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Identification
NameDehydroepiandrosterone
Accession NumberDB01708  (DB06593, EXPT00519)
Typesmall molecule
Groupsnutraceutical
Description

Dehydroepiandrosterone (DHEA) is 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.

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.

In Canada, a prescription is required to buy DHEA.

Structure
Thumb
Synonyms
SynonymLanguageCode
3-beta-Hydroxy-5-androsten-17-oneNot AvailableNot Available
5-DehydroepiandrosteroneNot AvailableNot Available
5-DHEANot AvailableNot Available
DHANot AvailableNot Available
DHEANot AvailableNot Available
PrasteroneNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
FidelinPaladin
OVIGYN-DAlembic Pharmaceuicals Ltd
Brand mixturesNot Available
Categories
CAS number53-43-0
WeightAverage: 288.4244
Monoisotopic: 288.20893014
Chemical FormulaC19H28O2
InChI KeyInChIKey=FMGSKLZLMKYGDP-USOAJAOKSA-N
InChI
InChI=1S/C19H28O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h3,13-16,20H,4-11H2,1-2H3/t13-,14-,15-,16-,18-,19-/m0/s1
IUPAC Name
(1S,2R,5S,10R,11S,15S)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-7-en-14-one
SMILES
[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@]([H])(O)CC[C@]12C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassLipids
ClassSteroids and Steroid Derivatives
SubclassAndrogens and Derivatives
Direct parentAndrogens and Derivatives
Alternative parentsHydroxysteroids; Ketosteroids; Cyclohexanols; Cyclic Alcohols and Derivatives; Ketones; Polyamines
Substituentscyclohexanol; cyclic alcohol; secondary alcohol; ketone; polyamine; alcohol; carbonyl group
Classification descriptionThis compound belongs to the androgens and derivatives. These are hydroxylated C19 steroid hormones. They are known to favour the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
Pharmacology
IndicationDHEA is taken as a supplement for a variety of unsubstantiated indications. The following indications have shown promise and are backed up by some scientific evidence: schizophrenia (DHEA may be more effective in women than men); improving the appearance of older people’s skin (taking DHEA by mouth seems to increase skin thickness and moisture, and decrease facial “age spots” in elderly men and women); improving ability to achieve an erection in men with sexual dysfunction. Additionally, DHEA has shown promise in improving symptoms of lupus (SLE). Taking DHEA by mouth along with conventional treatment may help reduce the number of times symptoms flare up and may allow a reduction in the dose of prescription drugs needed. DHEA may also help SLE symptoms such as muscle ache and mouth ulcers. DHEA also seems to strengthen bones in SLE patients being treated with high-dose steroids (corticosteroids). DHEA also shows promise in the treatment of osteoporosis. Taking DHEA by mouth daily seems to improve bone mineral density (BMD) in older women and men with osteoporosis or osteopenia (pre-osteoporosis). DHEA may also increase BMD in young women with the eating disorder called anorexia nervosa. DHEA is often prescribed in India for the induction of ovulation to improve chances of pregnancy.
PharmacodynamicsDHEA is naturally 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. Regular exercise is known to increase DHEA production in the body. Calorie restriction has also been shown to increase DHEA in primates. 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.
Mechanism of actionDHEA 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.
AbsorptionFollowing a 50-mg DHEA PO dose in cynomolgus monkeys, systemic availability was only 3.1 +/- 0.4%. [PMID: 12970301]
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. As shown by their high conversion ratios (in a study involving cynomolgus monkeys), the major circulating metabolites of DHEA are DHEA-S, androsterone glucuronide, and androstane-3 alpha,17 beta-diol-glucuronide. [PMID: 12970301]

SubstrateEnzymesProduct
Dehydroepiandrosterone
    Dehydroepiandrosterone sulfateDetails
    Dehydroepiandrosterone
      Dehydroepiandrosterone 3-glucuronideDetails
      Route of eliminationNot Available
      Half life12 hours
      ClearanceNot Available
      ToxicityAcute oral toxicity (LD50): >10000 mg/kg [Rat]. Lowest Published Toxic Dose (TDL) [Man] - Route: Oral; Dose: 10 mg/kg/2W intermittent.
      Affected organisms
      • Humans and other mammals
      PathwaysNot Available
      SNP Mediated EffectsNot Available
      SNP Mediated Adverse Drug ReactionsNot Available
      ADMET
      Predicted ADMET features
      Property Value Probability
      Human Intestinal Absorption + 1.0
      Blood Brain Barrier + 0.9611
      Caco-2 permeable + 0.8816
      P-glycoprotein substrate Substrate 0.6176
      P-glycoprotein inhibitor I Inhibitor 0.6272
      P-glycoprotein inhibitor II Non-inhibitor 0.9014
      Renal organic cation transporter Non-inhibitor 0.7596
      CYP450 2C9 substrate Non-substrate 0.8415
      CYP450 2D6 substrate Non-substrate 0.9116
      CYP450 3A4 substrate Substrate 0.7404
      CYP450 1A2 substrate Non-inhibitor 0.9313
      CYP450 2C9 substrate Non-inhibitor 0.9672
      CYP450 2D6 substrate Non-inhibitor 0.9476
      CYP450 2C19 substrate Non-inhibitor 0.9025
      CYP450 3A4 substrate Non-inhibitor 0.8399
      CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9013
      Ames test Non AMES toxic 0.9382
      Carcinogenicity Non-carcinogens 0.947
      Biodegradation Not ready biodegradable 0.8998
      Rat acute toxicity 1.5214 LD50, mol/kg Not applicable
      hERG inhibition (predictor I) Weak inhibitor 0.8861
      hERG inhibition (predictor II) Non-inhibitor 0.7176
      Pharmacoeconomics
      ManufacturersNot Available
      PackagersNot Available
      Dosage forms
      FormRouteStrength
      CapsuleOral25mg
      PricesNot Available
      PatentsNot Available
      Properties
      Statesolid
      Experimental Properties
      PropertyValueSource
      melting point140-141 °CPhysProp
      water solubility63.5 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
      logP3.23HANSCH,C ET AL. (1995)
      Predicted Properties
      PropertyValueSource
      water solubility4.38e-02 g/lALOGPS
      logP3.53ALOGPS
      logP3.36ChemAxon
      logS-3.8ALOGPS
      pKa (strongest acidic)18.2ChemAxon
      pKa (strongest basic)-1.4ChemAxon
      physiological charge0ChemAxon
      hydrogen acceptor count2ChemAxon
      hydrogen donor count1ChemAxon
      polar surface area37.3ChemAxon
      rotatable bond count0ChemAxon
      refractivity84.66ChemAxon
      polarizability34.09ChemAxon
      number of rings4ChemAxon
      bioavailability1ChemAxon
      rule of fiveYesChemAxon
      Ghose filterYesChemAxon
      Veber's ruleYesChemAxon
      MDDR-like ruleNoChemAxon
      Spectra
      Spectra
      References
      Synthesis Reference

      Isao Sugimoto, Yoko Sawase, “Stable preparation of water-soluble salts of dehydroepiandrosterone sulfate for parenteral administration.” U.S. Patent US4061744, issued January, 1977.

      US4061744
      General Reference
      1. The NIH National Library of Medicine
      2. Baker WL, Karan S, Kenny AM: Effect of dehydroepiandrosterone on muscle strength and physical function in older adults: a systematic review. J Am Geriatr Soc. 2011 Jun;59(6):997-1002. doi: 10.1111/j.1532-5415.2011.03410.×. Epub 2011 Jun 7. Pubmed
      3. Alkatib AA, Cosma M, Elamin MB, Erickson D, Swiglo BA, Erwin PJ, Montori VM: A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab. 2009 Oct;94(10):3676-81. Epub 2009 Sep 22. Pubmed
      4. Arlt W: Dehydroepiandrosterone and ageing. Best Pract Res Clin Endocrinol Metab. 2004 Sep;18(3):363-80. Pubmed
      5. Wallace MB, Lim J, Cutler A, Bucci L: Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med Sci Sports Exerc. 1999 Dec;31(12):1788-92. Pubmed
      6. Grimley Evans J, Malouf R, Huppert F, van Niekerk JK: Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD006221. Pubmed
      7. Fuller SJ, Tan RS, Martins RN: Androgens in the etiology of Alzheimer’s disease in aging men and possible therapeutic interventions. J Alzheimers Dis. 2007 Sep;12(2):129-42. Pubmed
      8. Casson PR, et al. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod, 2000;15:2129-2132.
      9. Thijs L, Fagard R, Forette F, Nawrot T, Staessen JA: Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiol. 2003 Oct;58(5):403-10. Pubmed
      10. Barrett-Connor E, Khaw KT, Yen SS: A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986 Dec 11;315(24):1519-24. Pubmed
      11. Arnlov J, Pencina MJ, Amin S, Nam BH, Benjamin EJ, Murabito JM, Wang TJ, Knapp PE, D’Agostino RB Sr, Bhasin S, Vasan RS: Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med. 2006 Aug 1;145(3):176-84. Pubmed
      12. Crosbie D, Black C, McIntyre L, Royle PL, Thomas S: Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114. Pubmed
      13. Chang DM, Lan JL, Lin HY, Luo SF. Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002 Nov;46(11):2924-7.
      14. Mattison JA, Lane MA, Roth GS, Ingram DK: Calorie restriction in rhesus monkeys. Exp Gerontol. 2003 Jan-Feb;38(1-2):35-46. Pubmed
      15. Roberts E: The importance of being dehydroepiandrosterone sulfate (in the blood of primates): a longer and healthier life? Biochem Pharmacol. 1999 Feb 15;57(4):329-46. Pubmed
      16. Leblanc M, Labrie C, Belanger A, Candas B, Labrie F: Bioavailability and pharmacokinetics of dehydroepiandrosterone in the cynomolgus monkey. J Clin Endocrinol Metab. 2003 Sep;88(9):4293-302. Pubmed
      External Links
      ResourceLink
      KEGG CompoundC01227
      PubChem Compound5881
      PubChem Substance46508824
      ChemSpider5670
      ChEBI28689
      ChEMBL
      Therapeutic Targets DatabaseDNC001146
      PharmGKBPA451993
      IUPHAR2370
      Guide to Pharmacology2370
      HETAND
      WikipediaDehydroepiandrosterone
      ATC CodesA14AA07
      AHFS CodesNot Available
      PDB Entries
      FDA labelNot Available
      MSDSshow(19.8 KB)
      Interactions
      Drug InteractionsNot Available
      Food InteractionsNot Available

      1. Steroid Delta-isomerase

      Kind: protein

      Organism: Pseudomonas putida

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Steroid Delta-isomerase P07445 Details

      References:

      1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
      2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
      3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

      2. Bile salt sulfotransferase

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Bile salt sulfotransferase Q06520 Details

      References:

      1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
      2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
      3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

      3. Cholesterol oxidase

      Kind: protein

      Organism: Brevibacterium sterolicum

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Cholesterol oxidase P22637 Details

      References:

      1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
      2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
      3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

      4. Estradiol 17-beta-dehydrogenase 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Estradiol 17-beta-dehydrogenase 1 P14061 Details

      References:

      1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
      2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
      3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

      5. Sulfotransferase family cytosolic 2B member 1

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Components

      Name UniProt ID Details
      Sulfotransferase family cytosolic 2B member 1 O00204 Details

      References:

      1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
      2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
      3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

      1. Cytochrome P450 3A4

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate

      Components

      Name UniProt ID Details
      Cytochrome P450 3A4 P08684 Details

      References:

      1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

      2. Cytochrome P450 3A7

      Kind: protein

      Organism: Human

      Pharmacological action: unknown

      Actions: substrate inhibitor

      Components

      Name UniProt ID Details
      Cytochrome P450 3A7 P24462 Details

      References:

      1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

      Comments
      Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:15