease or Parkinson's disease.

* Malignant cancer and tumors

* Diabetes

Other areas in which DHEA may be beneficial:

* Impaired memory and learning abilities

* HIV infection and AIDS

* Chronic Fatigue Syndrome

* Aging and the lifespan

* Obesity

* Autoimmune disease

* Epstein-Barr virus infection

* Other viruses such as herpes viral infection

* Osteoporosis

Following are more detailed discussions of some of these potential benefits.

DHEA AND ANTI-ARTERIOSCLEROSIS EFFECTS

Administration of DHEA was shown to significantly inhibit the progression of arteriosclerosis in laboratory rabbits. The animals that had their arteries damaged in order to encourage formation of arteriosclerotic plaques, and DHEA reduced the plaque by almost 50 percent. The amount of reduction in plaque was inversely proportional to the level of serum DHEA (Gordon 1988), meaning simply that the more DHEA in the blood, the less arteriosclerotic plaque. This finding is especially important to those who have undergone coronary bypass surgery because grafted blood vessels are particularly susceptible to new arteriosclerotic formation. In a separate study spanning over 20 years, DHEA levels were found to be lower in men who died of coronary artery disease, when compared to men who did not (Lacroix 1992). And in a related test, DHEA produced a decrease in the LDL cholesterol levels of men by seven percent, and provided added protection against cardiovascular disease (Nestler 1988).

Cardiovascular mortality was also examined in. one study, and there emerged interesting relationships, which differed between sexes. It was found that low DHEA levels in men were related to high mortality, while in women, the highest DHEA levels were correlated with cardiovascular disease.

DREA AND ANTI-CANCER EFFECTS

Epidemiologic studies indicate that the risk of developing a wide variety of cancers is directly related to serum levels of DHEA. In laboratory animal studies, DHEA has prevented the occurrence of many types of chemically-induced tumors including colon cancer (Schulz 1992), lung cancer (Pashko 1984), skin cancer (Pashko 1985), and breast cancer (Schwartz 1981). In addition, many cancers are associated with low blood levels of DHEA. Examples include gastric cancer (Gordon 1993), prostate cancer (Stahl 1992), bladder cancer (Gordon 1992), and breast cancer (Bulbrook 1971).

In one such study of 5,000 women, it was found that those who developed breast cancer had subnormal secretion of DHEA metabolites as long as nine years prior to development of the cancer. This meant they had low blood DHEA levels.

Extremely relevant to these findings is the suggestion of in vitro test results that there occurs an inhibitory effect of DHEA on cell division and growth (Sonka 1976).

DHEA AND ITS EFFECTS IN INCREASING MEMORY, COMPREHENSION, AND LEARNING, AS WELL AS ITS USE IN TREATING DEMENTIA AND ALZHEIMER'S DISEASE

The ability of DHEA to help reverse age-related loss of cognitive function was demonstrated in laboratory animal studies. Even small amounts of DHEA were found to lessen amnesia and enhance long-term memory in mice (Birkenhager-Gillesse et al.:  DHEAS in Oldest Old). Improved memory was also found in mice when DHEA was administered after the given learning experience had already occurred (Floord 1988).

Eugene Roberts, M.D., at the City of Hope Medical Center in Duarte, California (1987) suggested that DHEA might help in the treatment of neural degenerative memory loss in men. He prescribed 90 mg of DHEA daily, over a three-month period, to 31 elderly volunteers with moderate memory loss. when compared to a control group, those given DHEA scored higher on two of the four memory tests.

Studies related to Alzheimer's disease have lead researchers to believe that DHEA plays a significant role in the process of neuronal loss or damage and thereby slows or eliminates the progress of Alzheimer's disease (Booga 1987). In a related study, the circulatory levels of DHEA were tested in 86 patients with Alzheimer's disease, it was found that they had lower blood levels of this hormone than did those in the control group. It was concluded that DHEA may relieve amnesia (Nasman 1991).

Finally, an extensive research project undertaken by E. G. Birkenhager-Gifiesse, J. Derksen, and A. M. Lagaay at Leiden University Hospital also studied the relationship between DHEA Sulphate (DHEA) levels and age, sex, health status, survival and Alzheimer's disease in the elderly. It was stated that their aim was "to establish reference values for DHEA levels in the healthy oldest old, aged 85 and over, the so-called SENIEUR individuals" (Birkenhager-Gillesse et al.: DHEA in Oldest Old). In addition to confirming the reduced plasma concentration of DHEAS in patients with Alzheimer's, it was discovered that in men the age-related DHEA decrease continues even after the age of 85. mis observation confirmed and extended data showing that the decrease of DHEAS is more pronounced in men than in women.

Organic brain syndrome, or changes in brain function due to an organic cause, has also been studied in relationship to DHEA. In 61 men in nursing homes, ages 57 to 104, blood levels of DHEA were discovered to be inversely related to the presence of organic brain syndrome. These men had mean DHEA levels that were significantly lower than the mean levels of similarly-aged men living outside the nursing home, and 80 percent of those who had deteriorated to the point at which they required total care, had subnormal blood DHEA levels (Rudman 1990).  DHEA AND IMMUNITY-ENHANCING EFFECTS, AND DHEA AS THERAPY FOR VIRAL INFECTIONS SUCH AS HIV AND EPSTEIN-BARR

It is believed that DHEA stimulates T-cells, B-cells, and microphages (Loria 1988), all of which help to keep us in good health. In addition, the immune system's T-cells contain a DHEA receptor, and it is believed that due to this, DHEA regulates the production of interleukin-2, another mechanism by which it improves immune function (Meikle 1992).

The following research demonstrates some of the ways in which DHEA strengthens immunity and protects against bacterial growth and viral infections.

Several studies have been undertaken with laboratory mice as subjects. In one such study DHEA reduced viremia and death rate (Ben-Nathan 1991).  In another, at the Kentucky University's Sanders-Brown Center for Aging, DHEA significantly enhanced the antibody response of mice, which normally declines with age (Garg 1998). Other studies have shown similar immune function reversals with DHEA (Araneo 1998). In a study with mice involving simulation of the disease lupus, the production of auto-antibodies was restrained by treatment with DHEA (Lucas 1985).

DHEA and lupus have been researched in humans as well. Lupus is an incurable, and sometimes fatal, autoimmune disease that results when a person's immune system attacks the body's own connective tissues including the skin, joints, and internal organs for unknown reasons. It affects about nine times more women than men, usually during childbearing years. 

At a national meeting of rheumatologists in November of 1993, Dr. Ronald Von Vollenhaven, Dr. James McGuire, and Dr. Edgar Engleman of the Stanford University School of Medicine reported that they conducted a double blind controlled study of 30 women with lupus. Results showed that symptoms improved among those who took DHEA compared with those who took placebo capsules. Dr. Von Vollenhaven has said, "We know that many women with lupus have unusually low levels of this hormone in their blood, so we felt that bolstering the levels of the hormone might alleviate some of the symptoms of the disease." Supplemental DHEA has also been used successfully to treat other autoimmune diseases in men, such as ulcerative colitis and rheumatoid arthritis.

Several studies have shown the ability of DHEA to reduce replication of the HIV virus. Relevant to this is the discovery that abnormally low levels of DHEA are associated with increased progression of HIV infection (Jacobson 1991), and it has also been shown that the AIDS syndrome does not develop from the infection until DHEA levels begin to fall, meaning that the decline of DHEA portends the onset of MDS. Clinical trials are underway for the use of DHEA as an adjunct therapy for people infected with HIV (Henderson 1992).

DHEA has also been shown to have an inhibitory effect on Epstein-Barr viral DNA synthesis in human lymphocytes (Henderson 1981). It has also been used successfully to treat patients with chronic fatigue syndrome.

THE ANTI-OBESITY EFFECTS OF DHEA

One of the most striking effects of DHEA is the weight loss it can induce. A test on laboratory animals demonstrated weight loss with DHEA, even while these animals were given all of the food that was desired. This remarkable finding, by Dr. Arthur Schwartz of Temple University Medical School in the 1980s, produced a tremendous interest in the possibility of using the hormone as a weight loss therapy in humans.

Even in very healthy and fit people, muscle mass is lost gradually each year after age 30. Both those who exercise, and those who don't, lose muscle and strength at a comparable rate, therefore those who have more muscle mass at the outset have the advantage over time. In addition, overtraining and stress are responsible for depressing DHEA and contribute to hormonal and metabolic problems regardless of age. In one human study, 1600 mg DHEA was given to five males with normal weights each day, divided into four doses. After 28 days with diet and physical activity remaining normal, at least four exhibited a mean body fat decrease of 31 percent with no overall weight change (Nestler 1988). It is important to note that this meant that their fat loss was balanced by a gain in lean muscle mass, characteristic of youth, and that a change in metabolism had occurred. DHEA affects the thyroid hormone which in turn regulates metabolic rate. Logically therefore, in people with slow metabolisms, low levels of DHEA are often noted, and in these people a restoration of the hormone can help reduce bodyfat.

DHEA AND OSTEOPOROSIS

DHEA hormone levels in the blood begin to drop significantly in women once they reach menopause. It was found that blood levels of DHEA were lower in women with osteoporosis than in those without the affliction, and in 1987 Dr. R. A. Wild reported that DHEA was positively correlated with bone density in postmenopausal women. There is therefore a strong association of declining DHEA production with decreasing bone density during progressive aging.

THE ANTI-AGING AND LIFE EXTENSION BENEFITS OF DHEA

A wide array of tests have been conducted in order to asses the life extension potential of DHEA.

While men with higher DHEA levels tended to survive less long, women with higher DHEA levels survived longer. DHEA is one of the few compounds that shows a gradual decrease with advancing age, reaching an asymptotic low at the age of the maximum recorded life span. This then raises the possibility of DHEA being one of the most important factors in the determination of length of life.

In a 1986 study published in the New England Journal of Medicine, Dr. Barrett-Conner of UC San Diego found that DHEA levels were inversely related to deaths due to all causes in men over 50, but particularly in deaths resulting from cardiovascular disease. Furthermore, Dr. Barrett-Conner found that 100 mc Wml of increase in DHEA blood sulfate levels was associated with a 48 percent reduction in cardiovascular disease. In laboratory animals, studies have shown that DHEA can increase life span by 50 percent (Rogelson 1986). Mice did not age as rapidly when. they were fed DHEA, and maintained their youthful hair color and sleekness compared to the graying, coarser hair of the control animals that were not fed DHEA (Rogelson 1986).

Also of interest is the discovery that replacing DHEA in elderly men and women can induce an increase in IGF-I (a type of insulin growth factor). IGF-I is the protein made in the liver which, upon stimulation by human growth hormone, is the protein that generates age reversal effects, as reported in the New England Journal on Medicine in 1990.

Muscle and Fitness magazine published an article by T. D. Fahey in August of 1995 which discussed these potential benefits at length. He cited work in France by Dr. Emile-Etienne Baulieu (the inventor of the "morning after pill") and in California by Dr. Samuel Yen. Their work proved that DHEA can provide dramatic improvements in physical and psychological well being in middle-aged and elderly men and women. The magazine emphasizes that in tests that brought levels of this hormone back to the levels that are normal for a young person, restored energy levels, increases in muscle mass, and improved mental and immune functions were exhibited. Fahey stated that "subjects noted a reversal in the catabolic slide associated with aging and told researchers they felt more like they did in their 20s" (p.94). The author went on to explain some of the aging processes that begin around age 35, such as the loss of muscle, fatigue, and the impairment of the immune system, and likened the effects of aging to those of a slightly catabolic state. He emphasized the role of hormones like DHEA in maintaining a healthy anabolic state, recommended that attempts be made to maximize them, and asserted that supplements of DHEA as well as testosterone and insulin-like growth factor "may turn out to lessen the ravages of old age" (p.212).

FACTS ABOUT DHEA ADMINISTRATION AND DOSAGE

Researchers have demonstrated that DHEA has little toxicity in humans (Morales and Yen 1994) and animals (Pasliko 1991). It is available only by prescription from a physician.

It is important that one have his or her DHEA level tested before beginning a DHEA replacement program, so that the physician will know how much should be replaced. A second test should be drawn one month after beginning the treatment, three hours after the normal morning dose of DHEA is administered.

Additionally, men over the age of 40 should obtain prostate specific antigen (PSA) test results, in order to assure they do not have underlying prostate cancer. DHEA may not be recommended for men with prostate cancer, although this decision is made individually by the physician after the consideration of other factors.

The commonly used dosage levels of DHEA range from 50 mg to 3000 mg per day, depending on the condition that the physician intends to treat. There is no universal standard yet developed to determine the optimal dose. It is common practice, however, for a physician to use whatever dosage will bring the serum level of DHEA sulfate to 600 mg/ml for men, and 400 mg/ml for women. This is usually between 50 mg to 250 mg each day.