| Systematic (IUPAC) name | |
|---|---|
| (3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-17-one | |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | Commercially available (US), Rx Only (CA) |
| Routes | Oral |
| Pharmacokinetic data | |
| Metabolism | Hepatic |
| Half-life | 12 hours |
| Excretion | Urinary:?% |
| Identifiers | |
| CAS number | 53-43-0 |
| ATC code | A14AA07 |
| PubChem | CID 5881 |
| IUPHAR ligand | 2370 |
| DrugBank | DB01708 |
| ChemSpider | 5670 |
| UNII | 459AG36T1B |
| ChEBI | CHEBI:28689 |
| ChEMBL | CHEMBL90593 |
| Synonyms | (3β)-3-Hydroxyandrost-5-en-17-one |
| Chemical data | |
| Formula | C19H28O2 |
| Mol. mass | 288.424 g/mol |
| SMILES | eMolecules & PubChem |
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| Physical data | |
| Melt. point | 148.5 °C (299 °F) |
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5-Dehydroepiandrosterone (5-DHEA) is a 19-carbon endogenous[1] steroid hormone. It is the major secretory steroidal product of the adrenal glands[2] and is also produced by the gonads and the brain.[3] DHEA is the most abundant circulating steroid in humans.[4]
DHEA has been implicated in a broad range of biological effects in humans and other mammals. It acts on the androgen receptor both directly and through its metabolites, which include androstenediol and androstenedione, which can undergo further conversion to produce the androgen testosterone and the estrogens, including estrone, estradiol, and estriol.[5] DHEA is also a potent sigma-1 agonist.[6] It is considered a neurosteroid.[5]
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In women with adrenal insufficiency and the healthy elderly evidence there is insufficient evidence to support the use of DHEA.[7][8]
Evidence is inconclusive with respect to if DHEA has an effect on strength in the elderly.[9]
In younger men, no statistically significant effect of DHEA supplementation on lean body mass, strength, or testosterone levels was found in a randomized placebo-controlled trial.[10]
DHEA supplementation has not been found to be useful for memory function in normal middle aged or older adults.[11] It has been studied as a treatment for Alzheimer's disease, but there is no evidence that it is effective.[12]
Since 2000, DHEA supplementation has been used in reproductive medicine in combination with gonadotropins as a way to treat female infertility. [13]
A review in 2003 found the then-extant evidence sufficient to suggest that low serum levels of DHEAS may be associated with coronary heart disease in men, but insufficient to determine whether DHEA supplementation would have any cardiovascular benefit.[14]
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.[15] However, a more recent 2006 study found no correlation between DHEA levels and risk of cardiovascular disease or death in men.[16] A 2007 study found the DHEA restored oxidative balance in diabetic patients, reducing tissue levels of pentosidine—a biomarker for advanced glycation endproducts.[17]
There is some evidence of short term benefit in those with systemic lupus erythematosus but little evidence of long term benefit or safety.[18]
An anonymous 2002 review, in the French journal Prescrire, concluded: DHEA plasma levels are so low in most animals that they are difficult to measure, hindering studies on DHEA and aging. DHEA had not yet, at the time of writing, been linked to any specific health disorder. Side effects are linked to its androgenic effects, unfavorable lipid metabolism effects, and "possible growth-stimulating effect" on hormone dependent malignancies. "In practice, there is currently no scientific reason to prescribe DHEA for any purpose whatsoever."[19]
As a hormone precursor, there has been a smattering of reports of side effects possibly caused by the hormone metabolites of DHEA.[20][21] Some of these include possibly serious cardiovascular effects such as heart palpitations.[22] and increased blood pressure.
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 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. From a practical point of view, 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 by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA.[23]
DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal cortex, 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.[24]
Regular exercise is known to increase DHEA production in the body.[25][26][27] Calorie restriction has also been shown to increase DHEA in primates.[28] Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.[29]
The term "dehydroepiandrosterone" is ambiguous chemically because it does not include the specific positions within epiandrosterone at which hydrogen atoms are missing. DHEA has a number of naturally occurring isomers that may have similar pharmacological effects. Some isomers of DHEA are 1-dehydroepiandrosterone and 4-dehydroepiandrosterone. These isomers are also technically DHEA, since they are dehydroepiandrosterones in which hydrogens are removed from the epiandrosterone skeleton.
A bill has been introduced, in March 2009, in the U.S. Senate (S. 641) 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).[30] This bill was referred to the Senate Judiciary Committee. In December 2007, Charles Grassley introduced the "S. 2470: Dehydroepiandrosterone Abuse Reduction Act of 2007," in an attempt to amend the Controlled Substances Act to make "unlawful for any person to knowingly selling, causing another to sell, or conspiring to sell a product containing dehydroepiandrosterone to an individual under the age of 18 years, including any such sale using the Internet," without a prescription. Only civil (noncriminal) penalties are provided. The bill was read twice and referred to the Senate Judiciary Committee, where it died.[31]
In Canada, a prescription is required to buy DHEA.[32]
DHEA is a prohibited substance under the World Anti-Doping Code of the World Anti-Doping Agency,[33] which manages drug testing for Olympics and other sports. In January 2011, NBA player O.J. Mayo was given a 10-game suspension after testing positive for DHEA. Mayo termed his use of DHEA as "an honest mistake".[34] Mayo is the seventh player to test positive for performance-enhancing drugs since the league began testing in 1999. Rashard Lewis, then with the Orlando Magic, tested positive for DHEA and was suspended 10 games before the start of the 2009-10 season.[35]
Synonyms for dehydroepiandrosterone:
The International Nonproprietary Name is "prasterone". Systematic names include 3-beta-hydroxy-5-androsten-17-one, 3-beta-hydroxyandrost-5-en-17-one, 3beta-hydroxy-5-androsten-17-one, 3beta-hydroxy-androst-5-en-17-one, 3beta-hydroxy-D5-androsten-17-one, 3beta-hydroxyandrost-5-en-17-one, 3beta-hydroxyandrost-5-ene-17-one, 3-beta-hydroxy-etioallocholan-5-ene-17-one, and 5-androsten-3beta-ol-17-one. Fidelin is Paladin's trade name for DHEA.
Fluasterone is a synthetic derivative of DHEA.
In the United States, 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 marketed as over-the-counter dietary supplements.[36] A 2004 review in the American Journal of Sports Medicine concluded that "The marketing of this supplement's effectiveness far exceeds its science."[37] Because DHEA must first be converted to androstenedione and then to testosterone in men, it has two chances to aromatize into estrogen - estrone from androstenedione, and estradiol from testosterone. As such, it is possible that supplementation with DHEA could increase estrogen levels more than testosterone levels in men.
Some in vitro studies have found DHEA to have both antiproliferative and yet also apoptotic effect on cancer cell lines.[38][39][40] The clinical significance of these findings, if any, is unknown. Higher levels of DHEA and other endogenous sex hormones are strongly associated with an increased risk of developing breast cancer in both pre- and postmenopausal women.[41][42]
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