Estrone (medication)のソースを表示

{{Short description|Estrogen medication}}
{{About|estrone as a medication|its role as a hormone|Estrone}}
{{Use dmy dates|date=August 2018}}
{{Drugbox
| Verifiedfields = verified
| Watchedfields = verified
| verifiedrevid = 389314385
| IUPAC_name = (8''R'',9''S'',13''S'',14''S'')-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6''H''-cyclopenta[''a'']phenanthren-17-one
| image = Estron.svg
| width = 215px
| image2 = Estrone molecule ball.png
| width2 = 235px

<!--Clinical data-->
| tradename = Estragyn, Kestrin, Theelin, many others
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
| legal_UK = <!-- GSL / P / POM / CD -->
| legal_US = Rx-only 
| legal_status = 
| routes_of_administration = [[Intramuscular injection]], [[vaginal administration|vaginal]], [[oral administration|by mouth]] (as {{abbrlink|E2/E1/E3|estradiol/estrone/estriol}} or as [[estrone sulfate (medication)|estrone sulfate]])<ref name="Martindale" /><ref name="GuoHahn2000" /><ref name="Speroff2015" /><ref name="HelmsQuan2006" /><ref name="pmid16112947" />
| class = [[Estrogen (medication)|Estrogen]]

<!--Pharmacokinetic data-->
| bioavailability = [[Oral administration|Oral]]: very low<ref name="MelmonCarruthers2000" />
| protein_bound = 96.0–98.0%:<ref name="pmid16112947" /><ref name="JamesonGroot2010" /><br />• [[Human serum albumin|Albumin]]: ~80%<br />• {{abbr|SHBG|sex hormone-binding globulin}}: ~16%<br />• Free: 2.0–4.0%
| metabolism = [[Liver]] (via [[hydroxylation]], [[sulfation]], [[glucuronidation]])<ref name="pmid16112947" />
| metabolites = • [[Estradiol (medication)|Estradiol]]<ref name="pmid16112947" /><br />• [[Estrone sulfate (medication)|Estrone sulfate]]<ref name="pmid16112947" /><br />• [[Estrone glucuronide]]<ref name="pmid16112947" /><br />• Others<ref name="pmid16112947" />
| elimination_half-life = {{abbrlink|IV|Intravenous injection}}: 20–30 minutes<ref name="pmid16112947" />
| excretion = [[Urine]]<ref name="pmid16112947" />

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 53-16-7
| ATC_prefix = G03
| ATC_suffix = CA07
| ATC_supplemental = <br />{{ATC|G03|CC04}}
| PubChem = 5870
| IUPHAR_ligand = 2818
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00655
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 5660
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 2DI9HA706A
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00067
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17263
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1405
| synonyms = Oestrone; E1; Follicular hormone; Folliculin; Folliculine; Follikulin; Theelin; Ketohydroxyestrin; Oxohydroxyestrin; 3-Hydroxyestra-1,3,5(10)-trien-17-one

<!--Chemical data-->
| C=18 | H=22 | O=2
| 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

<!--Physical data-->
| melting_point = 254.5
}}
<!-- Definition and medical uses -->
'''Estrone''' ('''E1'''), sold under the brand names '''Estragyn''', '''Kestrin''', and '''Theelin''' among many others, is an [[estrogen (medication)|estrogen]] medication and [[natural product|naturally occurring]] [[steroid hormone]] which has been used in [[menopausal hormone therapy]] and for other indications.<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 | year = 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf}}</ref><ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA899|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=899–}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA407|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=407–}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA207|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=207–}}</ref><ref name="Martindale">{{cite book | veditors = Sweetman SC |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |page=2101 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|url=https://www.medicinescomplete.com/mc/martindale/2009/9092-j.htm}}</ref><ref name="GuoHahn2000">{{cite book| vauthors = Guo JZ, Hahn DW, Wachter MP |title=Kirk-Othmer Encyclopedia of Chemical Technology|chapter=Hormones, Estrogens and Antiestrogens|year=2000|publisher=Wiley |doi=10.1002/0471238961.05192018072115.a01|isbn=0471238961}}</ref> It has been provided as an [[aqueous suspension]] or [[oil solution]] given by [[intramuscular injection|injection into muscle]] and as a [[vaginal estrogen|vaginal]] [[cream (pharmacy)|cream]] applied [[vaginal administration|inside of the vagina]].<ref name="Martindale" /><ref name="GuoHahn2000" /><ref name="Speroff2015">{{cite book | veditors = Speroff L | chapter = Women's Hormonal Health Issues | title = Blood and Marrow Transplant Handbook: Comprehensive Guide for Patient Care. |year=2015|pages=341–354|doi=10.1007/978-3-319-13832-9_28|isbn=978-3-319-13831-2 | last1 = Speroff | first1 = Leon }}</ref><ref name="HelmsQuan2006">{{cite book| vauthors = Vuong LK | chapter = Gynecological Disorders | veditors = Helms RA, Quan DJ |title=Textbook of Therapeutics: Drug and Disease Management| chapter-url=https://books.google.com/books?id=aVmRWrknaWgC&pg=PA397|year=2006|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-5734-8|pages=397–}}</ref> It can also be taken [[oral administration|by mouth]] as [[estradiol/estrone/estriol]] (brand name '''Hormonin''') and in the form of [[prodrug]]s like [[estropipate]] ([[estrone sulfate (medication)|estrone sulfate]]; brand name '''Ogen''') and [[conjugated estrogens]] (mostly estrone sulfate; brand name '''Premarin''').<ref name="Buchsbaum2012">{{cite book| vauthors = Quirk Jr JG, Wendel Jr GD | chapter = Biologic effects of natural and synthetic estrogens | veditors = Buchsbaum HJ |title=The Menopause| chapter-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=60, 62, 64}}</ref><ref name="GuoHahn2000" /><ref name="pmid16112947" />

<!-- Side effects and mechanism -->
[[Side effect]]s of estrogens like estrone include [[breast tenderness]], [[breast enlargement]], [[headache]], [[nausea]], [[water retention (medicine)|fluid retention]], and [[edema]], among others.<ref name="pmid16112947" /> Estrone is a [[natural product|naturally occurring]] and [[bioidentical hormone therapy|bioidentical]] estrogen, or an [[agonist]] of the [[estrogen receptor]], the [[biological target]] of [[estrogen]]s like [[endogenous]] [[estradiol]].<ref name="pmid16112947" /> It is a relatively weak estrogen, with much lower [[biological activity|activity]] than [[estradiol (medication)|estradiol]].<ref name="pmid16112947" /> However, estrone is [[biotransformation|converted]] in the body into estradiol, which provides most or all of its estrogenic [[potency (pharmacology)|potency]].<ref name="pmid16112947" /><ref name="FishmanMartucci1980" /> As such, estrone is a [[prodrug]] of estradiol.<ref name="pmid16112947" />

<!-- History, society, and culture -->
Estrone was first discovered in 1929, and was introduced for medical use shortly thereafter.<ref name="Bullough1995" /><ref name="pmid18744783" /><ref name="Watkins2007" /> Although it has been used clinically in the past, estrone has largely been discontinued and is mostly no longer marketed.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

{{TOC limit|3}}

==Medical uses==
Estrone has been marketed in [[intramuscular injection|intramuscular]] and [[vaginal administration|vaginal]] formulations and was used as an [[estrogen (medication)|estrogen]] in the treatment of [[symptom]]s of [[hypoestrogenism|low estrogen levels]] such as [[hot flash]]es and [[atrophic vaginitis|vaginal atrophy]] in [[menopause|postmenopausal]] or [[ovariectomy|ovariectomized]] women.<ref name="pmid18744783" /> Estrone has also been used as an [[antigonadotropin]] and form of [[high-dose estrogen]] to treat [[prostate cancer]] in men as well as a form of high-dose estrogen to treat [[breast cancer]] in women.<ref name="ThomasKeenan1986a">{{cite book| vauthors = Thomas JA, Keenan EJ |chapter=Estrogens and Antiestrogenic Drugs|pages=135–165|doi=10.1007/978-1-4684-5036-1_7|title=Principles of Endocrine Pharmacology|chapter-url=https://books.google.com/books?id=mTagBQAAQBAJ&pg=PA150|date=6 December 1986|publisher=Springer Science & Business Media|isbn=978-1-4684-5036-1}}</ref><ref name="Estrone-FDA-Review-1979a" /> It has since largely been discontinued and is mostly no longer available, having been superseded by other estrogens with better [[potency (pharmacology)|potency]] and [[pharmacokinetics]] (namely [[oral administration|oral]] [[bioavailability]] and [[duration of action|duration]]).<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 Drugs}}</ref><ref name="Drugs.com" />

Regardless of [[route of administration]], if estrone is taken by a woman with an intact [[uterus]], it should be combined with a [[progestogen]] such as [[progesterone (medication)|progesterone]] to offset the risk of [[endometrial hyperplasia]] and [[endometrial cancer|cancer]].<ref name="Martindale" /><ref name="pmid16112947" />

Estrone has been used by intramuscular injection at a dosage of 0.1 to 2&nbsp;mg per week, or 0.1 to 0.5&nbsp;mg given 2 or 3&nbsp;times per week, for the treatment of [[menopausal symptoms]] such as hot flashes and vaginal atrophy,<ref name="AMA1977">{{cite book |chapter=Estrogens, Progestagens, Oral Contraceptives, and Ovulatory Agents |pages=540–572 |author1=American Medical Association. Dept. of Drugs |author2=Council on Drugs (American Medical Association) |author3=American Society for Clinical Pharmacology and Therapeutics |title=AMA drug evaluations |url=https://books.google.com/books?id=0h7s_rfEZgkC |date=1 February 1977 |publisher=Publishing Sciences Group |isbn=978-0-88416-175-2 }}</ref><ref name="ThomasKeenan2012">{{cite book| vauthors = Thomas JA, Keenan EJ | chapter = Estrogen and Antiestrogenic Drugs |title=Principles of Endocrine Pharmacology| chapter-url=https://books.google.com/books?id=mTagBQAAQBAJ&pg=PA153|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4684-5036-1|pages=153–}}</ref> and at a dosage of 0.1 to 1.0&nbsp;mg weekly in single or divided doses for the treatment of female [[hypogonadism]], [[surgical castration]], and [[primary ovarian failure]].<ref name="Rivlin1990">{{cite book| vauthors = Rivlin ME |title=Handbook of drug therapy in reproductive endocrinology and infertility|url=https://books.google.com/books?id=7kZsAAAAMAAJ&q=Estrone|year=1990|publisher=Little, Brown|isbn=978-0-316-74772-1|page=23|quote=The following are dosages for parenteral [estrogens]: [...] Estrone. For vasomotor symptoms or atrophic vaginitis, 0.1 to 0.5 mg is given 2 or 3 times weekly. For female hypogonadism, castration, or primary ovarian failure, 0.1 to 1.0 mg is given weekly in single or divided doses. Further dosage adjusted according to response.}}</ref> The range of single doses of estrone by intramuscular injection that are typically used clinically in women is 0.1 to 5&nbsp;mg.<ref name="Fluhmann1944" /> High doses of intramuscular estrone have been used for prostate cancer in men and for breast cancer in women.<ref name="ThomasKeenan1986a" /><ref name="Estrone-FDA-Review-1979a">{{Cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/anda/pre96/85239_Estrone%20Suspension_Medr.pdf|title=Enforcement Reports}}</ref>

===Available forms===
{{See also|Estradiol/estrone/estriol|Estrone/progesterone}}

Estrone for [[intramuscular injection]] was provided as 1, 2, 2.5, 3, 4, and 5&nbsp;mg/mL [[aqueous suspension]]s and/or [[oil solution]]s.<ref name="Becker2001">{{cite book| vauthors = Misra D, Magee MF, Nylén ES | chapter = Compendium of Endocrine-Related Drugs | veditors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism|chapter-url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA2153|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=2153–}}</ref><ref name="ThomasKeenan1986a" /><ref name="Micromedex">https://www.micromedexsolutions.com/micromedex2/ {{Dead link|date=February 2022}}</ref><ref name="Modell2013">{{cite book| vauthors = Modell W | chapter = Estrone |title=Drugs in Current Use 1958| chapter-url = https://books.google.com/books?id=v2vwCAAAQBAJ&pg=PA52|date=21 November 2013|publisher=Springer|isbn=978-3-662-40303-7|pages=52–}}</ref><ref name="PaolettiPasetto2012">{{cite book | vauthors = Deghenghi R | chapter = Chemistry and biochemistry of natural estrogens | veditors = Paoletti R, Pasetto N, Ambrus JL |title=The Menopause and Postmenopause: The Proceedings of an International Symposium held in Rome, June 1979| chapter-url = https://books.google.com/books?id=wZF9CAAAQBAJ&pg=PA3|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-7230-1|pages=3–}}</ref><ref name="UC1952">{{cite book|author=University of California (1868-1952)|title=Hospital Formulary and Compendium of Useful Information|url=https://books.google.com/books?id=t7VW3PucgboC&pg=PA49|year=1952|publisher=University of California Press|pages=49–|id=GGKEY:2UAAZRZ5LN0}}</ref> It has also been available in the form of [[vaginal administration|vaginal]] [[cream (pharmacy)|cream]]s (1&nbsp;mg/g (0.1%)) and [[suppository|suppositories]] (0.2&nbsp;mg, 0.25&nbsp;mg) as well as [[subcutaneous implant|subcutaneous pellet implant]]s and [[oral administration|oral]] [[tablet (pharmacy)|tablet]]s (1.25&nbsp;mg).<ref name="Fluhmann1944" /><ref name="Speroff2015" /><ref name="Martindale" /><ref name="Micromedex" /><ref name="Modell2013" /><ref name="PaolettiPasetto2012" /> A combined [[oral administration|oral]] [[tablet (pharmacy)|tablet]] formulation containing [[estradiol (medication)|estradiol]] (0.3&nbsp;mg, 0.6&nbsp;mg), estrone (0.7&nbsp;mg, 1.4&nbsp;mg), and [[estriol (medication)|estriol]] (0.135&nbsp;mg, 0.27&nbsp;mg) has been marketed under the brand name Hormonin as well.<ref name="Micromedex" /><ref name="KrishnaShah1996">{{cite book| vauthors = Krishna UR, Sheriar NK, Mandlekar A | chapter = Hormone Replacement Therapy | veditors = Krishna UR, Sheriar NK |title=Menopause|chapter-url=https://books.google.com/books?id=n16P1r9cBG8C&pg=PA70|year=1996|publisher=Orient Blackswan|isbn=978-81-250-0910-8|pages=70–}}</ref><ref name="Buchsbaum2012" /><ref name="CampbellCompston1993">{{cite book | chapter = Osteoporosis | vauthors = Campbell G, Compston J, Crisp A | title = The Management of Common Metabolic Bone Disorders| chapter-url=https://books.google.com/books?id=gGmx03rQVyoC&pg=PA48|date=25 November 1993|publisher=Cambridge University Press|isbn=978-0-521-43623-6|pages=48–}}</ref><ref name="Erkkola2006">{{cite book| vauthors = Erkkola R |title=The Menopause|url=https://books.google.com/books?id=1AU_NI__fpUC&pg=PA264|date=1 January 2006|publisher=Elsevier|isbn=978-0-444-51830-9|pages=264–}}</ref> In addition, a combined injectable preparation containing estrone (1&nbsp;mg) and [[progesterone (medication)|progesterone]] (10&nbsp;mg) is available in the form of [[ampoule]]s under the brand name Synergon.<ref name="Martindale2009">{{cite book |veditors = Sweetman SC  |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |pages=2101, 2127 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|quote=Estrone [...] Progesterone [...] Multi-ingredient: [...] Fr.: Synergon [...] Turk.: Synergon}}</ref><ref name="pmid19232600">{{cite journal |vauthors=Addo VN, Tagoe-Darko ED |title=Knowledge, practices, and attitudes regarding emergency contraception among students at a university in Ghana |journal=Int J Gynaecol Obstet |volume=105 |issue=3 |pages=206–9 |date=June 2009 |pmid=19232600 |doi=10.1016/j.ijgo.2009.01.008 |s2cid=22216977 |quote=Synergon, a combination of progesterone and oestrone in an injectable form, is marketed to induce withdrawal bleeding in women with nongravid amenorrhea; however, it can be used as an arbortifacient [11].}}</ref><ref name="pmid17634106">{{cite journal |vauthors=Kongnyuy EJ, Ngassa P, Fomulu N, Wiysonge CS, Kouam L, Doh AS |title=A survey of knowledge, attitudes and practice of emergency contraception among university students in Cameroon |journal=BMC Emerg Med |volume=7 |pages=7 |date=July 2007 |pmid=17634106 |pmc=1933435 |doi=10.1186/1471-227X-7-7 |doi-access=free }}</ref><ref name="McDonnell1986">{{cite book| vauthors = McDonnell K |title=Adverse Effects: Women and the Pharmaceutical Industry|url=https://books.google.com/books?id=SgA-AAAAYAAJ|year=1986|publisher=International Organization of Consumers Unions, Regional Office for Asia and the Pacific|isbn=978-967-9973-17-4|page=15|quote=Synergon. 10 mg progesterone. 1 mg folliculine [estrone].}}</ref>

Although estrone by intramuscular injection was originally formulated as an oil solution, it was soon replaced by formulations of estrone as an aqueous suspension due to a longer duration of action of these formulations.<ref name="FreedGreenhill1941" /><ref name="Freed1946" /><ref name="PaolettiPasetto2012" /><ref name="Estrone-FDA-Review-1979a" /><ref name="Ferin1952">{{cite journal | vauthors = Ferin J | title = Relative duration of action of natural and synthetic estrogens administered parenterally in women with estrogen deficiency | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 12 | issue = 1 | pages = 28–35 | date = January 1952 | pmid = 14907837 | doi = 10.1210/jcem-12-1-28 }}</ref><ref name="Freed1941">{{cite journal| vauthors = Freed SC|title=Present status of commercial endocrine preparations|journal=JAMA: The Journal of the American Medical Association|volume=117|issue=14|year=1941|pages=1175|issn=0098-7484|doi=10.1001/jama.1941.72820400003010}}</ref><ref name="Stempel1959">{{cite journal| vauthors = Stempel E |title=prolonged drug action|journal=Journal of the American Pharmaceutical Association (Practical Pharmacy Ed.)|volume=20|issue=6|year=1959|pages=334–336|issn=0095-9561|doi=10.1016/S0095-9561(16)35628-6}}</ref>

==Side effects==
{{See also|Estrogen (medication)#Side effects}}

[[Side effect]]s of estrogens like estrone include [[breast tenderness]], [[breast enlargement]], [[headache]], [[nausea]], [[water retention (medicine)|fluid retention]], and [[edema]], among others.<ref name="pmid16112947" /> It can also cause [[endometrial hyperplasia]].<ref name="Werner1932" /><ref name="WernerCollier1933" /><ref name="Werner1937" />

==Pharmacology==

===Pharmacodynamics===

====Mechanism of action====
Estrone is an estrogen, specifically an [[agonist]] of the [[estrogen receptor]]s (ERs) [[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 | title = Evaluation of ligand selectivity using reporter cell lines stably expressing estrogen receptor alpha or beta | journal = Biochem. Pharmacol. | volume = 71 | issue = 10 | pages = 1459–69 | year = 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" /> Given by [[subcutaneous injection]] in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than [[estriol (medication)|estriol]].<ref name="Labhart2012">{{cite book | vauthors = Schriener WE | chapter = The Ovary | veditors = Labhart A |title=Clinical Endocrinology: Theory and Practice| chapter-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" /> Other studies have reported that estrone has about one-tenth of the potency of estradiol in activating the ERs ''in vitro''.<ref name="pmid9294720">{{cite journal | vauthors = Coldham NG, Dave M, Sivapathasundaram S, McDonnell DP, Connor C, Sauer MJ | title = Evaluation of a recombinant yeast cell estrogen screening assay | journal = Environ. Health Perspect. | volume = 105 | issue = 7 | pages = 734–42 | date = July 1997 | pmid = 9294720 | pmc = 1470103 | doi = 10.1289/ehp.97105734 }}</ref><ref name="pmid12387416">{{cite journal | vauthors = Legler J, Zeinstra LM, Schuitemaker F, Lanser PH, Bogerd J, Brouwer A, Vethaak AD, De Voogt P, Murk AJ, Van der Burg B | title = Comparison of in vivo and in vitro reporter gene assays for short-term screening of estrogenic activity | journal = Environ. Sci. Technol. | volume = 36 | issue = 20 | pages = 4410–5 | date = October 2002 | pmid = 12387416 | doi = 10.1021/es010323a | bibcode = 2002EnST...36.4410L | url = https://research.vu.nl/en/publications/625a3378-95d3-44aa-8075-223e0a4f4b45}}</ref><ref name="pmid21195753">{{cite journal | vauthors = Dang Z, Ru S, Wang W, Rorije E, Hakkert B, Vermeire T | title = Comparison of chemical-induced transcriptional activation of fish and human estrogen receptors: regulatory implications | journal = Toxicol. Lett. | volume = 201 | issue = 2 | pages = 152–75 | date = March 2011 | pmid = 21195753 | doi = 10.1016/j.toxlet.2010.12.020 }}</ref> Because estrone can be [[biotransformation|transformed]] into estradiol, which is far more potent as an estrogen in comparison, 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, similarly to the case of [[estrone sulfate (medication)|estrone sulfate]], estrone is considered to be a [[prodrug]] of estradiol.<ref name="pmid16112947" /><ref name="pmid2170822">{{cite journal | vauthors = Kuhl H | title = Pharmacokinetics of oestrogens and progestogens | journal = Maturitas | volume = 12 | issue = 3 | pages = 171–97 | date = September 1990 | pmid = 2170822 | doi = 10.1016/0378-5122(90)90003-O }}</ref> Some ''[[in vitro]]'' research has suggested that estrone might be able to [[partial agonist|partially]] [[receptor antagonist|antagonize]] the actions of estradiol,<ref name="Pasqualini2008">{{cite book| veditors = Pasqualini JR | vauthors = Kloosterboer HJ, Schoonen WG, Verheul HA | title = Breast Cancer: Prognosis, Treatment, and Prevention | chapter = Proliferation of Breast Cells by Steroid Hormones and Their Metabolites | url = https://books.google.com/books?id=VQDLBQAAQBAJ | 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 = J. Biol. Chem. | volume = 258 | issue = 13 | pages = 8118–22 | date = July 1983 | doi = 10.1016/S0021-9258(20)82036-5 | pmid = 6863280 | url = http://www.jbc.org/content/258/13/8118.short| 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 = Gynecol. Endocrinol. | volume = 31 | issue = 9 | pages = 747–9 | date = 2015 | pmid = 26190536 | doi = 10.3109/09513590.2015.1062866 | s2cid = 13617050 }}</ref> but this does not appear to be of clinical significance.<ref name="pmid16112947" /><ref name="pmid2512035" /><ref name="pmid2992279" /><ref name="pmid6818806" /> 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 = Pharmacol. Rev. | volume = 67 | issue = 3 | pages = 505–40 | date = July 2015 | pmid = 26023144 | pmc = 4485017 | doi = 10.1124/pr.114.009712 }}</ref>

{{Affinities of estrogen receptor ligands for the ERα and ERβ}}

{{Relative affinities of estrogens for steroid hormone receptors and blood proteins}}

{{Selected biological properties of endogenous estrogens in rats}}

====Effects in the body and brain====
In [[clinical research]] in the 1930s, estrone was given via intramuscular injection to [[ovariectomy|ovariectomized]] women in order to study its effects and to elucidate the [[function (biology)|biological properties]] of estrogens in humans.<ref name="Werner1932">{{cite journal| vauthors = Werner AA |title=Effect of Theelin Injections upon the Castrated Woman|journal=Experimental Biology and Medicine|volume=29|issue=9|year=1932|pages=1142–1143|issn=1535-3702|doi=10.3181/00379727-29-6259|s2cid=75441739}}</ref><ref name="WernerCollier1933">{{cite journal| vauthors = Werner AA, Collier WD|title=Production of Endometrial Growth in Castrated Women|journal=Journal of the American Medical Association|volume=101|issue=19|year=1933|pages=1466|issn=0002-9955|doi=10.1001/jama.1933.02740440026008}}</ref><ref name="Werner1937">{{cite journal| vauthors = Werner AA |title=Effective Clinical Dosages of Theelin in Oil|journal=Journal of the American Medical Association|volume=109|issue=13|year=1937|pages=1027|issn=0002-9955|doi=10.1001/jama.1937.02780390029011}}</ref> In these studies, prior to administration of estrone, [[amenorrhea]], [[atrophy]] of the [[breast]]s (as well as [[wikt:flaccid|flaccidity]] and small and non-erectile [[nipple]]s), [[vagina]], and [[endometrium]], [[vaginal dryness]], and [[symptom|subjective symptom]]s of ovariectomy (e.g., [[hot flashes]], [[mood (psychology)|mood]] changes) were all present in the women.<ref name="Werner1932" /><ref name="WernerCollier1933" /><ref name="Werner1937" /> Treatment with estrone was found to dose- and time-dependently produce a variety of effects, including breast changes, [[reproductive tract]] changes of the vagina, [[cervix]], and [[endometrium]]/[[uterus]], and relief from the subjective symptoms of ovariectomy, as well as increased [[libido]].<ref name="Werner1932" /><ref name="WernerCollier1933" /><ref name="Werner1937" /> Breast changes specifically included [[breast enlargement|enlargement]] and a sense of [[breast fullness|fullness]], increased [[nipple sensitivity|sensitivity]] and [[pigmentation]] of the nipples as well as [[nipple erection]], [[paresthesia|tingling]] within the breast [[mammary gland]]ular tissue, and [[breast pain|aching and soreness]] of the breasts.<ref name="Werner1932" /><ref name="WernerCollier1933" /><ref name="Werner1937" /> [[Reproductive tract]] changes included increased [[cell growth|growth]], thickness, and [[Cellular differentiation|differentiation]] of the endometrium, and reversal of vaginal and cervical atrophy, which were accompanied by increased [[water retention (medicine)|congestion]] of the cervix and [[vaginal discharge|mucous discharge]] from the cervix, uterine [[cramp]]s and [[paresthesia|needle-like pains]], pelvic fullness, a "bearing-down" sensation, and increased [[vaginal lubrication]], as well as [[uterine bleeding]] both during treatment and in the days following cessation of injections.<ref name="Werner1932" /><ref name="WernerCollier1933" /><ref name="Werner1937" /> [[Endometrial hyperplasia]] also occurred with sufficiently high doses of estrone.<ref name="Werner1932" /><ref name="WernerCollier1933" /><ref name="Werner1937" />

Clinical research has confirmed the nature of estrone as an [[inactive prodrug]] 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 = Clin. Endocrinol. (Oxf) | volume = 30 | issue = 3 | pages = 241–9 | 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 = Am. J. Obstet. Gynecol. | volume = 152 | issue = 8 | pages = 1099–106 | 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 Endocrinol. | volume = 101 | issue = 4 | pages = 592–6 | 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 = Ann. N. Y. Acad. Sci. | volume = 1057 | pages = 506–24 | date = December 2005 | issue = 1 | pmid = 16399916 | doi = 10.1196/annals.1356.039 | bibcode = 2005NYASA1057..506W | s2cid = 38877163 }}</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 = Altern Med Rev | 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 doses 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 | title = Biological effects of estradiol-17 beta in postmenopausal women: oral versus percutaneous administration | journal = J. Clin. Endocrinol. Metab. | volume = 62 | issue = 3 | pages = 536–41 | 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"/><ref name="pmid6863280"/><ref name="pmid26190536"/>

{{Relative oral potencies of estrogens}}

{{Parenteral potencies and durations of steroidal estrogens}}

{{Pharmacology of estrone}}

===Pharmacokinetics===

====Absorption====
Like estradiol, estrone has poor [[oral administration|oral]] [[bioavailability]].<ref name="Buchsbaum2012" /><ref name="MelmonCarruthers2000">{{cite book| vauthors = Melmon KL, Carruthers SG, Morrelli HF, Hoffman BB, Nierenberg DW |title=Melmon and Morrelli's Clinical Pharmacology: Basic Principles in Therapeutics|url=https://books.google.com/books?id=s515nY4F3WcC|year=2000|publisher=McGraw Hill Professional|isbn=978-0-07-105406-5|pages=614–615}}</ref> It has been said that, taken by mouth in non-[[micronization|micronized]] form, a dose of 25&nbsp;mg estrone is approximately equivalent to 2.5&nbsp;mg [[conjugated estrogens]], 50&nbsp;μg [[ethinylestradiol]], or 1&nbsp;mg [[diethylstilbestrol]] in terms of estrogenic potency.<ref name="pmid13638626">{{cite journal | vauthors = Swyer GI | title = The oestrogens | journal = Br Med J | volume = 1 | issue = 5128 | pages = 1029–31 | date = April 1959 | pmid = 13638626 | pmc = 1993181 | doi = 10.1136/bmj.1.5128.1029 | quote = Oestrone is weakly active by mouth, its potency (see Table) being approximately 1/25th that of stilboestrol (25 mg E1 = 1 mg DES = 2.5 mg CEEs = 0.05 mg EE).}}</ref> Due to its weak oral activity, estrone has been used [[parenteral]]ly instead, for instance by [[intramuscular injection]] or [[vaginal administration]].<ref name="GuoHahn2000" /><ref name="Speroff2015" /><ref name="HelmsQuan2006" /> The [[pharmacokinetics]] of vaginal estrone have been studied.<ref name="pmid908445">{{cite journal | vauthors = Schiff I, Tulchinsky D, Ryan KJ | title = Vaginal absorption of estrone and 17beta-estradiol | journal = Fertil. Steril. | volume = 28 | issue = 10 | pages = 1063–6 | date = October 1977 | pmid = 908445 | doi = 10.1016/S0015-0282(16)42855-4 | doi-access = free }}</ref>

Estrone in oil solution by intramuscular injection has a shorter duration than estrone in aqueous suspension by intramuscular injection.<ref name="FreedGreenhill1941">{{cite journal| vauthors = Freed SC, Greenhill JP |title=Therapeutic Use of Estrone Suspensions1|journal=The Journal of Clinical Endocrinology & Metabolism|volume=1|issue=12|year=1941|pages=983–985|issn=0021-972X|doi=10.1210/jcem-1-12-983}}</ref> Estrone in oil solution by intramuscular injection is rapidly absorbed, while estrone in aqueous suspension has a prolonged period of absorption.<ref name="James1998">{{cite journal | vauthors = James DW | title = Management of the Menopause | journal = The Permanente Journal | date = Summer 1998 | volume = 2 | issue = 3 | pages = 25–29 | doi = 10.7812/TPP/98.930 | s2cid = 248135901 | url = http://www.thepermanentejournal.org/files/PDF/Summer1998.pdf#page=27 | quote = Using the same principle of delayed absorption, however, we have been able to improve the efficiency of estrone by suspending this fat soluble substance in an aqueous medium, reversing the procedure of suspending water soluble substances such as penicillin. in oil.3 The action of estrone in suspension is prolonged because the water vehicle is rapidly absorbed leaving a deposit of crystals in the tissues thus behaving like small implants of crystals which we know are relatively long acting.}}</ref> Upon intramuscular injection of estrone in aqueous solution, the water from the preparation is absorbed and a microcrystalline depot of estrone that is slowly absorbed by the body is formed.<ref name="Freed1946">{{cite journal | vauthors = Freed SC | title = Some Fundamentals in Estrogen Therapy | journal = California Medicine | date = December 1946 | volume = 65 | issue = 6 | pages = 277–278 | pmid = 18731134 | pmc=1642736}}</ref> This is responsible for the prolonged duration of estrone in aqueous suspension compared to oil solution.<ref name="FreedGreenhill1941" /><ref name="Freed1946" />

====Distribution====
Unlike estradiol and estriol, estrone is not accumulated in target [[tissue (biology)|tissue]]s.<ref name="pmid16112947" /><ref name="pmid6847874">{{cite journal | vauthors = Wiegerinck MA, Poortman J, Donker TH, Thijssen JH | title = In vivo uptake and subcellular distribution of tritium-labeled estrogens in human endometrium, myometrium, and vagina | journal = J. Clin. Endocrinol. Metab. | volume = 56 | issue = 1 | pages = 76–86 | date = January 1983 | pmid = 6847874 | doi = 10.1210/jcem-56-1-76 | doi-access = free }}</ref> In terms of [[plasma protein binding]], estrone is bound approximately 16% to [[sex hormone-binding globulin]] (SHBG) and 80% to [[human serum albumin|albumin]],<ref name="pmid16112947" /> with the remainder (2.0 to 4.0%) circulating free or unbound.<ref name="JamesonGroot2010">{{cite book | vauthors = Nakamoto J, Salameh WA, Carlton E | chapter = Endocrine Testing | veditors = Jameson JL, De Groot LJ |title=Endocrinology – E-Book: Adult and Pediatric| chapter-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> Estrone has about 24% of the relative binding affinity of estradiol for SHBG, and hence is relatively poorly bound to SHBG.<ref name="pmid16112947" /><ref name="Buchsbaum2012" />

====Metabolism====
{{Estradiol metabolism|align=right}}

Estrone is [[conjugation (biochemistry)|conjugated]] into [[estrogen conjugate]]s such as [[estrone sulfate (medication)|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 (medication)|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-hydroxysteroid dehydrogenase]]s (17β-HSDs), and this accounts for most or all of its estrogenic activity.<ref name="pmid16112947" /><ref name="FishmanMartucci1980" /> 17β-HSD [[isoform]]s that are involved in the conversion of estrone into estradiol include [[HSD17B1|17β-HSD1]], [[HSD17B3|17β-HSD3]], [[HSD17B4|17β-HSD4]], [[HSD17B7|17β-HSD7]], [[HSD17B8|17β-HSD8]], and [[HSD17B15|17β-HSD12]], although the relative contributions of the different isoforms is unknown.<ref name="pmid20645882">{{cite journal | vauthors = Poirier D | title = 17beta-Hydroxysteroid dehydrogenase inhibitors: a patent review | journal = Expert Opin Ther Pat | volume = 20 | issue = 9 | pages = 1123–45 | date = September 2010 | pmid = 20645882 | doi = 10.1517/13543776.2010.505604 | s2cid = 35732314 }}</ref>{{Additional citation needed|date=June 2020}}

The [[biological half-life|biological half-lives]] of estrone and estradiol in the circulation are both about 10 to 70&nbsp;minutes, whereas the biological half-life of estrone sulfate in the circulation is about 10 to 12&nbsp;hours.<ref name="pmid16112947" /><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> The [[metabolic clearance rate]] of estrone is 1,050&nbsp;L/day/m<sup>2</sup> and of estradiol is 580&nbsp;L/day/m<sup>2</sup>, while that of estrone sulfate is 80&nbsp;L/day/m<sup>2</sup>.<ref name="pmid16112947" /> For comparison, the metabolic clearance rate of estriol is 1,110&nbsp;L/day/m<sup>2</sup>.<ref name="pmid16112947" /> A single 1 to 2&nbsp;mg dose of estrone in oil solution by intramuscular injection has a duration of about 2 or 3&nbsp;days.<ref name="Labhart2012" /><ref name="Brown1957">{{cite journal | vauthors = Brown JB | title = The relationship between urinary oestrogens and oestrogens produced in the body | journal = The Journal of Endocrinology | volume = 16 | issue = 2 | pages = 202–212 | date = December 1957 | pmid = 13491750 | doi = 10.1677/joe.0.0160202 }}</ref><ref name="pmid14367392">{{cite journal | vauthors = Beer CT, Gallagher TF | title = Excretion of estrogen metabolites by humans. I. The fate of small doses of estrone and estradiol-17beta | journal = The Journal of Biological Chemistry | volume = 214 | issue = 1 | pages = 335–349 | date = May 1955 | pmid = 14367392 | doi = 10.1016/S0021-9258(18)70972-1 | doi-access = free }}</ref> As an [[aqueous suspension]] by [[intramuscular injection]], estrone was used at a dose of 0.1 to 0.5&nbsp;mg 2 to 3&nbsp;times per week, or at a dose of 0.1 to 2&nbsp;mg once a week or in divided doses.<ref name="Micromedex2003">{{cite book|author=Micromedex|title=USP DI 2003: Drug Information for Healthcare Professionals|url=https://books.google.com/books?id=zEzWtsVl-KgC|date=1 January 2003|publisher=Thomson Micromedex|isbn=978-1-56363-429-1|page=1246|quote=ESTRONE Parenteral Dosage Forms ESTRONE INJECTABLE SUSPENSION USP Usual adult dose Atrophic vaginitis or Menopausal (vasomotor) symptoms or Vulvar atrophy—Intramuscular, 100 to 500 mcg (0.1 to 0.5 mg) two or three times a week, cyclically or continuously as appropriate. Estrogen deficiency, due to ovariectomy or Female hypogonadism or Primary ovarian failure—Intramuscular, 100 mcg (0.1 mg) to 1 mg a week, administered as a single dose or in divided doses, cyclically or continuously. A few patients may need doses of up to 2 mg a week.}}</ref> In one rodent study, [[exogenous]] estrone was administered and increased circulating estradiol levels by about 10-fold; co-administration of a [[binding selectivity|selective]] 17β-HSD1 [[enzyme inhibitor|inhibitor]] decreased estradiol levels by about 50%.<ref name="pmid18183589">{{cite journal | vauthors = Day JM, Foster PA, Tutill HJ, Parsons MF, Newman SP, Chander SK, Allan GM, Lawrence HR, Vicker N, Potter BV, Reed MJ, Purohit A | display-authors = 6 | title = 17beta-hydroxysteroid dehydrogenase Type 1, and not Type 12, is a target for endocrine therapy of hormone-dependent breast cancer | journal = International Journal of Cancer | volume = 122 | issue = 9 | pages = 1931–1940 | date = May 2008 | pmid = 18183589 | doi = 10.1002/ijc.23350 | doi-access = free }}</ref>

The ratio of circulating estrone to circulating estradiol is the same at about 5:1 with both oral estradiol and oral estrone sulfate.<ref name="pmid16112947" /> An investigational estrone [[vaginal ring]] was found to result in a ratio of estrone to estradiol of 4:1 or 5:1 initially, but this decreased to about 1:1 with continuous therapy.<ref name="pmid7231201" />

====Excretion====
Estrone is [[excretion|excreted]] in [[urine]] in the form of [[estrogen conjugate]]s such as [[estrone sulfate (medication)|estrone sulfate]] and [[estrone glucuronide]].<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" />

==Chemistry==
{{See also|List of estrogens#Estrone derivatives|List of estrogen esters#Estrone esters}}
{{Chemical structures of major endogenous estrogens medication version|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.<ref name="Elks2014" /><ref name="IndexNominum2000" /> The name ''estrone'' was derived from the chemical terms ''[[estrin (compound)|'''estr'''in]]'' (estra-1,3,5(10)-triene) and ''ket'''one'''''.<ref name="Elks2014" /><ref name="IndexNominum2000" />

A variety of [[estrone ester]]s have been [[chemical synthesis|synthesized]] and described.<ref name="Elks2014" /><ref name="IndexNominum2000" /> These include the marketed esters [[estrone acetate]], [[estrone sulfate (medication)|estrone sulfate]], [[estrone tetraacetylglucoside]], and [[estropipate]] (piperazine estrone sulfate), and the never-marketed esters [[estrone benzoate]], [[estrone cyanate]], [[estrone glucuronide]], and [[estrone sulfamate]].<ref name="Elks2014" /><ref name="IndexNominum2000" />

==History==
{{See also|Estrone#History}}

In 1927, [[Bernhard Zondek]] and [[Selmar Aschheim]] discovered that large amounts of estrogens were [[excretion|excreted]] in the [[urine]] of [[pregnancy|pregnant]] women.<ref name="Josimovich2013">{{cite book | vauthors = Gruhn JG | chapter = Historical Introduction to Gonadal Regulation of the Uterus and the Menses. | veditors = Josimovich JB |title=Gynecologic Endocrinology| chapter-url=https://books.google.com/books?id=9vv2BwAAQBAJ&pg=PA8|date=11 November 2013|publisher=Springer Science & Business Media|isbn=978-1-4613-2157-6|pages=8–}}</ref><ref name="Ravina2011">{{cite book| vauthors = Ravina E |title=The Evolution of Drug Discovery: From Traditional Medicines to Modern Drugs|url=https://books.google.com/books?id=iDNy0XxGqT8C&pg=PA175|date=18 April 2011|publisher=John Wiley & Sons|isbn=978-3-527-32669-3|pages=175–}}</ref> This rich source of estrogens allowed the development of potent estrogenic formulations for [[scientific research|scientific]] and [[clinical medicine|clinical]] use.<ref name="Ravina2011" /><ref name="Bullough1995" /> In 1929, pure crystalline estrone was isolated from the urine of pregnant women by various researchers.<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 2023 |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> By 1929, [[pharmaceutical drug|pharmaceutical preparations]] including ''Amniotin'' ([[Bristol-Myers Squibb|Squibb]]), ''Progynon'' ([[Schering AG|Schering]]), and ''Theelin'' ([[Parke-Davis]]), purified from pregnancy urine, [[placenta]]s, and/or [[amniotic fluid]] and containing purified estrone or [[estrogenic substances|mixtures of estrogens]] that included estrone, were being sold commercially for use by [[intramuscular injection]].<ref name="WallachHammond1982">{{cite journal | vauthors = Hammond CB, Maxson WS | title = Current status of estrogen therapy for the menopause | journal = Fertility and Sterility | volume = 37 | issue = 1 | pages = 5–25 | date = January 1982 | pmid = 6277697 | doi = 10.1016/S0015-0282(16)45970-4 }}</ref><ref name="Bullough1995" /><ref name="pmid18744783" /><ref name="Biskind1935">{{cite journal| vauthors = Biskind MS |title=Commercial Glandular Products|journal=Journal of the American Medical Association|volume=105|issue=9|year=1935|pages=667|issn=0002-9955|doi=10.1001/jama.1935.92760350007009a}}</ref><ref name="Watkins2007">{{cite book| vauthors = Watkins ES |title=The Estrogen Elixir: A History of Hormone Replacement Therapy in America|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="pmid29648134" /> Other products and brand names of estrone marketed in the 1930s included ''Estrone'' ([[Abbott Laboratories|Abbott]], [[Eli Lilly|Lilly]]), ''Oestroform'' ([[British Drug Houses]]), ''Folliculin'' ([[Organon International|Organon]]), ''Menformon'' ([[Organon International|Organon]]), and ''Ketodestrin'' (Paines & Byrne), among others.<ref name="pmid18744783" /><ref name="Biskind1935" /><ref name="pmid29648134">{{cite journal | vauthors = Johnstone RW | title = Sex Hormone Therapy in Gynæcology | journal = Edinburgh Medical Journal | volume = 43 | issue = 11 | pages = 680–695 | date = November 1936 | pmid = 29648134 | pmc = 5303355 }}</ref><ref name="Burrows2003">{{cite book| vauthors = Burrows H |title=Biological Actions of Sex Hormones|url=https://books.google.com/books?id=MFw4AAAAIAAJ&pg=PA558|date=March 2003|publisher=CUP Archive|isbn=978-0-521-04394-6|pages=558–}}</ref> These formulations included [[ampoule]]s of [[oil solution|oil]] or [[aqueous solution]] for [[intramuscular injection]], [[oral administration|oral]] [[tablet (pharmacy)|tablet]]s, and [[vaginal administration|vaginal]] [[suppository|suppositories]].<ref name="pmid29648134" /><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><ref name="Fluhmann1944" /><ref name="Novak1935">{{cite journal| vauthors = Novak E |title=The Therapeutic Use of Estrogenic Substances|journal=JAMA: The Journal of the American Medical Association|volume=104|issue=20|year=1935|pages=1815|issn=0098-7484|doi=10.1001/jama.1935.92760200002012}}</ref> Estrone in [[aqueous suspension]] for use by intramuscular injection was first described in 1941 and was introduced for medical use under the brand name ''Theelin Aqueous Suspension'' by 1944.<ref name="FreedGreenhill1941" /><ref name="Fluhmann1944">{{cite journal| vauthors = Fluhmann CF |title=Clinical use of extracts from the ovaries|journal=Journal of the American Medical Association|volume=125|issue=1|year=1944|pages=1|issn=0002-9955|doi=10.1001/jama.1944.02850190003001}}</ref><ref name="pmid20988414">{{cite journal | vauthors = Freed SC | title = Diethylstilbestrol in aqueous suspension | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 6 | issue = 6 | pages = 420–422 | date = June 1946 | pmid = 20988414 | doi = 10.1210/jcem-6-6-420 | quote = We have already reported our employing injections of estrone crystals suspended in aqueous medium in order to obtain freedom from allergic reactions (1). This preparation, now available commercially, has proven satisfactory not only from this standpoint, but also because of its increased effectiveness over estrone dissolved in oil. }}</ref>

==Society and culture==

===Generic names===
''Estrone'' is the [[generic term|generic name]] of estrone in [[American English]] and its {{abbrlink|INN|International Nonproprietary Name}}, {{abbrlink|USP|United States Pharmacopeia}}, {{abbrlink|BAN|British Approved Name}}, {{abbrlink|DCF|Dénomination Commune Française}}, {{abbrlink|DCIT|Denominazione Comune Italiana}}, and {{abbrlink|JAN|Japanese Accepted Name}}.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Drugs.com">{{Cite web |url=https://www.drugs.com/international/estrone.html |title=Estrone - Drugs.com |access-date=21 June 2018 |archive-date=21 June 2018 |archive-url=https://web.archive.org/web/20180621143924/https://www.drugs.com/international/estrone.html |url-status=dead }}</ref> ''Oestrone'', in which the "O" is silent, was the former {{abbrlink|BAN|British Approved Name}} of estrone and its name in [[British English]],<ref name="Elks2014" /><ref name="MortonHall2012" /><ref name="IndexNominum2000" /> but the spelling was eventually changed to ''estrone''.<ref name="Drugs.com" />

===Brand names===
Estrone has been marketed under a variety of brand names, including Andrestraq, Aquacrine, A.T.V., Bestrone, Centrogen, Cicatral, Cormone, Crinovaryl, Cristallovar, Crystogen, Destrone, Disynformon, Endofolliculina, Estragyn, Estroject, Estrol, Estrone, Estrone Aqueous Suspension, Estrone-A, Estrugenone, Estrusol, Femestrone, Femidyn, Folikrin, Folipex, Folisan, Folliculin, Follicunodis, Follidrin, Gineburno, Glandubolin, Grietalgen, Grietalgen Hidrocort, Gynogen, Hiestrone, Hormofollin, Hormonin, Hormovarine, Kestrin, Kestrone, Ketodestrin, Kolpon, Ladies Pearl, Livifolin, Menagen, Metharmon-F, Neo-Estrone, Oestrilin, Oestrin, Oestroform, Oestroperos, Ovex, Ovifollin, Perlatan, Progynon, Senikolp, Solliculin, Solutio Folliculinum, Synergon (in combination with [[progesterone (medication)|progesterone]]), Theelin, Thynestron, Tokokin, Unden, Unigen, Wehgen, and Wynestron.<ref name="Elks2014" /><ref name="MortonHall2012" /><ref name="IndexNominum2000" /><ref name="Martindale" /><ref name="Drugs.com"/><ref name="Cancer1979">{{cite book|author=International Agency for Research on Cancer|title=Sex Hormones (II).|url=https://books.google.com/books?id=nrhrAAAAMAAJ|year=1979|publisher=International Agency for Research on Cancer|isbn=978-92-832-1221-8}}</ref><ref name="Milne2017">{{cite book | vauthors = Milne GW |title=Ashgate Handbook of Endocrine Agents and Steroids|url=https://books.google.com/books?id=GFM8DwAAQBAJ&pg=PT138|date=1 November 2017|publisher=Taylor & Francis|isbn=978-1-351-74347-1|pages=138–}}</ref>

Brand names of estrone in aqueous suspension specifically include Bestrone, Estaqua, Estrofol, Estroject, Estrone-A, Estronol, Femogen, Foygen Aqueous, Gravigen Aqueous, Gynogen, Hormogen-A, Kestrin Aqueous, Kestrone, Theelin Aqueous, Theogen, Unigen, and Wehgen.<ref name="Convention1987">{{cite book|author=Inc United States Pharmacopeial Convention|title=Drug Information for the Health Care Provider|url=https://books.google.com/books?id=qYYQipCXoVcC|date=February 1987|publisher=United States Pharmacopeial|isbn=978-0-913595-15-2|pages=765, 770}}</ref>

===Availability===
{{See also|Estropipate#Availability|Conjugated estrogens#Availability|Esterified estrogens#Availability}}

Although estrone has been widely marketed in the past, it has mostly been discontinued and remains available in only a few countries.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> These countries reportedly include [[Canada]], [[Georgia (country)|Georgia]], [[Monaco]], and [[Taiwan]].<ref name="Drugs.com" /> However, estrone remains widely available throughout the world in the form of [[estrone sulfate (medication)|estrone sulfate]], which can be found in [[estropipate]] (piperazine estrone sulfate), [[conjugated estrogens]] (Premarin), and [[esterified estrogens]] (Estratab, Menest).<ref name="IndexNominum2000" /><ref name="Drugs.com-Estropipate">{{cite web |url=https://www.drugs.com/international/estropipate.html |title=Estropipate |author=<!--Not stated--> |website=Drugs.com }}</ref>

==Research==
An estrone [[vaginal ring]] was developed and studied for use in menopausal hormone therapy.<ref name="pmid7231201">{{cite journal | vauthors = Sipinen S, Lähteenmäki P, Luukkainen T | title = An oestrone-releasing vaginal ring in the treatment of climacteric women | journal = Maturitas | volume = 2 | issue = 4 | pages = 291–9 | date = December 1980 | pmid = 7231201 | doi = 10.1016/0378-5122(80)90031-6 }}</ref> It increased estrogen levels, suppressed [[gonadotropin]] levels, and relieved menopausal symptoms.<ref name="pmid7231201" /> [[Subcutaneous implant|Subcutaneous pellet implantation]] of estrone has also been studied.<ref name="pmid20781420">{{cite journal | vauthors = Bishop PM | title = Clinical Experiment in Oestrin Therapy | journal = Br Med J | volume = 1 | issue = 4034 | pages = 939–41 | date = April 1938 | pmid = 20781420 | pmc = 2086334 | doi = 10.1136/bmj.1.4034.939 }}</ref><ref name="pmid14862159">{{cite journal | vauthors = Bishop PM, Folley SJ | title = Absorption of hormone implants in man | journal = Lancet | volume = 2 | issue = 6676 | pages = 229–32 | date = August 1951 | pmid = 14862159 | doi = 10.1016/S0140-6736(51)93237-0 }}</ref>

==See also==
* [[Estradiol/estrone/estriol]]
* [[Estrone/progesterone]]
* [[Estrogenic substances]]

==References==
{{Reflist}}

==Further reading==
{{refbegin}}
* {{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|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-60107-1}}
* {{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 | year = 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf}}
{{refend}}

{{Estrogens and antiestrogens}}
{{Estrogen receptor modulators}}

[[Category:Abandoned drugs]]
[[Category:Hydroxyarenes]]
[[Category:Sterols]]
[[Category:Estranes]]
[[Category:Estrogens]]
[[Category:Ketones]]
[[Category:Sex hormone esters and conjugates]]