Dehydroepiandrosterone

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'''Dehydroepiandrosterone'''
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'''Dehydroepiandrosterone''' ('''DHEA''') is a natural [[steroid]] hormone precursor ([[prohormone]]) produced from [[cholesterol]] by the [[adrenal gland]]s, the [[gonad]]s, [[adipose tissue]], brain and in the skin (by an autocrine mechanism). DHEA is the [[Precursor (chemistry)|precursor]] of [[androstenedione]], which can undergo further conversion to produce the [[androgen]] [[testosterone]] and the [[estrogen]]s [[estrone]] and [[estradiol]].  DHEA is also a potent [[sigma-1 receptor|sigma-1]] agonist.<ref>Romieu, P., Martin-Fardon, R., Bowen, W. D., & Maurice, T. (2003). Sigma 1 Receptor-Related Neuroactive Steroids Modulate Cocaine-Induced Reward. 23(9): 3572.</ref>
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==Synonyms and brand names==
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Synonyms for Dehydroepiandrosterone are: Dehydroisoandrosterone; 3β-Hydroxy-5-androsten-17-one; 3β-Hydroxyandrost-5-en-17-one; Dehydroisoandrosterone; Hydroxyandrost-5-en-17-one; Prasterone; trans-Dehydroandrosterone.
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Brand names for DHEA include Prastera, Fidelin and Fluasterone; supplement versions are manufactured from wild Mexican yam.
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==Dehydroepiandrosterone sulfate==
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[[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 [[Circadian rhythm|diurnal]] variation.  From a practical point of view, measurement of DHEAS is preferable to DHEA, as levels are more stable.
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==Production==
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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.
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==Role==
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DHEA can be understood as a [[prohormone]] for the [[sex steroid]]s. 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.{{Who|date=July 2007}}
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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.
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==Effects and uses==
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Studies have shown that DHEA is useful in patients with [[systemic lupus erythematosus]]. An application of the evidence was discussed by the U.S. [[Food and Drug Administration]] in 2001 and is available online.<ref>[http://www.fda.gov/ohrms/dockets/ac/01/briefing/3740b1_01_gendlabs.pdf FDA document regading DHEA and SLE]</ref> 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).
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DHEA supplementation has been studied as a treatment for [[Alzheimer's disease]], but was found to be ineffective.<ref>{{cite journal |author=Wolkowitz OM, Kramer JH, Reus VI, ''et al'' |title=DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study |journal=Neurology |volume=60 |issue=7 |pages=1071–6 |year=2003 |pmid=12682308 |doi=}}</ref> Some small [[placebo|placebo-controlled]] [[randomized clinical trial]] studies have found long-term supplementation to improve mood and relieve [[depression (mood)|depression]]<ref>{{cite journal |author=Wolkowitz OM, Reus VI, Keebler A, ''et al'' |title=Double-blind treatment of major depression with dehydroepiandrosterone |journal=The American journal of psychiatry |volume=156 |issue=4 |pages=646–9 |year=1999 |pmid=10200751 |doi=}}</ref><ref>{{cite journal |author=Schmidt PJ, Daly RC, Bloch M, ''et al'' |title=Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression |journal=Arch. Gen. Psychiatry |volume=62 |issue=2 |pages=154–62 |year=2005 |pmid=15699292 |doi=10.1001/archpsyc.62.2.154}}</ref> or to decrease [[insulin resistance]].<ref>{{cite journal |author=Kawano H, Yasue H, Kitagawa A, ''et al'' |title=Dehydroepiandrosterone supplementation improves endothelial function and insulin sensitivity in men |journal=J. Clin. Endocrinol. Metab. |volume=88 |issue=7 |pages=3190–5 |year=2003 |pmid=12843164 |doi=}}</ref> However, a larger [[placebo|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]].<ref name="nejm">{{cite journal |author=Nair KS, Rizza RA, O'Brien P, ''et al'' |title=DHEA in elderly women and DHEA or testosterone in elderly men |journal=N. Engl. J. Med. |volume=355 |issue=16 |pages=1647–59 |year=2006 |pmid=17050889 |doi=10.1056/NEJMoa054629}}</ref>
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In contrast to the non-beneficial effects of DHEA on memory in the elderly, a  randomised UK study<ref>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 </ref> 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 (mood)|depression]]<ref>Young EA, Haskett RF, Grunhaus L, Pande A, Weinberg VM,
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Watson SJ, Akil H (1994) Increased evening activation of the hypothalamic–pituitary–adrenal axis in depressed patients. Arch
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Gen Psychiatry 51:701–707</ref>.  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.
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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.<ref>{{cite journal |author=Wallace MB, Lim J, Cutler A, Bucci L |title=Effects of dehydroepiandrosterone vs androstenedione supplementation in men |journal=Medicine and science in sports and exercise |volume=31 |issue=12 |pages=1788–92 |year=1999 |pmid=10613429 |doi=}}</ref>
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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]].<ref>{{cite journal |author=Barrett-Connor E, Khaw KT, Yen SS |title=A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease |journal=N. Engl. J. Med. |volume=315 |issue=24 |pages=1519–24 |year=1986 |pmid=2946952 |doi=}}</ref> However, a more recent 2006 study found no correlation between DHEA levels and risk of cardiovascular disease or death in men.<ref>{{cite journal |author=Arnlöv J, Pencina MJ, Amin S, ''et al'' |title=Endogenous sex hormones and cardiovascular disease incidence in men |journal=Ann. Intern. Med. |volume=145 |issue=3 |pages=176–84 |year=2006 |pmid=16880459 |doi=}}</ref>
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A 2007 study found the DHEA restored [[Oxidative stress|oxidative balance]] in [[Diabetes|diabetic]] patients, reducing tissue levels of [[pentosidine]]&mdash;a [[biomarker]] for [[advanced glycation endproduct]]s.<ref name="Mescape_DHEA">{{cite web |url=http://www.medscape.com/viewarticle/567316 |title=
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DHEA Restores Oxidative Balance in Type 2 Diabetes
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|author=Will Boggs
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|publisher=Medscape
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|accessdate=2007-12-14 |format= |work=}}</ref>
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Some ''[[in vitro]]'' studies have found DHEA to have an anti-proliferative or [[apoptosis|apoptotic]] effect on cancer cell lines.<ref>{{cite journal |author=Yang NC, Jeng KC, Ho WM, Hu ML |title=ATP depletion is an important factor in DHEA-induced growth inhibition and apoptosis in BV-2 cells |journal=Life Sci. |volume=70 |issue=17 |pages=1979–88 |year=2002 |pmid=12148690 |doi=}}</ref><ref>{{cite journal |author=Schulz S, Klann RC, Schönfeld S, Nyce JW |title=Mechanisms of cell growth inhibition and cell cycle arrest in human colonic adenocarcinoma cells by dehydroepiandrosterone: role of isoprenoid biosynthesis |journal=Cancer Res. |volume=52 |issue=5 |pages=1372–6 |year=1992 |pmid=1531325 |doi=}}</ref><ref>{{cite journal |author=Loria RM |title=Immune up-regulation and tumor apoptosis by androstene steroids |journal=Steroids |volume=67 |issue=12 |pages=953–66 |year=2002 |pmid=12398992 |doi=}}</ref> 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 [[menopause|pre- and postmenopausal]] women.<ref>{{cite journal |author=Tworoger SS, Missmer SA, Eliassen AH, ''et al'' |title=The association of plasma DHEA and DHEA sulfate with breast cancer risk in predominantly premenopausal women |journal=Cancer Epidemiol. Biomarkers Prev. |volume=15 |issue=5 |pages=967–71 |year=2006 |pmid=16702378 |doi=10.1158/1055-9965.EPI-05-0976}}</ref><ref>{{cite journal |author=Key T, Appleby P, Barnes I, Reeves G |title=Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies |journal=J. Natl. Cancer Inst. |volume=94 |issue=8 |pages=606–16 |year=2002 |pmid=11959894 |doi=}}</ref>
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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 liked 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."<ref>{{cite journal |author= |title=DHEA: the last elixir |journal=Prescrire international |volume=11 |issue=60 |pages=118–23 |year=2002 |pmid=12199273 |doi=}}</ref>
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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."<ref>{{cite journal |author= M . Fukui , Y . Kitagawa , N . Nakamura , M . Kadono , M . Yoshida , C . Hirata , K . Wada , G . Hasegawa , T . Yoshikawa |title= Serum dehydroepiandrosterone sulfate concentration and carotid atherosclerosis in men with type 2 diabetes |journal= Atherosclerosis |volume=Volume 181 |issue=2 |pages=339-344 |year=2005}}</ref>
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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 ciriculating levels of this hormone."<ref>{{cite journal |author=Martina V, Benso A, Gigliardi VR, et al. |title=Short-term dehydroepiandrosterone tereatment increases platelet cGMP production in elderly male subjects |journal=Clin Endocrinol (Oxf.) |volume=11 |issue=March;64(3) |pages=260-4 |year=2006}}</ref>
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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.<ref>{{cite journal |author= Enomoto, Mika MD, PhD |title=Serum Dehydroepiandrosterone Sulfate Levels Predict Longevity in Men: 27-Year Follow-Up Study in a Community-Based Cohort (Tanushimaru Study). |journal=Journal of the American Geriatrics Society |volume=56 |issue=6 |pages= |year=2008 |pmid= |doi=}}</ref>
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===Disputed effects===
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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 supplement]]s.<ref>{{cite journal |author=Calfee R, Fadale P |title=Popular ergogenic drugs and supplements in young athletes |journal=Pediatrics |volume=117 |issue=3 |pages=e577–89 |year=2006 |month=March |pmid=16510635 |doi=10.1542/peds.2005-1429 |url=||quote=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.}}</ref> A 2004 review in the ''American Journal of Sports Medicine'' concluded that "The marketing of this supplement's effectiveness far exceeds its science."<ref>{{cite journal |author=Tokish JM, Kocher MS, Hawkins RJ |title=Ergogenic aids: a review of basic science, performance, side effects, and status in sports |journal=The American journal of sports medicine |volume=32 |issue=6 |pages=1543–53 |year=2004 |pmid=15310585 |doi=10.1177/0363546504268041}}</ref> 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 is possible for increases in estrogen levels more than testosterone in men.
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==Increasing endogenous production==
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Regular [[exercise]] is known to increase DHEA production in the body.<ref>Eur J Appl Physiol Occup Physiol 1998 Oct;78(5):466-71</ref><ref>Eur J Appl Physiol. 2001 Jul;85(1- 2):177-84</ref><ref>J Gerontol A Biol Sci Med Sci. 2002 Apr;57(4):B158-65</ref> [[Caloric restriction]] has also been shown to increase DHEA in primates.<ref>Exp Gerontol. 2003 Jan-Feb; 38(1-2):35-46</ref> Some theorize that the increase in endogenous DHEA brought about by caloric restriction is partially responsible for the longer life expectancy known to be associated with caloric restriction.<ref>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.</ref>
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==Legality==
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===United States===
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A bill has been introduced, in March 2007, 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]] ([[Republican Party (United States)|R]]-[[Iowa|IA]]). The cosponsors are [[Richard Durbin]] ([[Democratic Party (United States)|D]]-[[Illinois|IL]]), and [[John McCain]] (R-[[Arizona|AZ]]).<ref>[http://www.govtrack.us/congress/bill.xpd?bill=s110-762 S. 762: A bill to include dehydroepiandrosterone as an anabolic steroid], from Govtrack.us. Accessed [[May 9]] [[2007]].</ref> This bill was referred to the Senate Judiciary Committee. Then 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. The bill was read twice and referred to the Senate Judiciary Committee.<ref>[http://www.govtrack.us/congress/bill.xpd?bill=s110-2470 S. 2470: Dehydroepiandrosterone Abuse Reduction Act of 2007 (GovTrack.us)<!-- Bot generated title -->]</ref>
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===Canada===
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In [[Canada]], a prescription is required to buy DHEA.<ref>Dr. Michael Colgin. The Deal With D.H.E.A. Vista Magazine Online. www.vistamag.com [http://www.vistamagonline.com/articles/page.php?tp=4&p=2&id=37&s=the_deal_with_the_dhea]</ref>
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==References==
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{{reflist|2}}
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==External links==
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*[http://www.mayoclinic.com/health/dhea/NS_patient-dhea Information on DHEA from the Mayo Clinic]
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*[http://www.cancer.org/docroot/ETO/content/ETO_5_3X_Dhea.asp?sitearea=ETO Information on DHEA] from the [[American Cancer Society]]
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*[http://content.nejm.org/cgi/content/abstract/355/16/1647 DHEA in elderly women and DHEA or testosterone in elderly men], published in the ''[[New England Journal of Medicine]]'' in 2006. "Neither DHEA nor low-dose testosterone replacement in elderly people has physiologically relevant beneficial effects on body composition, physical performance, insulin sensitivity, or quality of life."
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*[http://skepdic.com/dhea.html DHEA, from the Skeptic's Dictionary]
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{{Anabolic steroids}}
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{{Hormones}}
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{{Steroids}}
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[[Category:Androgens]]
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[[Category:Neurosteroids]]
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[[Category:Dietary supplements]]
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[[Category:Pheromones]]

Revision as of 05:38, 31 October 2008

Dehydroepiandrosterone (DHEA) is a natural steroid hormone precursor (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. DHEA is also a potent sigma-1 agonist.<ref>Romieu, P., Martin-Fardon, R., Bowen, W. D., & Maurice, T. (2003). Sigma 1 Receptor-Related Neuroactive Steroids Modulate Cocaine-Induced Reward. 23(9): 3572.</ref>

Pubchem(5881)

A major C19 steroid produced by the ADRENAL CORTEX. It is also produced in small quantities in the TESTIS and the OVARY. Dehydroepiandrosterone (DHEA) can be converted to TESTOSTERONE; ANDROSTENEDIONE; ESTRADIOL; and ESTRONE. Most of DHEA is sulfated (DEHYDROEPIANDROSTERONE SULFATE) before secretion.

Negative modulator of GABAA receptors.

Drug Type: Small Molecule; Experimental

KEGG Pathway(C01227)

  • Androgen and estrogen metabolism
  • Prostate cancer
List of PDB files having Dehydroepiandrosterone as a Ligand:
MMDB ID PDB ID Reference
15983 1E3R Ha NC, Kim MS, Lee W, Choi KY, Oh BHDetection of large pKa perturbations of an inhibitor and a catalytic group at an enzyme active site, a mechanistic basis for catalytic power of many enzymesJ. Biol. Chem. v275, p.41100-41106
55806 1COY Li J, Vrielink A, Brick P, Blow DMCrystal structure of cholesterol oxidase complexed with a steroid substrate: implications for flavin adenine dinucleotide dependent alcohol oxidasesBiochemistry v32, p.11507-11515
Physiochemical properties of Dehydroepiandrosterone:
Physical Property Value Units Temp (deg C) Source
Melting Point 140-141 deg C EXP
log P (octanol-water) 3.23 (none) EXP
Water Solubility 63.5 mg/L 25 EXP
Vapor Pressure 2.23E-08 mm Hg 25 EST
Henry's Law Constant 6.62E-09 atm-m3/mole 25 EST
Atmospheric OH Rate Constant 1.27E-10 cm3/molecule-sec 25 EST
Toxicity:
Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
man TDLo oral 10mg/kg/2W-I (10mg/kg) CARDIAC: ARRHYTHMIAS (INCLUDING CHANGES IN CONDUCTION) Annals of Internal Medicine. Vol. 129, Pg. 588, 1998.
mouse LD50 oral > 10gm/kg (10000mg/kg) British UK Patent Application. Vol. #2208473,
mouse LD50 subcutaneous 900mg/kg (900mg/kg) British UK Patent Application. Vol. #2208473,
rat LD50 oral > 10gm/kg (10000mg/kg) British UK Patent Application. Vol. #2208473,
rat LD50 subcutaneous 1gm/kg (1000mg/kg) British UK Patent Ap

Contents

Synonyms and brand names

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

Brand names for DHEA include Prastera, Fidelin and Fluasterone; supplement versions are manufactured from wild Mexican yam.

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.

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. 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.Template:Who

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 discussed by the U.S. Food and Drug Administration in 2001 and is available online.<ref>FDA document regading DHEA and SLE</ref> 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.<ref>Wolkowitz OM, Kramer JH, Reus VI, et al (2003). "DHEA treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled study". Neurology 60 (7): 1071–6. PMID 12682308. </ref> Some small placebo-controlled randomized clinical trial studies have found long-term supplementation to improve mood and relieve depression<ref>Wolkowitz OM, Reus VI, Keebler A, et al (1999). "Double-blind treatment of major depression with dehydroepiandrosterone". The American journal of psychiatry 156 (4): 646–9. PMID 10200751. </ref><ref>Schmidt PJ, Daly RC, 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. </ref> or to decrease insulin resistance.<ref>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. PMID 12843164. </ref> 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.<ref name="nejm">Nair KS, Rizza RA, 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. </ref> In contrast to the non-beneficial effects of DHEA on memory in the elderly, a randomised UK study<ref>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 </ref> 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<ref>Young EA, Haskett RF, Grunhaus L, Pande A, Weinberg VM, Watson SJ, Akil H (1994) Increased evening activation of the hypothalamic–pituitary–adrenal axis in depressed patients. Arch Gen Psychiatry 51:701–707</ref>. 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 effect on lean body mass, strength, or testosterone levels.<ref>Wallace MB, 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. PMID 10613429. </ref>

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.<ref>Barrett-Connor E, Khaw KT, Yen SS (1986). "A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease". N. Engl. J. Med. 315 (24): 1519–24. PMID 2946952. </ref> However, a more recent 2006 study found no correlation between DHEA levels and risk of cardiovascular disease or death in men.<ref>Arnlöv J, Pencina MJ, Amin S, et al (2006). "Endogenous sex hormones and cardiovascular disease incidence in men". Ann. Intern. Med. 145 (3): 176–84. PMID 16880459. </ref> A 2007 study found the DHEA restored oxidative balance in diabetic patients, reducing tissue levels of pentosidine—a biomarker for advanced glycation endproducts.<ref name="Mescape_DHEA">Template:Cite web</ref> Some in vitro studies have found DHEA to have an anti-proliferative or apoptotic effect on cancer cell lines.<ref>Yang NC, Jeng KC, Ho WM, Hu ML (2002). "ATP depletion is an important factor in DHEA-induced growth inhibition and apoptosis in BV-2 cells". Life Sci. 70 (17): 1979–88. PMID 12148690. </ref><ref>Schulz S, Klann RC, Schönfeld S, Nyce JW (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. </ref><ref>Loria RM (2002). "Immune up-regulation and tumor apoptosis by androstene steroids". Steroids 67 (12): 953–66. PMID 12398992. </ref> 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.<ref>Tworoger SS, Missmer SA, Eliassen AH, 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. </ref><ref>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. </ref>

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 liked 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."<ref> "DHEA: the last elixir" (2002). Prescrire international 11 (60): 118–23. PMID 12199273. </ref>

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."<ref>M . Fukui , Y . Kitagawa , N . Nakamura , M . Kadono , M . Yoshida , C . Hirata , K . Wada , G . Hasegawa , T . Yoshikawa (2005). "Serum dehydroepiandrosterone sulfate concentration and carotid atherosclerosis in men with type 2 diabetes". Atherosclerosis Volume 181 (2): 339-344. </ref>

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 ciriculating levels of this hormone."<ref>Martina V, Benso A, Gigliardi VR, et al. (2006). "Short-term dehydroepiandrosterone tereatment increases platelet cGMP production in elderly male subjects". Clin Endocrinol (Oxf.) 11 (March;64(3)): 260-4. </ref>

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.<ref>Enomoto, Mika MD, PhD (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). </ref>

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.<ref>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.” </ref> A 2004 review in the American Journal of Sports Medicine concluded that "The marketing of this supplement's effectiveness far exceeds its science."<ref>Tokish JM, Kocher MS, Hawkins RJ (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. </ref> 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 is possible for increases in estrogen levels more than testosterone in men.

Increasing endogenous production

Regular exercise is known to increase DHEA production in the body.<ref>Eur J Appl Physiol Occup Physiol 1998 Oct;78(5):466-71</ref><ref>Eur J Appl Physiol. 2001 Jul;85(1- 2):177-84</ref><ref>J Gerontol A Biol Sci Med Sci. 2002 Apr;57(4):B158-65</ref> Caloric restriction has also been shown to increase DHEA in primates.<ref>Exp Gerontol. 2003 Jan-Feb; 38(1-2):35-46</ref> Some theorize that the increase in endogenous DHEA brought about by caloric restriction is partially responsible for the longer life expectancy known to be associated with caloric restriction.<ref>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.</ref>

Legality

United States

A bill has been introduced, in March 2007, 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).<ref>S. 762: A bill to include dehydroepiandrosterone as an anabolic steroid, from Govtrack.us. Accessed May 9 2007.</ref> This bill was referred to the Senate Judiciary Committee. Then 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. The bill was read twice and referred to the Senate Judiciary Committee.<ref>S. 2470: Dehydroepiandrosterone Abuse Reduction Act of 2007 (GovTrack.us)</ref>

Canada

In Canada, a prescription is required to buy DHEA.<ref>Dr. Michael Colgin. The Deal With D.H.E.A. Vista Magazine Online. www.vistamag.com [1]</ref>

References

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External links

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