​EstrADIol(17β-estradiol;E2;1,3,5(10)-estratriene-3,17β-diol)isoneofthethreemainestrogenicsteroidhormonespresentinhumans. Itisthemostactivenaturallysecretedestrogen.(1) Inmenstruatingwomen,estradiolisproducedprimarilybytheovarianfolliclesfromtestosterone,withadditionalamountsproducedbyextraglandularconversionoftestosteroneinperipheraltissues.(1,2,3,4) Concentrationspeakmid-cycle,markingovulation,followedbyarapiddeclinewithasmallersecondaryincreaseduringthelutealphase.(5,6) Inwomenofreproductiveage,estradiolexhibitsadiurnalrhythmwherethepeakstendtooccurintheearlymorning;thetimingofthepeaksisshiftedlaterduringthemenstrualphase.Therearealsoultradianharmonicssuperimposeduponthebasicdiurnalrhythm.(7) Inpost-menstrualwomen,smallamountsofestradiolcontinuetobemadefromestroneandtestosteroneintheperipheraltissues,butestrone,alsoproducedperipherally,replacesitasthepredominantformofestrogen.(8,9) Inwomen,estradiolisresponsIBLeforthedevelopmentofsecondarysexualcharacteristics,enhancingbreastdevelopmentandaffectingbodyshape,bones,joints,andfatdeposition.(10) 

Inmenandpre-pubertalchildren,estradioloriginatesprincipallyfromextraglandularconversionofandrogens;menalsohavesmallamountsproducedinthetestes.(11,12) Inmenthereisnodiurnalrhythmtoestradiolproduction.(13)

Inadditiontoitsroleinsexualandreproductivefunctioning,estradiolalsoaffectsotherpartsofthebody,includingthecardio-vascularsystem,thebrain,andtheimmunesystem.(14,15,16,17)Estradiolalsohasalsobeenstudiedforstrongrelationshipswithcancersofthebreast,ovary,anduterinelining.(18,19,20)

Inthebloodonly1to15%ofestradiolisinitsunboundorBIOLOGicallyactiveform.Theremainingestradiolisboundtoserumproteins.Unboundserumestradiolenterssalivaviaintracellularmechanisms,andinsalivathemajorityofestradiolremainsunboundtoprotein.(21)Thecorrelationbetweenserumandsalivasamplesishigh.(22,23,24)​

1. Abraham,G.E.(1975).Theapplicationsofsteroidradioimmunoassaytogynecologicendocrinology.In:Taymor,M.L.andGreen,T.H.(eds.):Progressingynecology,Vol.1,111-144.NewYork:GruneandStratton.
2. Faiman,C.,Winter,S.D.,&Reyes,F.I.(1976).Patternsofgonadotropinsandgonadalsteroidsthroughoutlife.ClinObstetGynecol,3(3),467-483.
3. Kirschner,M.A.,Schneider,G.,Ertel,N.H.,Worton,E.(1982). Obesity,androgens,estrogens,andcancerrisk. CancerRes,42(8suppl),3281s-3285s.
4. Labrie,F.,Bélanger,A.,Cusan,L.,Candas,B.(1997). Physiologicalchangesindehydroepiandrosteronearenotreflectedbyserumlevelsofactiveandrogensandestrogensbutoftheirmetabolites:Intracrinology. JClinEndocrinolMetab,82(8),2403-9.
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6. Choe,J.K.,Khan-Dawood,F.S.,Dawood,M.Y.(1982).Progesteroneandestradiolinsalivaandplasmaduringthemenstrualcycle.AmJObstetGynecol,146,557-62.
7. Bao,A.-M.,Liu,R.-Y.,vanSomeren,E.J.,etal.(2003). Diurnalrhythmoffreeestradiolduringthemenstrualcycle. EurJEndocrinol,148(2),227-32.
8. Chang,R.J.,PlouffeJr.,L.Schaffer,K. Physiologyofthemenopause.In:Comprehensivemanagementofmenopause,Lorrain,J.,FlouffeJr.,L.,Ravnikar,V.,Speroff,L.,Watts,N.,eds. NewYork:Springer,1993.
9. Reed,M.J.,Lai,L.C.,Owen,A.M.,etal.(1990). Effectoftreatmentwith4-hydroxyandrostenedioneontheperipheralconversionofandrostenedionetoestroneandinvitrotumoraromataseactivityinpostmenopausalwomenwithbreastcancer. CancerRes,50(1),193-96.
10. Shirtcliff,E.A.,Dahl,R.E.,Pollak,S.D.(2009).Pubertaldevelopment:Correspondencebetweenhormonalandphysicaldevelopment. ChildDev,80(2),327-37.
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12. Winters,S.J.,Troen,P.(1986). Testosteroneandestradiolareco-secretedepisodicallybythehumantestis. JClinInvest,78(4),870-73.
13. Nankin,H.R.,Pinto,R.,Fan,D.-F.,Troen,P.(1975). Daytimetitersoftestosterone,LH,estrone,estradiol,andtestosterone-bindingprotein:AcuteeffectsofLHandLH-releasinghormoneinmen. JClinEndocrinolMetab,41(2),271-81.
14. Ouyang,P.,Michos,E.D.,Kara,R.H.(2006).Hormonereplacementtherapyandthecardiovascularsystem:Lessonslearnedandunansweredquestions. JAmCollegeCardiol,47(9),1741-53.
15. McCarthy,M.M.(2008).Estradiolandthedevelopingbrain.PhysiolRev,88(1),91-134.
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17. Karpuzoglu,E.,Ahmed,S.A.(2006). Estrogenregulationofnitricoxideandinduciblenitricoxidesynthase(iNOS)inimmunecells:Implicationsforimmunity,autoimmunediseases,andapoptosis. NitricOxide,15(3),177-86.
18. Colditz,G.A.1998. Relationshipbetweenestrogenlevels,useofhormonereplacementtherapy,andbreastcancer.JNatlCancerInst,90(11),814-23.
19. Lépine,J.,Audet-Walsh,E.,Grégoire,J.,etal.(2010) Circulatingestrogensinendometrialcancercasesandtheirrelationshipwithtissularexpressionofkeyestrogenbiosynthesisandmetabolicpathways. JClinEndocinolMetab,95(6),2689-98.
20. Sasano,H.,Harada,N.(1998).Intratumoralaromataseinhumanbreast,endometrial,andovarianmalilgnancies. Endocr Rev,19(5),593-607.
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24. Ellison,P.T.,Lipson,S.F.(1999).Salivaryestradiol–Aviablealternative?FertilSteril,72(5),951-52.)