View source for Estradiol enantate

{{Distinguish|Ethinylestradiol}}
{{Drugbox
| Verifiedfields = 
| Watchedfields = 
| verifiedrevid = 
| IUPAC_name = [(8''R'',9''S'',13''S'',14''S'',17''S'')-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[''a'']phenanthren-17-yl] heptanoate
| image = Estradiol enanthate.png
| width = 250px
| image2 = Estradiol enanthate molecule ball.png
| width2 = 250px

<!--Clinical data-->
| tradename = Perlutal, Topasel, Unalmes, Yectames, others
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category = 
| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA = 
| legal_UK = 
| legal_US = 
| legal_status = Rx-only
| routes_of_administration = [[Intramuscular injection]]<ref name="pmid8910663" /><ref name="pmid12290848" />
| class = [[Estrogen (medication)|Estrogen]]; [[Estrogen ester]]

<!--Pharmacokinetic data-->
| bioavailability = {{abbr|IM|Intramuscular injection}}: High
| protein_bound = Estradiol: ~98% (to [[human serum albumin|albumin]] and {{abbrlink|SHBG|sex hormone-binding globulin}})<ref name="pmid23375353">{{cite journal|last1=Stanczyk|first1=Frank Z.|last2=Archer|first2=David F.|last3=Bhavnani|first3=Bhagu R.|title=Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment|journal=Contraception|volume=87|issue=6|year=2013|pages=706–727|issn=0010-7824|doi=10.1016/j.contraception.2012.12.011|pmid=23375353}}</ref><ref name="FalconeHurd2007">{{cite book|author1=Tommaso Falcone|author2=William W. Hurd|title=Clinical Reproductive Medicine and Surgery|url=https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA22|year=2007|publisher=Elsevier Health Sciences|isbn=0-323-03309-1|pages=22,362,388}}</ref>
| metabolism = [[Bond cleavage|Cleavage]] via [[esterase]]s in the [[liver]], [[blood]], and [[tissue (biology)|tissue]]s<ref name="OettelSchillinger2012" /><ref name="pmid16112947" />
| metabolites = [[Estradiol (medication)|Estradiol]], [[heptanoic acid]], and [[metabolite]]s of estradiol<ref name="OettelSchillinger2012" /><ref name="pmid16112947" />
| elimination_half-life = {{abbr|IM|Intramuscular injection}}: 5.6–7.5&nbsp;days<ref name="pmid3814225" /><ref name="pmid8910663" /><ref name="pmid8013220" /><ref name="ConsultaRemédios">{{cite web | url = https://consultaremedios.com.br/algestona-acetofenida-enantato-de-estradiol/bula | archive-url = https://web.archive.org/web/20180918105310/https://consultaremedios.com.br/algestona-acetofenida-enantato-de-estradiol/bula | archive-date = 2018-09-18 | title = Bula do Algestona Acetofenida + Enantato de Estradiol | website = Consulta Remédios | accessdate = 2018-09-18 | format = HTML}}</ref>
| duration_of_action = {{abbr|IM|Intramuscular injection}} (10 mg): ~20–30 days<ref name="pmid8013219" /><ref name="OettelSchillinger2012" />
| excretion = [[Urine]]<ref name="pmid8910663" />

<!-- Identifiers -->
| CAS_number_Ref = 
| CAS_number = 4956-37-0
| CAS_supplemental = 
| ATC_prefix = G03
| ATC_suffix = CA03
| ATC_supplemental = 
| PubChem = 21070
| IUPHAR_ligand = 
| DrugBank_Ref = 
| DrugBank = 
| ChemSpiderID_Ref = 
| ChemSpiderID = 19815
| UNII = PAP315WZIA
| KEGG = D04064
| ChEBI = 
| ChEMBL = 1697792
| synonyms = EE; E2E; E2-EN; EEn; Estradiol enanthate; Estradiol heptanoate; SQ-16150

<!--Chemical data-->
| C=25 | H=36 | O=3
| molecular_weight = 384.56 g/mol
| SMILES = CCCCCCC(=O)O[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4=C3C=CC(=C4)O)C
| StdInChI_Ref = 
| StdInChI = 1S/C25H36O3/c1-3-4-5-6-7-24(27)28-23-13-12-22-21-10-8-17-16-18(26)9-11-19(17)20(21)14-15-25(22,23)2/h9,11,16,20-23,26H,3-8,10,12-15H2,1-2H3/t20-,21-,22+,23+,25+/m1/s1
| StdInChIKey_Ref = 
| StdInChIKey = RFWTZQAOOLFXAY-BZDYCCQFSA-N
}}
<!-- Definition and medical uses -->
'''Estradiol enantate''' ('''E2-EN''' or '''EEn'''), also spelled '''estradiol enanthate''' and sold under the brand names '''Perlutal''' and '''Topasel''' among others, is an [[estrogen (medication)|estrogen]] medication which is used in [[hormonal contraception|hormonal birth control]] for women.<ref name="pmid8910663">{{cite journal | vauthors = Jarquín González JD, Elda de Aguirre L, Rodríguez C, Abrego de Aguilar M, Carrillo F, León DA, Lima M, Trigueros S, Acosta R | title = Dihydroxyprogesterone acetophenide 150 mg + estradiol enantate 10 mg as monthly injectable contraceptives | journal = Adv Contracept | volume = 12 | issue = 3 | pages = 213–25 | date = September 1996 | pmid = 8910663 | doi = 10.1007/BF01849664   | url = }}</ref><ref name="pmid12290848" /><ref name="BagadePawar2014">{{cite journal | vauthors = Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S | title = Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control | journal = World J Pharm Pharm Sci | volume = 3 | issue = 10 | pages = 364–392 | year = 2014 | issn = 2278-4357 | doi = | url = http://www.wjpps.com/download/article/1412071798.pdf}}</ref> It is formulated in [[combination drug|combination]] with [[dihydroxyprogesterone acetophenide]] (DHPA; algestone acetophenide), a [[progestin]], and is used specifically as a [[combined injectable contraceptive]].<ref name="pmid8910663" /><ref name="pmid12290848" /> Estradiol enantate is not available for medical use alone.<ref name="Martindale" /><ref name="Micromedex" /><ref name="Drugs.com" /><ref name="IndexNominum2000" /> The medication, in combination with DHPA, is given by [[intramuscular injection|injection into muscle]] once a month.<ref name="pmid8910663" /><ref name="pmid12290848" />

<!-- Side effects and mechanism -->
[[Side effect]]s of estradiol enantate include [[breast tenderness]], [[breast enlargement]], [[nausea]], [[headache]], and [[water retention (medicine)|fluid retention]].<ref name="Ghosh2010" /> Estradiol enantate is a [[synthetic compound|synthetic]] [[estrogen (medication)|estrogen]] and hence is an [[agonist]] of the [[estrogen receptor]], the [[biological target]] of [[estrogen]]s like [[estradiol]].<ref name="pmid16112947">{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 Suppl 1 | issue = | pages = 3–63 | year = 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | url = http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf}}</ref><ref name="OettelSchillinger2012" /> It is an [[estrogen ester]] and a long-lasting [[prodrug]] of [[estradiol (medication)|estradiol]] in the body.<ref name="OettelSchillinger2012">{{cite book|author1=Michael Oettel|author2=Ekkehard Schillinger|title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen|url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA261|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-60107-1|pages=261,271|quote=Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens. [...] Wiemeyer et al. (1986) measured elevated estradiol levels up to 31 days after an intramuscular dose of 10mg estradiol enanthate.}}</ref><ref name="pmid16112947" /> Because of this, it is considered to be a [[natural product|natural]] and [[bioidentical hormone replacement therapy|bioidentical]] form of estrogen.<ref name="OettelSchillinger2012" /><ref name="ArunNarendra2012">{{cite book|author1=Nagrath Arun|author2=Malhotra Narendra|author3=Seth Shikha|title=Progress in Obstetrics and Gynecology--3|url=https://books.google.com/books?id=AS3UBAAAQBAJ&pg=PA419|date=15 December 2012|publisher=Jaypee Brothers Medical Publishers Pvt. Ltd.|isbn=978-93-5090-575-3|pages=419–}}</ref>

<!-- History, society, and culture -->
Estradiol enantate was first described by 1954,<ref name="Symposium1954" /> and was first studied in combination with DHPA as a combined injectable contraceptive in 1964.<ref name="pmid14236841" /><ref name="pmid14236842" /> The combination was introduced for clinical use by the mid-1970s.<ref name="BringerHedon1995" /><ref name="pmid865726" /><ref name="pmid8013216" /> Estradiol enantate is not available as a standalone medication (i.e., by itself without DHPA).<ref name="IndexNominum2000" /> The combination is available in [[Latin America]] and [[Hong Kong]], and was also previously marketed in [[Spain]] and [[Portugal]].<ref name="IndexNominum2000" /><ref name="pmid12290848" /><ref name="Micromedex" />

{{TOC limit|3}}

==Medical uses==
{{See also|Estradiol (medication)#Medical uses}}

Estradiol enantate is used in combination with the progestin DHPA as a once-monthly combined injectable contraceptive for women in [[Latin America]] and [[Hong Kong]].<ref name="pmid8910663" /><ref name="pmid12290848" /><ref name="Zutshi2005">{{cite book | author = Zutshi | title = Hormones in Obstetrics and Gynaecology | url = https://books.google.com/books?id=IBxBbaDjXw0C&pg=PA138 | accessdate = 20 May 2012 | date = 1 January 2005 | publisher = Jaypee Brothers Publishers | isbn = 978-81-8061-427-9 | page = 138}}</ref><ref name="IndexNominum2000" /> Estradiol enantate has been studied in [[feminizing hormone therapy]] for transgender women as well.<ref name="pmid10604171">{{cite journal | vauthors = Becerra Fernández A, de Luis Román DA, Piédrola Maroto G | title = Morbilidad en pacientes transexuales con autotratamiento hormonal para cambio de sexo | trans-title = Morbidity in transsexual patients with cross-gender hormone self-treatment | language = Spanish| journal = Med Clin (Barc) | volume = 113 | issue = 13 | pages = 484–7 | date = October 1999 | issn = 0025-7753 | pmid = 10604171 | doi = | url = https://www.saludtrans.cl/wp-content/uploads/2012/10/morbilidad-automedicacic3b3n-en-transexuales.pdf}}</ref> The combination of estradiol enantate and DHPA has likewise been used by transgender women (referred to as "[[travesti (gender identity)|travesti]]s" in some [[culture]]s, especially in [[South America]]) for such purposes.<ref name="Kulick2009">{{cite book|author=Don Kulick|title=Travesti: Sex, Gender, and Culture among Brazilian Transgendered Prostitutes|url=https://books.google.com/books?id=jbZyBfio-hcC&pg=PA64|date=12 January 2009|publisher=University of Chicago Press|isbn=978-0-226-46101-4|pages=64–66}}</ref>

===Available forms===
{{See also|Estradiol enantate/algestone acetophenide|Estradiol/estradiol enanthate}}

The following forms of estradiol enantate are or have been available for use:<ref name="BagadePawar2014" /><ref name="HumansOrganization2007">{{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=World Health Organization|author3=International Agency for Research on Cancer|title=Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy|url=https://books.google.com/books?id=aGDU5xibtNgC&pg=PA431|year=2007|publisher=World Health Organization|isbn=978-92-832-1291-1|pages=431–433,467}}</ref><ref name="HumansCancer1999">{{cite book|author1=IARC Working Group on the Evaluation of Carcinogenic Risks to Humans|author2=International Agency for Research on Cancer|title=Hormonal Contraception and Post-menopausal Hormonal Therapy|date=1 January 1999|publisher=IARC|isbn=978-92-832-1272-0|page=65|url=https://monographs.iarc.fr/wp-content/uploads/2018/06/mono72.pdf#page=76}}</ref><ref name="pmid8013216" /><ref name="pmid12290848">{{cite journal | vauthors = Newton JR, D'arcangues C, Hall PE | title = A review of "once-a-month" combined injectable contraceptives | journal = J Obstet Gynaecol (Lahore) | volume = 4 Suppl 1 | issue = | pages = S1–34 | year = 1994 | pmid = 12290848 | doi = 10.3109/01443619409027641 | url = }}</ref>

* Estradiol enantate 10&nbsp;mg and DHPA 150&nbsp;mg (brand names Perlutal, Topasel, many others)
* Estradiol enantate 5&nbsp;mg and DHPA 75&nbsp;mg (brand names Anafertin, Patector NF, Yectames)
* Estradiol enantate 10&nbsp;mg and DHPA 120&nbsp;mg (brand names Unalmes, Yectuna)
* Estradiol enantate 10&nbsp;mg and DHPA 75&nbsp;mg (brand name Ova Repos; discontinued)

A 6&nbsp;mg estradiol enantate and 90&nbsp;mg DHPA formulation was also studied, but was never marketed.<ref name="d’ArcanguesSnow1999">{{cite journal|last1=d’Arcangues|first1=Catherine|last2=Snow|first2=Rachel C.|title=Injectable Contraceptives|year=1999|pages=121–149|doi=10.1007/978-3-642-86696-8_6}}</ref><ref name="pmid9115007">{{cite journal | vauthors = Coutinho EM, Spinola P, Barbosa I, Gatto M, Tomaz G, Morais K, Yazlle ME, de Souza RN, Pinho Neto JS, Leal Wde B, Leal C, Hippolito SB, Abranches AD | title = Multicenter, double-blind, comparative clinical study on the efficacy and acceptability of a monthly injectable contraceptive combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate compared to a monthly injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide and 6 mg estradiol enanthate | journal = Contraception | volume = 55 | issue = 3 | pages = 175–81 | date = March 1997 | pmid = 9115007 | doi = 10.1016/S0010-7824(97)00018-8 | url = }}</ref><ref name="pmid10899484">{{cite journal | vauthors = Coutinho EM, Spinola P, Tomaz G, Morais K, Nassar de Souza R, Sabino Pinho Neto J, de Barros Leal W, Bomfim Hippolito S, D'Aurea Abranches A | title = Efficacy, acceptability, and clinical effects of a low-dose injectable contraceptive combination of dihydroxyprogesterone acetophenide and estradiol enanthate | journal = Contraception | volume = 61 | issue = 4 | pages = 277–80 | date = April 2000 | pmid = 10899484 | doi = 10.1016/S0010-7824(00)00099-8 | url = }}</ref> The combination of estradiol enantate and DHPA has also been studied at other doses ranging from 5 to 50&nbsp;mg estradiol enantate and 75 to 200&nbsp;mg DHPA.<ref name="pmid8013221">{{cite journal | vauthors = Koetsawang S | title = Once-a-month injectable contraceptives: efficacy and reasons for discontinuation | journal = Contraception | volume = 49 | issue = 4 | pages = 387–98 | date = April 1994 | pmid = 8013221 | doi = 10.1016/0010-7824(94)90034-5 | url = }}</ref>

The combination of estradiol enantate and DHPA is provided in [[ampoule]]s at estradiol enantate concentrations of 5&nbsp;mg/mL and 10&nbsp;mg/mL.

{{Available forms of estradiol}}

==Contraindications==
{{See also|Estradiol (medication)#Contraindications}}

[[Contraindication]]s of estrogens include [[coagulation]] problems, [[cardiovascular disease]]s, [[liver disease]], and certain [[hormone-sensitive cancer]]s such as [[breast cancer]] and [[endometrial cancer]], among others.<ref name="pmid2215269" /><ref name="LauritzenStudd2005">{{cite book|author1=Christian Lauritzen|author2=John W. W. Studd|title=Current Management of the Menopause|url=https://books.google.com/books?id=WD7S7677xUUC&pg=PA95|date=22 June 2005|publisher=CRC Press|isbn=978-0-203-48612-2|pages=95–98,488}}</ref><ref name="Lauritzen2001">{{cite book | last1 = Laurtizen | first1 = Christian | chapter = Hormone Substitution Before, During and After Menopause | pages = 67–88 | url = https://www.kup.at/kup/pdf/4978.pdf | editor1-last = Fisch | editor1-first = Franz H. | title = Menopause – Andropause: Hormone Replacement Therapy Through the Ages | year = 2001 | publisher = Krause & Pachernegg: Gablitz | isbn = 978-3-901299-34-6}}</ref><ref name="Midwinter1976">{{cite book|last1=Midwinter|first1=Audrey|chapter=Contraindications to estrogen therapy and management of the menopausal syndrome in these cases|pages=377–382|doi=10.1007/978-94-011-6165-7_33|editor1-last=Campbell|editor1-first=Stuart|title=The Management of the Menopause & Post-Menopausal Years: The Proceedings of the International Symposium held in London 24–26 November 1975 Arranged by the Institute of Obstetrics and Gynaecology, The University of London|year=1976|isbn=978-94-011-6167-1|publisher=MTP Press Limited}}</ref>

==Side effects==
{{Main article|Estradiol (medication)#Side effects}}

The [[side effect]]s of estradiol enantate are the same as those of estradiol. Examples of such side effects include [[breast tenderness]] and [[breast enlargement|enlargement]], [[nausea]], [[bloating]], [[edema]], [[headache]], and [[melasma]].<ref name="Ghosh2010">{{cite book|author=Amit K. Ghosh|title=Mayo Clinic Internal Medicine Board Review|url=https://books.google.com/books?id=LS65jBzoD40C&pg=PA222|date=23 September 2010|publisher=OUP USA|isbn=978-0-19-975569-1|pages=222–}}</ref> The combination of estradiol enantate and DHPA as a combined injectable contraceptive has shown no adverse effects on [[liver]] function, [[lipid metabolism]], or [[coagulation]].<ref name="pmid9404550" /><ref name="pmid12290848" />

A [[case report]] of a [[prolactinoma]] in a [[transgender women]] treated with 10&nbsp;mg estradiol enantate every 2&nbsp;weeks exists.<ref name="CamaraZanardi2010">Camara, V. L., Zanardi, U. V., Glezer, A., Paraiba, D. B., Bronstein, M. D., Mendonca, B. B., & Costa, E. M. F. (2010, June). Estrogen as a Presumed Risk Factor for Prolactinoma in a Male-to-Female Transsexual Patient. Endocrine Reviews, Supplement 1, 31(3), S347–S347. 10.1210/endo-meetings.2010.PART1.P6.P1-288. https://www.endocrine.org/-/media/endocrine/files/endo-annual-meetings/endo_abstracts_2010_02.pdf</ref><ref>Camara, V. L. (2010). Estradiol enantate First report of prolactinoma, in a transsexual. Reactions, 1311, 24. 10.2165/00128415-201013110-00077. https://link.springer.com/article/10.2165/00128415-201013110-00077</ref>

==Overdose==
{{See also|Estradiol (medication)#Overdose}}

Estradiol enantate has been studied at very high doses of up to 100 to 200&nbsp;mg per month by [[intramuscular injection]], without overt signs of acute [[toxicity]] observed.<ref name="pmid10604171" /> [[Symptom]]s of estrogen [[overdose|overdosage]] may include [[nausea]], [[vomiting]], [[bloating]], [[weight gain|increased weight]], [[water retention (medicine)|water retention]], [[breast tenderness]], [[vaginal discharge]], [[heavy legs]], and [[leg cramps]].<ref name="pmid2215269">{{cite journal | vauthors = Lauritzen C | title = Clinical use of oestrogens and progestogens | journal = Maturitas | volume = 12 | issue = 3 | pages = 199–214 | date = September 1990 | pmid = 2215269 | doi = 10.1016/0378-5122(90)90004-P | url = }}</ref> These side effects can be diminished by reducing the estrogen dosage.<ref name="pmid2215269" />

==Interactions==
{{See also|Estradiol (medication)#Interactions}}

[[Enzyme inhibitor|Inhibitor]]s and [[enzyme inducer|inducer]]s of [[cytochrome P450]] may influence the [[metabolism]] of estradiol and by extension circulating estradiol levels.<ref name="pmid11741520">{{cite journal |vauthors=Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH | title = Role of cytochrome P450 in estradiol metabolism in vitro | journal = Acta Pharmacol. Sin. | volume = 22 | issue = 2 | pages = 148–54 |date=February 2001 | pmid = 11741520 | doi = | url = }}</ref>

==Pharmacology==
[[File:Estradiol.svg|thumb|right|225px|[[Estradiol (medication)|Estradiol]], the [[active metabolite|active form]] of estradiol enantate.]]

===Pharmacodynamics===
{{See also|Pharmacodynamics of estradiol}}

Estradiol enantate is an [[estradiol ester]], or a [[prodrug]] of [[estradiol (medication)|estradiol]].<ref name="OettelSchillinger2012" /><ref name="pmid16112947" /> As such, it is an [[estrogen (medication)|estrogen]], or an [[agonist]] of the [[estrogen receptor]]s.<ref name="OettelSchillinger2012" /><ref name="pmid16112947" /> Estradiol enantate is of about 41% higher [[molecular weight]] than estradiol due to the presence of its C17β [[enanthic acid|enantate]] ester.<ref name="Elks2014" /><ref name="IndexNominum2000" /> Because estradiol enantate is a prodrug of estradiol, it is considered to be a [[natural product|natural]] and [[bioidentical hormone replacement therapy|bioidentical]] form of estrogen.<ref name="OettelSchillinger2012" /><ref name="ArunNarendra2012" />

The combination of 10&nbsp;mg estradiol enantate and 150&nbsp;mg DHPA as a once-monthly combined injectable contraceptive (which achieves levels of estradiol of around 350&nbsp;pg/mL)<ref name="pmid8013219" /><ref name="pmid3769482" /><ref name="pmid3396358" /> has been found to have little to no effect on many markers of estrogen-modulated [[liver protein synthesis]], including circulating levels of [[HDL cholesterol|HDL]] and [[LDL cholesterol]], [[copper]], [[ceruloplasmin]], total and free [[cortisol]], [[corticosteroid-binding globulin]], and [[sex hormone-binding globulin]].<ref name="pmid2117515">{{cite journal | vauthors = Wiemeyer JC, Sagasta CL, Roncales Mateo JM, Lavarello AC, Angel de Toro LA, Salas Diaz R | title = Multicentred clinical study of the metabolic effect of the monthly injectable contraceptive containing dihydroxyprogesterone acetophenide 150 mg + estradiol enanthate 10 mg | journal = Contraception | volume = 42 | issue = 1 | pages = 13–28 | date = July 1990 | pmid = 2117515 | doi = 10.1016/0010-7824(90)90088-D | url = }}</ref> However, it was found to significantly increase levels of [[triglyceride]]s and to significantly decrease levels of total and free [[testosterone]].<ref name="pmid2117515" /> In contrast to the estradiol enantate-containing combined injectable contraceptive, an [[ethinylestradiol]]-containing [[birth control pill]] produced highly significant changes in all of the preceding parameters.<ref name="pmid2117515" />

Studies in women and female [[capuchin monkey]]s have found that injections of estradiol enantate and DHPA significantly alter levels of [[coagulation factor]]s.<ref name="OlivaFilhoSantos1992">Oliva Filho, W. M., & Santos, N. da C. (1992). Efeitos na coagulação sanguinea em usuárias da associação acetofenido de dihidroxiprogesterona 150mg e enantato de estradiol 10mg como metodo anticoncepcional injetavel. Universidade de São Paulo, São Paulo. https://bdpi.usp.br/item/000736190</ref><ref name="TavaresBelham2018">{{cite journal|last1=Tavares|first1=Maria Clotilde H.|last2=Belham|first2=Flávia Schechtman|last3=Duarte|first3=Rosangela Correa Rodrigues|title=Risco de doenca tromboliticas apos o uso de algestona acetofenida e enantato de estradiol|journal=Revista de Patologia do Tocantins|volume=5|issue=1|year=2018|pages=17|issn=2446-6492|doi=10.20873/uft.2446-6492.2018v5n1p17}}</ref>

The clinical [[estrogen (medication)|estrogen]]ic effects of estradiol enantate and [[ethinylestradiol]] have been compared in other studies as well.<ref name="pmid3101711">{{cite journal | vauthors = Moguilevsky JA, Wiemeyer JC, Sagasta CL, Leiderman S | title = Estrogenic activities of estradiol enantate and ethinylestradiol compared at a clinical level | journal = Arzneimittelforschung | volume = 36 | issue = 11 | pages = 1671–4 | date = November 1986 | pmid = 3101711 | doi = | url = }}</ref>

{{Parenteral potencies and durations of steroidal estrogens}}

===Pharmacokinetics===
{{See also|Pharmacokinetics of estradiol}}

When estradiol enantate is administered in an [[oil solution]] by [[intramuscular injection]], a [[depot injection|depot]] effect occurs, and this results in it having a long [[duration of action]].<ref name="pmid8013219" /><ref name="pmid16112947" /><ref name="pmid1231448" /> The duration of action of estradiol enantate is considerably longer than that of various other [[estradiol ester]]s, such as [[estradiol benzoate]], [[estradiol valerate]], and [[estradiol cypionate]], whereas its duration is shorter than that of [[estradiol undecylate]].<ref name="pmid8013219" /><ref name="pmid7389356">{{cite journal | vauthors = Oriowo MA, Landgren BM, Stenström B, Diczfalusy E | title = A comparison of the pharmacokinetic properties of three estradiol esters | journal = Contraception | volume = 21 | issue = 4 | pages = 415–24 | year = 1980 | pmid = 7389356 | doi = 10.1016/s0010-7824(80)80018-7 | url = }}</ref><ref name="WildeCoombs1959">{{cite book|author1=Percy Roberts Wilde|author2=Carey Franklin Coombs|author3=Arthur J. Rendle Short|title=The Medical Annual: A Year Book of Treatment and Practitioner's Index ...|url=https://books.google.com/books?id=Y1REAQAAIAAJ|year=1959|publisher=Publishing Science Group | quote = As in the case of progestogens the esters of oestradiol vary in the duration of their effect. Oestradiol benzoate is short-acting (three days to a week). Oestradiol valerianate is somewhat longer-acting, and oestradiol enanthate and undecylate have considerably more prolonged duration of effectiveness. The undecylate may remain effective for some months, and should not be employed, [...]}}</ref> In general, the longer the [[fatty acid]] ester [[side chain|chain]], the more [[lipophilic]] the estradiol ester, the more slowly it is released from the depot and absorbed into the circulation, and the longer its duration of action.<ref name="pmid16112947" /><ref name="pmid1231448">{{cite journal | vauthors = Vermeulen A | title = Longacting steroid preparations | journal = Acta Clin Belg | volume = 30 | issue = 1 | pages = 48–55 | date = 1975 | pmid = 1231448 | doi = 10.1080/17843286.1975.11716973 | url = }}</ref>

The [[pharmacokinetics]] of estradiol enantate have been assessed in a number of studies.<ref name="pmid8013219">{{cite journal | vauthors = Garza-Flores J | title = Pharmacokinetics of once-a-month injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 347–59 | date = April 1994 | pmid = 8013219 | doi = 10.1016/0010-7824(94)90032-9 | url = }}</ref><ref name="GualPérez-Palacios1973">{{cite journal|last1=Gual|first1=C.|last2=Pérez-Palacios|first2=G.|last3=Pérez|first3=A.E.|last4=Ruiz|first4=M.R.|last5=Solis|first5=J.|last6=Cervantes|first6=A.|last7=Iramain|first7=C.|last8=Schreiber|first8=E.C.|title=Metabolic fate of a long-acting injectable estrogen-progestogen contraceptive 1,2|journal=Contraception|volume=7|issue=4|year=1973|pages=271–287|issn=00107824|doi=10.1016/0010-7824(73)90145-5}}</ref><ref name="pmid3769482">{{cite journal | vauthors = Recio R, Garza-Flores J, Schiavon R, Reyes A, Diaz-Sanchez V, Valles V, Luz de la Cruz D, Oropeza G, Perez-Palacios G | title = Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive | journal = Contraception | volume = 33 | issue = 6 | pages = 579–89 | date = June 1986 | pmid = 3769482 | doi = 10.1016/0010-7824(86)90046-6 | url = }}</ref><ref name="pmid3814225">{{cite journal | vauthors = Wiemeyer JC, Fernandez M, Moguilevsky JA, Sagasta CL | title = Pharmacokinetic studies of estradiol enantate in menopausic women | journal = Arzneimittelforschung | volume = 36 | issue = 11 | pages = 1674–7 | year = 1986 | pmid = 3814225 | doi = | url = }}</ref><ref name="pmid3396358">{{cite journal | vauthors = Schiavon R, Benavides S, Oropeza G, Garza-Flores J, Recio R, Díaz-Sanchez V, Pérez-Palacios G | title = Serum estrogens and ovulation return in chronic users of a once-a-month injectable contraceptive | journal = Contraception | volume = 37 | issue = 6 | pages = 591–8 | date = June 1988 | pmid = 3396358 | doi = 10.1016/0010-7824(88)90005-4 | url = }}</ref><ref name="pmid2524362">{{cite journal | vauthors = Garza-Flores J, Alba VM, Cravioto MC, Hernandez L, Perez-Palacios G, Alvarado G, Rivera R, Recio R, Bassol S | title = Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin | journal = Contraception | volume = 39 | issue = 5 | pages = 519–29 | date = May 1989 | pmid = 2524362 | doi = 10.1016/0010-7824(89)90107-8 | url = }}</ref> It has usually been studied in combination with DHPA.<ref name="pmid8013219" /><ref name="GualPérez-Palacios1973" /><ref name="pmid3769482" /><ref name="pmid3396358" /> Following an [[intramuscular injection]] of estradiol enantate, levels of estradiol have been found to peak after 3 to 8&nbsp;days.<ref name="pmid8013219" /><ref name="pmid3396358" /><ref name="pmid3814225" /> Maximal levels of estradiol after a 5&nbsp;mg injection of estradiol enantate have been found to be about 163 to 209&nbsp;pg/mL and after a 10&nbsp;mg injection of estradiol enantate have been found to be about 283 to 445&nbsp;pg/mL.<ref name="pmid8013219" /><ref name="pmid3769482" /><ref name="pmid3396358" /> However, one outlying study reported peak estradiol levels of 850&nbsp;pg/mL after an intramuscular injection of 10&nbsp;mg estradiol enantate in three postmenopausal women.<ref name="pmid3814225" /> It used [[radioimmunoassay]] for the determinations, with no mention of [[chromatographic separation]].<ref name="pmid3814225" /> Estradiol levels following an intramuscular injection of 10&nbsp;mg estradiol enantate have been found to return to baseline levels of around 50&nbsp;pg/mL after about 20 to 30&nbsp;days.<ref name="pmid3769482" /><ref name="pmid3814225" /><ref name="OettelSchillinger2012" /><ref name="pmid2524362" /><ref name="pmid8013219" /> However, a [[metabolism|metabolic]] study found that traces of [[radiolabel]]ed estradiol enantate remained detectable in blood for at least 30 to 40&nbsp;days and for as long as 60&nbsp;days.<ref name="GualPérez-Palacios1973" /> Studies have reported that the [[elimination half-life]] of estradiol enantate after a single 10&nbsp;mg intramuscular injection was 5.6 to 7.5&nbsp;days.<ref name="pmid3814225" /><ref name="pmid8910663" /><ref name="pmid8013220" /> The [[volume of distribution]] of estradiol enantate has been reported to be 5.087&nbsp;L.<ref name="ConsultaRemédios" /> Estradiol enantate is [[excretion|excreted]] preferentially in [[urine]].<ref name="pmid865726">{{cite journal | vauthors = Toppozada M | title = The clinical use of monthly injectable contraceptive preparations | journal = Obstet Gynecol Surv | volume = 32 | issue = 6 | pages = 335–47 | date = June 1977 | pmid = 865726 | doi = 10.1097/00006254-197706000-00001 | url = }}</ref>

There were concerns about possible accumulation of estradiol enantate and consequent estrogenic overexposure with once-monthly combined injectable contraceptives containing the medication due its long [[duration of action|duration]], and this may have limited the use of such combined injectable contraceptives.<ref name="pmid8013220">{{cite journal | vauthors = Sang GW | title = Pharmacodynamic effects of once-a-month combined injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 361–85 | date = April 1994 | pmid = 8013220 | doi = 10.1016/0010-7824(94)90033-7 | url = }}</ref><ref name="pmid8013219" /> Subsequent clinical studies have found that there is very limited or no accumulation of estradiol enantate when it is used in once-a-month injectable contraceptives.<ref name="pmid8013220" /><ref name="pmid9404550">{{cite journal | vauthors = De Aguilar MA, Altamirano L, Leon DA, De Fung RC, Grillo AE, Gonzalez JD, Canales JR, Sanchez Jdel C, Pozuelos JL, Ramirez L, Rigionni R, Salgado JS, Torres L, Vallecillos G, Zambrano EJ, Zea C | title = Current status of injectable hormonal contraception, with special reference to the monthly method | journal = Adv Contracept | volume = 13 | issue = 4 | pages = 405–17 | date = December 1997 | pmid = 9404550 | doi = 10.1023/A:1006501526018 | url = }}</ref><ref name="pmid12290848" />

{{Hormone levels with intramuscular estradiol enantate}}

==Chemistry==
{{See also|Estrogen ester|List of estrogen esters#Estradiol esters}}

Estradiol enantate, also known as estradiol 17β-enantate or estra-1,3,5(10)-triene-3,17β-diol 17β-heptanoate, is a [[synthetic compound|synthetic]] [[estrane]] [[steroid]] and the C17β [[heptanoic acid|enantate]] (heptanoate) [[fatty acid]] [[ester]] of [[estradiol (medication)|estradiol]].<ref name="Elks2014" /><ref name="IndexNominum2000" /> Other common esters of estradiol used clinically include [[estradiol benzoate]], [[estradiol cypionate]], [[estradiol undecylate]], and [[estradiol valerate]].<ref name="IndexNominum2000" /> [[Estradiol dienantate]] (component of [[Climacteron]]), or estradiol 3,17β-dienantate, has also been used.<ref name="Elks2014" /><ref name="Ginsburg1999">{{cite book |last1=Ginsburg |first1=Elizabeth S. |editor-first=David B. |editor-last=Seifer |editor-first2=Elizabeth A. |editor-last2=Kennard |title=Menopause |date=1999 |volume=18 |pages=209–219 |doi=10.1007/978-1-59259-246-3_13 |chapter=Androgen Replacement in Postmenopausal Women |isbn=978-1-61737-129-5}}</ref><ref name="pmid13901504">{{cite journal | title=The treatment of the menopause | journal=Can Med Assoc J | author=Robert B. Greenblatt | author2=William E. Barfield | author3=Edwin C. Jungck | date=January 1962 | volume=86 | issue=3 | pages=113–4 | pmc=1848811 | pmid=13901504}}</ref><ref name="Seifer1999">{{cite book | url=https://books.google.com/books?id=t0zMBgAAQBAJ&pg=PT183 | title=Menopause: Endocrinology and Management | publisher=Springer Science & Business Media | date=27 July 1999 | author=David B. Seifer | pages=183– | isbn=978-1-59259-246-3 | doi=10.1007/978-1-59259-246-3}}</ref>

The experimental [[octanol/water partition coefficient]] (logP) of estradiol enanthate is 6.7 to 7.3.<ref name="HanschSammes1990">{{cite book|author1=Corwin Hansch|author2=Peter George Sammes|author3=John Bodenhan Taylor|title=Comprehensive Medicinal Chemistry: Cumulative subject index & drug compendium|url=https://books.google.com/books?id=8wttAAAAMAAJ|year=1990|publisher=Elsevier Science Limited|isbn=978-0-08-037062-0}}</ref><ref name="ChemSpider">http://www.chemspider.com/Chemical-Structure.19815.html</ref>

{{Structural properties of selected estradiol esters}}

==History==
Estradiol enantate was first described, along with a variety of other [[estradiol ester]]s, by Karl Junkmann of [[Schering AG]] in 1953.<ref name="Junkmann1953">{{cite journal | last1 = Junkmann | first1 = Karl | title = Über protrahiert wirksame Östrogene | trans-title = Over protracted effective estrogens | journal = Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie | volume = 220 | issue = 5 | year = 1953 | issn = 0028-1298 | doi = 10.1007/BF00246561}}</ref><ref name="Symposium1954">{{cite book | author = International Neurochemical Symposium | title = Proceedings | url = https://books.google.com/books?id=gmhFAAAAYAAJ | year = 1954 | publisher = Academic Press | page = 453}}</ref><ref name="Waelsch1955">{{cite book | author = Heinrich Waelsch | title = Biochemistry of the Developing Nervous System: Proceedings | url = https://books.google.com/books?id=55oTAQAAMAAJ | year = 1955 | publisher = Academic Press | page = 453}}</ref><ref name="IAC1958">{{cite book | title = Acta Cytologica | url = https://books.google.com/books?id=r2xOAQAAIAAJ | year = 1958 | publisher = International Academy of Cytology | page = 378}}</ref><ref name="WildeCoombs1959" /><ref name="GauthierLeDreff1958">{{cite journal | last1 = Gauthier | first1 = B | last2 = Le Dreff | first2 = L | last3 = Aubry | first3 = R | title = Hormone derivatives of long-lasting action. I. Esters of estradiol | journal = Annales Pharmaceutiques Francaises | volume = 16 | pages = 757-66 | year = 1958 | issn = 0003-4509 | quote = Treating 10 g. estradiol benzoate in 30 cc.dry C5H5N dropwise with 4.3 g. n-C6H13COCl (b20 71-2°), heating 1 hr. at 50-60°, pouring into 100 cc. 10% H2SO4, sepg. the oil after its solidification, washing with petr. ether, heating with 50 cc. MeOH, and cooling gave 10 g. 17-heptoyl-3β-benzoylestradiol, m. 95-8°.  Dissolving 10 g. of this in 210 cc. 0.1N NaOH in MeOH and 40 cc. Me2CO with stirring, adding HCl to pH 7, filtering, evapg. in vacuo, and stirring the residue with petr. ether gave 7.9 g. 17-heptoyl-β-estradiol, m. 94-6° (iso-Pr2O).  Adding to 5 g. estradiol stirred in 10 cc. anhyd. pyridine 8 g. n-C10H21COCl (b20 135-6°), keeping 1 hr. at 100°, cooling, adding 50 cc. 10% H2SO4, dissolving the sepd. ester in 50 cc. iso-Pr2O, washing with satd. NaHCO3 soln. and H2O, drying, and evapg. at room temp. gave 10.7 g. 3,17-diundecanoylestradiol, m. 48-9° (MeOH-Me2CO, then Me2O-Et2O), λmax. (0.005% in MeOH contg. 4% iso-Pr2O) 268 mμ, λmin. 282 and 250 mμ, inflexion 215 mμ.  Stirring 8.8 g. estradiol divalerate in 90 cc. MeOH and 0.4 g. NaOH under N 210 min. to soln., adding 20% HCl to pH 7, evapg. in vacuo to 10 cc., keeping overnight at a low temp., and washing with H2O, MeOH, and petr. ether gave 4.4 g. 17-valeryl-β-estradiol, m. 145-6°, λmax. (0.005% in EtOH) 282 mμ, λmin. 248 mμ, inflexion 215 mμ.  A single dose of 25 mg. of the diundecanate gave a therapeutic effect lasting 3 weeks.}}</ref><ref name="ES241206">{{cite patent | last = Alter | first = SA | title = Esters of cortical hormones, androgens, or esterogens by transesterification and alcoholysis | number = ES 241206 | date = Apr 22, 1958 | quote = Hormone esters are prepd. by transesterification of a com. ester with a Me or Et ester of the desired acid.  Thus, to 350 g. testosterone (I) propionate and 1500 cc. Me enanthate is added 20-50 cc. of the catalyst, 2-5% NaOMe.  The mixt. is boiled gently with the temp. not exceeding 50°, and the remainder of the catalyst added in small portions over 1 to 2 hrs.  Boiling is maintained 0.5 hr. with regulation by addn. of N or MeOH through a capillary.  The pressure is then reduced to 20 mm., the contents of the flask cooled, dild. with ether, washed with water, and dried.  The following day the ether is evapd. and the remainder of the Me enanthate distd. in vacuo to give 345 g. (crude) I enanthate, m. 35° (alc.-ether).  Similarly prepd. with some changes in the procedure were: I valerate, m. 109-10°; I isovalerate, m. 138-40°; I caproate, oil; I caprate, oil; I laurate, oil; I myristate, oil; I 4-methoxybutyrate, m. 55-7°; I cyclopentanepropionate, m. 99-100°; I trimethylacetate, m. 156-7°; I benzoate, m. 198-9°.  17-Monoesters of estradiol (II) prepd. by application of this method were: II valerate, m. 143-5°; II caproate, oil; II enanthate, oil; II caprylate, m. 117-18°; II caprate, m. 112-13°; II cyclopentanepronionate, m. 90-1°.  Prepd. by the use of acid catalysts (hydroxyfluoboric acids) and neutral catalysts (zinc chloride) were: deoxycorticosterone (III) butyrate, m. 109-10°; III valerate, m. 83-5°; III caprylate, 62-3°; III palmitate, m. 59-60°; III benzoate, m. 208-9°; III trimethylacetate, m. 200-1°.}}</ref> The first clinical study of estradiol enantate and DHPA as a [[combined injectable contraceptive]] was conducted in 1964.<ref name="pmid14236841">{{cite journal | vauthors = Rutherford RN, Banks AL, Coburn WA | title = Deladroxate for the Prevention of Ovulation | journal = Fertil. Steril. | volume = 15 | issue = | pages = 648–52 | year = 1964 | pmid = 14236841 | doi = 10.1016/s0015-0282(16)35410-3| url = }}</ref><ref name="pmid14236842">{{cite journal | vauthors = Taymor ML, Planck S, Yahia C | title = Ovulation Inhibition with a Long-acting Parenteral Progestogen-Estrogen Combination | journal = Fertil. Steril. | volume = 15 | issue = | pages = 653–60 | year = 1964 | pmid = 14236842 | doi = 10.1016/s0015-0282(16)35411-5| url = }}</ref> The combination was marketed by the mid-1970s.<ref name="BringerHedon1995">{{cite book|author1=J. Bringer|author2=B. Hedon|title=Fertility and Sterility: A Current Overview|url=https://books.google.com/books?id=vZirsEgpXiMC&pg=PA47|date=15 September 1995|publisher=CRC Press|isbn=978-1-85070-694-6|pages=47–}}</ref><ref name="pmid865726">{{cite journal | vauthors = Toppozada M | title = The clinical use of monthly injectable contraceptive preparations | journal = Obstet Gynecol Surv | volume = 32 | issue = 6 | pages = 335–47 | date = June 1977 | pmid = 865726 | doi = 10.1097/00006254-197706000-00001 | url = }}</ref><ref name="pmid8013216">{{cite journal | vauthors = Toppozada MK | title = Existing once-a-month combined injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 293–301 | date = April 1994 | pmid = 8013216 | doi = 10.1016/0010-7824(94)90029-9 | url = }}</ref>

==Society and culture==

===Generic names===
''Estradiol enantate'' is the [[British English]] [[generic term|generic name]] of the medication and its {{abbrlink|INNM|International Nonproprietary Name}} and {{abbrlink|BANM|British Approved Name}}, while ''estradiol enanthate'' is its {{abbrlink|USAN|United States Adopted Name}} and [[American English]] generic name.<ref name="Elks2014">{{cite book|author=J. Elks|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA898|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=898–}}</ref><ref name="IndexNominum2000">{{cite book | title = Index Nominum 2000: International Drug Directory | url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA405 | accessdate = 20 May 2012 | year = 2000 | publisher = Taylor & Francis US | isbn = 978-3-88763-075-1 | page = 405}}</ref><ref name="Martindale" /><ref name="MortonHall2012">{{cite book|author1=I.K. Morton|author2=Judith M. Hall|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA206|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=206–}}</ref> Its generic names in other languages are as follows:<ref name="Micromedex" /><ref name="Martindale" />

* [[French language|French]]: ''enantate d'estradiol'' and ''estradiol enantate''
* [[German language|German]]: ''estradiol enantat''
* [[Italian language|Italian]]: ''estradiolo enantato''
* [[Portuguese language|Portuguese]] and [[Spanish language|Spanish]]: ''enantato de estradiol'' and ''estradiol enantato''

Estradiol enantate is also known by its former developmental code name ''SQ-16150''.<ref name="Milne2018">{{cite book|author=George W.A Milne|title=Drugs: Synonyms and Properties: Synonyms and Properties|url=https://books.google.com/books?id=xUlaDwAAQBAJ&pg=PT1404|date=8 May 2018|publisher=Taylor & Francis|isbn=978-1-351-78989-9|pages=1404–}}</ref> It has been referred to as ''estradiol heptanoate''.<ref name="IndexNominum2000" /><ref name="Elks2014" /><ref name="Drugs.com">https://www.drugs.com/international/estradiol.html</ref><ref name="Martindale" /><ref name="Micromedex" />

===Brand names===
Estradiol enantate has been marketed under a wide variety of brand names.<ref name="Micromedex" /><ref name="Martindale" /><ref name="Drugs.com-1" /><ref name="Drugs.com-2" /><ref name="BagadePawar2014" /><ref name="SenanayakePotts2008" /><ref name="HumansCancer1999" /><ref name="RabeRunnebaum2012" /><ref name="pmid8013216" /><ref name="pmid12290848" /><ref name="pmid8013219" /> It has been marketed in a few different preparations, with varying doses of estradiol enantate and DHPA.<ref name="HumansCancer1999" /><ref name="BagadePawar2014" /><ref name="SenanayakePotts2008" /><ref name="HumansOrganization2007" /><ref name="pmid8013216" /><ref name="pmid12290848" /><ref name="pmid8013219" /> These formulations all have different brand names, which include the following (<sup>†</sup> = discontinued):<ref name="Micromedex" /><ref name="Martindale" /><ref name="Drugs.com-1" /><ref name="Drugs.com-2" /><ref name="HumansOrganization2007" /><ref name="HumansCancer1999" /><ref name="BagadePawar2014" /><ref name="SenanayakePotts2008" /><ref name="pmid12290848" /><ref name="pmid23641480">{{cite journal | vauthors = Gallo MF, Grimes DA, Lopez LM, Schulz KF, d'Arcangues C | title = Combination injectable contraceptives for contraception | journal = Cochrane Database Syst Rev | volume = 3 | issue = | pages = CD004568 | date = 2013 | pmid = 23641480 | doi = 10.1002/14651858.CD004568.pub3 | url = | pmc = 6513542 }}</ref>

* E2-EN 10&nbsp;mg / DHPA 150&nbsp;mg: Acefil, Agurin<sup>†</sup>, Atrimon<sup>†</sup>, Ciclomes, Ciclovar, Ciclovular, Cicnor<sup>†</sup>, Clinomin, Cycloven, Daiva, Damix, Deprans, Deproxone, Exuna, Ginestest, Ginoplan<sup>†</sup>, Gynomes, Horprotal, Listen, Luvonal, Neogestar, Neolutin, Nomagest, Nonestrol, Normagest, Normensil, Novular, Oterol, Ovoginal, Patector, Patectro, Perludil, Perlumes, Perlutal, Perlutale, Perlutan, Perlutin, Perlutin-Unifarma, Permisil, Preg-Less, Pregnolan, Progestrol<sup>†</sup>, Protegin, Proter, Seguralmes, Synovular, Topasel, Unigalen, Uno-Ciclo, and Vagital.
* E2-EN 10&nbsp;mg / DHPA 120&nbsp;mg: Anafertin<sup>†</sup>, Patector NF, and Yectames.
* E2-EN 5&nbsp;mg / DHPA 75&nbsp;mg: Unalmes and Yectuna.
* E2-EN 10&nbsp;mg / DHPA 75&nbsp;mg: Ova Repos<sup>†</sup>.
* Unsorted: Evitas<sup>†</sup>, Femineo<sup>†</sup>, and Primyfar<sup>†</sup>.

The combination of E2-EN 10&nbsp;mg and DHPA 150&nbsp;mg was developed under the developmental brand name Deladroxate, but this brand name was never used commercially.<ref name="pmid8013216" /><ref name="pmid12290848" />

===Availability===
[[File:Estradiol enanthate availability.png|thumb|right|400px|Known availability of estradiol enantate in countries throughout the world (as of September 2018).]]

Estradiol enantate (E2-EN) has been marketed in combination with DHPA as a [[combined injectable contraceptive]] in at least 19&nbsp;countries, mostly in [[Latin America]].<ref name="BagadePawar2014" /><ref name="SenanayakePotts2008">{{cite book|author1=Pramilla Senanayake|author2=Malcolm Potts|title=Atlas of Contraception, Second Edition|url=https://books.google.com/books?id=7dDKBQAAQBAJ&pg=PA50|date=14 April 2008|publisher=CRC Press|isbn=978-0-203-34732-4|pages=50–}}</ref><ref name="HumansCancer1999" /><ref name="RabeRunnebaum2012">{{cite book|author1=Thomas Rabe|author2=Benno Runnebaum|title=Fertility Control — Update and Trends: Update and Trends|url=https://books.google.com/books?id=zLopBgAAQBAJ&pg=PT183|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-86696-8|pages=183–|quote=Two additional monthly, combined injectable methods warrant mention. Deladroxate (commercially labelled as Perlutan, Topasel, Agurin, Horprotal and Uno-Ciclo in various countries), is a combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate, and is available in many Latin American countries and Spain. The method is highly effective, without a single pregnancy reported in large clinical trials (Koetsawang 1994). Although available since the 1960s, the method has not been studied as extensively as Cyclofem or Mesigyna. The original manufacturer withdrew support due to toxicological concerns with dihydroxyprogesterone acetophenide, and clinical evaluations continue to be published. A recent dose-finding trial compared the standard available dose of 150/10 with a lower dose of 90/6, and concluded the lower dose was equally effective (Coutinho et al., 1997).}}</ref><ref name="Micromedex">http://www.micromedexsolutions.com/micromedex2/librarian/</ref><ref name="Martindale">{{cite book |editor=Sweetman, Sean C. |chapter=Sex hormones and their modulators |title=Martindale: The Complete Drug Reference |edition=36th |year=2009 |page=2082 |publisher=Pharmaceutical Press |location=London|isbn=978-0-85369-840-1|url=https://www.medicinescomplete.com/mc/martindale/}}</ref><ref name="Drugs.com-1">https://www.drugs.com/international/algestone.html</ref><ref name="Drugs.com-2">https://www.drugs.com/international/algestone-acetophenide.html</ref> A few different preparations, with varying doses of E2-EN and DHPA and varying availability, have been introduced.<ref name="HumansCancer1999" /><ref name="BagadePawar2014" /><ref name="SenanayakePotts2008" /><ref name="HumansOrganization2007" /><ref name="pmid8013216">{{cite journal | vauthors = Toppozada MK | title = Existing once-a-month combined injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 293–301 | date = April 1994 | pmid = 8013216 | doi = 10.1016/0010-7824(94)90029-9 | url = }}</ref><ref name="pmid12290848" /><ref name="pmid8013219" /> These formulations have the following approval and availability (<sup>†</sup> = discontinued in this country):<ref name="Micromedex" /><ref name="Martindale" /><ref name="Drugs.com-1" /><ref name="Drugs.com-2" /><ref name="HumansOrganization2007" /><ref name="HumansCancer1999" /><ref name="BagadePawar2014" /><ref name="SenanayakePotts2008" /><ref name="pmid12290848" />

* E2-EN 10&nbsp;mg / DHPA 150&nbsp;mg: at least 19&nbsp;countries, including [[Argentina]], [[Belize]], [[Brazil]], [[Chile]], [[Colombia]], [[Costa Rica]], the [[Dominican Republic]], [[Ecuador]], [[El Salvador]], [[Guatemala]], [[Honduras]], [[Hong Kong]], [[Mexico]], [[Nicaragua]], [[Panama]], [[Paraguay]], [[Peru]], [[Portugal]]<sup>†</sup>, and [[Spain]]<sup>†</sup>.
* E2-EN 10&nbsp;mg / DHPA 120&nbsp;mg: at least 3&nbsp;countries, including [[Brazil]]<sup>†</sup>, [[Chile]], and [[Paraguay]].
* E2-EN 5&nbsp;mg / DHPA 75&nbsp;mg: at least 9&nbsp;countries, including [[Costa Rica]], the [[Dominican Republic]], [[El Salvador]], [[Guatemala]], [[Honduras]], [[Mexico]], [[Nicaragua]], [[Panama]], and [[Spain]]<sup>†</sup>.

E2-EN is also available in [[Canada]] in combination with [[estradiol benzoate]] and [[testosterone enantate]] for [[veterinary medicine|veterinary]] use as Uni-Bol.<ref name="HealthCanada">https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=11012</ref>

===Usage===
E2-EN/DHPA is the most widely used combined injectable contraceptive in Latin America.<ref name="SperoffFritz2005">{{cite book|author1=Leon Speroff|author2=Marc A. Fritz|title=Clinical Gynecologic Endocrinology and Infertility|url=https://books.google.com/books?id=8sIkqPT2gh4C&pg=PA969|year=2005|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-4795-0|pages=969–}}</ref> It was estimated in 1995 that E2-EN/DHPA was used as a combined injectable contraceptive in Latin America by at least 1&nbsp;million women.<ref name="HumansCancer1999" /> However, combined injectable contraceptives like E2-EN/DHPA are unlikely to constitute a large proportion of total contraceptive use in the countries in which they are available.<ref name="HumansCancer1999" />

==See also==
* [[Estradiol enantate/algestone acetophenide]]
* [[Estradiol/estradiol enanthate]]

==References==
{{Reflist}}


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

[[Category:Antigonadotropins]]
[[Category:Estradiol esters]]
[[Category:Estranes]]
[[Category:Hormonal contraception]]
[[Category:Phenols]]
[[Category:Prodrugs]]
[[Category:Synthetic estrogens]]
[[Category:Veterinary drugs]]