Estetrol (medication)のソースを表示

{{Short description|Estrogen medication}}
{{About|estetrol as a medication|its role as a hormone|Estetrol}}
{{Drugbox
| Verifiedfields =
| Watchedfields =
| verifiedrevid = 437385642
| drug_name = Estetrol
| image = Estetrol.svg
| alt = Skeletal formula of estetrol
| width = 235px
| image2 = Estetrol 3D ball.png
| alt2 = Ball-and-stick model of the estetrol molecule
| width2 = 225px

<!-- Clinical data -->
| pronounce =
| tradename = ''With [[drospirenone]]:'' Estelle, Nextstellis
| Drugs.com =
| MedlinePlus =
| licence_EU = <!-- EMA uses INN (or special INN_EMA) -->
| DailyMedID = <!-- DailyMed may use generic or brand name (generic name preferred) -->
| licence_US = <!-- FDA may use generic or brand name (generic name preferred) -->
| pregnancy_AU = B3
| pregnancy_AU_comment = <ref>{{Cite web |date=21 December 2022 |title=Updates to the Prescribing Medicines in Pregnancy database |url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database |access-date=2 January 2023 |website=Therapeutic Goods Administration (TGA)}}</ref>
| pregnancy_category=
| routes_of_administration = [[Oral administration|By mouth]]<ref name="pmid18464023" /><ref name="pmid19167495" />
| class = [[Estrogen (medication)|Estrogen]]
| ATC_prefix = None
| ATC_suffix =
| ATC_supplemental = {{ATC|G03|AA18}}

<!-- Legal status -->
| legal_AU = <!-- S2, S3, S4, S5, S6, S7, S8, S9 or Unscheduled -->
| legal_AU_comment =
| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->
| legal_BR_comment =
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_CA_comment =
| legal_DE = <!-- Anlage I, II, III or Unscheduled -->
| legal_DE_comment =
| legal_NZ = <!-- Class A, B, C -->
| legal_NZ_comment =
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->
| legal_UK_comment =
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_US_comment =
| legal_EU =
| legal_EU_comment =
| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->
| legal_UN_comment =
| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->
| bioavailability = High<ref name="pmid18464021">{{Cite journal |vauthors=Visser M, Holinka CF, Coelingh Bennink HJ |date=2008 |title=First human exposure to exogenous single-dose oral estetrol in early postmenopausal women |journal=Climacteric |volume=11 |issue=Suppl 1 |pages=31–40 |doi=10.1080/13697130802056511 |pmid=18464021 |s2cid=23568599}}</ref>
| protein_bound = Moderately to [[human serum albumin|albumin]], not to {{abbrlink|SHBG|sex hormone-binding globulin}}<ref name="pmid18464021" /><ref name="pmid18464022">{{Cite journal |vauthors=Hammond GL, Hogeveen KN, Visser M, Coelingh Bennink HJ |date=2008 |title=Estetrol does not bind sex hormone binding globulin or increase its production by human HepG2 cells |journal=Climacteric |volume=11 |issue=Suppl 1 |pages=41–6 |doi=10.1080/13697130701851814 |pmid=18464022 |s2cid=22715507}}</ref>
| metabolism = Minimal, [[conjugation (biochemistry)|conjugation]] ([[glucuronidation]], [[sulfation]])<ref name="pmid18464023" /><ref name="pmid26212489">{{Cite journal |vauthors=Mawet M, Maillard C, Klipping C, Zimmerman Y, Foidart JM, Coelingh Bennink HJ |date=2015 |title=Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives |journal=Eur J Contracept Reprod Health Care |volume=20 |issue=6 |pages=463–75 |doi=10.3109/13625187.2015.1068934 |doi-broken-date=1 November 2024 |pmc=4699469 |pmid=26212489}}</ref>
| metabolites = Estetrol glucuronide<ref name="pmid26212489" /><ref name="pmid18464023" /><br />Estetrol sulfate<ref name="pmid26212489" />
| elimination_half-life = Mean: 28 hours<ref name="pmid18464021" /><ref name="pmid26212489" /><br />Range: 18–60 hours<ref name="pmid18464021" />
| excretion = [[Urine]]: 79.7% (as [[conjugation (biochemistry)|conjugate]]s)<ref name="pmid18464023" /><ref name="pmid26212489" />

<!--Identifiers-->
| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 15183-37-6
| CAS_supplemental =
| PubChem = 27125
| IUPHAR_ligand =
| DrugBank_Ref =
| DrugBank = DB12235
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 25245
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = ENB39R14VF
| KEGG_Ref =
| KEGG = D11513
| ChEBI_Ref =
| ChEBI = 142773
| ChEMBL_Ref =
| ChEMBL = 1230314
| NIAID_ChemDB =
| PDB_ligand = 4OH
| synonyms = Oestetrol; E4; 15α-Hydroxyestriol; Estra-1,3,5(10)-triene-3,15α,16α,17β-tetrol

<!-- Chemical and physical data -->
| IUPAC_name = (8''R'',9''S'',13''S'',14''S'',15''R'',16''R'',17''R'')-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[''a'']phenanthrene-3,15,16,17-tetrol
| C=18 | H=24 | O=4
| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1[C@H]([C@H]([C@@H]2O)O)O)CCC4=C3C=CC(=C4)O
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C18H24O4/c1-18-7-6-12-11-5-3-10(19)8-9(11)2-4-13(12)14(18)15(20)16(21)17(18)22/h3,5,8,12-17,19-22H,2,4,6-7H2,1H3/t12-,13-,14-,15-,16-,17+,18+/m1/s1
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = AJIPIJNNOJSSQC-NYLIRDPKSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility = 1.38
| sol_units =
| specific_rotation =
}}

<!-- Definition and medical uses -->
'''Estetrol''' ('''E4''') is an [[estrogen (medication)|estrogen]] medication and [[natural product|naturally occurring]] [[steroid hormone]] which is used in combination with a [[progestin]] in [[combined birth control pill]]s and is under development for various other indications. These investigational uses include [[menopausal hormone therapy]] to treat symptoms such as [[vaginal atrophy]], [[hot flash]]es, and [[osteoporosis|bone loss]] and the treatment of [[breast cancer]] and [[prostate cancer]].<ref name="pmid18464023">{{Cite journal |vauthors=Coelingh Bennink HJ, Holinka CF, Diczfalusy E |date=2008 |title=Estetrol review: profile and potential clinical applications |journal=Climacteric |volume=11 |issue=Suppl 1 |pages=47–58 |doi=10.1080/13697130802073425 |pmid=18464023 |s2cid=24003341}}</ref><ref name="pmid19167495">{{Cite journal |vauthors=Visser M, Coelingh Bennink HJ |date=March 2009 |title=Clinical applications for estetrol |url=http://www.kup.at/kup/pdf/9090.pdf |journal=J. Steroid Biochem. Mol. Biol. |volume=114 |issue=1–2 |pages=85–9 |doi=10.1016/j.jsbmb.2008.12.013 |pmid=19167495 |s2cid=32081001}}</ref><ref name="AdisInsight-E4">{{Cite web |title=Estetrol - Mithra Pharmaceuticals - AdisInsight |url=http://adisinsight.springer.com/drugs/800044874}}</ref><ref name="AdisInsight-E4/DRSP">{{Cite web |title=Drospirenone/estetrol - Mithra Pharmaceuticals |url=https://adisinsight.springer.com/drugs/800034634 |website=AdisInsight |publisher=Springer Nature Switzerland AG}}</ref> It is taken [[oral administration|by mouth]].<ref name="pmid18464023" /><ref name="pmid19167495" />

<!-- Side effects and mechanism -->
Estetrol 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="pmid18464023" /><ref name="pmid19167495" /> Due to its estrogenic activity, estetrol has [[antigonadotropic]] effects and can inhibit [[fertility]] and suppress [[sex hormone]] [[biosynthesis|production]] and levels in both women and men.<ref name="pmid18464023" /><ref name="pmid18464021" /><ref name="DutmanZimmerman2017" /> Estetrol differs in various ways both from other natural estrogens like [[estradiol (medication)|estradiol]] and [[synthetic compound|synthetic]] estrogens like [[ethinylestradiol]], with implications for [[tolerability]] and [[drug safety|safety]].<ref name="pmid18464023" /><ref name="pmid18464021" /> For instance, it appears to have minimal estrogenic effects in the [[breast]]s and [[liver]].<ref name="pmid18464023" /><ref name="pmid18464021" /><ref name="pmid25359896" /><ref name="pmid26212489" /> Estetrol interacts with nuclear ERα in a manner identical to that of the other estrogens <ref>{{Cite journal |display-authors=6 |vauthors=Abot A, Fontaine C, Buscato M, Solinhac R, Flouriot G, Fabre A, Drougard A, Rajan S, Laine M, Milon A, Muller I, Henrion D, Adlanmerini M, Valéra MC, Gompel A, Gerard C, Péqueux C, Mestdagt M, Raymond-Letron I, Knauf C, Ferriere F, Valet P, Gourdy P, Katzenellenbogen BS, Katzenellenbogen JA, Lenfant F, Greene GL, Foidart JM, Arnal JF |date=October 2014 |title=The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation |journal=EMBO Molecular Medicine |volume=6 |issue=10 |pages=1328–1346 |doi=10.15252/emmm.201404112 |pmc=4287935 |pmid=25214462}}</ref> and distinct from that observed with Selective Estrogen Receptor Modulators (SERMs).<ref name=":0">Foidart, JM; et al. (2019). "30th Annual Meeting of The North America Menopause Society September 25 – 28, 2019, Chicago, IL". Menopause. 26 (12): 1445–1481. doi:10.1097/GME.0000000000001456. ISSN 1530-0374</ref>

<!-- History, society, and culture -->
Estetrol was first discovered in 1965, and basic research continued up until 1984.<ref name="pmid18464023" /><ref name="pmid14303250" /> It started to be studied again as well as investigated for potential medical use in 2001, and by 2008, was of major interest for possible medical use.<ref name="pmid18464023" /><ref name="pmid19167495" /> As of 2021, estetrol is in mid- to late-stage clinical development for a variety of indications.<ref name="AdisInsight-E4" /><ref name="AdisInsight-E4/DRSP" />

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{{Estrogen dosages for menopausal hormone therapy}}