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DHEA (a.k.a. dehydroepiandrosterone) Print E-mail
by Ron Kennedy, M.D., Santa Rosa, CA

Dr. Kennedy Dehydroepiandrosterone (DHEA) is a natural steroid precursor hormone produced from cholesterol by the adrenal glands, the gonads, adipose tissue, brain and in the skin. DHEA is used as an autocrine - a messenger a cell uses to bind to its on membrane receptors and signal itself. DHEA is the precursor of androstenedione, which can undergo further conversion to produce the testosterone, estrone and estradiol. DHEA is also a potent sigma-1 agonist, a class of compounds which protect the brain against the effects of ishemia in the event of a stroke.

Dehydroepiandrosterone sulfate (DHEAS) is the sulfated version of DHEA. This conversion is reversibE in the adrenals, the liver, and small intestine. In the blood, most DHEA is found as DHEAS with levels that are about 300 times higher than those of free DHEA. Orally-ingested DHEA is converted to its sulfate when passing through intestines and liver. Whereas DHEA levels naturally reach their peak in the early morning hours, DHEAS levels show no diurnal variation. Therefore, measurement of DHEAS is preferable to DHEA, as levels are more stable.

DHEA is produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone which is then convered to DHEA. In humans, DHEA is the dominant steroid hormone and precursor of all the sex steroids. Therefore, DHEA can be understood as a prohormone for the sex steroids and DHEAS can be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal, it may have a role in the immune and stress response. As almost all DHEA is derived from the adrenal glands, blood measurements of DHEAS/DHEA are useful to detect excess adrenal activity as, for example, in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia (e.g. Cushing's syndrome). Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.

Studies have shown that DHEA is useful in patients with systemic lupus erythematosus. Cholesterol and other serum lipids decrease with the use of DHEA, especially a decrease in HDL-C and triglycerides in women. Some small placebo-controlled randomized clinical trial studies have found long-term supplementation to improve mood and relieve depression and decrease insulin resistance.

DHEA supplements are sometimes used as muscle-building or performance-enhancing drugs by athletes. This is probably not as effective as once thought and the excessive doses used by some bodybuilders may even be dangerous. At any rate, not enough is known in this area. For every study which reports benefits another study reports no benefits. One has to wonder if pharmaceutical funding of such studies introduces bias in conclusions not based on the actual evidence. For example, a 1986 study found that a higher level of endogenous DHEA correlated with a lower risk of death or cardiovascular disease. However, a more recent 2006 study found no correlation between DHEA levels and risk of cardiovascular disease or death in men.

Some in vitro studies have found DHEA to have an anti-proliferative or apoptotic effect on cancer cell lines; that is to say it may be useful as an adjunctive treatment in cancer. The clinical significance of these findings, if any, is unknown. Higher levels of DHEA, in fact, have been correlated with an increased risk of developing breast cancer in both pre- and postmenopausal women. So, once again, our knowledge is insufficient and the reports are perhaps in an oblique conflict with each other.

DHEA and DHEAS are readily available in the United States, where they are regulated as foods rather than as medications. Given the lack of any proven benefit from DHEA supplementation, a 2004 review in the American Journal of Sports Medicine concluded that "The marketing of this supplement's effectiveness far exceeds its science." Because DHEA is converted to androstenedione and then testosterone, it has two chances to aromatize into estrogen- estrone from androstenedione, and estradiol from testosterone. As such, it increases estrogen levels more than testosterone in men. As DHEAS and DHEA are both converted to sex steroids, their use is contraindicated in patients with any estrogen- or estosterone-dependent cancer.

In my practice I measure all adrenal and sex steroids before treatment and I believe it is a mistake, or at least a waste of resources to focus on any "magic bullit." While DHEA may be beneficial in the aging adrenal and sex steroid system, this should be proven by lab tests before being administered.

The information in this article is not meant to be medical advice.�Treatment for a medical condition should come at the recommendation of your personal physician.

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