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Dehydroepiandrosterone
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
Identifiers
CAS number 53-43-0
ATC code A14AA07
PubChem 5881
ChemSpider 5670
Chemical data
Formula C19H28O2 
Mol. mass 288.424 g/mol
SMILES eMolecules & PubChem
Synonyms (3β)-3-Hydroxyandrost-5-en-17-one
Physical data
Melt. point 148.5 °C (299 °F)
Pharmacokinetic data
Metabolism Hepatic
Half life 12 hours
Excretion Urinary:?%
Therapeutic considerations
Pregnancy cat.  ?
Legal status Commercially available
(US), Rx Only (CA)
Routes Oral
 Yes check.svgY(what is this?)  (verify)

5-Dehydroepiandrosterone (5-DHEA) is an endogenous[1] steroid that has been implicated in a broad range of biological effects in humans and other mammals. Together with its sulfate ester (DHEA-S), it is the most abundant steroid in humans.[citation needed] DHEA is produced by adrenal glands, but also synthesized de novo in the brain.[citation needed] 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 estrone and estradiol.[2] DHEA is also a potent sigma-1 agonist.[3] It is considered a neurosteroid.[2]

Contents

Synonyms and brand names

Synonyms for dehydroepiandrosterone are:

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 , 5-Androsten-3beta-ol-17-one,

Brand names for DHEA include Prastera, Prasterone, Fidelin and Fluasterone, although identical generics are available over the counter without a prescription.

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 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.[citation needed]

Production

Production of DHEA from Cholesterol
Comprehensive overview of Steroidogenesis, showing dehydroepiandrosterone at left among the androgens.

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.[4]

Role

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, 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.[5]

Effects and uses

DHEA supplementation has been studied as a treatment for Alzheimer's disease, but was found to be ineffective.[6] Some small placebo-controlled randomized clinical trial studies have found long-term supplementation to improve mood and relieve depression[7][8] or to decrease insulin resistance.[9] 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.[10]

In contrast to the non-beneficial effects of DHEA on memory in the elderly, a randomised UK study[11] found that a 7-day course of DHEA (150 mg twice daily) improved episodic memory in healthy young men. In this study, DHEA was also shown to improve subjective mood and decrease evening cortisol concentration, which is known to be elevated in depression[12]. The effect of DHEA on memory appeared to be related to an early activation of the anterior cingulate cortex (ACC) and it was suggested this was due to neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing.

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 (statistically significant) effect on lean body mass, strength, or testosterone levels.[13]

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.[14] However, a more recent 2006 study found no correlation between DHEA levels and risk of cardiovascular disease or death in men.[15] A 2007 study found the DHEA restored oxidative balance in diabetic patients, reducing tissue levels of pentosidine—a biomarker for advanced glycation endproducts.[16]

Some in vitro studies have found DHEA to have an anti-proliferative or apoptotic effect on cancer cell lines.[17][18][19] 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.[20][21]

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."[22]

A 2005 study, measured serum DHEA in 206 men with type-2 diabetes, and found an inverse relationship between serum DHEA and carotid atherosclerosis in men. The authors say the study "supports the notion that DHEA, which is sold in increasing amount as a food supplement, is atheroprotective in humans, and that androgen replacement therapy should be considered for men with hypogonadism."[23]

A 2006 study supplemented DHEA to men of average 65 years of age, and found that the men experienced significant increases in testosterone and cGMP (Cyclic guanosine monophosphate), and significant decreases in low-density liprotein (LDL). The authors say that the "findings...suggest that chronic DHEA supplementation would exert antiatherogenic effects, particularly in elderly subjects who display low circulating levels of this hormone."[24]

A 2008 study in the Journal of the American Geriatrics Society, June 2008, measured serum DHEA in 940 men and women ranging from age 21 to 88, following them from 1978 until 2005. The researches found that low levels of DHEA-s showed a significant association with shorter lifespan and that higher DHEA-s levels are a "strong predictor" of longevity in men, even after adjusting for age, blood pressure, and plasma glucose. No relationship was found between serum DHEA and longevity for women during the study period. The study did not find a significant difference in longevity until the 15-year follow-up point, which the researchers note may explain why some past research that followed men for less duration found no relationship.[25]

Disputed effects

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.[26] A 2004 review in the American Journal of Sports Medicine concluded that "The marketing of this supplement's effectiveness far exceeds its science."[27] 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.[citation needed]

Side effects

As a hormone precursor, there has been a smattering of reports of side effects possibly caused by the hormone metabolites of DHEA.[28][29] Some of these include possibly serious cardiovascular effects such as heart palpitations.[30]

Increasing endogenous production

Regular exercise is known to increase DHEA production in the body.[31][32][33] Calorie restriction has also been shown to increase DHEA in primates.[34] 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.[35]

Isomers

DHEA (Dehydroepiandrosterone) is an ambiguous term chemically, as it does not include the specific positions on the epiandrosterone molecule at which hydrogen atoms are missing. DHEA has a number of naturally occurring isomers that may have similar pharmacological effects. Some proven natural isomers of DHEA are 1-dehydroepiandrosterone (shown to be synthesized in pigs), 4-dehydroepiandrosterone (shown to occur in rats), 19NorDHEA (shown to occur in pigs and humans). These isomers are also technically DHEA, since they are dehydro epiandrosterones (removing hydrogens from the epiandrosterone skeleton).

Legality

United States

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).[36] 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 (non-criminal) penalties are provided. The bill was read twice and referred to the Senate Judiciary Committee.[37]

Canada

In Canada, a prescription is required to buy DHEA.[38]

Professional Cycling

DHEA is a prohibited substance under the World Anti-Doping Code of the World Anti-Doping Agency [2], that took over control of drug testing from the individual sports, such as international cycling body, Union Cycliste Internationale[39].

References

  1. ^ The NIH National Library of Medicine — Dehydroepiandrosterone http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-dhea.html
  2. ^ a b Mo Q, Lu SF, Simon NG (April 2006). "Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity". J. Steroid Biochem. Mol. Biol. 99 (1): 50–8. doi:10.1016/j.jsbmb.2005.11.011. PMID 16524719. http://linkinghub.elsevier.com/retrieve/pii/S0960-0760(06)00039-2. 
  3. ^ Romieu, P.; Martin-Fardon, R.; Bowen, W. D.; and Maurice, T. (2003). Sigma 1 Receptor-Related Neuroactive Steroids Modulate Cocaine-Induced Reward. 23(9): 3572.
  4. ^ Harper's illustrated Biochemistry, 27th edition, Ch.41 "The Diversity of the Endocrine system"
  5. ^ Roczniki Akademii Medycznej w Białymstoku · Vol. 48, 2003 Annales Academiae Medicae Bialostocensis Incidence of elevated LH/FSH ratioin polycystic ovary syndrome women with normo- and hyperinsulinemiaBanaszewska B, Spaczyński RZ, Pelesz M, Pawelczyk L
  6. ^ Wolkowitz, O. M.; Kramer, J. H.; Reus, V. I. et al. (2003). "DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study". Neurology 60 (7): 1071–6. PMID 12682308. 
  7. ^ Wolkowitz, O. M.; Reus, V. I.; Keebler, A. et al. (1999). "Double-blind treatment of major depression with dehydroepiandrosterone". The American Journal of Psychiatry 156 (4): 646–9. PMID 10200751. 
  8. ^ Schmidt, P. J.; Daly, R. C.; Bloch, M. et al. (2005). "Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression". Arch. Gen. Psychiatry 62 (2): 154–62. doi:10.1001/archpsyc.62.2.154. PMID 15699292. 
  9. ^ Kawano, H.; Yasue, H.; Kitagawa, A. et al. (2003). "Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men". J. Clin. Endocrinol. Metab. 88 (7): 3190–5. doi:10.1210/jc.2002-021603. PMID 12843164. 
  10. ^ Nair, K. S.; Rizza, R. A.; O'Brien, P. et al. (2006). "DHEA in elderly women and DHEA or testosterone in elderly men". N. Engl. J. Med. 355 (16): 1647–59. doi:10.1056/NEJMoa054629. PMID 17050889. 
  11. ^ Alhaj et al., Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study, Psychopharmacology (2006) 188: 541–551
  12. ^ Young, E. A.; Haskett, R. F.; Grunhaus, L.; Pande, A.; Weinberg, V. M.; Watson, S. J.; Akil, H. (1994) Increased evening activation of the hypothalamic–pituitary–adrenal axis in depressed patients. Arch. Gen. Psychiatry 51:701–707
  13. ^ Wallace, M. B.; Lim, J.; Cutler, A.; Bucci, L. (1999). "Effects of dehydroepiandrosterone vs androstenedione supplementation in men". Medicine and Science in Sports and Exercise 31 (12): 1788–92. doi:10.1097/00005768-199912000-00014. PMID 10613429. 
  14. ^ Barrett-Connor, E.; Khaw, K. T.; Yen, S. S. (1986). "A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease". N. Engl. J. Med. 315 (24): 1519–24. PMID 2946952. 
  15. ^ Arnlöv, J.; Pencina, M. J.; Amin, S. et al. (2006). "Endogenous sex hormones and cardiovascular disease incidence in men". Ann. Intern. Med. 145 (3): 176–84. PMID 16880459. 
  16. ^ Boggs, Will. "DHEA Restores Oxidative Balance in Type 2 Diabetes". Medscape. http://www.medscape.com/viewarticle/567316. Retrieved 2007-12-14. 
  17. ^ Yang, N. C.; Jeng, K. C.; Ho, W. M.; Hu, M. L. (2002). "ATP depletion is an important factor in DHEA-induced growth inhibition and apoptosis in BV-2 cells". Life Sci. 70 (17): 1979–88. doi:10.1016/S0024-3205(01)01542-9. PMID 12148690. 
  18. ^ Schulz, S.; Klann, R. C.; Schönfeld, S.; Nyce, J. W. (1992). "Mechanisms of cell growth inhibition and cell cycle arrest in human colonic adenocarcinoma cells by dehydroepiandrosterone: role of isoprenoid biosynthesis". Cancer Res. 52 (5): 1372–6. PMID 1531325. 
  19. ^ Loria, R. M. (2002). "Immune up-regulation and tumor apoptosis by androstene steroids". Steroids 67 (12): 953–66. doi:10.1016/S0039-128X(02)00043-0. PMID 12398992. 
  20. ^ Tworoger, S. S.; Missmer, S. A.; Eliassen, A. H. et al. (2006). "The association of plasma DHEA and DHEA sulfate with breast cancer risk in predominantly premenopausal women". Cancer Epidemiol. Biomarkers Prev. 15 (5): 967–71. doi:10.1158/1055-9965.EPI-05-0976. PMID 16702378. 
  21. ^ Key, T.; Appleby, P.; Barnes, I.; Reeves, G. (2002). "Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies". J. Natl. Cancer Inst. 94 (8): 606–16. PMID 11959894. 
  22. ^ "DHEA: the last elixir". Prescrire international 11 (60): 118–23. 2002. PMID 12199273. 
  23. ^ Fukui, M.; Kitagawa, Y.; Nakamura, N.; Kadono, M.; Yoshida, M.; Hirata, C.; Wada, K.; Hasegawa, G.; Yoshikawa, T. (2005). "Serum dehydroepiandrosterone sulfate concentration and carotid atherosclerosis in men with type 2 diabetes". Atherosclerosis 181 (2): 339–344. doi:10.1016/j.atherosclerosis.2005.01.014. 
  24. ^ Martina, V.; Benso, A.; Gigliardi, V. R. et al. (2006). "Short-term dehydroepiandrosterone tereatment increases platelet cGMP production in elderly male subjects". Clin. Endocrinol. (Oxf.) 11 (March;64(3)): 260–4. doi:10.1111/j.1365-2265.2006.02454.x. 
  25. ^ Enomoto, Mika (2008). "Serum Dehydroepiandrosterone Sulfate Levels Predict Longevity in Men: 27-Year Follow-Up Study in a Community-Based Cohort (Tanushimaru Study).". Journal of the American Geriatrics Society 56 (6): 994. doi:10.1111/j.1532-5415.2008.01692.x. 
  26. ^ Calfee, R.; Fadale, P. (March 2006). "Popular ergogenic drugs and supplements in young athletes". Pediatrics 117 (3): e577–89. doi:10.1542/peds.2005-1429. PMID 16510635. "In 2004, a new Steroid Control Act that placed androstenedione under Schedule III of controlled substances effective January 2005 was signed. DHEA was not included in this act and remains an over-the-counter nutritional supplement.". 
  27. ^ Tokish, J. M.; Kocher, M. S.; Hawkins, R. J. (2004). "Ergogenic aids: a review of basic science, performance, side effects, and status in sports". The American Journal of Sports Medicine 32 (6): 1543–53. doi:10.1177/0363546504268041. PMID 15310585. 
  28. ^ Medline Plus. "DHEA". Drugs and Supplements Information. National Library of Medicine. http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-dhea.html#Safety. Retrieved 18 February 2010. 
  29. ^ Medscape (2010). "DHEA Oral". Drug Reference. WebMD LLC.. http://www.medscape.com/druginfo/dosage?cid=med&drugid=3512&drugname=DHEA+Oral&monotype=default. Retrieved 18 February 2010. 
  30. ^ Sahelian, M.D., Ray (2005). "Honest DHEA Supplement Information". DHEA: A Practical Guide, Mind Boosters, and Natural Sex Boosters. http://www.raysahelian.com/dhea.html. Retrieved 18 February 2010. 
  31. ^ Eur. J. Appl. Physiol. Occup. Physiol. 1998 Oct; 78(5):466-71
  32. ^ Eur. J. Appl. Physiol. 2001 Jul; 85(1- 2):177-84
  33. ^ J. Gerontol. A. Biol. Sci. Med. Sci. 2002 Apr; 57(4):B158-65
  34. ^ Exp. Gerontol. 2003 Jan-Feb; 38(1-2):35-46
  35. ^ Roberts, E.; The importance of dehydroepiandrosterone sulfate in the blood of primates: a longer and healthier life? Biochem. Pharmacol. 1999 Feb 15;57(4):329-46.
  36. ^ S. 762: A bill to include dehydroepiandrosterone as an anabolic steroid, from http://thomas.loc.gov/cgi-bin/thomas . Accessed Sept. 9, 1009.
  37. ^ S. 2470: Dehydroepiandrosterone Abuse Reduction Act of 2007 (GovTrack.us)
  38. ^ Dr. Michael Colgin. The Deal With D.H.E.A. Vista Magazine Online. www.vistamag.com [1]
  39. ^ UCI Prohibited Substances

External links


Wiktionary

Up to date as of January 14, 2010

Definition from Wiktionary, a free dictionary

English

Initialism

DHEA

  1. dehydroepiandrosterone

Anagrams


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