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Revision as of 20:35, 7 August 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'ChEBI').← Previous edit		Latest revision as of 11:44, 15 November 2024 edit undoAnomieBOT (talk | contribs)Bots6,568,435 editsm Dating maintenance tags: {{Citation needed}}
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			{{About|DHEA as a hormone|its use as a medication or supplement|Prasterone|other uses|DHEA (disambiguation)|the precursor hormone of DHEA produced mainly in the adrenal cortex, DHEA sulfate or DHEA-S|Dehydroepiandrosterone sulfate}}
	{{drugbox
	| verifiedrevid = 420038371
	| IUPAC_name = (3''S'',8''R'',9''S'',10''R'',13''S'',14''S'')-3-hydroxy-10,13-dimethyl-1,2,3,4,7,8,9,11,12,14,15,16-dodecahydrocyclopentaphenanthren-17-one
	| image = DHEA.png
	| width =
	| image2 = Dehidroepiandrosterona3D.png
			{{Chembox
	<!--Clinical data-->
			<!-- Images -->
	| legal_status = Commercially available<br> (US), Rx Only (])
			| ImageFile = Dehydroepiandrosteron.svg
	| routes_of_administration = ]
			| ImageSize = 225px
			| ImageAlt =
	<!--Pharmacokinetic data-->
			| ImageClass = skin-invert-image
	| metabolism = ]
			| ImageFile1 = Dehydroepiandrosterone molecule ball.png
	| elimination_half-life = 12 hours
			| ImageSize1 = 235px
	| excretion = ]:?%
			| ImageAlt1 =
	<!--Identifiers-->		<!-- Names -->
			| IUPACName = 3β-Hydroxyandrost-5-en-17-one
	| CASNo_Ref = {{cascite|correct|CAS}}
			| SystematicName = (3a''S'',3b''R'',7''S'',9a''R'',9b''S'',11a''S'')-7-Hydroxy-9a,11a-dimethyl-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1''H''-cyclopentaphenanthren-1-one
	| CAS_number = 53-43-0
			| OtherNames = Androstenolone; Prasterone; Androst-5-en-3β-ol-17-one; 5,6-Didehydroepiandrosterone;<ref name="Devillers2009">{{cite book| first = James | last = Devillers | name-list-style = vanc |title=Endocrine Disruption Modeling|url=https://books.google.com/books?id=bWHMBQAAQBAJ&pg=PA339|date=27 April 2009|publisher=CRC Press|isbn=978-1-4200-7636-3|pages=339–}}</ref> Dehydroisoepiandrosterone
	| ATC_prefix = A14
			| Watchedfields = changed
	| ATC_suffix = AA07
			| verifiedrevid = 443682301
			<!-- Sections -->
			| Section1 = {{Chembox Identifiers
			| CASNo_Ref = {{cascite|correct|??}}
			| CASNo = 53-43-0
			| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 28689		| ChEBI = 28689
	| PubChem = 5881
	| IUPHAR_ligand = 2370
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| ChemSpiderID = 5670
	| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = 459AG36T1B
	| ChEMBL_Ref = {{ebicite|correct|EBI}}		| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 90593		| ChEMBL = 90593
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| ChemSpiderID = 5670
	<!--Chemical data-->
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| C=19 | H=28 | O=2
			| DrugBank = DB01708
	| molecular_weight = 288.424 g/mol
			| PubChem = 5881
	| smiles = O=C32(CC14(C(=C/C12CC3)\C(O)CC4)C)C
	| InChI = 1/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
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChI = 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		| StdInChI = 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
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
	| StdInChIKey = FMGSKLZLMKYGDP-USOAJAOKSA-N		| StdInChIKey = FMGSKLZLMKYGDP-USOAJAOKSA-N
			| SMILES = O=C32(CC14(C(=C/C12CC3)\C(O)CC4)C)C
	| synonyms = (3β)-3-Hydroxyandrost-5-en-17-one
			| UNII_Ref = {{fdacite|correct|FDA}}
	| melting_point = 148.5
			| UNII = 459AG36T1B
			}}
			| Section2 = {{Chembox Properties
			| C=19 | H=28 | O=2
			| MolarMass = 288.424 g/mol
			| Appearance =
			| Density =
			| MeltingPt = 148.5
			| BoilingPt =
			| Solubility =
			}}
			| Section3 = {{Chembox Hazards
			| MainHazards =
			| FlashPt =
			| AutoignitionPt =
			}}
			| Section6 = {{Chembox Pharmacology
			| ATCvet = yes
			| ATCCode_prefix = A14
			| ATCCode_suffix = AA07
			| ATC_Supplemental = <br />{{ATC|G03|EA03}} (combination with ])
			| AdminRoutes = ], ] (]), ] (as ]), ] (as ])
			| Bioavail = 50%<ref name="CuppTracy2002">{{cite book | first1 = Melanie Johns | last1 = Cupp | first2 = Timothy S. | last2 = Tracy | name-list-style = vanc | title=Dietary Supplements: Toxicology and Clinical Pharmacology|url=https://books.google.com/books?id=vuqPBAAAQBAJ&pg=PA135|date=10 December 2002|publisher=Springer Science & Business Media|isbn=978-1-59259-303-3|pages=135–}}</ref>
			| Excretion = ]
			| HalfLife = {{abbr|DHEA|Dehydroepiandrosterone}}: 25&nbsp;minutes<ref name="OddensVermeulen1996">{{cite book | vauthors = Oddens BJ, Vermeulen A | title=Androgens and the Aging Male|url=https://books.google.com/books?id=efEnI1VdmtsC&pg=PA5|date=15 November 1996|publisher=CRC Press|isbn=978-1-85070-763-9|pages=5–}}</ref><br />{{abbr|DHEA-S|Dehydroepiandrosterone sulfate}}: 11&nbsp;hours<ref name="OddensVermeulen1996" />
			| Metabolism = ]<ref name="CuppTracy2002" />
			| ProteinBound =
			}}
	}}		}}
			'''Dehydroepiandrosterone''' ('''DHEA'''), also known as '''androstenolone''', is an ] ] precursor.<ref name="pmid16293766">{{cite journal | vauthors = Labrie F, Luu-The V, Bélanger A, Lin SX, Simard J, Pelletier G, Labrie C | title = Is dehydroepiandrosterone a hormone? | journal = J. Endocrinol. | volume = 187 | issue = 2 | pages = 169–96 | date = November 2005 | pmid = 16293766 | doi = 10.1677/joe.1.06264 | doi-access = free }}</ref> It is one of the most abundant circulating ]s in humans.<ref>William F Ganong MD, 'Review of Medical Physiology', 22nd Ed, McGraw Hill, 2005, p. 362.</ref> DHEA is produced in the ]s,<ref>''The Merck Index'', 13th Edition, '''7798'''</ref> the ]s, and the brain.<ref>{{cite book | last1 = Schulman | first1 = Robert A. | last2 = Dean | first2 = Carolyn | name-list-style = vanc | year = 2007 | title = Solve It With Supplements | publisher = Rodale, Inc. | location = New York City | page = 100 | isbn = 978-1-57954-942-8 | quote = DHEA (Dehydroepiandrosterone) is a common hormone produced in the adrenal glands, the gonads, and the brain.}}</ref> It functions as a ] in the ] of the ] and ] ]s both in the gonads and in various other ]s.<ref name="pmid16293766" /><ref name="pmid16524719" /><ref name="Scott1996">{{cite book | first = Thomas | last = Scott | name-list-style = vanc | title = Concise Encyclopedia Biology | url = https://archive.org/details/conciseencyclope00scot | url-access = registration | access-date = 25 May 2012 | year = 1996 | publisher = Walter de Gruyter | isbn = 978-3-11-010661-9 | page = }}</ref> However, DHEA also has a variety of potential biological effects in its own right, binding to an array of ] and ]s,<ref name="pmid16684650">{{cite journal | vauthors = Webb SJ, Geoghegan TE, Prough RA, Michael Miller KK | title = The biological actions of dehydroepiandrosterone involves multiple receptors | journal = Drug Metabolism Reviews | volume = 38 | issue = 1–2 | pages = 89–116 | year = 2006 | pmid = 16684650 | pmc = 2423429 | doi = 10.1080/03602530600569877 }}</ref> and acting as a ] and modulator of ]s.<ref name="pmid11281367">{{cite journal | vauthors = Friess E, Schiffelholz T, Steckler T, Steiger A | title = Dehydroepiandrosterone--a neurosteroid | journal = European Journal of Clinical Investigation | volume = 30 | pages = 46–50 | date = December 2000 | issue = Suppl 3 | pmid = 11281367 | doi = 10.1046/j.1365-2362.2000.0300s3046.x | s2cid = 30733847 }}</ref>
	'''5-Dehydroepiandrosterone''' ('''5-DHEA''') is a 19-carbon endogenous<ref>The NIH National Library of Medicine — Dehydroepiandrosterone http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-dhea.html</ref> natural ]. It is the major secretory steroidal product of the ]<ref>''The Merck Index'', 13th Edition, '''7798'''</ref> and is also produced by the ] and the brain.<ref>
	{{cite book
	| author = Schulman, Robert A., M.D.
	| coauthors = Dean, Carolyn, M.D.
	| year = 2007
	| title = Solve It With Supplements
	| publisher = Rodale, Inc.
	| location = New York City
	| page = 100
	| isbn = 978-1-57954-942-8
	| quote = DHEA (Dehydroepiandrosterone) is a common hormone produced in the adrenal glands, the gonads, and the brain.
	}}</ref> DHEA is the most abundant circulating steroid in humans.<ref>William F Ganong MD, 'Review of Medical Physiology', 22nd Ed, McGraw Hill, 2005, page 362.</ref>
			In the United States, DHEA is sold as an ] ], and medication called ].
	DHEA has been implicated in a broad range of biological effects in humans and other mammals. It acts on the ] both directly and through its ], which include ] and ], which can undergo further conversion to produce the ] ] and the ]s, including ], ], and ].<ref name="pmid16524719">{{cite journal |author=Mo Q, Lu SF, Simon NG |title=Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity |journal=J. Steroid Biochem. Mol. Biol. |volume=99 |issue=1 |pages=50–8 |year=2006 |month=April |pmid=16524719 |doi=10.1016/j.jsbmb.2005.11.011 |url=http://linkinghub.elsevier.com/retrieve/pii/S0960-0760(06)00039-2}}</ref> DHEA is also a potent ] agonist.<ref>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.</ref> It is considered a ].<ref name="pmid16524719"/>
			{{TOC limit|3}}
	==Dehydroepiandrosterone sulfate==
	] (DHEAS) is the sulfated version of DHEA. This conversion is reversibly catalyzed by ] (]) primarily in the adrenals, the ], and ]. 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 ] variation. From a practical point of view, measurement of DHEAS is preferable to DHEA, as levels are more stable.{{Citation needed|date=January 2009}}
			==Biological function==
	==Production==
	]
	], showing dehydroepiandrosterone at left among the androgens.]]
	DHEA is produced from cholesterol through two ] enzymes. Cholesterol is converted to ] by the enzyme ] (] cleavage); then another enzyme, ], converts ] to ] and then to DHEA.<ref>Harper's illustrated Biochemistry, 27th edition, Ch.41 "The Diversity of the Endocrine system"</ref>
			===As an androgen===
	==Role==
			DHEA and other adrenal androgens such as ], although relatively weak androgens, are responsible for the androgenic effects of ], such as early ] and ] growth, adult-type ], increased oiliness of hair and skin, and mild ].<ref name="PescovitzEugster2004">{{cite book| first1 = Ora Hirsch | last1 = Pescovitz | first2 =Erica A. | last2 = Eugster | name-list-style = vanc | title=Pediatric Endocrinology: Mechanisms, Manifestations, and Management|url=https://books.google.com/books?id=9gvBlktAT6YC&pg=PA362|year=2004|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-4059-3|pages=362–}}</ref><ref name="Lifshitz2006">{{cite book|author=Fima Lifshitz|title=Pediatric Endocrinology: Growth, Adrenal, Sexual, Thyroid, Calcium, and Fluid Balance Disorders|url=https://books.google.com/books?id=1CTNBQAAQBAJ&pg=PA289|date=26 December 2006|publisher=CRC Press|isbn=978-1-4200-4272-6|pages=289–}}</ref><ref name="Salhan2011">{{cite book | first = Sudha | last = Salhan | name-list-style = vanc |title=Textbook of Gynecology|url=https://books.google.com/books?id=YUYx1neUEIoC&pg=PA94|date=1 August 2011|publisher=JP Medical Ltd|isbn=978-93-5025-369-4|pages=94–}}</ref> DHEA is potentiated locally via conversion into ] and ] (DHT) in the skin and ]s.<ref name="pmid16293766" /> Women with ] (CAIS), who have a non-functional ] (AR) and are immune to the androgenic effects of DHEA and other androgens, have absent or only sparse/scanty pubic and axillary hair and ] in general, demonstrating the role of DHEA and other androgens in body hair development at both adrenarche and ].<ref name="LaverySanfilippo2012">{{cite book | vauthors = Lavery JP, Sanfilippo JS |title=Pediatric and Adolescent Obstetrics and Gynecology|url=https://books.google.com/books?id=l9XTBwAAQBAJ&pg=PA45|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5064-7|pages=45–}}</ref><ref name="NussbaumMcInnes2015">{{cite book | first1 = Robert L. | last1 = Nussbaum | first2 = Roderick R. | last2 = McInnes | first3 = Huntington F | last3 = Willard | name-list-style = vanc |title=Thompson & Thompson Genetics in Medicine|url=https://books.google.com/books?id=4yV1CQAAQBAJ&pg=PA102|date=28 April 2015|publisher=Elsevier Health Sciences|isbn=978-0-323-39206-8|pages=102–}}</ref><ref name="SetchellHudson2013">{{cite book | first1 = Marcus E | last1 = Setchell | first2 = C. N. | last2 = Hudson | name-list-style = vanc |title=Shaw's Textbook of Operative Gynaecology|url=https://books.google.com/books?id=XHcWNRVHWsEC&pg=PA129|date=4 April 2013|publisher=Elsevier Health Sciences|isbn=978-81-312-3481-5|pages=129–}}</ref><ref name="BissonnetteDalens2006">{{cite book | first1 = Bruno | last1 = Bissonnette | first2 = Bernard | last2 = Dalens | name-list-style = vanc | title=Syndromes: Rapid Recognition and Perioperative Implications|url=https://books.google.com/books?id=uRR1MYa-w5wC|date=20 July 2006|publisher=McGraw Hill Professional|isbn=978-0-07-135455-4|page=184}}</ref>
	DHEA can be understood as a ] for the ]s. DHEAS may be viewed as ] and ]. As most DHEA is produced by the ] of the adrenal cortex, it is argued that there is a role in the immune and stress response.{{Who|date=July 2007}}
			===As an estrogen===
	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 ]. Women with ] tend to have elevated levels of DHEAS.<ref>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 hyperinsulinemia''Banaszewska B, Spaczyński RZ, Pelesz M, Pawelczyk L</ref>
			DHEA is a weak ].<ref name="pmid16293766" /><ref name="pmid16684650" /><ref name="pmid15994348" /> In addition, it is transformed into potent estrogens such as ] in certain tissues such as the ], and thereby produces estrogenic effects in such tissues.<ref name="pmid16293766" />
	==Effects and uses==		===As a neurosteroid===
			As a ] and ], DHEA has important effects in the ].<ref name="Weizman2008" /><ref name="GravanisMellon2011">{{cite book | first1 = Achille G. | last1 = Gravanis | first2 =Synthia H. | last2 = Mellon | name-list-style = vanc |title=Hormones in Neurodegeneration, Neuroprotection, and Neurogenesis|url=https://books.google.com/books?id=YmQAhOeaFtUC&pg=PT349|date=24 June 2011|publisher=John Wiley & Sons|isbn=978-3-527-63397-5|pages=349–}}</ref><ref>{{cite book|title=Sex difference in the human brain, their underpinnings and implications|url=https://books.google.com/books?id=JFpq6hYQRhQC&pg=PA127|date=3 December 2010|publisher=Elsevier|isbn=978-0-444-53631-0|pages=127–}}</ref>
	===Depression===
	DHEA is a ] antagonist. Research studies indicate that DHEA supplementation has an anti-depressant effect and protects from cortisol overconcentration over long time scales.
	<ref>{{cite journal|author=O. Hechter, A. Grossman and R.T. Chatterton Jr|journal=Medical Hypotheses|title=Relationship of dehydroepiandrosterone and cortisol in disease|volume=49|year=1887|pages=85–91|doi=|pmid=9247914|issue=1}}</ref>
	<ref>{{cite journal|author=Oberbeck R, Benschop RJ, Jacobs R, Hosch W, Jetschmann JU, Schürmeyer TH, Schmidt RE and Schedlowski M.|journal=PubMed.gov|title=Endocrine mechanisms of stress-induced DHEA-secretion|volume=21|year=1998|pages=148–53|doi=}}</ref>
	<ref>{{cite journal|author=Peter Gallagher BSc(Hons) and Allan Young MB, ChB, MPhil, Ph.D, MRCPsych|journal=Neuropsychopharmacology|title=Cortisol/DHEA Ratios in Depression|volume=26|year=2002|pages=|doi=}}</ref>
			==Biological activity==
	===Memory===
	DHEA supplementation has been studied as a treatment for ], but was not found to be effective.<ref>{{cite journal |author=Wolkowitz, O. M.; Kramer, J. H.; Reus, V. I. ''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 ] ] studies have found long-term supplementation to improve mood and relieve ]<ref>{{cite journal |author=Wolkowitz, O. M.; Reus, V. I.; Keebler, A. ''et al.'' |title=Double-blind treatment of major depression with dehydroepiandrosterone |journal=Psychopharmacology |volume=188 |issue=4 |pages=541–551 |year=2006 |doi=10.1007/s00213-005-0136-y |pmid=16231168 |postscript=<!--None--> |place=bo-controlled study }}.</ref> found that a 7-day course of DHEA (150&nbsp;mg twice daily) improved ] in healthy young men. In this study, DHEA was also shown to improve subjective mood and decrease evening ] concentration, which is known to be elevated in ].<ref>{{Cite journal |last=Young |first=E. A. |last2=Haskett |first2=R. F. |last3=Grunhaus |first3=L. |last4=''et al.'' |year=1994 |title=Increased evening activation of the hypothalamic–pituitary–adrenal axis in depressed patients |journal=Archives of General Psychiatry |volume=51 |issue=9 |pages=701–707 |doi=10.1001/archpsyc.1994.03950090033005 |pmid=8080346 |first4=A |last5=Weinberg |first5=VM |last6=Watson |first6=SJ |last7=Akil |first7=H |postscript=<!--None--> }}.</ref> The effect of DHEA on memory appeared to be related to an early activation of the ] and it was suggested this was due to neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing.
			===Hormonal activity===
	Consistent with this hypothesis are DHEA-S data from several studies of military special operations units. In these studies, warfighters who exhibited higher levels of DHEA and higher DHEA/cortisol ratios during extreme stress were those who also exhibited superior hippocampal and prefrontal dependent cognitive abilities during stress.<ref>{{Cite journal |last=Morgan |first=C. A. |last2=Hazlett |first2=G. A. |last3=Rasmusson |first3=A. |last4=''et al.'' |year=2004 |title=Relationships Among Plasma Dehydroepiandrosteron Sulfate and Cortisol Levels, Symptoms of Dissociation and Objective Performance in Humans Exposed to Acute Stress |journal=Archive of General Psychiatry |volume=61 |issue=8 |pages=819–825 |doi=10.1001/archpsyc.61.8.819 |pmid=15289280 |first4=A |last5=Hoyt |first5=G |last6=Zimolo |first6=Z |last7=Charney |first7=D |postscript=<!--None--> }}.</ref><ref>{{Cite journal |last=Morgan |first=C. A. |last2=Rasmusson |first2=A. |last3=Pitrzak |first3=R. H. |last4=Coric |first4=V. |last5=Southwick |first5=S. M. |year=2009 |title=Relationships among Plasma Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate, Cortisol, Symptoms of Dissociation and Objective Performance in Humans exposed to Underwater Navigation Stress |journal=Biological Psychiatry |volume=66 |issue=4 |pages=334–340 |doi=10.1016/j.biopsych.2009.04.004 |pmid=19500775 |postscript=<!--None--> }}.</ref>
	===Physical performance===		====Androgen receptor====
			Although it functions as an endogenous ] to more ] androgens such as testosterone and DHT, DHEA has been found to possess some degree of ]ic activity in its own right, acting as a low ] (K<sub>i</sub> = 1 μM), weak ] of the ] (AR). However, its ] at the receptor is quite weak, and on account of that, due to ] for ] with ]s like testosterone, it can actually behave more like an antagonist depending on circulating testosterone and ] (DHT) levels, and hence, like an ]. However, its affinity for the receptor is very low, and for that reason, is unlikely to be of much significance under normal circumstances.<ref name="pmid15994348">{{cite journal | vauthors = Chen F, Knecht K, Birzin E, Fisher J, Wilkinson H, Mojena M, Moreno CT, Schmidt A, Harada S, Freedman LP, Reszka AA | title = Direct agonist/antagonist functions of dehydroepiandrosterone | journal = Endocrinology | volume = 146 | issue = 11 | pages = 4568–76 | date = November 2005 | pmid = 15994348 | doi = 10.1210/en.2005-0368 | doi-access = free }}</ref><ref name="pmid16159155">{{cite journal | vauthors = Gao W, Bohl CE, Dalton JT | title = Chemistry and structural biology of androgen receptor | journal = Chemical Reviews | volume = 105 | issue = 9 | pages = 3352–70 | date = September 2005 | pmid = 16159155 | pmc = 2096617 | doi = 10.1021/cr020456u }}</ref>
	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 ] levels.<ref>{{cite journal |author=Wallace, M. B.; 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=10.1097/00005768-199912000-00014}}</ref>
	===Infertility and Reproduction===		====Estrogen receptors====
			In addition to its affinity for the androgen receptor, DHEA has also been found to bind to (and activate) the ] and ] ]s with K<sub>i</sub> values of 1.1 μM and 0.5 μM, respectively, and ] values of >1 μM and 200 nM, respectively. Though it was found to be a partial agonist of the ERα with a maximal efficacy of 30–70%, the concentrations required for this degree of activation make it unlikely that the activity of DHEA at this receptor is physiologically meaningful. Remarkably however, DHEA acts as a full agonist of the ERβ with a maximal response similar to or actually slightly greater than that of ], and its levels in circulation and local tissues in the human body are high enough to activate the receptor to the same degree as that seen with circulating estradiol levels at somewhat higher than their maximal, non-] concentrations; indeed, when combined with estradiol with both at levels equivalent to those of their physiological concentrations, overall activation of the ERβ was doubled.<ref name="pmid16684650" /><ref name="pmid15994348" />
	Since 2000, DHEA supplementation has been used in reproductive medicine in combination with gonadotropins as a way to treat female infertility. <ref>Casson PR, et al. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod, 2000;15:2129-2132.</ref>The hormone is believed to act on the chromosomal integrity of eggs, creating healthier embryos and increasing the chances of a successful pregnancy. <ref> .</ref> A study released in 2010 from Tel Aviv University showed that women who took DHEA supplements prior to an infertility treatment were three times more likely to conceive than those who did not. <ref> .</ref> Additionally, studies conducted by the Center for Human Reproduction in New York found that women with ] who were supplemented with DHEA 4 to 12 weeks prior to an IVF cycle had a 22% reduction in number of chromosomally abnormal embryos and a 50-80% reduction in miscarriages. <ref>Gleicher N., Ryan, E., Weghofer, A., Blanco-Mejia, S., and Barad, D.H. (2009). . Reproductive Biology and Endocrinology 2009, 7:108 </ref> <ref>Gleicher N, Weghofer, A, and Barad, D.H. (2010). . Reproductive Biology and Endocrinology 2010, 8:140 </ref>
			====Other nuclear receptors====
	===Cardiovascular disease and risk of death===
			DHEA does not bind to or activate the ], ], or ]s.<ref name="pmid15994348" /><ref name="pmid21747041">{{cite journal | vauthors = Lindschau C, Kirsch T, Klinge U, Kolkhof P, Peters I, Fiebeler A | title = Dehydroepiandrosterone-induced phosphorylation and translocation of FoxO1 depend on the mineralocorticoid receptor | journal = Hypertension | volume = 58 | issue = 3 | pages = 471–8 | date = September 2011 | pmid = 21747041 | doi = 10.1161/HYPERTENSIONAHA.111.171280 | url = http://hyper.ahajournals.org/cgi/pmidlookup?view=long&pmid=21747041 | doi-access = free }}</ref> Other ] targets of DHEA besides the androgen and estrogen receptors include the ], ], and ].<ref name="pmid26908835" /> However, whereas DHEA is a ] of the PPARα and PXR in rodents, it is not in humans.<ref name="Watson2011">{{cite book| first = Ronald Ross | last = Watson | name-list-style = vanc |title=DHEA in Human Health and Aging|url=https://books.google.com/books?id=pKXMBQAAQBAJ&pg=PA208|date=22 July 2011|publisher=CRC Press|isbn=978-1-4398-3884-6|pages=208–}}</ref> In addition to direct interactions, DHEA is thought to regulate a handful of other ]s via indirect, genomic mechanisms, including the ]s ] and ] – the latter of which is essential for the biosynthesis of the ]s such as ] and has been suggested to be involved in the ] effects of DHEA – and the ] ].<ref name="pmid15994348" /><ref name="pmid8035785">{{cite journal | vauthors = Kalimi M, Shafagoj Y, Loria R, Padgett D, Regelson W | title = Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA) | journal = Molecular and Cellular Biochemistry | volume = 131 | issue = 2 | pages = 99–104 | date = February 1994 | pmid = 8035785 | doi = 10.1007/BF00925945 | s2cid = 26893297 }}</ref>
	A 1986 study found that a higher level of ] DHEA, as determined by a single measurement, correlated with a lower risk of death or ].<ref>{{cite journal |author=Barrett-Connor, E.; Khaw, K. T.; Yen, S. S. |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=10.1056/NEJM198612113152405}}</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, M. J.; 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>
	A 2007 study found the DHEA restored ] in ] patients, reducing tissue levels of ]—a ] for ]s.<ref name="Mescape_DHEA">{{cite web |url=http://www.medscape.com/viewarticle/567316 |title=DHEA Restores Oxidative Balance in Type 2 Diabetes
	|author=Boggs, Will
	|publisher=Medscape
	|accessdate=2007-12-14 |archiveurl = http://web.archive.org/web/20080107124413/http://www.medscape.com/viewarticle/567316 <!-- Bot retrieved archive --> |archivedate = 2008-01-07}}</ref>
	===Cancer===		===Neurosteroid activity===
	Some '']'' studies have found DHEA to have both anti-proliferative and yet also ] effect on cancer cell lines.<ref>{{cite journal |author=Yang, N. C.; Jeng, K. C.; Ho, W. M.; Hu, M. L. |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=10.1016/S0024-3205(01)01542-9}}</ref><ref>{{cite journal |author=Schulz, S.; Klann, R. C.; Schönfeld, S.; Nyce, J. W. |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, R. M. |title=Immune up-regulation and tumor apoptosis by androstene steroids |journal=Steroids |volume=67 |issue=12 |pages=953–66 |year=2002 |pmid=12398992 |doi=10.1016/S0039-128X(02)00043-0}}</ref> 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 ] in both ] women.<ref>{{cite journal |author=Tworoger, S. S.; Missmer, S. A.; Eliassen, A. H. ''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>
			====Neurotransmitter receptors====
	===Diabetes and carotid atherosclerosis===
			DHEA has been found to directly act on several ]s, including acting as a ] of the ], as a ] of the ], and as an ] of the ].<ref name="King2012" /><ref name="pmid26908835" />
	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= Fukui, M.; Kitagawa, Y.; Nakamura, N.; Kadono, M.; Yoshida, M.; Hirata, C.; Wada, K.; Hasegawa, G.; Yoshikawa, T. |title= Serum dehydroepiandrosterone sulfate concentration and carotid atherosclerosis in men with type 2 diabetes |journal= Atherosclerosis |volume= 181 |issue=2 |pages=339–344 |year=2005 |doi= 10.1016/j.atherosclerosis.2005.01.014 |pmid= 16039288}}</ref>
	===Men over 65===		====Neurotrophin receptors====
			{{main|Neurotrophic factor receptor}}
	A 2006 study supplemented DHEA to men of average 65 years of age, and found that the men experienced significant increases in testosterone and ] (Cyclic guanosine monophosphate), and significant decreases in ] (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."<ref>{{cite journal |author=Martina, V.; Benso, A.; Gigliardi, V. R. ''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 |doi=10.1111/j.1365-2265.2006.02454.x |pmid=16487434}}</ref><ref>See also Symposium On Role of Prasterone In Aging, Annals of the New York Academy of Science vol. 774, pp. 1-350 (1995)</ref>
			In 2011, the surprising discovery was made that DHEA, as well as its sulfate ester, ], directly bind to and activate ] and ], receptors of ]s like ] (NGF) and ] (BDNF), with high affinity.<ref name="pmid26908835">{{cite journal | vauthors = Prough RA, Clark BJ, Klinge CM | title = Novel mechanisms for DHEA action | journal = Journal of Molecular Endocrinology | volume = 56 | issue = 3 | pages = R139–55 | date = April 2016 | pmid = 26908835 | doi = 10.1530/JME-16-0013 | doi-access = free }}</ref><ref name="pmid21541365">{{cite journal | vauthors = Lazaridis I, Charalampopoulos I, Alexaki VI, Avlonitis N, Pediaditakis I, Efstathopoulos P, Calogeropoulou T, Castanas E, Gravanis A | title = Neurosteroid dehydroepiandrosterone interacts with nerve growth factor (NGF) receptors, preventing neuronal apoptosis | journal = PLOS Biology | volume = 9 | issue = 4 | pages = e1001051 | date = April 2011 | pmid = 21541365 | pmc = 3082517 | doi = 10.1371/journal.pbio.1001051 | doi-access = free }}</ref> DHEA was subsequently also found to bind to ] and ] with high affinity, though it only activated TrkC not TrkB.<ref name="pmid26908835" /><ref name="pmid25330101">{{cite journal | vauthors = Pediaditakis I, Iliopoulos I, Theologidis I, Delivanoglou N, Margioris AN, Charalampopoulos I, Gravanis A | title = Dehydroepiandrosterone: an ancestral ligand of neurotrophin receptors | journal = Endocrinology | volume = 156 | issue = 1 | pages = 16–23 | date = January 2015 | pmid = 25330101 | doi = 10.1210/en.2014-1596 | url = https://zenodo.org/record/894291 | doi-access = free }}</ref> DHEA and DHEA-S bound to these receptors with affinities in the low ] range (around 5&nbsp;nM), which were nonetheless approximately two orders of magnitude lower relative to highly potent ] neurotrophins like NGF (0.01–0.1&nbsp;nM).<ref name="pmid26908835" /><ref name="pmid21541365" /><ref name="pmid25330101" /> In any case, DHEA and DHEA-S both circulate at requisite concentrations to activate these receptors and were thus identified as important endogenous ]s.<ref name="pmid26908835" /><ref name="pmid21541365" /> They have since been labeled "steroidal microneurotrophins", due to their ] and steroidal nature relative to their polypeptide neurotrophin counterparts.<ref name="pmid23074265">{{cite journal | vauthors = Gravanis A, Calogeropoulou T, Panoutsakopoulou V, Thermos K, Neophytou C, Charalampopoulos I | title = Neurosteroids and microneurotrophins signal through NGF receptors to induce prosurvival signaling in neuronal cells | journal = Science Signaling | volume = 5 | issue = 246 | pages = pt8 | date = October 2012 | pmid = 23074265 | doi = 10.1126/scisignal.2003387 | s2cid = 26914550 }}</ref> Subsequent research has suggested that DHEA and/or DHEA-S may in fact be phylogenetically ancient "ancestral" ligands of the neurotrophin receptors from early on in the ] of the ].<ref name="pmid26908835" /><ref name="pmid25330101" /> The findings that DHEA binds to and potently activates ]s may explain the positive association between decreased circulating DHEA levels with age and age-related ]s.<ref name="pmid26908835" /><ref name="pmid21541365" />
	===Longevity===
	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 |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 |year=2008 |doi= 10.1111/j.1532-5415.2008.01692.x |pages= 994–8 |pmid= 18422949 |last2= Adachi |first2= H |last3= Fukami |first3= A |last4= Furuki |first4= K |last5= Satoh |first5= A |last6= Otsuka |first6= M |last7= Kumagae |first7= S |last8= Nanjo |first8= Y |last9= Shigetoh |first9= Y }}</ref>
			====Microtubule-associated protein 2====
	==="No reason to prescribe"===
			Similarly to ], its synthetic derivative ] (MAP-4343), and ], DHEA has been found to bind to ] (MAP2), specifically the MAP2C subtype (K<sub>d</sub> = 27&nbsp;μM).<ref name="pmid26908835"/> However, it is unclear whether DHEA increases binding of MAP2 to ] like pregnenolone.<ref name="pmid26908835" />
	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."<ref>{{cite journal |title=DHEA: the last elixir |journal=Prescrire international |volume=11 |issue=60 |pages=118–23 |year=2002 |pmid=12199273 |doi=}}</ref>
	===Disputed effects===		====ADHD====
			Some research has shown that DHEA levels are too low in people with ADHD, and treatment with methylphenidate or bupropion (stimulant type of medications) normalizes DHEA levels. <ref>{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/17763937/ | pmid=17763937 | year=2008 | last1=Lee | first1=M. S. | last2=Yang | first2=J. W. | last3=Ko | first3=Y. H. | last4=Han | first4=C. | last5=Kim | first5=S. H. | last6=Lee | first6=M. S. | last7=Joe | first7=S. H. | last8=Jung | first8=I. K. | title=Effects of methylphenidate and bupropion on DHEA-S and cortisol plasma levels in attention-deficit hyperactivity disorder | journal=Child Psychiatry and Human Development | volume=39 | issue=2 | pages=201–209 | doi=10.1007/s10578-007-0081-6 | s2cid=11041447 }}</ref>
	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 ]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, J. M.; Kocher, M. S.; Hawkins, R. J. |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 must first be converted to androstenedione and then to testosterone in men, it has two chances to aromatize into ] - 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|date=October 2009}}
	===Side effects===		===Other activity===
	As a hormone precursor, there has been a smattering of reports of side effects possibly caused by the hormone metabolites of DHEA.<ref>{{cite web|url=http://www.nlm.nih.gov/medlineplus/druginfo/natural/patient-dhea.html#Safety|title=DHEA|last=Medline Plus|work=Drugs and Supplements Information|publisher=National Library of Medicine|accessdate=18 February 2010}}</ref><ref>{{cite web|url=http://www.medscape.com/druginfo/dosage?cid=med&drugid=3512&drugname=DHEA+Oral&monotype=default|title=DHEA Oral|last=Medscape|year=2010|work=Drug Reference|publisher=WebMD LLC.|accessdate=18 February 2010}}</ref> Some of these include possibly serious cardiovascular effects such as heart palpitations.<ref>{{cite web|url=http://www.raysahelian.com/dhea.html|title=Honest DHEA Supplement Information|last=Sahelian, M.D.|first=Ray|year=2005|work=DHEA: A Practical Guide, Mind Boosters, and Natural Sex Boosters|accessdate=18 February 2010}}</ref>
			====G6PDH inhibitor====
	==Increasing endogenous production==
			DHEA is an ] of {{abbrlink|G6PDH|glucose-6-phosphate dehydrogenase}} (K<sub>i</sub> = 17&nbsp;μM; ] = 18.7&nbsp;μM), and is able to lower {{abbrlink|NADPH|nicotinamide adenine dinucleotide phosphate}} levels and reduce NADPH-dependent ] production.<ref name="pmid15177053">{{cite journal | vauthors = Schwartz AG, Pashko LL | title = Dehydroepiandrosterone, glucose-6-phosphate dehydrogenase, and longevity | journal = Ageing Research Reviews | volume = 3 | issue = 2 | pages = 171–87 | date = April 2004 | pmid = 15177053 | doi = 10.1016/j.arr.2003.05.001 | s2cid = 11871872 }}</ref><ref name="pmid12097275">{{cite journal | vauthors = Ciolino HP, MacDonald CJ, Yeh GC | title = Inhibition of carcinogen-activating enzymes by 16alpha-fluoro-5-androsten-17-one | journal = Cancer Research | volume = 62 | issue = 13 | pages = 3685–90 | date = July 2002 | pmid = 12097275 }}</ref> It is thought that this action may possibly be responsible for much of the ], ], ], ], ], and ], as well as certain ] activities of DHEA (with some experimental evidence to support this notion available).<ref name="pmid15177053" /><ref name="pmid12097275"/><ref name="pmid16952912">{{cite journal | vauthors = McCormick DL, Johnson WD, Kozub NM, Rao KV, Lubet RA, Steele VE, Bosland MC | title = Chemoprevention of rat prostate carcinogenesis by dietary 16alpha-fluoro-5-androsten-17-one (fluasterone), a minimally androgenic analog of dehydroepiandrosterone | journal = Carcinogenesis | volume = 28 | issue = 2 | pages = 398–403 | date = February 2007 | pmid = 16952912 | doi = 10.1093/carcin/bgl141 | doi-access = free }}</ref><ref name="pmid17911478">{{cite journal | vauthors = Auci D, Kaler L, Subramanian S, Huang Y, Frincke J, Reading C, Offner H | title = A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the mouse: androstene hormones as regulators of regulatory T cells | journal = Annals of the New York Academy of Sciences | volume = 1110 | pages = 630–40 | date = September 2007 | issue = 1 | pmid = 17911478 | doi = 10.1196/annals.1423.066 | bibcode = 2007NYASA1110..630A | s2cid = 32258529 }}</ref> However, it has also been said that inhibition of G6PDH activity by DHEA '']'' has not been observed and that the concentrations required for DHEA to inhibit G6PDH '']'' are very high, thus making the possible contribution of G6PDH inhibition to the effects of DHEA uncertain.<ref name="pmid12097275" />
	Regular ] is known to increase DHEA production in the body.<ref>Eur. J. Appl. Physiol. Occup. Physiol. 1998 Oct; 78(5):466-71</ref><ref>{{Cite journal |last=Tissandier |first=O. |last2=Péres |first2=G. |last3=Fiet |first3=J. |last4=Piette |first4=F. |year=2001 |title=Testosterone, dehydroepiandrosterone, insulin-like growth factor 1, and insulin in sedentary and physically trained aged men |journal=European Journal of Applied Physiology |volume=85 |issue=1–2 |pages=177–184 |doi=10.1007/s004210100420 |pmid=11513313 |postscript=<!--None--> }}.</ref><ref>J. Gerontol. A. Biol. Sci. Med. Sci. 2002 Apr; 57(4):B158-65</ref> ] has also been shown to increase DHEA in primates.<ref>{{Cite journal |last=Mattison |first=Julie A. |last2=Lane |first2=Mark A. |last3=Roth |first3=George S. |last4=Ingram |first4=Donald K. |year=2003 |title=Calorie restriction in rhesus monkeys |journal=Experimental Gerontology |volume=38 |issue=1–2 |pages=35–46 |doi=10.1016/S0531-5565(02)00146-8 |pmid=12543259 |postscript=<!--None--> }}.</ref> 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.<ref>{{Cite journal |last=Roberts |first=E. |title=The importance of dehydroepiandrosterone sulfate in the blood of primates: a longer and healthier life? |journal=Biochemical Pharmacology |year=1999 |volume=57 |issue=4 |pages=329–346 |doi=10.1016/S0006-2952(98)00246-9 |pmid=9933021 |postscript=<!--None--> }}.</ref>
	==Isomers==		====Cancer====
			DHEA supplements have been promoted in supplement form for its claimed cancer prevention properties; there is no scientific evidence to support these claims.<ref>{{cite book |publisher=American Cancer Society |title=American Cancer Society Complete Guide to Complementary and Alternative Cancer Therapies |chapter-url=https://archive.org/details/americancancerso0000unse |chapter-url-access=registration |edition=2nd |year=2009 |isbn=9780944235713 |veditors=Russell J, Rovere A |pages= |chapter=DHEA}}</ref>
	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 ] (shown to be synthesized in pigs) and ] (shown to occur in rats). These isomers are also technically DHEA, since they are dehydroepiandrosterones in which hydrogens are removed from the ] skeleton.
			====Miscellaneous====
	==Legality==
			DHEA has been found to competitively inhibit ].<ref name="King2012">{{cite book | first = Steven R. | last = King | name-list-style = vanc | title = Neurosteroids and the Nervous System|url=https://books.google.com/books?id=D1fOTC6CP3kC&pg=PA1|date=9 November 2012|publisher=Springer Science & Business Media|isbn=978-1-4614-5559-2|pages=15–16}}</ref>
	===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 ]. The sponsor is ] (]-]). The cosponsors are ] (]-]), and ] (]-]).<ref>, from http://thomas.loc.gov/cgi-bin/thomas . Accessed Sept. 9, 2009.</ref> 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 where it died.<ref></ref>
	===Canada===		==Biochemistry==
			], showing DHEA at left among the androgens.<ref name="HäggströmRichfield2014">{{cite journal|last1=Häggström|first1=Mikael|last2=Richfield|first2=David|title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|year=2014|issn=2002-4436|doi=10.15347/wjm/2014.005|doi-access=free}}</ref>
	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 </ref>
			]]
	=== Sports and athletics ===		===Biosynthesis===
			DHEA is produced in the ] of the ] under the control of ] (ACTH) and by the ]s under the control of ] (GnRH).<ref name="Erkkola2006">{{cite book | first = Risto | last = Erkkola | name-list-style = vanc |title=The Menopause|url=https://books.google.com/books?id=1AU_NI__fpUC&pg=PA5|year=2006|publisher=Elsevier|isbn=978-0-444-51830-9|pages=5–}}</ref><ref name="KleineRossmanith2016">{{cite book| first1 = Bernhard | last1 = Kleine | first2 = Winfried G. | last2 = Rossmanith | name-list-style = vanc | title=Hormones and the Endocrine System: Textbook of Endocrinology|url=https://books.google.com/books?id=boqRCwAAQBAJ&pg=PA264|date=11 February 2016|publisher=Springer|isbn=978-3-319-15060-4|pages=264–265}}</ref> It is also produced in the brain.<ref name="Pizzorno2013">{{cite book | first = Joseph E. | last = Pizzorno | name-list-style = vanc |title=Textbook of Natural Medicine|url=https://books.google.com/books?id=6cjgo1IixvEC&pg=PA711|year=2013|publisher=Elsevier Health Sciences|isbn=978-1-4377-2333-5|pages=711–}}</ref> DHEA is synthesized from ] via the ]s ] (CYP11A1; P450scc) and ] (CYP17A1), with ] and ] as ]s.<ref name="pmid17945481">{{cite journal | vauthors = Rainey WE, Nakamura Y | title = Regulation of the adrenal androgen biosynthesis | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 108 | issue = 3–5 | pages = 281–6 | date = February 2008 | pmid = 17945481 | pmc = 2699571 | doi = 10.1016/j.jsbmb.2007.09.015 }}</ref> It is derived mostly from the ], with only about 10% being secreted from the ]s.<ref name="Adler2009">{{cite book | first = Robert A. | last = Adler | name-list-style = vanc |title=Osteoporosis: Pathophysiology and Clinical Management|url=https://books.google.com/books?id=eShjlIWB7gEC&pg=PA387|date=14 December 2009|publisher=Springer Science & Business Media|isbn=978-1-934115-19-0|pages=387–}}</ref><ref name="SchillComhaire2006">{{cite book | first1= Wolf-Bernhard | last1 = Schill | first2 = Frank H. | last2 = Comhaire | first3 = Timothy B. | last3 = Hargreave | name-list-style = vanc |title=Andrology for the Clinician|url=https://books.google.com/books?id=5Ts_AAAAQBAJ&pg=PA243|date=26 August 2006|publisher=Springer Science & Business Media|isbn=978-3-540-33713-3|pages=243–}}</ref><ref name="LinosHeerden2005">{{cite book | first1 = Dimitrios A. | last1 = Linos | first2 = Jon A. | last2 = van Heerden | name-list-style = vanc |title=Adrenal Glands: Diagnostic Aspects and Surgical Therapy|url=https://books.google.com/books?id=r8OLj1LLw3IC&pg=PA161|date=5 December 2005|publisher=Springer Science & Business Media|isbn=978-3-540-26861-1|pages=161–}}</ref> Approximately 50 to 70% of circulating DHEA originates from desulfation of DHEA-S in peripheral tissues.<ref name="Adler2009" /> DHEA-S itself originates almost exclusively from the adrenal cortex, with 95 to 100% being secreted from the adrenal cortex in women.<ref name="Erkkola2006"/><ref name="LinosHeerden2005" />
	DHEA is a prohibited substance under the World Anti-Doping Code of the World Anti-Doping Agency,<ref></ref> which manages drug testing for Olympics and other sports. In January 2011, ] player ] was given a 10-game suspension after testing positive for DHEA. Mayo termed his use of DHEA as "an honest mistake".<ref></ref> 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.<ref></ref>
			====Increasing endogenous production====
	==Synonyms and brand names==
			Regular exercise is known to increase DHEA production in the body.<ref>{{cite journal | vauthors = Filaire E, Duché P, Lac G | title = Effects of amount of training on the saliva concentrations of cortisol, dehydroepiandrosterone and on the dehydroepiandrosterone: cortisol concentration ratio in women over 16 weeks of training | journal = European Journal of Applied Physiology and Occupational Physiology | volume = 78 | issue = 5 | pages = 466–71 | date = October 1998 | pmid = 9809849 | doi = 10.1007/s004210050447 | s2cid = 20583279 }}</ref><ref>{{cite journal | vauthors = Copeland JL, Consitt LA, Tremblay MS | title = Hormonal responses to endurance and resistance exercise in females aged 19-69 years | journal = The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences | volume = 57 | issue = 4 | pages = B158–65 | date = April 2002 | pmid = 11909881 | doi = 10.1093/gerona/57.4.B158 | doi-access = free }}</ref> ] has also been shown to increase DHEA in primates.<ref>{{cite journal | vauthors = Mattison JA, Lane MA, Roth GS, Ingram DK | title = Calorie restriction in rhesus monkeys | journal = Experimental Gerontology | volume = 38 | issue = 1–2 | pages = 35–46 | year = 2003 | pmid = 12543259 | doi = 10.1016/S0531-5565(02)00146-8 | s2cid = 41481691 | url = https://zenodo.org/record/1260075 }}.</ref> 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.<ref>{{cite journal | vauthors = Roberts E | title = The importance of being dehydroepiandrosterone sulfate (in the blood of primates): a longer and healthier life? | journal = Biochemical Pharmacology | volume = 57 | issue = 4 | pages = 329–46 | date = February 1999 | pmid = 9933021 | doi = 10.1016/S0006-2952(98)00246-9 }}.</ref>
			===Distribution===
	Synonyms for dehydroepiandrosterone:
			In the ], DHEA is mainly bound to ], with a small amount bound to ] (SHBG).<ref name="CoatesPaul2004">{{cite book | first1 = Salvatore | last1 = Alesci | first2 = Irini | last2 = Manoli | first3 = Marc R. | last3 = Blackman | editor-first1 = Paul M. | editor-last1 = Coates | editor-first2 = Marc R. | editor-last2 = Blackman | editor-first3 = Gordon M. | editor-last3 = Cragg | editor-first4 = Mark | editor-last4 = Levine | editor-first5 = Joel | editor-last5 = Moss | editor-first6 = Jeffry D. | editor-last6 = White | name-list-style = vanc |title= Encyclopedia of Dietary Supplements (Print) | chapter = Dehydroepiandrosterone (DHEA) |chapter-url= https://books.google.com/books?id=Sfmc-fRCj10C&pg=PA169|date=29 December 2004|publisher=CRC Press|isbn=978-0-8247-5504-1|pages=169–}}</ref><ref name="Becker2001">{{cite book | first = Kenneth L. | last = Becker | name-list-style = vanc |title=Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA712|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=712–}}</ref> The small remainder of DHEA not associated with albumin or SHBG is unbound and free in the circulation.<ref name="CoatesPaul2004" />
			DHEA easily crosses the ] into the ].<ref name="Pizzorno2013" />
	The ] 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'', ''5-androsten-3beta-ol-17-one''.
			===Metabolism===
	] is a synthetic derivative of DHEA. Fidelin is a 3-part combination of DHEA, dehydroepiandrosterone and prasterone; it was investigated by Paladin Labs Inc. of Canada circa 2003, but by 2010 Paladin had abandoned this project
			DHEA is transformed into DHEA-S by ] at the C3β position via the ] ]s ] and to a lesser extent ].<ref name="pmid17945481" /><ref name="pmid26213785">{{cite journal | vauthors = Mueller JW, Gilligan LC, Idkowiak J, Arlt W, Foster PA | title = The Regulation of Steroid Action by Sulfation and Desulfation | journal = Endocr Rev | volume = 36 | issue = 5 | pages = 526–63 | date = October 2015 | pmid = 26213785 | pmc = 4591525 | doi = 10.1210/er.2015-1036 }}</ref><ref name="Lash2005">{{cite book | first = Lawrence H | last = Lash | name-list-style = vanc |title=Drug Metabolism and Transport: Molecular Methods and Mechanisms|url=https://books.google.com/books?id=-sK8NM_9UVsC&pg=PA353|year=2005|publisher=Springer Science & Business Media|isbn=978-1-59259-832-8|pages=353–}}</ref> This occurs naturally in the adrenal cortex and during ] in the ] and ] when ] DHEA is administered orally.<ref name="pmid26213785" /> Levels of DHEA-S in circulation are approximately 250 to 300 times those of DHEA.<ref name="Weizman2008">{{cite book | first = Abraham | last = Weizman | name-list-style = vanc |title=Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment|url=https://books.google.com/books?id=uABKkFdPjhkC&pg=PA229|date=1 February 2008|publisher=Springer Science & Business Media|isbn=978-1-4020-6854-6|pages=229–}}</ref> DHEA-S in turn can be converted back into DHEA in peripheral tissues via ] (STS).<ref name="Morfin2003">{{cite book | first = Robert | last = Morfin | name-list-style = vanc |title=DHEA and the Brain|url=https://books.google.com/books?id=uZp62ctguF0C&pg=PA28|date=2 September 2003|publisher=CRC Press|isbn=978-0-203-30121-0|pages=28–}}</ref><ref name="Karasek2006">{{cite book | first = Michał | last = Karasek | name-list-style = vanc |title=Aging and Age-related Diseases: The Basics|url=https://books.google.com/books?id=A_PN9oxKpP0C&pg=PA66|year=2006|publisher=Nova Publishers|isbn=978-1-59454-426-2|pages=66–}}</ref>
			The ] of DHEA is short at only 15 to 30&nbsp;minutes.<ref name="WhitePorterfield2013">{{cite book | first1 = Bruce Alan | last1 = White | first2 =Susan P. | last2 = Porterfield | name-list-style = vanc | title=Endocrine and Reproductive Physiology, Mosby Physiology Monograph Series (with Student Consult Online Access),4: Endocrine and Reproductive Physiology|url=https://books.google.com/books?id=zMb4uoiXzzcC&pg=PA164|year=2013|publisher=Elsevier Health Sciences|isbn=978-0-323-08704-9|pages=164–}}</ref> In contrast, the terminal half-life of DHEA-S is far longer, at 7 to 10&nbsp;hours.<ref name="WhitePorterfield2013" /> As DHEA-S can be converted back into DHEA, it serves as a circulating reservoir for DHEA, thereby extending the ] of DHEA.<ref name="KalimiRegelson2000">{{cite book | first1 = Mohammed Y. | last1 = Kalimi | first2 = William | last2 = Regelson | name-list-style = vanc | title = Dehydroepiandrosterone (DHEA): Biochemical, Physiological and Clinical Aspects|url=https://books.google.com/books?id=Cn0tcGjTD8YC&pg=PA41|year=2000|publisher=Walter de Gruyter|isbn=978-3-11-016111-3|pages=41–}}</ref><ref name="Weizman2008" />
	==References==
	{{reflist|colwidth=30em}}
			]s of DHEA include DHEA-S, ], ], ], ], and ], as well as ] and ].<ref name="pmid16524719">{{cite journal | vauthors = Mo Q, Lu SF, Simon NG | title = Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 99 | issue = 1 | pages = 50–8 | date = April 2006 | pmid = 16524719 | doi = 10.1016/j.jsbmb.2005.11.011 | s2cid = 30489004 }}</ref>
	==External links==
			====Pregnancy====
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			During pregnancy, DHEA-S is ] into the sulfates of ] and ] in the ] ] as ]s in the production of the estrogens ] and ], respectively.<ref>{{Cite journal |last1=Zbella |first1=E. A. |last2=Ilekis |first2=J. |last3=Scommegna |first3=A. |last4=Benveniste |first4=R. |title=Competitive studies with dehydroepiandrosterone sulfate and 16 alpha-hydroxydehydroepiandrosterone sulfate in cultured human choriocarcinoma JEG-3 cells: effect on estrone, 17 beta-estradiol, and estriol secretion |url=https://pubmed.ncbi.nlm.nih.gov/2942557/ |journal=The Journal of Clinical Endocrinology and Metabolism |year=1986 |volume=63 |issue=3 |pages=751–757 |doi=10.1210/jcem-63-3-751 |issn=0021-972X |pmid=2942557}}</ref>
	<!--| DO NOT ADD MORE LINKS TO THIS ARTICLE. WIKIPEDIA IS NOT A COLLECTION OF |-->
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			===Levels===
	<!--| but put it on this article's discussion page first or submit your link |-->
			Prior to ] in humans, DHEA and DHEA-S levels elevate upon ] of the ] of the ].<ref name="pmid26908835" /> Peak levels of DHEA and DHEA-S are observed around age 20, which is followed by an age-dependent decline throughout life eventually back to prepubertal concentrations.<ref name="pmid26908835" /> Plasma levels of DHEA in adult men are 10 to 25&nbsp;nM, in premenopausal women are 5 to 30&nbsp;nM, and in postmenopausal women are 2 to 20&nbsp;nM.<ref name="pmid26908835" /> Conversely, DHEA-S levels are an order of magnitude higher at 1–10&nbsp;μM.<ref name="pmid26908835" /> Levels of DHEA and DHEA-S decline to the lower nanomolar and micromolar ranges in men and women aged 60 to 80&nbsp;years.<ref name="pmid26908835" />
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			DHEA levels are as follows:<ref name="QuestDiagnostics">{{Cite web |title=DHEA (Dehydroepiandrosterone) |url=https://www.questdiagnostics.com/hcp/intguide/EndoMetab/EndoManual_AtoZ_PDFs/DHEA.pdf |archive-url=https://web.archive.org/web/20200927033608/https://www.questdiagnostics.com/hcp/intguide/EndoMetab/EndoManual_AtoZ_PDFs/DHEA.pdf |archive-date=Sep 27, 2020 |website=]}}</ref>
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			* Adult men: 180–1250&nbsp;ng/dL
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			* Adult women: 130–980&nbsp;ng/dL
	<!--| See ] and ] for details |-->
			* Pregnant women: 135–810&nbsp;ng/dL
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			* Prepubertal children (<1 year): 26–585&nbsp;ng/dL
	*
			* Prepubertal children (1–5 years): 9–68&nbsp;ng/dL
	*, published in the '']'' 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."
			* Prepubertal children (6–12 years): 11–186&nbsp;ng/dL
	*
			* Adolescent boys (Tanner II–III): 25–300&nbsp;ng/dL
	*
			* Adolescent girls (Tanner II–III): 69–605&nbsp;ng/dL
			* Adolescent boys (Tanner IV–V): 100–400&nbsp;ng/dL
			* Adolescent girls (Tanner IV–V): 165–690&nbsp;ng/dL
			===Measurement===
			As almost all DHEA is derived from the adrenal glands, blood measurements of DHEA-S/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of ]. Women with ] tend to have elevated levels of DHEA-S.<ref name="pmid14737959">{{cite journal | vauthors = Banaszewska B, Spaczyński RZ, Pelesz M, Pawelczyk L | title = Incidence of elevated LH/FSH ratio in polycystic ovary syndrome women with normo- and hyperinsulinemia | journal = Roczniki Akademii Medycznej W Bialymstoku | volume = 48 | pages = 131–4 | year = 2003 | pmid = 14737959}}</ref>
			==Chemistry==
			{{See also|List of androgens/anabolic steroids|List of neurosteroids}}
			DHEA, also known as androst-5-en-3β-ol-17-one, is a ] ] ] and a ].<ref name="Elks2014">{{cite book | vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA641|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=641–}}</ref> It is closely related structurally to ] (androst-5-ene-3β,17β-diol), ] (androst-4-ene-3,17-dione), and ] (androst-4-en-17β-ol-3-one).<ref name="Elks2014" /> DHEA is the 5-] ] of ] (5α-androstan-3β-ol-17-one) and is also known as 5-dehydroepiandrosterone or as δ<sup>5</sup>-epiandrosterone.<ref name="Elks2014" />
			===Isomers===
			The term "dehydroepiandrosterone" is ambiguous chemically because it does not include the specific positions within epiandrosterone at which hydrogen atoms are missing. DHEA itself is 5,6-didehydroepiandrosterone or 5-dehydroepiandrosterone. A number of naturally occurring isomers also exist and may have similar activities. Some isomers of DHEA are ] (1-androsterone) and ].<ref name="JosephyRadt2013">{{cite book|author1=Edith Josephy|author2=F. Radt|title=Elsevier's Encyclopaedia of Organic Chemistry: Series III: Carboisocyclic Condensed Compounds|url=https://books.google.com/books?id=HqHzCAAAQBAJ&pg=PA2608|date=1 December 2013|publisher=Springer|isbn=978-3-662-25863-7|pages=2608–}}</ref> These isomers are also technically "DHEA", since they are dehydroepiandrosterones in which hydrogens are removed from the ] skeleton.{{citation needed|date=November 2024}}
			] (DHA) is the 3α-] of DHEA and is also an endogenous androgen.
			==History==
			{{See also|Prasterone#History}}
			DHEA was first isolated from human ] in 1934 by ] and Kurt Tscherning.<ref name="pmid11478328">{{cite journal | vauthors = Schwartz AG, Pashko LL | title = Potential therapeutic use of dehydroepiandrosterone and structural analogs | journal = Diabetes Technology & Therapeutics | volume = 3 | issue = 2 | pages = 221–4 | year = 2001 | pmid = 11478328 | doi = 10.1089/152091501300209589 }}</ref>
			==See also==
			* ]
			==References==
			{{Reflist|32em}}
			==Further reading==
			{{Refbegin}}
			* {{cite journal | vauthors = Labrie F, Martel C, Bélanger A, Pelletier G | title = Androgens in women are essentially made from DHEA in each peripheral tissue according to intracrinology | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 168 | pages = 9–18 | date = April 2017 | pmid = 28153489 | doi = 10.1016/j.jsbmb.2016.12.007 | s2cid = 2620899 }}
			{{Refend}}
	{{Hormones}}		{{Hormones}}
			{{Endogenous steroids}}
	{{Steroids}}
			{{Androgens and antiandrogens}}
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