Array ( [0] => {{About|estradiol as a hormone|its use as a medication|Estradiol (medication)}} [1] => {{Use dmy dates|date=August 2018}} [2] => {{Chembox [3] => [4] => | ImageFile1 = Estradiol.svg [5] => | ImageSize1 = 225px [6] => | ImageAlt1 = The chemical structure of estradiol. [7] => | ImageFile2 = Estradiol 3D ball.png [8] => | ImageSize2 = 225px [9] => | ImageAlt2 = A ball-and-stick model of estradiol. [10] => [11] => | pronounce = {{IPAc-en|ˌ|ɛ|s|t|r|ə|ˈ|d|aɪ|oʊ|l}} {{respell|ES|trə|DY|ohl}} [12] => | IUPACName = Estra-1,3,5(10)-triene-3,17β-diol [13] => | SystematicName = (1''S'',3a''S'',3b''R'',9b''S'',11a''S'')-11a-Methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1''H''-cyclopenta[''a'']phenanthrene-1,7-diol [14] => | OtherNames = Oestradiol; E2; 17β-Estradiol; 17β-Oestradiol [15] => | Watchedfields = changed [16] => | verifiedrevid = 488623959 [17] => [18] => | Section1 = {{Chembox Identifiers [19] => | CASNo_Ref = {{cascite|correct|CAS}} [20] => | CASNo = 50-28-2 [21] => | ChEBI_Ref = {{ebicite|correct|EBI}} [22] => | ChEBI = 16469 [23] => | ChEMBL_Ref = {{ebicite|correct|EBI}} [24] => | ChEMBL = 135 [25] => | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} [26] => | ChemSpiderID = 5554 [27] => | DrugBank_Ref = {{drugbankcite|correct|drugbank}} [28] => | DrugBank = DB00783 [29] => | EINECS = 200-023-8 [30] => | KEGG_Ref = {{keggcite|correct|kegg}} [31] => | KEGG = D00105 [32] => | PubChem = 5757 [33] => | SMILES = C[C@]12CC[C@@H]3c4ccc(cc4CC[C@H]3[C@@H]1CC[C@@H]2O)O [34] => | StdInChI_Ref = {{stdinchicite|correct|chemspider}} [35] => | StdInChI = 1S/C18H24O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-17,19-20H,2,4,6-9H2,1H3/t14-,15-,16+,17+,18+/m1/s1 [36] => | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} [37] => | StdInChIKey = VOXZDWNPVJITMN-ZBRFXRBCSA-N [38] => | UNII_Ref = {{fdacite|correct|FDA}} [39] => | UNII = 4TI98Z838E [40] => }} [41] => | Section2 = {{Chembox Properties [42] => | C=18 | H=24 | O=2 [43] => | MolarMass = 272.38 g/mol [44] => | Appearance = [45] => | Density = [46] => | MeltingPt = [47] => | BoilingPt = [48] => | Solubility = [49] => | MagSus = -186.6·10−6 cm3/mol [50] => }} [51] => | Section3 = {{Chembox Hazards [52] => | MainHazards = [53] => | FlashPt = [54] => | AutoignitionPt = [55] => }} [56] => | Section6 = {{Chembox Pharmacology [57] => | ATCvet = [58] => | ATCCode_prefix = G03 [59] => | ATCCode_suffix = CA03 [60] => | ATC_Supplemental = [61] => | Licence_EU=yes [62] => | AdminRoutes = [[Oral administration|Oral]], [[sublingual administration|sublingual]], [[intranasal administration|intranasal]], [[topical medication|topical]]/[[transdermal]], [[intravaginal administration|vaginal]], [[intramuscular injection|intramuscular]] or [[subcutaneous injection|subcutaneous]] (as an [[estradiol ester|ester]]), [[subdermal implant]] [63] => | Bioavail = Oral: <5% [64] => | Excretion = [[Urine]]: 54%
[[Feces]]: 6% [65] => | HalfLife = Oral: 13–20 hours
Sublingual: 8–18 hours
Topical (gel): 36.5 hours [66] => | Metabolism = [[Liver]] (via [[hydroxylation]], [[sulfation]], [[glucuronidation]]) [67] => | ProteinBound = ~98%:
• [[Human serum albumin|Albumin]]: 60%
• {{abbr|SHBG|sex hormone-binding globulin}}: 38%
• Free: 2% [68] => }} [69] => }} [70] => [71] => '''Estradiol''' ('''E2'''), also spelled '''oestradiol''', is an [[estrogen]] [[steroid hormone]] and the major [[female]] [[sex hormone]]. It is involved in the regulation of female [[reproductive cycle]]s such as [[estrous cycle|estrous]] and [[menstrual cycle]]s. Estradiol is responsible for the development of female [[secondary sexual characteristic]]s such as the [[breast]]s, [[widening of the hips]] and a [[gynoid fat distribution|female pattern of fat distribution]]. It is also important in the development and maintenance of female [[reproductive organ|reproductive tissue]]s such as the [[mammary gland]]s, [[uterus]] and [[vagina]] during [[puberty]], [[adulthood]] and [[pregnancy]]. It also has important effects in many other [[tissue (biology)|tissue]]s including [[bone]], [[fat]], [[skin]], [[liver]], and the [[brain]]. [72] => [73] => Though estradiol levels in males are much lower than in females, estradiol has important roles in males as well. Apart from humans and other [[mammal]]s, estradiol is also found in most [[vertebrate]]s and [[crustacean]]s, [[insect]]s, [[fish]], and other [[animal]] [[species]]. [74] => [75] => Estradiol is produced especially within the [[ovarian follicle|follicles]] of the [[ovary|ovaries]], but also in other tissues including the [[testicle]]s, the [[adrenal gland]]s, fat, [[liver]], the breasts, and the brain. Estradiol is [[biosynthesis|produced in the body]] from [[cholesterol]] through a series of [[chemical reaction|reaction]]s and [[chemical intermediate|intermediate]]s.Saldanha, Colin J., Luke Remage-Healey, and Barney A. Schlinger. "Synaptocrine signaling: steroid synthesis and action at the synapse." Endocrine reviews 32.4 (2011): 532–549. The major [[metabolic pathway|pathway]] involves the formation of [[androstenedione]], which is then converted by [[aromatase]] into [[estrone]] and is subsequently converted into estradiol. Alternatively, androstenedione can be converted into [[testosterone]], which can then be converted into estradiol. Upon [[menopause]] in females, production of estrogens by the ovaries stops and estradiol levels decrease to very low levels. [76] => [77] => In addition to its role as a natural hormone, estradiol is used as a [[medication]], for instance in [[menopausal hormone therapy]] and [[feminizing hormone therapy]] for [[Trans woman|transgender women]]; for information on estradiol as a medication, see the [[estradiol (medication)]] article. [78] => [79] => {{TOC limit|3}} [80] => [81] => ==Biological function== [82] => [83] => ===Sexual development=== [84] => {{See also|Breast development#Biochemistry}} [85] => [86] => The development of [[secondary sex characteristics]] in women is driven by estrogens, to be specific, estradiol. These changes are initiated at the time of [[puberty]], most are enhanced during the reproductive years, and become less pronounced with declining estradiol support after [[menopause]]. Thus, estradiol produces [[breast development]], and is responsible for changes in the [[body shape]], affecting bones, joints, and [[fat deposition]]. In females, estradiol induces breast development, [[widening of the hips]], a [[gynoid fat distribution|feminine fat distribution]] (with fat deposited particularly in the breasts, hips, thighs, and buttocks), and maturation of the [[vagina]] and [[vulva]], whereas it mediates the [[pubertal growth spurt]] (indirectly via increased [[growth hormone]] secretion) and [[epiphyseal closure]] (thereby limiting [[human height|final height]]) in both sexes. [87] => [88] => ===Reproduction=== [89] => [90] => ====Female reproductive system==== [91] => In the female, estradiol acts as a growth hormone for tissue of the reproductive organs, supporting the lining of the [[vagina]], the cervical glands, the [[endometrium]], and the lining of the fallopian tubes. It enhances growth of the [[myometrium]]. Estradiol appears necessary to maintain [[oocyte]]s in the [[ovary]]. During the [[menstrual cycle]], estradiol produced by the growing follicles triggers, via a positive feedback system, the hypothalamic-pituitary events that lead to the [[luteinizing hormone]] surge, inducing ovulation. In the luteal phase, estradiol, in conjunction with [[progesterone]], prepares the endometrium for [[Implantation (human embryo)|implantation]]. During [[pregnancy]], estradiol increases due to [[placenta]]l production. The effect of estradiol, together with [[estrone]] and [[estriol]], in [[pregnancy]] is less clear. They may promote uterine blood flow, myometrial growth, stimulate breast growth and at term, promote cervical softening and expression of myometrial [[oxytocin]] receptors.{{citation needed|date=February 2013}} In baboons, blocking of estrogen production leads to pregnancy loss, suggesting estradiol has a role in the maintenance of pregnancy. Research is investigating the role of estrogens in the process of initiation of [[Childbirth|labor]]. Actions of estradiol are required before the exposure of progesterone in the luteal phase.{{citation needed|date=February 2013}} [92] => [93] => ====Male reproductive system==== [94] => The effect of estradiol (and estrogens in general) upon male reproduction is complex. Estradiol is produced by action of [[aromatase]] mainly in the [[Leydig cell]]s of the [[mammal]]ian [[testicle|testis]], but also by some [[germ cell]]s and the [[Sertoli cell]]s of immature mammals.{{cite journal | vauthors = Carreau S, Lambard S, Delalande C, Denis-Galeraud I, Bilinska B, Bourguiba S | title = Aromatase expression and role of estrogens in male gonad : a review | journal = Reproductive Biology and Endocrinology | volume = 1 | pages = 35 | date = April 2003 | pmid = 12747806 | pmc = 155680 | doi = 10.1186/1477-7827-1-35 | doi-access = free }} It functions (''[[in vitro]]'') to prevent [[apoptosis]] of male [[sperm]] cells.{{cite journal | vauthors = Pentikäinen V, Erkkilä K, Suomalainen L, Parvinen M, Dunkel L | title = Estradiol acts as a germ cell survival factor in the human testis in vitro | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 85 | issue = 5 | pages = 2057–67 | date = May 2000 | pmid = 10843196 | doi = 10.1210/jcem.85.5.6600 | doi-access = free }} [95] => While some studies in the early 1990s claimed a connection between globally declining [[sperm count]]s and estrogen exposure in the environment,{{cite journal | vauthors = Sharpe RM, Skakkebaek NE | title = Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? | journal = Lancet | volume = 341 | issue = 8857 | pages = 1392–5 | date = May 1993 | pmid = 8098802 | doi = 10.1016/0140-6736(93)90953-E | s2cid = 33135527 }} later studies found no such connection, nor evidence of a general decline in sperm counts.{{cite journal | vauthors = Handelsman DJ | title = Estrogens and falling sperm counts | journal = Reproduction, Fertility, and Development | volume = 13 | issue = 4 | pages = 317–24 | date = 2001 | pmid = 11800170 | doi=10.1071/rd00103}}{{cite journal |vauthors=Fisch H, Goldstedin R |title=Environmental estrogens and sperm counts |journal=Pure and Applied Chemistry |date=2003 |volume=75 |issue=11–12 |pages=2181–2193 |url=http://pac.iupac.org/publications/pac/pdf/2003/pdf/7511x2181.pdf |doi=10.1351/pac200375112181 |s2cid=11068097 |access-date=29 December 2015 |archive-date=4 March 2016 |archive-url=https://web.archive.org/web/20160304102628/http://pac.iupac.org/publications/pac/pdf/2003/pdf/7511x2181.pdf |url-status=dead }} [96] => Suppression of estradiol production in a subpopulation of subfertile men may improve the [[semen]] analysis.{{cite journal | vauthors = Raman JD, Schlegel PN | title = Aromatase inhibitors for male infertility | journal = The Journal of Urology | volume = 167 | issue = 2 Pt 1 | pages = 624–9 | date = February 2002 | pmid = 11792932 | doi = 10.1016/S0022-5347(01)69099-2 }} [97] => [98] => Males with certain [[sex chromosome]] [[genetic condition]]s, such as [[Klinefelter's syndrome]], will have a higher level of estradiol.{{cite journal | vauthors = Visootsak J, Graham JM | title = Klinefelter syndrome and other sex chromosomal aneuploidies | journal = Orphanet Journal of Rare Diseases | volume = 1 | issue = 42 | pages = 42 | date = October 2006 | pmid = 17062147 | pmc = 1634840 | doi = 10.1186/1750-1172-1-42 | doi-access = free }} [99] => [100] => ===Skeletal system=== [101] => Estradiol has a profound effect on bone. Individuals without it (or other estrogens) will become tall and [[eunuch]]oid, as [[epiphyseal]] closure is delayed or may not take place.{{cite journal | vauthors = Vanderschueren D, Laurent MR, Claessens F, Gielen E, Lagerquist MK, Vandenput L, Börjesson AE, Ohlsson C | display-authors = 6 | title = Sex steroid actions in male bone | journal = Endocrine Reviews | volume = 35 | issue = 6 | pages = 906–60 | date = December 2014 | pmid = 25202834 | pmc = 4234776 | doi = 10.1210/er.2014-1024 }} [[Bone density]] is also affected, resulting in early [[osteopenia]] and [[osteoporosis]].{{cite journal | vauthors = Carani C, Qin K, Simoni M, Faustini-Fustini M, Serpente S, Boyd J, Korach KS, Simpson ER | display-authors = 6 | title = Effect of testosterone and estradiol in a man with aromatase deficiency | journal = The New England Journal of Medicine | volume = 337 | issue = 2 | pages = 91–5 | date = July 1997 | pmid = 9211678 | doi = 10.1056/NEJM199707103370204 | doi-access = free }} Low levels of estradiol may also predict fractures, with post-menopausal women having the highest incidence of [[bone fracture]].{{cite journal | vauthors = Bergh C, Wennergren D, Möller M, Brisby H | title = Fracture incidence in adults in relation to age and gender: A study of 27,169 fractures in the Swedish Fracture Register in a well-defined catchment area | journal = PLOS ONE | volume = 15 | issue = 12 | pages = e0244291 | date = 2020-12-21 | pmid = 33347485 | pmc = 7751975 | doi = 10.1371/journal.pone.0244291 | bibcode = 2020PLoSO..1544291B | doi-access = free }} Women past menopause experience an accelerated loss of bone mass due to a relative estrogen deficiency.{{cite journal| vauthors = Albright F, Smith PH, Richardson AM |title=Postmenopausal Osteoporosis: Its Clinical Features|journal=[[JAMA (journal)|JAMA]]|author-link1 = Fuller Albright|date=31 May 1941 |volume=116 |issue=22 |pages=2465–2474 |doi=10.1001/jama.1941.02820220007002 }} [102] => [103] => ===Skin health=== [104] => The [[estrogen receptor]], as well as the [[progesterone receptor]], have been detected in the [[human skin|skin]], including in [[keratinocyte]]s and [[fibroblast]]s.{{cite journal | vauthors = Raine-Fenning NJ, Brincat MP, Muscat-Baron Y | title = Skin aging and menopause : implications for treatment | journal = American Journal of Clinical Dermatology | volume = 4 | issue = 6 | pages = 371–8 | year = 2003 | pmid = 12762829 | doi = 10.2165/00128071-200304060-00001 | s2cid = 20392538 }}{{cite journal | vauthors = Holzer G, Riegler E, Hönigsmann H, Farokhnia S, Schmidt JB, Schmidt B | s2cid = 6077829 | title = Effects and side-effects of 2% progesterone cream on the skin of peri- and postmenopausal women: results from a double-blind, vehicle-controlled, randomized study | journal = The British Journal of Dermatology | volume = 153 | issue = 3 | pages = 626–34 | date = September 2005 | pmid = 16120154 | doi = 10.1111/j.1365-2133.2005.06685.x }} At [[menopause]] and thereafter, decreased levels of female [[sex hormone]]s result in [[atrophy]], thinning, and increased [[wrinkling]] of the skin and a reduction in skin [[elasticity (physics)|elasticity]], firmness, and strength. These skin changes constitute an acceleration in [[Human skin#Aging|skin aging]] and are the result of decreased [[collagen]] content, irregularities in the [[morphology (biology)|morphology]] of [[epidermis (skin)|epidermal]] [[skin cell]]s, decreased [[ground substance]] between [[skin fiber]]s, and reduced [[capillary|capillaries]] and [[blood flow]]. The skin also becomes more [[dry skin|dry]] during menopause, which is due to reduced skin [[tissue hydration|hydration]] and [[sebum|surface lipids]] (sebum production). Along with chronological aging and photoaging, estrogen deficiency in menopause is one of the three main factors that predominantly influences skin aging. [105] => [106] => [[Hormone replacement therapy]] consisting of systemic treatment with estrogen alone or in combination with a progestogen, has well-documented and considerable beneficial effects on the skin of postmenopausal women. These benefits include increased skin collagen content, skin thickness and elasticity, and skin hydration and surface lipids. Topical estrogen has been found to have similar beneficial effects on the skin. In addition, a study has found that topical 2% progesterone cream significantly increases skin elasticity and firmness and observably decreases wrinkles in peri- and postmenopausal women. Skin hydration and surface lipids, on the other hand, did not significantly change with topical progesterone. These findings suggest that progesterone, like estrogen, also has beneficial effects on the skin, and may be independently protective against skin aging. [107] => [108] => ===Nervous system=== [109] => {{further|Hypothalamic–pituitary–gonadal axis}} [110] => [111] => Estrogens can be produced in the [[brain]] from steroid precursors. As [[antioxidants]], they have been found to have [[neuroprotective]] function.{{cite journal | vauthors = Behl C, Widmann M, Trapp T, Holsboer F | title = 17-beta estradiol protects neurons from oxidative stress-induced cell death in vitro | journal = Biochemical and Biophysical Research Communications | volume = 216 | issue = 2 | pages = 473–82 | date = November 1995 | pmid = 7488136 | doi = 10.1006/bbrc.1995.2647 }} [112] => [113] => The positive and negative [[feedback loop]]s of the [[menstrual cycle]] involve ovarian estradiol as the link to the hypothalamic-pituitary system to regulate [[gonadotropin]]s.{{cite journal | vauthors = Meethal SV, Liu T, Chan HW, Ginsburg E, Wilson AC, Gray DN, Bowen RL, Vonderhaar BK, Atwood CS | title = Identification of a regulatory loop for the synthesis of neurosteroids: a steroidogenic acute regulatory protein-dependent mechanism involving hypothalamic-pituitary-gonadal axis receptors | journal = Journal of Neurochemistry | volume = 110 | issue = 3 | pages = 1014–27 | date = August 2009 | pmid = 19493163 | pmc = 2789665 | doi = 10.1111/j.1471-4159.2009.06192.x }} [114] => [115] => Estrogen is considered to play a significant role in women's mental health, with links suggested between the hormone level, mood and well-being. Sudden drops or fluctuations in, or long periods of sustained low levels of estrogen may be correlated with significant mood-lowering. Clinical recovery from depression postpartum, perimenopause, and postmenopause was shown to be effective after levels of estrogen were stabilized and/or restored.{{cite journal | vauthors = Douma SL, Husband C, O'Donnell ME, Barwin BN, Woodend AK | title = Estrogen-related mood disorders: reproductive life cycle factors | journal = Advances in Nursing Science | volume = 28 | issue = 4 | pages = 364–75 | year = 2005 | pmid = 16292022 | doi = 10.1097/00012272-200510000-00008 | s2cid = 9172877 }}{{cite journal | vauthors = Lasiuk GC, Hegadoren KM | title = The effects of estradiol on central serotonergic systems and its relationship to mood in women | journal = Biological Research for Nursing | volume = 9 | issue = 2 | pages = 147–60 | date = October 2007 | pmid = 17909167 | doi = 10.1177/1099800407305600 | s2cid = 37965502 }} [116] => [117] => The volumes of [[sexual dimorphism|sexually dimorphic]] brain structures in [[transgender women]] were found to change and approximate typical female brain structures when exposed to estrogen concomitantly with androgen deprivation over a period of months,{{cite journal | vauthors = Hulshoff HE, Cohen-Kettenis PT, Van Haren NE, Peper JS, Brans RG, Cahn W, Schnack HG, Gooren LJ, Kahn RS | date = July 2006 | title = Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure | journal = European Journal of Endocrinology | volume = 155 | issue = suppl_1 | pages = 107–114 | doi = 10.1530/eje.1.02248 | doi-access = free }} suggesting that estrogen and/or androgens have a significant part to play in sex differentiation of the brain, both [[prenatal]]ly and later in life. [118] => [119] => There is also evidence the programming of adult male sexual behavior in many vertebrates is largely dependent on estradiol produced during prenatal life and early infancy.{{cite journal | vauthors = Harding CF | title = Hormonal modulation of singing: hormonal modulation of the songbird brain and singing behavior | journal = Annals of the New York Academy of Sciences | volume = 1016 | pages = 524–39 | date = June 2004 | issue = 1 | pmid = 15313793 | doi = 10.1196/annals.1298.030 | bibcode = 2004NYASA1016..524H | s2cid = 12457330 | url = http://www.annalsnyas.org/content/vol1016/issue1/index.dtl | archive-url = https://web.archive.org/web/20070927225947/http://www.annalsnyas.org/content/vol1016/issue1/index.dtl | url-status = dead | archive-date = 27 September 2007 }} It is not yet known whether this process plays a significant role in human sexual behavior, although evidence from other mammals tends to indicate a connection.{{cite journal | vauthors = Simerly RB | title = Wired for reproduction: organization and development of sexually dimorphic circuits in the mammalian forebrain | journal = Annual Review of Neuroscience | volume = 25 | pages = 507–36 | date = 27 March 2002 | pmid = 12052919 | doi = 10.1146/annurev.neuro.25.112701.142745 | url = http://www.healthsystem.virginia.edu/internet/neuroscience/BehavioralNeuroscience/Simerley-EFR-1-4.pdf | access-date = 7 March 2007 | archive-date = 1 October 2008 | archive-url = https://web.archive.org/web/20081001223447/http://www.healthsystem.virginia.edu/internet/neuroscience/BehavioralNeuroscience/Simerley-EFR-1-4.pdf | url-status = dead }} [120] => [121] => Estrogen has been found to increase the [[secretion]] of oxytocin and to increase the [[gene expression|expression]] of its [[receptor (biochemistry)|receptor]], the [[oxytocin receptor]], in the [[brain]].{{cite book | vauthors = Goldstein I, Meston CM, Davis S, Traish A | title = Women's Sexual Function and Dysfunction: Study, Diagnosis and Treatment|url=https://books.google.com/books?id=3J7TnwpbZQwC&pg=PA205|date=17 November 2005|publisher=CRC Press|isbn=978-1-84214-263-9|pages=205–}} In women, a single dose of estradiol has been found to be sufficient to increase circulating oxytocin concentrations.{{cite journal | vauthors = Acevedo-Rodriguez A, Mani SK, Handa RJ | title = Oxytocin and Estrogen Receptor β in the Brain: An Overview | journal = Frontiers in Endocrinology | volume = 6 | pages = 160 | year = 2015 | pmid = 26528239 | pmc = 4606117 | doi = 10.3389/fendo.2015.00160 | doi-access = free }} [122] => [123] => ===Gynecological cancers=== [124] => Estradiol has been tied to the development and progression of cancers such as breast cancer, ovarian cancer and endometrial cancer. Estradiol affects target tissues mainly by interacting with two [[nuclear receptor]]s called [[estrogen receptor α]] (ERα) and [[estrogen receptor β]] (ERβ).{{cite journal | vauthors = Bulzomi P, Bolli A, Galluzzo P, Leone S, Acconcia F, Marino M | title = Naringenin and 17beta-estradiol coadministration prevents hormone-induced human cancer cell growth | journal = IUBMB Life | volume = 62 | issue = 1 | pages = 51–60 | date = January 2010 | pmid = 19960539 | doi = 10.1002/iub.279 | s2cid = 7903757 | doi-access = free }}{{cite journal | vauthors = Sreeja S, Santhosh Kumar TR, Lakshmi BS, Sreeja S | title = Pomegranate extract demonstrate a selective estrogen receptor modulator profile in human tumor cell lines and in vivo models of estrogen deprivation | journal = The Journal of Nutritional Biochemistry | volume = 23 | issue = 7 | pages = 725–32 | date = July 2012 | pmid = 21839626 | doi = 10.1016/j.jnutbio.2011.03.015 }} One of the functions of these estrogen receptors is the modulation of [[gene expression]]. Once estradiol binds to the ERs, the receptor complexes then bind to specific [[DNA sequences]], possibly causing damage to the DNA and an increase in cell division and [[DNA replication]]. [[Eukaryotic cell]]s respond to damaged DNA by stimulating or impairing G1, S, or G2 phases of the cell cycle to initiate [[DNA repair]]. As a result, cellular transformation and cancer cell proliferation occurs.{{cite journal | vauthors = Thomas CG, Strom A, Lindberg K, Gustafsson JA | title = Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G₂/M checkpoint signaling | journal = Breast Cancer Research and Treatment | volume = 127 | issue = 2 | pages = 417–27 | date = June 2011 | pmid = 20623183 | doi = 10.1007/s10549-010-1011-z | s2cid = 6752694 }} [125] => [126] => ===Cardiovascular system=== [127] => Estrogen affects certain [[blood vessel]]s. Improvement in arterial blood flow has been demonstrated in [[coronary artery|coronary arteries]].{{cite journal | vauthors = Collins P, Rosano GM, Sarrel PM, Ulrich L, Adamopoulos S, Beale CM, McNeill JG, Poole-Wilson PA | title = 17 beta-Estradiol attenuates acetylcholine-induced coronary arterial constriction in women but not men with coronary heart disease | journal = Circulation | volume = 92 | issue = 1 | pages = 24–30 | date = July 1995 | pmid = 7788912 | doi = 10.1161/01.CIR.92.1.24 }} 17-beta-estradiol (E2) is considered the most potent estrogen found in humans. E2 influences vascular function, apoptosis, and damage during cardiac ischemia and reperfusion. E2 can protect the heart and individual cardiac myocytes from injuries related to ischemia. After a heart attack or long periods of hypertension, E2 inhibits the adverse effects of pathologic remodeling of the heart.{{cite journal |last1=Knowlton |first1=A.A. |last2=Lee |first2=A.R. |title=Estrogen and the cardiovascular system |journal=Pharmacology & Therapeutics |date=July 2012 |volume=135 |issue=1 |pages=54–70 |doi=10.1016/j.pharmthera.2012.03.007 |pmid=22484805 |pmc=5688223 }} [128] => [129] => During [[pregnancy]], high levels of estrogens, namely estradiol, increase [[coagulation]] and the risk of [[venous thromboembolism]]. [130] => [131] => {{Venous thromboembolism incidence during pregnancy and the postpartum period}} [132] => [133] => ===Other functions=== [134] => Estradiol has complex effects on the [[liver]]. It affects the production of multiple [[protein]]s, including [[lipoprotein]]s, binding proteins, and proteins responsible for [[blood clotting]].{{citation needed|date=February 2013}} In high amounts, estradiol can lead to [[cholestasis]], for instance [[intrahepatic cholestasis of pregnancy|cholestasis of pregnancy]]. [135] => [136] => Certain gynecological conditions are dependent on estrogen, such as [[endometriosis]], [[leiomyoma]]ta uteri, and [[uterine bleeding]].{{Citation needed|date=February 2013}} [137] => [138] => ==Biological activity== [139] => {{See also|Pharmacodynamics of estradiol#Mechanism of action}} [140] => [141] => Estradiol acts primarily as an [[agonist]] of the [[estrogen receptor]] (ER), a [[nuclear receptor|nuclear]] [[steroid hormone receptor]]. There are two subtypes of the ER, [[estrogen receptor alpha|ERα]] and [[estrogen receptor beta|ERβ]], and estradiol potently binds to and activates both of these receptors. The result of ER activation is a modulation of [[gene transcription]] and [[gene expression|expression]] in ER-expressing [[Cell (biology)|cell]]s, which is the predominant mechanism by which estradiol mediates its biological effects in the body. Estradiol also acts as an agonist of [[membrane estrogen receptor]]s (mERs), such as [[GPER]] (GPR30), a recently discovered non-nuclear receptor for estradiol, via which it can mediate a variety of rapid, non-[[genomic]] effects.{{cite journal | vauthors = Prossnitz ER, Barton M | title = Estrogen biology: new insights into GPER function and clinical opportunities | journal = Molecular and Cellular Endocrinology | volume = 389 | issue = 1–2 | pages = 71–83 | date = May 2014 | pmid = 24530924 | pmc = 4040308 | doi = 10.1016/j.mce.2014.02.002 }} Unlike the case of the ER, GPER appears to be [[binding selectivity|selective]] for estradiol, and shows very low [[affinity (pharmacology)|affinities]] for other endogenous estrogens, such as estrone and [[estriol]].{{cite journal | vauthors = Prossnitz ER, Arterburn JB, Sklar LA | title = GPR30: A G protein-coupled receptor for estrogen | journal = Mol. Cell. Endocrinol. | volume = 265–266 | pages = 138–42 | year = 2007 | pmid = 17222505 | pmc = 1847610 | doi = 10.1016/j.mce.2006.12.010 }} Additional mERs besides GPER include [[ER-X]], [[ERx]], and [[Gq-mER|Gq-mER]].{{cite journal | vauthors = Soltysik K, Czekaj P | title = Membrane estrogen receptors - is it an alternative way of estrogen action? | journal = Journal of Physiology and Pharmacology | volume = 64 | issue = 2 | pages = 129–42 | date = April 2013 | pmid = 23756388 }}{{cite journal | vauthors = Micevych PE, Kelly MJ | title = Membrane estrogen receptor regulation of hypothalamic function | journal = Neuroendocrinology | volume = 96 | issue = 2 | pages = 103–10 | year = 2012 | pmid = 22538318 | pmc = 3496782 | doi = 10.1159/000338400 }} [142] => [143] => ERα/ERβ are in inactive state trapped in multimolecular chaperone complexes organized around the heat shock protein 90 (HSP90), containing p23 protein, and immunophilin, and located in majority in cytoplasm and partially in nucleus. In the E2 classical pathway or estrogen classical pathway, estradiol enters the [[cytoplasm]], where it interacts with ERs. Once bound E2, ERs dissociate from the molecular chaperone complexes and become competent to dimerize, migrate to nucleus, and to bind to specific DNA sequences ([[estrogen response element]], ERE), allowing for gene transcription which can take place over hours and days. [144] => [145] => Given by [[subcutaneous injection]] in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol.{{cite book| vauthors = Labhart A |title=Clinical Endocrinology: Theory and Practice|url=https://books.google.com/books?id=DAgJCAAAQBAJ&pg=PA548|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-96158-8|pages=548–}}{{cite book| vauthors = Tucker SB |title=Maternal, Fetal, & Neonatal Physiology: A Clinical Perspective|url=https://books.google.com/books?id=2y6zOSQcn14C&pg=PA43|year=2007|publisher=Elsevier Health Sciences|isbn=978-1-4160-2944-1|pages=43–}}{{cite book| vauthors = Hall JE |title=Guyton and Hall Textbook of Medical Physiology E-Book|url=https://books.google.com/books?id=krLSCQAAQBAJ&pg=PA1043|date=31 May 2015|publisher=Elsevier Health Sciences|isbn=978-0-323-38930-3|pages=1043–}} As such, estradiol is the main estrogen in the body, although the roles of estrone and estriol as estrogens are said not to be negligible. [146] => [147] => {{Selected biological properties of endogenous estrogens in rats}} [148] => [149] => ==Biochemistry== [150] => [[File:Steroidogenesis.svg|thumb|450px|right|Human [[steroidogenesis]], showing estradiol at bottom right.{{cite journal | vauthors = Häggström M, Richfield D | year=2014 |title=Diagram of the pathways of human steroidogenesis|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.005|issn=2002-4436|doi-access=free}}]] [151] => [152] => ===Biosynthesis=== [153] => Estradiol, like other [[steroid hormone]]s, is derived from [[cholesterol]]. After [[side chain]] cleavage and using the Δ5 or the Δ4- pathway, [[androstenedione]] is the key intermediary. A portion of the androstenedione is converted to testosterone, which in turn undergoes conversion to estradiol by aromatase. In an alternative pathway, androstenedione is [[aromaticity|aromatized]] to [[estrone]], which is subsequently converted to estradiol via [[17β-hydroxysteroid dehydrogenase]] (17β-HSD).{{cite book | vauthors = Boron WF, Boulpaep EL |title=Medical Physiology: A Cellular And Molecular Approach |publisher=Elsevier/Saunders |year=2003 |page=1300 |isbn=978-1-4160-2328-9}} [154] => [155] => During the reproductive years, most estradiol in women is produced by the [[granulosa cell]]s of the ovaries by the aromatization of androstenedione (produced in the theca folliculi cells) to estrone, followed by conversion of estrone to estradiol by 17β-HSD. Smaller amounts of estradiol are also produced by the [[adrenal cortex]], and, in men, by the testes.{{medcn|date=February 2019}} [156] => [157] => Estradiol is not produced in the [[gonad]]s only; in particular, [[adipose tissue|fat cells]] produce active precursors to estradiol, and will continue to do so even after menopause.{{Cite book| vauthors = Mutschler E, Schäfer-Korting M | title = Arzneimittelwirkungen|language=de|location=Stuttgart|publisher=Wissenschaftliche Verlagsgesellschaft|year=2001|edition=8|pages=434, 444|isbn=978-3-8047-1763-3}} Estradiol is also produced in the [[brain]] and in [[artery|arterial wall]]s. [158] => [159] => In men, approximately 15 to 25% of circulating estradiol is produced in the [[testicle]]s.{{cite book| vauthors = Melmed S |title=Williams Textbook of Endocrinology|url=https://books.google.com/books?id=YZ8_CwAAQBAJ&pg=PA710|date=1 January 2016|publisher=Elsevier Health Sciences|isbn=978-0-323-29738-7|pages=710–}}{{cite book| vauthors = Marcus R, Feldman D, Dempster DW, Luckey M, Cauley JA |title= Osteoporosis |url= https://books.google.com/books?id=b1FtazykqzMC&pg=PA331 |date=13 June 2013|publisher=Academic Press|isbn=978-0-12-398252-0|pages=331–}} The rest is synthesized via peripheral aromatization of testosterone into estradiol and of androstenedione into estrone (which is then transformed into estradiol via peripheral 17β-HSD). This peripheral aromatization occurs predominantly in [[adipose tissue]], but also occurs in other [[tissue (biology)|tissue]]s such as [[bone]], [[liver]], and the [[brain]]. Approximately 40 to 50 µg of estradiol is produced per day in men. [160] => [161] => ===Distribution=== [162] => In plasma, estradiol is largely bound to SHBG and [[human serum albumin|albumin]]. Only about 2.21% (± 0.04%) of estradiol is free and biologically active. The percentage remains constant throughout the [[menstrual cycle]].{{cite journal | vauthors = Wu CH, Motohashi T, Abdel-Rahman HA, Flickinger GL, Mikhail G | title = Free and protein-bound plasma estradiol-17 beta during the menstrual cycle | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 43 | issue = 2 | pages = 436–45 | date = August 1976 | pmid = 950372 | doi = 10.1210/jcem-43-2-436 }} [163] => [164] => ===Metabolism=== [165] => {{See also|Catechol estrogen|Estrogen conjugate|Hydroxylation of estradiol}} [166] => {{Estradiol metabolism|align=right}} [167] => [168] => Inactivation of estradiol includes conversion to less-active estrogens, such as estrone and estriol. Estriol is the major urinary [[metabolite]].{{Citation needed|date=December 2016}} Estradiol is [[conjugation (biochemistry)|conjugated]] in the [[liver]] to form [[estrogen conjugate]]s like [[estradiol sulfate]], [[estradiol glucuronide]] and, as such, excreted via the [[kidney]]s. Some of the water-soluble conjugates are excreted via the [[bile duct]], and partly reabsorbed after [[hydrolysis]] from the [[gastrointestinal tract|intestinal tract]]. This [[enterohepatic circulation]] contributes to maintaining estradiol levels. [169] => [170] => Estradiol is also metabolized via [[hydroxylation]] into [[catechol estrogen]]s. In the liver, it is non-specifically metabolized by [[CYP1A2]], [[CYP3A4]], and [[CYP2C9]] via 2-hydroxylation into [[2-hydroxyestradiol]], and by [[CYP2C9]], [[CYP2C19]], and [[CYP2C8]] via 17β-hydroxy dehydrogenation into [[estrone]],{{cite journal | vauthors = Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH | title = Role of cytochrome P450 in estradiol metabolism in vitro | journal = Acta Pharmacologica Sinica | volume = 22 | issue = 2 | pages = 148–54 | date = February 2001 | pmid = 11741520 }} with various other [[cytochrome P450]] (CYP) [[enzyme]]s and [[metabolic reaction|metabolic transformation]]s also being involved.{{cite journal | vauthors = Lee AJ, Cai MX, Thomas PE, Conney AH, Zhu BT | title = Characterization of the oxidative metabolites of 17beta-estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms | journal = Endocrinology | volume = 144 | issue = 8 | pages = 3382–98 | date = August 2003 | pmid = 12865317 | doi = 10.1210/en.2003-0192 | doi-access = free }} [171] => [172] => Estradiol is additionally [[conjugation (biochemistry)|conjugated]] with an [[ester]] into [[lipoidal estradiol]] forms like [[estradiol palmitate]] and [[estradiol stearate]] to a certain extent; these esters are stored in [[adipose tissue]] and may act as a very long-lasting reservoir of estradiol.{{cite book| vauthors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens I: Physiology and Mechanisms of Action of Estrogens and Antiestrogens|url=https://books.google.com/books?id=0BfrCAAAQBAJ&pg=PA235|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-58616-3|pages=235–237}}{{cite book| vauthors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen|url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA268|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|pages=268, 271}} [173] => [174] => ===Excretion=== [175] => Estradiol is [[excretion|excreted]] in the form of [[glucuronide]] and [[sulfate]] [[estrogen conjugate]]s in [[urine]]. Following an [[intravenous injection]] of [[radiolabel|labeled]] estradiol in women, almost 90% is excreted in urine and [[feces]] within 4 to 5 days.{{cite book|last1=Dorfman|first1=Ralph I.|title=Radioactive Isotopes in Physiology Diagnostics and Therapy / Künstliche Radioaktive Isotope in Physiologie Diagnostik und Therapie|chapter=Steroid Hormone Metabolism|year=1961|pages=1223–1241|doi=10.1007/978-3-642-49761-2_39|isbn=978-3-642-49477-2}}{{cite journal | vauthors = Sandberg AA, Slaunwhite WR | title = Studies on phenolic steroids in human subjects. II. The metabolic fate and hepato-biliary-enteric circulation of C14-estrone and C14-estradiol in women | journal = J. Clin. Invest. | volume = 36 | issue = 8 | pages = 1266–78 | date = August 1957 | pmid = 13463090 | pmc = 1072719 | doi = 10.1172/JCI103524}} [[Enterohepatic recirculation]] causes a delay in excretion of estradiol. [176] => [177] => ===Levels=== [178] => [[File:Estradiol levels across the normal menstrual cycle in women.png|thumb|right|475px|Estradiol levels across the menstrual cycle in 36 normally cycling, ovulatory women, based on 956 specimens. The horizontal dashed lines are the mean integrated levels for each curve. The vertical dashed line in the center is mid-cycle.]] [179] => [180] => Levels of estradiol in premenopausal women are highly variable throughout the menstrual cycle and reference ranges widely vary from source to source.{{cite book | vauthors = Becker JB, Berkley KJ, Geary N, Hampson E, Herman JP, Young E |author-link5=James P. Herman |title=Sex Differences in the Brain: From Genes to Behavior|url=https://books.google.com/books?id=IeaLXPWsbuAC&pg=PA64|date=4 December 2007|publisher=Oxford University Press|isbn=978-0-19-804255-6|pages=64–|quote=Estradiol levels are minimal during the earliest days of the follicular phase, but increasing concentrations are released into the general circulation as the follicle matures. The highest levels are reached about 24 to 48 hours before the LH peak. In fact, the pre-ovulatory peak in estradiol represents its highest concentration during the entire menstrual cycle. Serum concentrations at this time are typically about 130–200 pg/mL, but concentrations as high as 300–400 pg/mL can be achieved in some women. Following a transient fall in association with ovulation, estradiol secretion is restored by production from the corpus luteum during the luteal phase. Plateau levels of around 100–150 pg/mL (Abraham, 1978; Thorneycroft et al., 1971) are most often seen during the period from −10 to −5 days before the onset of menses. With the regression of the corpus luteum, estradiol levels fall, gradually in some women and precipitously in others, during the last few days of the luteal phase. This ushers in the onset of menses, the sloughing of the endometrium. Serum estradiol during menses is approximately 30–50 pg/mL. (Source.)}} Estradiol levels are minimal and according to most laboratories range from 20 to 80 pg/mL during the early to mid follicular phase (or the first week of the menstrual cycle, also known as menses).{{cite book | vauthors = Strauss JR, Barbieri RL |title=Yen and Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management |url= https://books.google.com/books?id=NudwnhxY8kYC&pg=PA807 |year=2009 |publisher=Elsevier Health Sciences|isbn=978-1-4160-4907-4|pages=807–|quote=In most laboratories, serum estradiol levels range from 20 to 80 pg/mL during the early to midfollicular phase of the menstrual cycle and peak at 200 to 500 pg/mL during the preovulatory surge. During the midluteal phase, serum estradiol levels range from 60 to 200 pg/mL.}} Levels of estradiol gradually increase during this time and through the mid to late follicular phase (or the second week of the menstrual cycle) until the pre-ovulatory phase. At the time of pre-ovulation (a period of about 24 to 48 hours), estradiol levels briefly surge and reach their highest concentrations of any other time during the menstrual cycle. Circulating levels are typically between 130 and 200 pg/mL at this time, but in some women may be as high as 300 to 400 pg/mL, and the upper limit of the reference range of some laboratories are even greater (for instance, 750 pg/mL).{{cite book | vauthors = Jameson JL, De Groot LJ | title=Endocrinology: Adult and Pediatric | url = https://books.google.com/books?id=W4dZ-URK8ZoC&pg=PA2812|date=18 May 2010|publisher=Elsevier Health Sciences|isbn=978-1-4557-1126-0|pages=2812–|quote=Midcycle: 150-750 pg/mL}}{{cite book | vauthors = Hay ID, Wass JA |title=Clinical Endocrine Oncology|url=https://books.google.com/books?id=fGio-5vtqqkC&pg=PA623|date=26 January 2009|publisher=John Wiley & Sons|isbn=978-1-4443-0023-9|pages=623–|quote=Mid-cycle: 110-330 pg/mL}}{{cite book| vauthors = Dons RF |title=Endocrine and Metabolic Testing Manual|url=https://books.google.com/books?id=w8jGxo_xoI4C&pg=SA8-PA8|date=12 July 1994|publisher=CRC Press|isbn=978-0-8493-7657-3|pages=8–|quote=Ovulatory: 200-400 pg/mL}} Following ovulation (or mid-cycle) and during the latter half of the menstrual cycle or the luteal phase, estradiol levels plateau and fluctuate between around 100 and 150 pg/mL during the early and mid luteal phase, and at the time of the late luteal phase, or a few days before menstruation, reach a low of around 40 pg/mL. The mean integrated levels of estradiol during a full menstrual cycle have variously been reported by different sources as 80, 120, and 150 pg/mL.{{cite book | vauthors = Christian C, von Schoultz B| title = Hormone Replacement Therapy: Standardized or Individually Adapted Doses?|url=https://books.google.com/books?id=apU4AfUqSGwC&pg=PA60|date=15 March 1994|publisher=CRC Press|isbn=978-1-85070-545-1|pages=60–|quote=Plasma levels of estradiol range from 40 to 80 pg/ml during the 1st week of the ovarian cycle (early follicular phase) and from 80 to 300 pg/ml during the 2nd week (mid- and late follicular phase including periovulatory peak). Then during the 3rd and 4th weeks, estradiol fluctuates between 100 and 150 pg/ml (early and mid-luteal phase) to 40 pg/ml a few days before menstruation (late luteal phase). The mean integrated estradiol level during a full 28-day normal cycle is around 80 pg/ml.}}{{cite book | vauthors = Notelovitz M, van Keep PA |title=The Climacteric in Perspective: Proceedings of the Fourth International Congress on the Menopause, held at Lake Buena Vista, Florida, October 28 – November 2, 1984|url=https://books.google.com/books?id=VM0hBQAAQBAJ&pg=PA397|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-009-4145-8|pages=397–|quote=[...] following the menopause, circulating estradiol levels decrease from a premenopausal mean of 120 pg/ml to only 13 pg/ml.}}{{cite book | vauthors = Müller EE, MacLeod RM | title = Neuroendocrine Perspectives |url=https://books.google.com/books?id=TUXtBwAAQBAJ&pg=PA121|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-3554-5|pages=121–|quote=[...] [premenopausal] mean [estradiol] concentration of 150 pg/ml [...]}} Although contradictory reports exist, one study found mean integrated estradiol levels of 150 pg/mL in younger women whereas mean integrated levels ranged from 50 to 120 pg/mL in older women. [181] => [182] => During the reproductive years of human females, levels of estradiol are somewhat higher than that of estrone, except during the early follicular phase of the menstrual cycle; thus, estradiol may be considered the predominant estrogen during human female reproductive years in terms of absolute serum levels and estrogenic activity.{{citation needed|date=June 2014}} During pregnancy, estriol becomes the predominant circulating estrogen, and this is the only time at which estetrol occurs in the body, while during menopause, estrone predominates (both based on serum levels).{{citation needed|date=June 2014}} The estradiol produced by male humans, from testosterone, is present at serum levels roughly comparable to those of [[postmenopausal]] women (14–55 versus <35 pg/mL, respectively).{{citation needed|date=June 2014}} It has also been reported that if concentrations of estradiol in a 70-year-old man are compared to those of a 70-year-old woman, levels are approximately 2- to 4-fold higher in the man.{{cite journal | vauthors = Sayed Y, Taxel P | title = The use of estrogen therapy in men | journal = Current Opinion in Pharmacology | volume = 3 | issue = 6 | pages = 650–4 | date = December 2003 | pmid = 14644018 | doi = 10.1016/j.coph.2003.07.004}} [183] => [184] => {| class="wikitable sortable mw-collapsible" style="margin: 1em auto;" [185] => |+ class="nowrap" | Endogenous [[estradiol (medication)|estradiol]]estradiol production rates and plasma [[estrogen (medication)|estrogen]]estrogen levels [186] => |- [187] => ! Group !! {{abbr|E2|Estradiol}} ({{abbr|prod|production rate}}) !! {{abbr|E2|Estradiol}} (levels) !! {{abbr|E1|Estrone}} (levels) !! {{abbr|Ratio|Ratio (E2:E1)}} [188] => |- [189] => | [[Puberty|Pubertal]] girlsa
  [[Tanner scale#Definitions of stages|Tanner stage I]] (childhood)
  [[Tanner scale#Definitions of stages|Tanner stage II]] (ages 8–12)
  [[Tanner scale#Definitions of stages|Tanner stage III]] (ages 10–13)
  [[Tanner scale#Definitions of stages|Tanner stage IV]] (ages 11–14)
  [[Tanner scale#Definitions of stages|Tanner stage V]] (ages 12–15)
    [[Follicular phase|Follicular]] (days 1–14)
    [[Luteal phase|Luteal]] (days 15–28) ||  
?
?
?
?
 
?
? ||  
9 (<9–20) pg/mL
15 (<9–30) pg/mL
27 (<9–60) pg/mL
55 (16–85) pg/mL
 
50 (30–100) pg/mL
130 (70–300) pg/mL ||  
13 (<9–23) pg/mL
18 (10–37) pg/mL
26 (17–58) pg/mL
36 (23–69) pg/mL
 
44 (30–89) pg/mL
75 (39–160) pg/mL ||  
?
?
?
?
 
?
? [190] => |- [191] => | [[Prepuberty|Prepubertal]] boys || ? || 2–8 pg/mL || ? || ? [192] => |- [193] => | [[Premenopause|Premenopausal]] women
  [[Follicular phase|Early follicular phase]] (days 1–4)
  [[Follicular phase|Mid follicular phase]] (days 5–9)
  [[Follicular phase|Late follicular phase]] (days 10–14)
  [[Luteal phase]] (days 15–28)
  [[Oral contraceptive]] ([[anovulation|anovulatory]]) ||  
30–100 µg/day
100–160 µg/day
320–640 µg/day
300 µg/day
? ||  
40–60 pg/mL
60–100 pg/mL
200–400 pg/mL
190 pg/mL
12–50 pg/mL ||  
40–60 pg/mL
?
170–200 pg/mL
100–150 pg/mL
? ||  
0.5–1
?
1–2
1.5
? [194] => |- [195] => | [[Menopause|Postmenopausal]] women || 18 µg/day || 5–20 pg/mL || 30–70 pg/mL || 0.3–0.8 [196] => |- [197] => | [[Pregnancy|Pregnant]] women
  [[First trimester]] (weeks 1–12)
  [[Second trimester]] (weeks 13–26)
  [[Third trimester]] (weeks 27–40) ||  
?
?
? ||  
1,000–5,000 pg/mL
5,000–15,000 pg/mL
10,000–40,000 pg/mL ||  
?
?
? ||  
?
?
? [198] => |- [199] => | Mena || 20–60 µg/day || 27 (20–55) pg/mL || 20–90 pg/mL || 0.4–0.6 [200] => |- class="sortbottom" [201] => | colspan="5" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Footnotes:''' a = Format is "mean value (range)" or just "range". '''Sources:''' {{cite journal | vauthors = Nichols KC, Schenkel L, Benson H | title = 17 beta-estradiol for postmenopausal estrogen replacement therapy | journal = Obstet Gynecol Surv | volume = 39 | issue = 4 | pages = 230–45 | year = 1984 | pmid = 6717863 | doi = 10.1097/00006254-198404000-00022 }}{{cite book|author1=Cynthia C. Chernecky|author2=Barbara J. Berger|title=Laboratory Tests and Diagnostic Procedures – E-Book|url=https://books.google.com/books?id=dWHYcOJK-cgC&pg=PA488|date=31 October 2012|publisher=Elsevier Health Sciences|isbn=978-1-4557-4502-9|pages=488–}}{{cite journal | vauthors = Powers MS, Schenkel L, Darley PE, Good WR, Balestra JC, Place VA | title = Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement | journal = Am. J. Obstet. Gynecol. | volume = 152 | issue = 8 | pages = 1099–106 | date = August 1985 | pmid = 2992279 | doi = 10.1016/0002-9378(85)90569-1 }}{{cite book|author=Kenneth L. Becker|title=Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA1059|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=889, 1059–1060, 2153}}See template. [202] => |} [203] => [204] => ====Measurement==== [205] => In women, serum estradiol is measured in a [[clinical laboratory]] and reflects primarily the activity of the ovaries. The Estradiol blood test measures the amount of estradiol in the blood. It is used to check the function of the ovaries, placenta, adrenal glands. This can detect baseline estrogen in women with [[amenorrhea]] or menstrual dysfunction, and to detect the state of hypoestrogenicity and menopause. Furthermore, estrogen monitoring during fertility therapy assesses follicular growth and is useful in monitoring the treatment. Estrogen-producing tumors will demonstrate persistent high levels of estradiol and other estrogens. In [[precocious puberty]], estradiol levels are inappropriately increased. [206] => [207] => ====Ranges==== [208] => Individual laboratory results should always be interpreted using the ranges provided by the laboratory that performed the test. [209] => [210] => {| class="wikitable" align="left" [211] => |+ [[Reference ranges for blood tests|Reference ranges for serum]] estradiol [212] => |- [213] => ! Patient type [214] => ! Lower limit [215] => ! Upper limit [216] => ! Unit [217] => |- [218] => | rowspan=2| Adult male || 50[http://www.gpnotebook.co.uk/simplepage.cfm?ID=570818627&linkID=24801&cook=yes GPNotebook — reference range (oestradiol)] Retrieved on 27 September 2009 || 200 || pmol/L [219] => |- [220] => | 14 || 55 || pg/mL [221] => |- [222] => | rowspan=4| Adult female ([[Follicular phase|follicular
phase]], day 5) || 70
95% [[prediction interval|PI]] (standard) || 500
95% PI || rowspan=2 | pmol/L [223] => |- [224] => | 110Values taken from day 1 after LH surge in: {{cite journal | vauthors = Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P, Stricker R | title = Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT analyzer | journal = Clinical Chemistry and Laboratory Medicine | volume = 44 | issue = 7 | pages = 883–7 | year = 2006 | pmid = 16776638 | doi = 10.1515/CCLM.2006.160 | s2cid = 524952 }} [https://web.archive.org/web/20110706224350/https://www.dianalabs.ch/documents/ajouts/Hormones.pdf as PDF]
90% [[prediction interval|PI]] (used
in [[:File:Estradiol during menstrual cycle.png|diagram]]) || 220
90% PI [225] => |- [226] => | 19 (95% PI) || 140 (95% PI) || rowspan=2 | pg/mL [227] => |- [228] => | 30 (90% PI) || 60 (90% PI) [229] => |- [230] => | rowspan=2| Adult female ([[preovulatory]]
peak) || 400 || 1500 || pmol/L [231] => |- [232] => | 110 || 410 || pg/mL [233] => |- [234] => | rowspan=2| Adult female
([[luteal phase]]) || 70 || 600 || pmol/L [235] => |- [236] => | 19 || 160 || pg/mL [237] => |- [238] => | rowspan=2| Adult female – free
(not protein bound) || 0.5Total amount multiplied by 0.022 according to 2.2% presented in: {{cite journal | vauthors = Wu CH, Motohashi T, Abdel-Rahman HA, Flickinger GL, Mikhail G | title = Free and protein-bound plasma estradiol-17 beta during the menstrual cycle | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 43 | issue = 2 | pages = 436–45 | date = August 1976 | pmid = 950372 | doi = 10.1210/jcem-43-2-436 }}{{Original research inline|date=June 2014}}{{Original research inline|date=June 2014}} || 9{{Original research inline|date=June 2014}} || pg/mL [239] => |- [240] => | 1.7{{Original research inline|date=June 2014}} || 33{{Original research inline|date=June 2014}} || pmol/L [241] => |- [242] => | rowspan=2| Post-menopausal female || N/A || < 130 || pmol/L [243] => |- [244] => | N/A || < 35 || pg/mL [245] => |- [246] => |} [247] => {{clear}} [248] => [249] => {{Hidden begin|toggle=left|title=Reference ranges for the blood content of estradiol during the menstrual cycle}} [250] => [[File:Estradiol during menstrual cycle.png|thumb|left|upright=4.75|[[Reference ranges for blood tests|Reference ranges for the blood content]] of estradiol during the [[menstrual cycle]] [251] =>
- The ranges denoted '''By biological stage''' may be used in closely monitored menstrual cycles in regard to other markers of its biological progression, with the time scale being compressed or stretched to how much faster or slower, respectively, the cycle progresses compared to an average cycle. [252] =>
- The ranges denoted '''Inter-cycle variability''' are more appropriate to use in unmonitored cycles with only the beginning of menstruation known, but where the woman accurately knows her average cycle lengths and time of ovulation, and that they are somewhat averagely regular, with the time scale being compressed or stretched to how much a woman's average cycle length is shorter or longer, respectively, than the average of the population. [253] =>
- The ranges denoted '''Inter-woman variability''' are more appropriate to use when the average cycle lengths and time of ovulation are unknown, but only the beginning of menstruation is given.{{cite journal|year=2014|title=Reference ranges for estradiol, progesterone, luteinizing hormone and follicle-stimulating hormone during the menstrual cycle|journal=WikiJournal of Medicine|volume=1|issue=1|doi=10.15347/wjm/2014.001|issn=2002-4436| vauthors = Häggström M |doi-access=free}}]] [254] => {{Hidden end}} [255] => [256] => In the normal menstrual cycle, estradiol levels measure typically <50 pg/mL at menstruation, rise with follicular development (peak: 200 pg/mL), drop briefly at ovulation, and rise again during the luteal phase for a second peak. At the end of the luteal phase, estradiol levels drop to their menstrual levels unless there is a pregnancy. [257] => [258] => During pregnancy, estrogen levels, including estradiol, rise steadily toward term. The source of these estrogens is the [[placenta]], which aromatizes [[prohormone]]s produced in the fetal adrenal gland. [259] => [260] => {{Production rates, secretion rates, clearance rates, and blood levels of major sex hormones}} [261] => [262] => ==Medical use== [263] => {{Main|Estradiol (medication)|Pharmacodynamics of estradiol|Pharmacokinetics of estradiol}} [264] => [265] => Estradiol is used as a [[medication]], primarily in [[hormone replacement therapy|hormone therapy]] for [[menopause|menopausal]] [[symptom]]s as well as [[feminizing hormone therapy]] for trans individuals. [266] => [267] => ==Chemistry== [268] => {{See also|List of estrogens}} [269] => {{Chemical structures of major endogenous estrogens|align=right|caption=Note the [[hydroxyl group|hydroxyl]] (–OH) [[functional group|group]]s: estrone (E1) has one, estradiol (E2) has two, estriol (E3) has three, and estetrol (E4) has four.}} [270] => [271] => Estradiol is an [[estrane]] [[steroid]].{{cite journal | vauthors = Kuhl H | s2cid = 24616324 | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | issue = 1 Suppl 1 | pages = 3–63 | date = August 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 }} It is also known as 17β-estradiol (to distinguish it from [[17α-estradiol]]) or as estra-1,3,5(10)-triene-3,17β-diol. It has two [[hydroxyl group]]s, one at the C3 position and the other at the 17β position, as well as three [[double bond]]s in the A [[ring (chemistry)|ring]]. Due to its two hydroxyl groups, estradiol is often abbreviated as E2. The structurally related estrogens, estrone (E1), estriol (E3), and [[estetrol]] (E4) have one, three, and four hydroxyl groups, respectively. [272] => [273] => ==Neuropsychopharmacology== [274] => In a randomized, double-blind, placebo-controlled study, estradiol was shown to have gender-specific effects on fairness sensitivity. Overall, when the division of a given amount of money was framed as either fair or unfair in a modified version of the [[ultimatum game]], estradiol increased the acceptance rate of fair-framed proposals among men and decreased it among women. However, among the placebo-group "the mere belief of receiving estradiol treatment significantly increased the acceptance of unfair-framed offers in both sexes", indicating that so-called "environmental" factors played a role in organising the responses towards these presentations of the [[ultimatum game]].{{cite journal | vauthors = Coenjaerts M, Pape F, Santoso V, Grau F, Stoffel-Wagner B, Philipsen A, Schultz J, Hurlemann R, Scheele D |title=Sex differences in economic decision-making: Exogenous estradiol has opposing effects on fairness framing in women and men. |journal=Eur. Neuropsychopharmacol. |volume=50 |issue=2 |pages=46–54 |date= September 2021|pmid=33957337|doi= 10.1016/j.euroneuro.2021.04.006 | issn=0924-977X|s2cid=233982738 |hdl=20.500.11811/11066 |hdl-access=free }} [275] => [276] => ==History== [277] => {{See also|Estrone#History}} [278] => [279] => The discovery of estrogen is usually credited to the [[United States|American]] [[scientist]]s [[Edgar Allen]] and [[Edward Adelbert Doisy|Edward A. Doisy]].{{cite book | vauthors = Loriaux DL, Loriaux L |title=A Biographical History of Endocrinology|url=https://books.google.com/books?id=pkWhCwAAQBAJ&pg=PA345|date=14 March 2016|publisher=John Wiley & Sons|isbn=978-1-119-20246-2|pages=345–}}{{cite book | vauthors = Lauritzen C, Studd JW |title=Current Management of the Menopause|url=https://books.google.com/books?id=WD7S7677xUUC&pg=PA44|date=22 June 2005|publisher=CRC Press|isbn=978-0-203-48612-2|pages=44–}} In 1923, they observed that injection of fluid from [[porcine]] [[ovarian follicle]]s produced [[puberty|pubertal]]- and [[estrus]]-type changes (including [[vagina]]l, [[uterus|uterine]], and [[mammary gland]] changes and [[sexual receptivity]]) in [[sexual maturity|sexually immature]], [[ovariectomy|ovariectomized]] mice and rats.{{cite journal | vauthors = Allen E, Doisy EA | title = An Ovarian Hormone | journal = Journal of the American Medical Association |volume=81 |issue=10 |year=1923 |pages=819 |issn=0002-9955 |doi=10.1001/jama.1923.02650100027012 }} These findings demonstrated the existence of a [[hormone]] which is produced by the [[ovaries]] and is involved in [[sexual maturation]] and [[sexual reproduction|reproduction]]. At the time of its discovery, Allen and Doisy did not name the hormone, and simply referred to it as an "ovarian hormone" or "follicular hormone"; others referred to it variously as ''feminin'', ''folliculin'', ''menformon'', ''thelykinin'', and ''emmenin''.{{cite book | vauthors = Gruhn JG, Kazer RR |title=Hormonal Regulation of the Menstrual Cycle: The Evolution of Concepts|url=https://books.google.com/books?id=lFn0BwAAQBAJ&pg=PA69|date=11 November 2013|publisher=Springer Science & Business Media|isbn=978-1-4899-3496-3|pages=69–73}}{{cite journal| vauthors = Newerla GJ |title=The History of the Discovery and Isolation of the Female Sex Hormones|journal=New England Journal of Medicine|volume=230|issue=20|year=1944|pages=595–604|issn=0028-4793|doi=10.1056/NEJM194405182302001}} In 1926, Parkes and Bellerby coined the term ''estrin'' to describe the hormone on the basis of it inducing estrus in animals.{{cite book | vauthors = Fritz MA, Speroff L |title=Clinical Gynecologic Endocrinology and Infertility|url=https://books.google.com/books?id=KZLubBxJEwEC&pg=PA750|date=28 March 2012|publisher=Lippincott Williams & Wilkins|isbn=978-1-4511-4847-3|pages=750–}} [[Estrone]] was isolated and purified independently by Allen and Doisy and [[Germany|German]] scientist [[Adolf Butenandt]] in 1929, and [[estriol]] was isolated and purified by Marrian in 1930; they were the first estrogens to be identified.{{cite book| vauthors = Parl FF |title=Estrogens, Estrogen Receptor and Breast Cancer|url=https://books.google.com/books?id=v7ai5Mz9TZQC&pg=PA4|year=2000|publisher=IOS Press|isbn=978-0-9673355-4-4|pages=4–}}{{cite book | vauthors = Sartorelli AC, Johns DG |title=Antineoplastic and Immunosuppressive Agents|url=https://books.google.com/books?id=aU_oCAAAQBAJ&pg=PA104|date=27 November 2013|publisher=Springer Science & Business Media|isbn=978-3-642-65806-8|pages=104–}} [280] => [281] => Estradiol, the most potent of the three major estrogens, was the last of the three to be identified. It was discovered by Schwenk and Hildebrant in 1933, who [[chemical synthesis|synthesized]] it via [[redox|reduction]] of estrone. Estradiol was subsequently isolated and purified from sow ovaries by Doisy in 1935, with its [[chemical structure]] determined simultaneously,{{cite book | vauthors = Shoupe D, Haseltine FP |title=Contraception|url=https://books.google.com/books?id=cpDhBwAAQBAJ&pg=PA2|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-2730-4|pages=2–}} and was referred to variously as ''dihydrotheelin'', ''dihydrofolliculin'', ''dihydrofollicular hormone'', and ''dihydroxyestrin''.{{cite journal | vauthors = MacCorquodale DW, Thayer SA, Doisy EA |title=The Crystalline Ovarian Follicular Hormone|journal=Experimental Biology and Medicine|volume=32|issue=7|year=1935|pages=1182|issn=1535-3702|doi=10.3181/00379727-32-8020P|s2cid=83557813}}{{cite book|title=Chemicals Identified in Human Biological Media: A Data Base|url=https://books.google.com/books?id=Gr-0CeNE0Z8C&pg=PA114|year=1981|publisher=Design and Development Branch, Survey and Analysis Division, Office of Program Integration and Information, Office of Pesticides and Toxic Substances, Environmental Protection Agency|pages=114–}} In 1935, the name ''estradiol'' and the term ''estrogen'' were formally established by the Sex Hormone Committee of the Health Organization of the [[League of Nations]]; this followed the names estrone (which was initially called theelin, progynon, folliculin, and ketohydroxyestrin) and estriol (initially called theelol and trihydroxyestrin) having been established in 1932 at the first meeting of the International Conference on the Standardization of Sex Hormones in [[London]].{{cite book| vauthors = Fausto-Sterling A |title=Sexing the Body: Gender Politics and the Construction of Sexuality|url=https://archive.org/details/isbn_9780465077137|url-access=registration|year=2000|publisher=Basic Books|isbn=978-0-465-07714-4|pages=[https://archive.org/details/isbn_9780465077137/page/189 189]–}} Following its discovery, a [[partial synthesis]] of estradiol from [[cholesterol]] was developed by Inhoffen and Hohlweg in 1940, and a [[total synthesis]] was developed by Anner and Miescher in 1948. [282] => [283] => ==Society and culture== [284] => [285] => ===Etymology=== [286] => The name ''estradiol'' derives from ''{{not a typo|estra-}}'', [[Greek language|Gk.]] ''{{lang|grc|οἶστρος}}'' ({{transl|grc|oistros}}, literally meaning "verve or inspiration"),{{cite web|url=https://www.perseus.tufts.edu/hopper/morph?l=oistros&la=greek|title=Greek Word Study Tool: oistros|publisher=[[Perseus Project|Perseus Digital Library]]|access-date=28 December 2011}} which refers to the [[estrane]] [[steroid]] [[ring (chemistry)|ring]] system, and ''{{not a typo|-diol}}'', a chemical term and suffix indicating that the compound is a type of [[Alcohol (chemistry)|alcohol]] bearing two [[hydroxyl]] [[functional group|group]]s. [287] => [288] => == References == [289] => {{reflist|refs= [290] => [291] => {{cite web |url=https://medlineplus.gov/ency/article/003711.htm |title=Estradiol blood test: MedlinePlus Medical Encyclopedia |website=medlineplus.gov |language=en |access-date=2019-05-06}} [292] => [293] => http://www.ilexmedical.com/files/PDF/Estradiol_ARC.pdf {{Bare URL PDF|date=March 2022}} [294] => [295] => {{cite book |author1=Lalit Bajaj |author2=Stephen Berman |title=Berman's Pediatric Decision Making |url=https://books.google.com/books?id=NPhnHrDQ1_kC&pg=PA160 |date=1 January 2011 |publisher=Elsevier Health Sciences |isbn=978-0-323-05405-8 |pages=160–}} [296] => [297] => {{cite book |vauthors=Craig CR, Stitzel RE |title=Modern Pharmacology with Clinical Applications |url=https://books.google.com/books?id=KqA29hQ-m3AC&pg=PA706 |year=2004 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-3762-3 |pages=706–}} [298] => [299] => {{cite book |vauthors=Falcone T, Hurd WW |title=Clinical Reproductive Medicine and Surgery |url=https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA22 |year=2007 |publisher=Elsevier Health Sciences |isbn=978-0-323-03309-1 |pages=22–}} [300] => [301] => {{cite book |vauthors=Ford SR, Roach SS |title=Roach's Introductory Clinical Pharmacology |url=https://books.google.com/books?id=LwOaAgAAQBAJ&pg=PA525 |date=7 October 2013 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4698-3214-2 |pages=525–}} [302] => [303] => {{cite book |vauthors=Hochadel M |title=Mosby's Drug Reference for Health Professions |url=https://books.google.com/books?id=IuF1BwAAQBAJ&pg=PA602 |date=1 April 2015 |publisher=Elsevier Health Sciences |isbn=978-0-323-31103-8 |pages=602–}} [304] => [305] => {{cite journal |vauthors=Kuhl H |title=Östrogene für den Mann? |trans-title=Estrogens for the man? |journal=Blickpunkt der Mann |year=2003 |volume=1 |issue=3 |pages=6–12 |issn=1727-0669 |url=https://www.kup.at/journals/summary/3583.html}} [306] => [307] => {{cite book |vauthors=McMillan JA, Feigin RD, DeAngelis C, Jones MD |title=Oski's Pediatrics: Principles & Practice |url=https://books.google.com/books?id=VbjFQiz8aR0C&pg=PA550 |year=2006 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-3894-1 |pages=550–}} [308] => [309] => {{cite journal |vauthors=Mechoulam R, Brueggemeier RW, Denlinger DL |title=Estrogens in insects |journal=Cellular and Molecular Life Sciences |date=September 1984 |volume=40 |issue=9 |pages=942–944 |doi=10.1007/BF01946450 |s2cid=31950471}} [310] => [311] => {{cite journal |vauthors=Naunton M, Al Hadithy AF, Brouwers JR, Archer DF |title=Estradiol gel: review of the pharmacology, pharmacokinetics, efficacy, and safety in menopausal women |journal=Menopause |volume=13 |issue=3 |pages=517–27 |year=2006 |pmid=16735950 |doi=10.1097/01.gme.0000191881.52175.8c |s2cid=42748448}} [312] => [313] => {{cite book |editor=Idler DR |title=Steroids In Nonmammalian Vertebrates |date=1972 |publisher=Elsevier Science |location=Oxford |isbn=978-0323140980 |vauthors=Ozon R |chapter=Estrogens in Fishes, Amphibians, Reptiles, and Birds |pages=390–414 |chapter-url=https://books.google.com/books?id=Ei46GE-lj2wC&q=estradiol%20vertebrates&pg=PA393}} [314] => [315] => {{cite journal |vauthors=Ryan KJ |title=Biochemistry of aromatase: significance to female reproductive physiology |journal=Cancer Research |volume=42 |issue=8 Suppl |pages=3342s–3344s |date=August 1982 |pmid=7083198}} [316] => [317] => {{cite book |vauthors=Preedy VR |title=Handbook of Growth and Growth Monitoring in Health and Disease |url=https://books.google.com/books?id=9FQXunlUvz0C&pg=PA2661 |date=2 December 2011 |publisher=Springer Science & Business Media |isbn=978-1-4419-1794-2 |pages=2661–}} [318] => [319] => {{cite journal |vauthors=Price TM, Blauer KL, Hansen M, Stanczyk F, Lobo R, Bates GW |title=Single-dose pharmacokinetics of sublingual versus oral administration of micronized 17 beta-estradiol |journal=Obstetrics and Gynecology |volume=89 |issue=3 |pages=340–5 |date=March 1997 |pmid=9052581 |doi=10.1016/S0029-7844(96)00513-3 |s2cid=71641652}} [320] => [321] => {{cite journal |vauthors=Stanczyk FZ, Archer DF, Bhavnani BR |title=Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment |journal=Contraception |volume=87 |issue=6 |pages=706–27 |date=June 2013 |pmid=23375353 |doi=10.1016/j.contraception.2012.12.011}} [322] => [323] => }} [324] => [325] => {{Estradiol}} [326] => {{Hormones}} [327] => {{Endogenous steroids}} [328] => {{Estrogen receptor modulators}} [329] => {{Portal bar | Medicine}} [330] => {{Authority control}} [331] => [332] => [[Category:Estradiol| ]] [333] => [[Category:Secondary alcohols]] [334] => [[Category:Animal reproductive system]] [335] => [[Category:Antigonadotropins]] [336] => [[Category:Antioxidants]] [337] => [[Category:Estranes]] [338] => [[Category:Estrogens]] [339] => [[Category:GPER agonists]] [340] => [[Category:Hepatotoxins]] [341] => [[Category:Hormones of the hypothalamus-pituitary-gonad axis]] [342] => [[Category:Hormones of the hypothalamic-pituitary-prolactin axis]] [343] => [[Category:Hormones of the pregnant female]] [344] => [[Category:Human female endocrine system]] [345] => [[Category:Phenols]] [346] => [[Category:Prolactin releasers]] [347] => [[Category:Sex hormones]] [] => )
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Estradiol

Estradiol is a type of estrogen hormone found in both males and females. It is produced in the ovaries of females and testes of males, as well as in small amounts by the adrenal glands.

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It is produced in the ovaries of females and testes of males, as well as in small amounts by the adrenal glands. Estradiol plays a crucial role in various physiological processes, such as the development of female secondary sexual characteristics, regulation of the menstrual cycle, and maintenance of bone density. In women, estradiol is mainly responsible for the development and maintenance of reproductive tissues, such as the uterus and breasts. It also plays a role in regulating the production of other hormones, such as progesterone. Additionally, estradiol has a significant impact on mood, cognitive function, and the overall sense of well-being. In men, estradiol is essential for maintaining healthy cardiovascular and bone health. It also contributes to sperm production and sexual function. However, an imbalance of estradiol levels in men can lead to various health issues, such as gynecomastia (enlarged breast tissue) and decreased libido. Estradiol can be produced synthetically and is commonly used in hormone replacement therapy for menopausal women to alleviate menopause symptoms and prevent osteoporosis. It is also prescribed to transgender individuals as a part of their hormone therapy to feminize their secondary sexual characteristics. The use of estradiol has been associated with certain risks and side effects, including an increased risk of blood clots, stroke, and certain types of cancer. Therefore, the dosage and administration of estradiol should be carefully monitored by healthcare professionals. Overall, estradiol is a vital hormone that plays a crucial role in the development and function of reproductive and non-reproductive tissues in both males and females. Its regulation and administration are significant in maintaining hormonal balance and overall health.

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