「Estrone」の版間の差分

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{{About|estrone as a hormone|its use as a medication|Estrone (medication)}}
#転送 [[エストロゲン]]
{{Use dmy dates|date=August 2018}}
{{Chembox
<!-- Images -->
| ImageFile = Estron.svg
| ImageClass = skin-invert-image
| ImageSize = 215px
| ImageAlt =
| ImageFile1 = Estrone molecule ball.png
| ImageSize1 = 235px
| ImageAlt1 =
<!-- Names -->
| IUPACName = 3-Hydroxyestra-1,3,5(10)-trien-17-one
| SystematicName = (3a''S'',3b''R'',9b''S'',11a''S'')-7-Hydroxy-11a-methyl-2,3,3a,3b,4,5,9b,10,11,11a-decahydro-1''H''-cyclopenta[''a'']phenanthren-1-one
| OtherNames = Oestrone; E1
<!-- Sections -->
| Section1 = {{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 53-16-7
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17263
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1405
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5660
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00067
| PubChem = 5870
| SMILES = O=C4[C@]3(CC[C@@H]2c1ccc(O)cc1CC[C@H]2[C@@H]3CC4)C
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C18H22O2/c1-18-9-8-14-13-5-3-12(19)10-11(13)2-4-15(14)16(18)6-7-17(18)20/h3,5,10,14-16,19H,2,4,6-9H2,1H3/t14-,15-,16+,18+/m1/s1
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = DNXHEGUUPJUMQT-CBZIJGRNSA-N
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2DI9HA706A
  }}
| Section2 = {{Chembox Properties
| C=18 | H=22 | O=2
| MolarMass = 270.366 g/mol
| Appearance =
| Density =
| MeltingPt = 254.5
| BoilingPt =
| Solubility =
  }}
| Section3 = {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
  }}
}}
 
'''Estrone''' ('''E1'''), also spelled '''oestrone''', is a [[steroid]], a weak [[estrogen]], and a minor female [[sex hormone]].<ref name="pmid16112947">{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | issue = Suppl 1 | pages = 3–63 | date = August 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 }}</ref> It is one of three major [[endogenous]] estrogens, the others being [[estradiol]] and [[estriol]].<ref name="pmid16112947" /> Estrone, as well as the other estrogens, are [[biosynthesis|synthesized]] from [[cholesterol]] and [[secretion|secreted]] mainly from the [[gonad]]s, though they can also be formed from [[adrenal gland|adrenal]] [[androgen]]s in [[adipose tissue]].<ref name="HornsteinSchwerin2012">{{cite book| vauthors = Hornstein T, Schwerin JL |title=Biology of Women|url=https://books.google.com/books?id=ibgKAAAAQBAJ&pg=PA369|date=1 January 2012|publisher=Cengage Learning|isbn=978-1-285-40102-7|pages=369–}}</ref> Relative to estradiol, both estrone and estriol have far weaker activity as estrogens.<ref name="pmid16112947" /> Estrone can be converted into estradiol, and serves mainly as a [[precursor (biochemistry)|precursor]] or [[metabolic intermediate]] of estradiol.<ref name="pmid16112947" /><ref name="KeepUtian2012" /> It is both a precursor and [[metabolite]] of estradiol.<ref name="pmid19766414">{{cite journal | vauthors = Chervenak J | title = Bioidentical hormones for maturing women | journal = Maturitas | volume = 64 | issue = 2 | pages = 86–89 | date = October 2009 | pmid = 19766414 | doi = 10.1016/j.maturitas.2009.08.002 | doi-access = free }}</ref><ref name="pmid16112947" />
 
In addition to its role as a natural hormone, estrone has been used as a [[medication]], for instance in [[menopausal hormone therapy]]; for information on estrone as a medication, see the [[estrone (medication)]] article.
 
==Biological activity==
Estrone is an estrogen, specifically an [[agonist]] of the [[estrogen receptor]]s [[ERα]] and [[ERβ]].<ref name="pmid16112947" /><ref name="pmid16554039">{{cite journal | vauthors = Escande A, Pillon A, Servant N, Cravedi JP, Larrea F, Muhn P, Nicolas JC, Cavaillès V, Balaguer P | display-authors = 6 | title = Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta | journal = Biochemical Pharmacology | volume = 71 | issue = 10 | pages = 1459–1469 | date = May 2006 | pmid = 16554039 | doi = 10.1016/j.bcp.2006.02.002 }}</ref> It is a far less [[potency (pharmacology)|potent]] estrogen than is estradiol, and as such, is a relatively weak estrogen.<ref name="pmid16112947" /><ref name="pmid16554039" /><ref name="pmid12071379">{{cite journal | vauthors = Ruggiero RJ, Likis FE | title = Estrogen: physiology, pharmacology, and formulations for replacement therapy | journal = Journal of Midwifery & Women's Health | volume = 47 | issue = 3 | pages = 130–138 | year = 2002 | pmid = 12071379 | doi = 10.1016/s1526-9523(02)00233-7 }}</ref> Given by [[subcutaneous injection]] in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than [[estriol]].<ref>{{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–}}</ref> According to one study, the [[relative binding affinities]] of estrone for the human ERα and ERβ were 4.0% and 3.5% of those estradiol, respectively, and the [[relative transactivational capacities]] of estrone at the ERα and ERβ were 2.6% and 4.3% of those of estradiol, respectively.<ref name="pmid16554039" /> In accordance, the estrogenic activity of estrone has been reported to be approximately 4% of that of estradiol.<ref name="pmid16112947" /> In addition to its low estrogenic potency, estrone, unlike estradiol and estriol, is not accumulated in estrogen target tissues.<ref name="pmid16112947" /> Because estrone can be [[biotransformation|transformed]] into estradiol, most or all of the estrogenic potency of estrone ''[[in vivo]]'' is actually due to conversion into estradiol.<ref name="pmid16112947" /><ref name="FishmanMartucci1980">{{cite book| vauthors = Fishman J, Martucci CP |chapter=New Concepts of Estrogenic Activity: The Role of Metabolites in the Expression of Hormone Action |pages=43–52|doi=10.1007/978-94-011-7230-1_5| veditors = Pasetto N, Paoletti R, Ambrus JL |title=The Menopause and Postmenopause|isbn=978-94-011-7232-5|year=1980|publisher=Springer }}</ref> As such, estrone is considered to be a [[precursor (biochemistry)|precursor]] or [[prohormone]] of estradiol.<ref name="KeepUtian2012">{{cite book | vauthors = van Keep PA, Utian WH, Vermeulen A |title=The Controversial Climacteric: The workshop moderators' reports presented at the Third International Congress on the Menopause, held in Ostend, Belgium, in June 1981, under the auspices of the International Menopause Society|url=https://books.google.com/books?id=4KVyBgAAQBAJ&pg=PA92|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-7253-0|pages=92}}</ref> In contrast to estradiol and estriol, estrone is not a [[ligand (biochemistry)|ligand]] of the [[G protein-coupled estrogen receptor]] (affinity >10,000&nbsp;nM).<ref name="pmid26023144">{{cite journal | vauthors = Prossnitz ER, Arterburn JB | title = International Union of Basic and Clinical Pharmacology. XCVII. G Protein-Coupled Estrogen Receptor and Its Pharmacologic Modulators | journal = Pharmacological Reviews | volume = 67 | issue = 3 | pages = 505–540 | date = July 2015 | pmid = 26023144 | pmc = 4485017 | doi = 10.1124/pr.114.009712 }}</ref>
 
[[Clinical study|Clinical research]] has confirmed the nature of estrone as a relatively inert precursor of estradiol.<ref name="pmid16112947" /><ref name="pmid2512035">{{cite journal | vauthors = Selby P, McGarrigle HH, Peacock M | title = Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women | journal = Clinical Endocrinology | volume = 30 | issue = 3 | pages = 241–249 | date = March 1989 | pmid = 2512035 | doi = 10.1111/j.1365-2265.1989.tb02232.x | s2cid = 26077537 }}</ref><ref name="pmid2992279">{{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 = American Journal of Obstetrics and Gynecology | volume = 152 | issue = 8 | pages = 1099–1106 | date = August 1985 | pmid = 2992279 | doi = 10.1016/0002-9378(85)90569-1 }}</ref><ref name="pmid6818806">{{cite journal | vauthors = Fåhraeus L, Larsson-Cohn U | title = Oestrogens, gonadotrophins and SHBG during oral and cutaneous administration of oestradiol-17 beta to menopausal women | journal = Acta Endocrinologica | volume = 101 | issue = 4 | pages = 592–596 | date = December 1982 | pmid = 6818806 | doi = 10.1530/acta.0.1010592 }}</ref> With [[oral administration]] of estradiol, the ratio of estradiol levels to estrone levels is about 5&nbsp;times higher on average than under normal [[physiological]] circumstances in [[premenopause|premenopausal]] women and with [[parenteral]] (non-oral) [[route of administration|route]]s of estradiol.<ref name="pmid16112947" /> Oral administration of [[menopausal hormone therapy|menopausal replacement]] dosages of estradiol results in low, [[follicular phase]] levels of estradiol, whereas estrone levels resemble the high levels seen during the [[first trimester]] of [[pregnancy]].<ref name="pmid16112947" /><ref name="pmid16399916">{{cite journal | vauthors = Wright JV | title = Bio-identical steroid hormone replacement: selected observations from 23 years of clinical and laboratory practice | journal = Annals of the New York Academy of Sciences | volume = 1057 | issue = 1 | pages = 506–524 | date = December 2005 | pmid = 16399916 | doi = 10.1196/annals.1356.039 | s2cid = 38877163 | bibcode = 2005NYASA1057..506W }}</ref><ref name="pmid15771561">{{cite journal | vauthors = Friel PN, Hinchcliffe C, Wright JV | title = Hormone replacement with estradiol: conventional oral doses result in excessive exposure to estrone | journal = Alternative Medicine Review | volume = 10 | issue = 1 | pages = 36–41 | date = March 2005 | pmid = 15771561 }}</ref> In spite of markedly elevated levels of estrone with oral estradiol but not with [[transdermal administration|transdermal]] estradiol, clinical studies have shown that dosages of oral and transdermal estradiol achieving similar levels of estradiol possess equivalent and non-significantly different [[potency (pharmacology)|potency]] in terms of measures including suppression of [[luteinizing hormone]] and [[follicle-stimulating hormone]] levels, inhibition of [[bone resorption]], and relief of [[menopausal symptoms]] such as [[hot flash]]es.<ref name="pmid16112947" /><ref name="pmid2512035" /><ref name="pmid2992279"/><ref name="pmid6818806"/><ref name="pmid3080464">{{cite journal | vauthors = De Lignieres B, Basdevant A, Thomas G, Thalabard JC, Mercier-Bodard C, Conard J, Guyene TT, Mairon N, Corvol P, Guy-Grand B | display-authors = 6 | title = Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 62 | issue = 3 | pages = 536–541 | date = March 1986 | pmid = 3080464 | doi = 10.1210/jcem-62-3-536 }}</ref> In addition, estradiol levels were found to correlate with these effects, while estrone levels did not.<ref name="pmid2512035" /><ref name="pmid2992279" /> These findings confirm that estrone has very low estrogenic activity, and also indicate that estrone does not diminish the estrogenic activity of estradiol.<ref name="pmid16112947" /><ref name="pmid2512035" /><ref name="pmid2992279" /><ref name="pmid6818806" /> This contradicts some [[cell-free system|cell-free]] ''[[in vitro|in-vitro]]'' research suggesting that high concentrations of estrone might be able to [[partial agonist|partially]] [[receptor antagonist|antagonize]] the actions of estradiol.<ref name="Pasqualini2008">{{cite book | vauthors = Kloosterboer HJ, Schoonen WG, Verheul HA | veditors = Pasqualini JR  | chapter = Proliferation of Breast Cells by Steroid Hormones and Their Metabolites | chapter-url = https://books.google.com/books?id=VQDLBQAAQBAJ | title = Breast Cancer: Prognosis, Treatment, and Prevention  | date = 11 April 2008 | publisher = CRC Press | isbn = 978-1-4200-5873-4 | pages = 343–366 }}</ref><ref name="pmid6863280">{{cite journal | vauthors = Sasson S, Notides AC | title = Estriol and estrone interaction with the estrogen receptor. II. Estriol and estrone-induced inhibition of the cooperative binding of [3H]estradiol to the estrogen receptor | journal = The Journal of Biological Chemistry | volume = 258 | issue = 13 | pages = 8118–8122 | date = July 1983 | pmid = 6863280 | doi = 10.1016/S0021-9258(20)82036-5 | doi-access = free }}</ref><ref name="pmid26190536">{{cite journal | vauthors = Lundström E, Conner P, Naessén S, Löfgren L, Carlström K, Söderqvist G | title = Estrone - a partial estradiol antagonist in the normal breast | journal = Gynecological Endocrinology | volume = 31 | issue = 9 | pages = 747–749 | date = 2015 | pmid = 26190536 | doi = 10.3109/09513590.2015.1062866 | s2cid = 13617050 }}</ref>
 
{{Selected biological properties of endogenous estrogens in rats}}
 
==Biochemistry==
[[File:Steroidogenesis.svg|thumb|450px|right|Comprehensive overview of [[steroidogenesis]], showing estrone on the lower right among the estrogens.<ref name="HäggströmRichfield2014">{{cite journal| vauthors = Häggström M, Richfield D |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>]]
 
===Biosynthesis===
Estrone is [[biosynthesis|biosynthesized]] from [[cholesterol]]. The principal pathway involves [[androstenedione]] as an [[metabolic intermediate|intermediate]], with androstenedione being [[biotransformation|transformed]] into estrone by the [[enzyme]] [[aromatase]]. This reaction occurs in both the [[gonad]]s and in certain other [[tissue (biology)|tissue]]s, particularly [[adipose tissue]], and estrone is subsequently [[secretion|secreted]] from these tissues.<ref name="HornsteinSchwerin2012" /> In addition to aromatization of androstenedione, estrone is also formed [[reversible reaction|reversibly]] from estradiol by the enzyme [[17β-hydroxysteroid dehydrogenase]] (17β-HSD) in various tissues, including the [[liver]], [[uterus]], and [[mammary gland]].<ref name="pmid16112947" />
 
'''<big>Mechanism of Action:</big>'''
 
The way estrone works is by entering the cells of certain tissues in the body and attaching to nuclear receptors. This interaction then influences how genes are expressed, leading to various physiological responses in the body.<ref>{{Cite journal | vauthors = Kuhl H |title=Pharmacology of estrogens and progestogens: influence of different routes of administration |journal=Climacteric |date=2005 |volume=8 |issue=Suppl 1 |pages=3–63 |doi=10.1080/13697130500148875 |pmid=16112947 |s2cid=24616324 |url=https://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf}}</ref>
 
===Distribution===
Estrone is bound approximately 16% to [[sex hormone-binding globulin]] (SHBG) and 80% to [[human serum albumin|albumin]] in the [[circulatory system|circulation]],<ref name="pmid16112947" /> with the remainder (2.0 to 4.0%) circulating freely or unbound.<ref name="JamesonGroot2010">{{cite book| vauthors = Jameson JL, De Groot LJ  |title=Endocrinology – E-Book: Adult and Pediatric|url=https://books.google.com/books?id=W4dZ-URK8ZoC&pg=PA2813|date=18 May 2010|publisher=Elsevier Health Sciences|isbn=978-1-4557-1126-0|pages=2813–}}</ref> It has about 24% of the relative binding affinity of estradiol for SHBG.<ref name="pmid16112947" /> As such, estrone is relatively poorly bound to SHBG.<ref name="Buchsbaum2012">{{cite book| vauthors = Buchsbaum HJ |title=The Menopause|url=https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA64|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5525-3|pages=62, 64}}</ref>
 
===Metabolism===
Estrone is [[conjugation (biochemistry)|conjugated]] into [[estrogen conjugate]]s such as [[estrone sulfate]] and [[estrone glucuronide]] by [[sulfotransferase]]s and [[glucuronidase]]s, and can also be [[hydroxylation|hydroxylated]] by [[cytochrome P450]] enzymes into [[catechol estrogen]]s such as [[2-hydroxyestrone]] and [[4-hydroxyestrone]] or into [[estriol]].<ref name="pmid16112947" /> Both of these transformations take place predominantly in the [[liver]].<ref name="pmid16112947" /> Estrone can also be reversibly converted into estradiol by 17β-HSD.<ref name="pmid16112947" /> The [[blood half-life]] of estrone is about 10 to 70&nbsp;minutes and is similar to that of estradiol.<ref name="Dorfman1961">{{cite book| vauthors = Dorfman RI |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|publisher=Springer |doi=10.1007/978-3-642-49761-2_39|isbn=978-3-642-49477-2}}</ref>
<ref name="pmid13463090">{{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 = The Journal of Clinical Investigation | volume = 36 | issue = 8 | pages = 1266–1278 | date = August 1957 | pmid = 13463090 | pmc = 1072719 | doi = 10.1172/JCI103524 }}</ref>
{{Estradiol metabolism}}
 
===Excretion===
Estrone is [[excretion|excreted]] in [[urine]] in the form of [[estrogen conjugate]]s such as [[estrone sulfate]].<ref name="pmid16112947" /> Following an intravenous injection of [[radiolabel|labeled]] estrone in women, almost 90% is excreted in urine and [[feces]] within 4 to 5&nbsp;days.<ref name="Dorfman1961" /> [[Enterohepatic recirculation]] causes a delay in excretion of estrone.<ref name="Dorfman1961" />
 
It is one of the three primary types of estrogen and is produced in various parts of the body, including the placenta, ovaries, and peripheral tissues.<ref name="PubChem">{{Cite web |title=Estrogen |url=https://pubchem.ncbi.nlm.nih.gov/compound/5870 | work = PubChem | publisher = U.S. National Library of Medicine }}</ref>
 
===Levels===
{{Production rates, secretion rates, clearance rates, and blood levels of major sex hormones}}'''<big>Toxicity:</big>'''
 
When estrone is used too much or taken in large amounts, it can cause toxicity, leading to symptoms like nausea and vomiting. Estrone should be stored in its original package or container to maintain its quality and effectiveness.<ref name="PubChem" />
 
==Chemistry==
{{See also|List of estrogens}}
{{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.}}
 
Estrone, also known as estra-1,3,5(10)-trien-3-ol-17-one, is a [[natural product|naturally occurring]] [[estrane]] [[steroid]] with [[double bond]]s at the C1, C3, and C5 positions, a [[hydroxyl group]] at the C3 position, and a [[ketone]] [[functional group|group]] at the C17 position. The name ''estrone'' was derived from the chemical terms ''[[estrin (compound)|'''estr'''in]]'' (estra-1,3,5(10)-triene) and ''ket'''one'''''.
 
The [[chemical formula]] of estrone is C<sub>18</sub>H<sub>22</sub>O<sub>2</sub> and its [[molecular weight]] is 270.366&nbsp;g/mol. It is a white, odorless, [[solid]] [[crystalline]] [[powder (substance)|powder]], with a [[melting point]] of 254.5&nbsp;°C (490&nbsp;°F) and a [[specific gravity]] of 1.23.<ref name=science1 /><ref>{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5870&loc=ec_rcs|title=Estrone -PubChem|publisher=National Center for Biotechnology Information|access-date=6 September 2009}}</ref> Estrone is [[combustion|combustible]] at high temperatures, with the products [[carbon monoxide]] (CO) and [[carbon dioxide]] (CO<sub>2</sub>).<ref name=science1>{{cite web|title=Material Safety Data Sheet Estrone|url=http://www.hmdb.ca/system/metabolites/msds/000/000/100/original/HMDB00145.pdf?1358894245|publisher=ScienceLab.com|access-date=21 February 2013}}</ref>
 
==Medical use==
{{Main|Estrone (medication)}}
 
Estrone has been available as an [[injection (medicine)|injected]] estrogen for medical use, for instance in [[hormone therapy]] for [[menopausal symptoms]], but it is now mostly no longer marketed.<ref name="FDA">{{Cite web | url=http://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&varApplNo=003977 | title=Drugs@FDA: FDA Approved Drug Products}}</ref>
 
Estrone, as part of hormone replacement therapy (HRT), is frequently used to treat symptoms caused by estrogen deficiency in peri and post-menopausal women. This therapy aims to enhance overall health and relieve menopausal symptoms related to estrogen imbalance. Additionally, estrone and other estrogens are used to prevent osteoporosis in postmenopausal women who are at high risk of fractures and cannot tolerate alternative medications. Estrogens are absorbed efficiently by the body and subsequently inactivated in the liver, making them effective in HRT and osteoporosis prevention.<ref name="PubChem" />
 
== Contraindications ==
The use of estrone has several [[Contraindication|contraindications]], some examples including: [[hypersensitivity]], history of some cancers, stroke, [[Venous thrombosis|venous thromboembolism]] (VTE), and those currently pregnant or breastfeeding. Estrogens hold a [[boxed warning]] to be used at the lowest effective dose and for the shortest possible treatment period if used alone or with another hormone in the progestogen class.<ref name="Cusi_2022" />
 
=== Breast Cancer ===
Estrone is contraindicated for those that have or are suspected of having [[breast cancer]]. The use of estrogens hold a boxed warning with breast cancer for post-menopausal women as this can increase the risk of developing invasive breast cancer.<ref name="Crandall_2018">{{cite journal | vauthors = Crandall CJ, Hovey KM, Andrews CA, Chlebowski RT, Stefanick ML, Lane DS, Shifren J, Chen C, Kaunitz AM, Cauley JA, Manson JE | display-authors = 6 | title = Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study | journal = Menopause | volume = 25 | issue = 1 | pages = 11–20 | date = January 2018 | pmid = 28816933 | pmc = 5734988 | doi = 10.1097/GME.0000000000000956 }}</ref> Those with breast cancer become at a greater risk of [[Hypercalcaemia|hypercalcemia]] and [[Bone metastasis|bone metastases]] when taking estrogens.<ref>{{cite journal | title = The 2017 hormone therapy position statement of The North American Menopause Society | journal = Menopause | volume = 24 | issue = 7 | pages = 728–753 | date = July 2017 | pmid = 28650869 | doi = 10.1097/GME.0000000000000921 | author1 = The NAMS 2017 Hormone Therapy Position Statement Advisory Panel }}</ref> Post-menopausal women with breast cancer can be seen to develop [[frailty syndrome]] when there are changes in blood hormonal levels, including an increased level of estrone. Estrone, the major type of estrogen produced in post-menopausal women, was seen in greater concentrations from standard levels in those that were categorized as prefrail and in those that classified as frail.<ref>{{cite journal | vauthors = García-Sánchez J, Mafla-España MA, Tejedor-Cabrera C, Avellán-Castillo O, Torregrosa MD, Cauli O | title = Plasma Aromatase Activity Index, Gonadotropins and Estrone Are Associated with Frailty Syndrome in Post-Menopausal Women with Breast Cancer | journal = Current Oncology | volume = 29 | issue = 3 | pages = 1744–1760 | date = March 2022 | pmid = 35323344 | pmc = 8947022 | doi = 10.3390/curroncol29030144 | doi-access = free }}</ref>
 
=== Venous Thromboembolism ===
The risk of VTE is increased in those that use estrogens, those that currently have or have a history with VTE are at a greater risk of reoccurring VTE with the usage of estrogens.<ref name="Crandall_2018" /><ref>{{Cite web |title=Different kinds of oral contraceptive pills in polycystic ovary syndrome: a systematic review and meta-analysis |url=https://academic.oup.com/ejendo/article/189/1/S1/7223903?login=false |access-date=2023-07-31 |website=academic.oup.com}}</ref> The use of estrogens within three weeks postpartum may increase the risk of developing a VTE.<ref name="Drugs and Lactation Database (LactMed®)_2006">{{Citation |title=Contraceptives, Oral, Combined |date=2006 |url=http://www.ncbi.nlm.nih.gov/books/NBK501295/ |work=Drugs and Lactation Database (LactMed®) |access-date=2023-07-31 |place=Bethesda (MD) |publisher=National Institute of Child Health and Human Development |pmid=30000354}}</ref> Risk of developing initial VTE is also increased with familial history, genetic mutations: [[factor V Leiden]] and [[Prothrombin G20210A|prothrombin-G20210A]], and pregnancy-postpartum with the use of estrogens.<ref>{{cite journal | vauthors = van Vlijmen EF, Veeger NJ, Middeldorp S, Hamulyák K, Prins MH, Büller HR, Meijer K | title = Thrombotic risk during oral contraceptive use and pregnancy in women with factor V Leiden or prothrombin mutation: a rational approach to contraception | journal = Blood | volume = 118 | issue = 8 | pages = 2055–61; quiz 2375 | date = August 2011 | pmid = 21659542 | doi = 10.1182/blood-2011-03-345678 | doi-access = free }}</ref>
 
=== Breastfeeding ===
The use of estrogens may affect the ability to breastfeed and can change the composition of breastmilk. Estrogens have been used to suppress lactation which can result in a reduced total duration of lactation and reduced volume or inability to produce breastmilk. Composition of breastmilk produced was also seen to be different resulting in a reduced concentration of proteins in the milk. Babies of mothers that were taking estrogens while breastfeeding were seen to experience slower weight gain.<ref name="Drugs and Lactation Database (LactMed®)_2006" />
 
== Side effects ==
 
=== Common ===
Some common side effects seen with the usage of estrogens include: breast swelling, breast tenderness, vaginal itching, abnormal uterine bleeding, weight gain, hair loss, [[jaundice]], and [[anaphylaxis]].<ref name="Delgado_2023">{{cite book | vauthors = Delgado BJ, Lopez-Ojeda W | chapter = Estrogen |date=2023 | chapter-url= http://www.ncbi.nlm.nih.gov/books/NBK538260/ | title = StatPearls |access-date=2023-07-31 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=30855848 }}</ref>
 
=== Adverse effect ===
Some [[Adverse effect|adverse effects]] seen with the usage of estrogens include: increased risk of venous thromboembolism (VTE), stroke, breast cancer, [[hypertension]], and [[vaginitis]].<ref name="Delgado_2023" /><ref name="Cusi_2022">{{cite journal | vauthors = Cusi K, Isaacs S, Barb D, Basu R, Caprio S, Garvey WT, Kashyap S, Mechanick JI, Mouzaki M, Nadolsky K, Rinella ME, Vos MB, Younossi Z | display-authors = 6 | title = American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD) | journal = Endocrine Practice | volume = 28 | issue = 5 | pages = 528–562 | date = May 2022 | pmid = 35569886 | doi = 10.1016/j.eprac.2022.03.010 | doi-access = free }}</ref>
 
==History==
{{See also|Estrone (medication)#History}}
 
Estrone was the first [[steroid hormone]] to be discovered.<ref name="Bullough1995">{{cite book|vauthors=Bullough VL|title=Science In The Bedroom: A History Of Sex Research|url=https://books.google.com/books?id=Z7__qJK470AC&pg=PA128|date=19 May 1995|publisher=Basic Books|isbn=978-0-465-07259-0|pages=128–|quote=When Allen and Doisy heard about the [Ascheim-Zondek test for the diagnosis of pregnancy], they realized there was a rich and easily handled source of hormones in urine from which they could develop a potent extract. [...] Allen and Doisy's research was sponsored by the committee, while that of their main rival, Adolt Butenandt (b. 1903) of the University of Gottingen was sponsored by a German pharmaceutical firm. In 1929, both terms announced the isolation of a pure crystal female sex hormone, estrone, in 1929, although Doisy and Allen did so two months earlier than Butenandt.27 By 1931, estrone was being commercially produced by Parke Davis in this country, and Schering-Kahlbaum in Germany. Interestingly, when Butenandt (who shared the Nobel Prize for chemistry in 1939) isolated estrone and analyzed its structure, he found that it was a steroid, the first hormone to be classed in this molecular family.}}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}</ref><ref name="NielschFuhrmann2016">{{cite book| vauthors = Nielsch U, Fuhrmann U, Jaroch S |title=New Approaches to Drug Discovery|url=https://books.google.com/books?id=elneCwAAQBAJ&pg=PA7|date=30 March 2016|publisher=Springer|isbn=978-3-319-28914-4|pages=7–|quote=The first steroid hormone was isolated from the urine of pregnant women by Adolf Butenandt in 1929 (estrone; see Fig. 1) (Butenandt 1931).}}</ref> It was discovered in 1929 independently by the [[United States|American]] scientists [[Edward Adelbert Doisy|Edward Doisy]] and [[Edgar Allen]] and the [[Germany|German]] [[biochemist]] [[Adolf Butenandt]], although Doisy and Allen isolated it two months before Butenandt.<ref name="Bullough1995" /><ref name="Parl2000">{{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=4–5|quote=[Doisy] focused his research on the isolation of female sex hormones from hundreds of gallons of human pregnancy urine based on the discovery by Ascheim and Zondeck in 1927 that the urine of pregnant women possessed estrogenic activity [9]. In the summer of 1929, Doisy succeeded in the isolated of estrone (named by him theelin), simultaneously with but independent of Adolf Butenandt of the University of Gottingen in Germany. Doisy presented his results on the crystallization of estrone at the XIII International Physiological Congress in Boston in August 1929 [10].}}</ref><ref name="Laylin1993">{{cite book| vauthors = Laylin JK |title=Nobel Laureates in Chemistry, 1901–1992|url=https://books.google.com/books?id=jEy67gEvIuMC&pg=PA255|date=30 October 1993|publisher=Chemical Heritage Foundation|isbn=978-0-8412-2690-6|pages=255–|quote=Adolt Friedrich Johann Butenandt was awarded the Nobel Prize in chemistry in 1939 "for his work on sex hormones"; [...] In 1929 Butenandt isolated estrone [...] in pure crystalline form. [...] Both Butenandt and Edward Doisy isolated estrone simultaneously but independently in 1929. [...] Butenandt took a big step forward in the history of biochemistry when he isolated estrone from the urine of pregnant women. [...] He named it "progynon" in his first publication, and then "folliculine", [...] By 1932, [...] he could determine its chemical structure, [...]}}</ref> They isolated and [[purification (chemistry)|purified]] estrone in [[crystalline]] form from the [[urine]] of [[pregnancy|pregnant]] women.<ref name="Parl2000" /><ref name="Laylin1993" /><ref name="Greenberg2014">{{cite book| vauthors = Greenberg A |title=Chemistry: Decade by Decade|url=https://books.google.com/books?id=zR0H9ArBSFQC&pg=PA127|date=14 May 2014|publisher=Infobase Publishing|isbn=978-1-4381-0978-7|pages=127–|quote=Rational chemical studies of human sex hormones began in 1929 with Adolph Butenandt's isolation of pure crystalline estrone, the follicular hormone, from the urine of pregnant women. [...] Butenandt and Ruzicka shared the 1939 Nobel Prize in chemistry.}}</ref> Doisy and Allen named it ''theelin'', while Butenandt named it ''progynon'' and subsequently referred to it as ''folliculin'' in his second publication on the substance.<ref name="Laylin1993" /><ref>{{cite book| vauthors = Labhart A |title=Clinical Endocrinology: Theory and Practice|url=https://books.google.com/books?id=DAgJCAAAQBAJ&pg=PA511|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-96158-8|pages=511–|quote=E. A. Doisy and A. Butenandt reported almost at the same time on the isolation of an estrogen-active substance in crystalline form from the urine of pregnant women. N. K. Adam suggested that this substance be named estrone because of the C-17-ketone group present (1933).}}</ref> Butenandt was later awarded the [[Nobel Prize]] in 1939 for the isolation of estrone and his work on [[sex hormone]]s in general.<ref name="Greenberg2014" /><ref name="Rooke2012">{{cite book| vauthors = Rooke T |title=The Quest for Cortisone|url=https://books.google.com/books?id=70vvFrtpePoC&pg=PT54|date=1 January 2012|publisher=MSU Press|isbn=978-1-60917-326-5|pages=54–|quote=In 1929 the first estrogen, a steroid called "estrone," was isolated and purified by Doisy; he later won a Nobel Prize for this work.}}</ref> The [[molecular formula]] of estrone was known by 1931,<ref name="Loriaux2016">{{cite book| vauthors = Loriaux DL | chapter = Russel Earl Marker (1902–1995) - The Mexican Yam |title=A Biographical History of Endocrinology| chapter-url = https://books.google.com/books?id=ve2hCwAAQBAJ&pg=PA345 |date=23 February 2016|publisher=Wiley|isbn=978-1-119-20247-9|pages=345–}}</ref> and its [[chemical structure]] had been determined by Butenandt by 1932.<ref name="Laylin1993" /><ref name="Parl2000" /> Following the elucidation of its structure, estrone was additionally referred to as ''ketohydroxyestrin'' or ''oxohydroxyestrin'',<ref name="Campbell1933">{{cite journal| vauthors = Campbell AD |title=Concerning Placental Hormones and Menstrual Disorders|journal=Annals of Internal Medicine|volume=7|issue=3|year=1933|pages=330|issn=0003-4819|doi=10.7326/0003-4819-7-3-330}}</ref><ref name="pmid18744783">{{cite journal | vauthors = Fluhmann CF | title = Estrogenic Hormones: Their Clinical Usage | journal = California and Western Medicine | volume = 49 | issue = 5 | pages = 362–366 | date = November 1938 | pmid = 18744783 | pmc = 1659459 }}</ref> and the name ''estrone'', on the basis of its C17 [[ketone]] group, was formally established in 1932 at the first meeting of the International Conference on the Standardization of Sex Hormones in London.<ref name="FritzSperoff2012">{{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–|quote=In 1926, Sir Alan S. Parkes and C.W Bellerby coined the basic word "estrin" to designate the hormone or hormones that induce estrus in animals, the time when female mammals are fertile and receptive to males. [...] The terminology was extended to include the principal estrogens in humans, estrone, estradiol, and estriol, in 1932 at the first meeting of the International Conference on the Standardization of Sex Hormones in London, [...]}}</ref><ref name="OettelSchillinger2012">{{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=PA2|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-58616-3|pages=2–|quote=The structure of the estrogenic hormones was stated by Butenandt, Thayer, Marrian, and Hazlewood in 1930 and 1931 (see Butenandt 1980). Following the proposition of the Marrian group, the estrogenic hormones were given the trivial names of estradiol, estrone, and estriol. At the first meeting of the International Conference on the Standardization of Sex Hormones, in London (1932), a standard preparation of estrone was established. [...] The partial synthesis of estradiol and estrone from cholesterol and dehydroepiandrosterone was accomplished by Inhoffen and Howleg (Berlin 1940); the total synthesis was achieved by Anner and Miescher (Basel, 1948).}}</ref>
 
A [[partial synthesis]] of estrone from [[ergosterol]] was accomplished by [[Russell Earl Marker]] in 1936, and was the first [[chemical synthesis]] of estrone.<ref name="Watkins2007">{{cite book| vauthors = Watkins ES | chapter = Beginnings |title=The Estrogen Elixir: A History of Hormone Replacement Therapy in America| chapter-url = https://books.google.com/books?id=-tz4J4_hgdIC&pg=PA21|date=6 March 2007|publisher=JHU Press|isbn=978-0-8018-8602-7|pages=21–}}</ref><ref name="PincusGregory2012">{{cite book| vauthors = Pincus G, Thimann KV|title=The Hormones V1: Physiology, Chemistry and Applications|url=https://books.google.com/books?id=Thtz7On_lhEC&pg=PA360|date=2 December 2012|publisher=Elsevier|isbn=978-0-323-14206-9|pages=360–}}</ref> An alternative partial synthesis of estrone from [[cholesterol]] by way of [[dehydroepiandrosterone]] (DHEA) was developed by [[:de:Hans Herloff Inhoffen|Hans Herloff Inhoffen]] and [[:de:Walter Hohlweg|Walter Hohlweg]] in 1939 or 1940,<ref name="Watkins2007" /> and a [[total synthesis]] of estrone was achieved by Anner and Miescher in 1948.<ref name="OettelSchillinger2012" />
 
'''<big>Approval</big>'''
 
The FDA has approved estrone based on its safety and effectiveness as per the rules outlined in sections 505 of the Federal Food, Drug, and Cosmetic Act.<ref name="PubChem" />
 
== References ==
{{Reflist}}
 
{{Endogenous steroids}}
{{Estrogen receptor modulators}}
 
[[Category:Sterols]]
[[Category:Hydroxyarenes]]
[[Category:Estranes]]
[[Category:Estrogens]]
[[Category:Hormones of the hypothalamus-pituitary-gonad axis]]
[[Category:Hormones of the pregnant female]]
[[Category:Ketones]]
[[Category:Sex hormones]]

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