Dehydroepiandrosterone

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Dehydroepiandrosterone (DHEA), is a natural steroid prohormone produced from cholesterol by the adrenal glands, the gonads, adipose tissue, brain and in the skin (by an autocrine mechanism). DHEA is the precursor of androstenedione, which can undergo further conversion to produce the androgen testosterone and the estrogens estrone and estradiol.

Synonyms and brand names
Synonyms for Dehydroepiandrosterone are: Dehydroisoandrosterone; 3β-Hydroxy-5-androsten-17-one; 3β-Hydroxyandrost-5-en-17-one; Androstenol; Androstenolone; Dehydroisoandrosterone; Hydroxyandrost-5-en-17-one; Prasterone; trans-Dehydroandrosterone.

Brand names for DHEA include Prastera® and Fidelin®.

DHEAS (Dehydroepiandrosterone sulfate)
Dehydroepiandrosterone sulfate (DHEAS, ) is the sulfated version of DHEA. This conversion is reversibly catalyzed by sulfotransferase (SULT2A1) primarily 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 free DHEA. Orally ingested DHEA is converted to its sulfate when passing through intestines and liver. While DHEA levels naturally reach their peak in the early morning hours, DHEAS levels show no diurnal variation.

From a practical point of view, measurement of DHEAS is preferable to DHEA as levels are more stable.

Production
DHEA is produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. In humans, DHEA is the dominant steroid hormone and precursor of all sex steroids.

Role
DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. Its production in the brain suggests that it also has a role as a neurosteroid. As most DHEA is produced by the zona reticularis of the adrenal, it is argued that there is 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 seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.

Effects and uses
Studies have shown that DHEA is useful in patients with systemic lupus erythematosus. An application of the evidence was reviewed by the U.S. Food and Drug Administration in 2001 and is available online. This review also shows that cholesterol and other serum lipids decrease with the use of DHEA (mainly a decrease in HDL-C and triglycerides can be expected in women, p110).

DHEA supplementation has been studied as a treatment for Alzheimer's disease, but was found to be ineffective. Some small placebo-controlled randomized clinical trial studies have found long-term supplementation to improve mood and relieve depression or to decrease insulin resistance. However, a larger placebo-controlled randomized clinical trial reported in the New England Journal of Medicine in 2006 found that DHEA supplementation in elderly men and women had no beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life.

DHEA supplements are sometimes used as muscle-building or performance-enhancing drugs by athletes. However, a randomized placebo-controlled trial found that DHEA supplementation had no effect on lean body mass, strength, or testosterone levels.

A 1986 study found that a higher level of endogenous DHEA, as determined by a single measurement, 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. 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.

A 2002 review found that DHEA was difficult to study in an animal model. The authors concluded that there was no evidence that DHEA was beneficial for any of the conditions for which it had been studied to that point, that it was associated with significant side effects, and that based on these findings, "there is currently no scientific reason to prescribe DHEA for any purpose whatsoever."

Disputed effects
In the United States, dietary supplements containing DHEA or DHEAS have been advertised with claims that they may be beneficial for a wide variety of ailments. 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."

Precautions
Some assert that DHEA should not be supplemented outside specialist centres under careful observation of experts in the field of endocrinology.

Side effects may include:
 * Stunted growth in teens who have not reached their height potential.
 * Palpitations and other arrhythmias
 * Extensive growth of body hair, or hirsutism
 * Hair loss, especially male pattern baldness
 * Acne

Contraindication
As DHEAS and DHEA are converted to sex steroids, their use is contraindicated in patients with any cancer that is estrogen- or testosterone-dependent.

Increasing endogenous production
Regular exercise is known to increase DHEA production in the body. Caloric restriction has also been shown to increase DHEA in primates. Some theorize that the increase in endogenous DHEA brought about by caloric restriction is partially responsible for the longer life known to be associated with caloric restriction.

Legality
A bill has been introduced on in the U.S. Senate (S. 762) that attempts to classify DHEA as a controlled substance under the category of anabolic steroids. The sponsor is Charles Grassley (R-IA). The cosponsors are Richard Durbin (D-IL), and John McCain (R-AZ). In Canada, a prescription is required to buy DHEA.