estradiol enantate

{{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.{{cite book | vauthors = Zutshi V, Rathore AM, Sharma K | title = Hormones in Obstetrics and Gynaecology | url = https://books.google.com/books?id=IBxBbaDjXw0C&pg=PA138 | access-date = 20 May 2012 | date = 1 January 2005 | location = New Delhi | publisher = Jaypee Brothers Publishers | isbn = 978-81-8061-427-9 | page = 138 }}{{Dead link|date=July 2024 |bot=InternetArchiveBot |fix-attempted=yes }} Estradiol enantate has been studied in feminizing hormone therapy for transgender women as well.{{cite journal | vauthors = Becerra Fernández A, de Luis Román DA, Piédrola Maroto G | title = [Morbidity in transsexual patients with cross-gender hormone self-treatment] | language = es | journal = Medicina Clinica | volume = 113 | issue = 13 | pages = 484–487 | date = October 1999 | pmid = 10604171 | url = https://www.saludtrans.cl/wp-content/uploads/2012/10/morbilidad-automedicacic3b3n-en-transexuales.pdf | trans-title = Morbidity in transsexual patients with cross-gender hormone self-treatment }} The combination of estradiol enantate and DHPA has likewise been used by transgender women for such purposes.{{cite book| vauthors = Kulick D |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}} Since at least the 2020s, it has grown in popularity among the transfeminine community as a means of DIY hormone therapy (without DHPA).{{Cite journal |last=Aly |date=2021-07-16 |title=An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations |url=https://transfemscience.org/articles/injectable-e2-meta-analysis/ |journal=Transfeminine Science |language=en-US}}

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

The following forms of estradiol enantate are or have been available for use:{{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}}{{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|access-date=19 September 2018|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828080855/https://monographs.iarc.who.int/wp-content/uploads/2018/06/mono72.pdf#page=76|url-status=dead}}{{cite journal | vauthors = Newton JR, D'arcangues C, Hall PE | title = A review of "once-a-month" combined injectable contraceptives | journal = Journal of Obstetrics and Gynaecology | volume = 4 | issue = Suppl 1 | pages = S1-34 | year = 1994 | pmid = 12290848 | doi = 10.3109/01443619409027641 }}

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

A 6 mg estradiol enantate and 90 mg DHPA formulation was also studied, but was never marketed.{{cite book| vauthors = d'Arcangues C, Snow RC | chapter = Injectable Contraceptives. | veditors = Rabe T, Runnebaum B | title = Fertility Control — Update and Trends|year=1999|pages=121–149|doi=10.1007/978-3-642-86696-8_6| isbn = 978-3-642-86698-2 }}{{cite journal | vauthors = Coutinho EM, Spinola P, Barbosa I, Gatto M, Tomaz G, Morais K, Yazlle ME, de Souza RN, Pinho Neto JS, Leal W, Leal C, Hippolito SB, Abranches AD | display-authors = 6 | 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 = 175–181 | date = March 1997 | pmid = 9115007 | doi = 10.1016/S0010-7824(97)00018-8 | url = http://www.repositorio.ufba.br/ri/handle/ri/8331 }}{{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 | display-authors = 6 | 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 = 277–280 | date = April 2000 | pmid = 10899484 | doi = 10.1016/S0010-7824(00)00099-8 | url = http://www.repositorio.ufba.br/ri/handle/ri/7874 }} The combination of estradiol enantate and DHPA has also been studied at other doses ranging from 5 to 50 mg estradiol enantate and 75 to 200 mg DHPA.{{cite journal | vauthors = Koetsawang S | title = Once-a-month injectable contraceptives: efficacy and reasons for discontinuation | journal = Contraception | volume = 49 | issue = 4 | pages = 387–398 | date = April 1994 | pmid = 8013221 | doi = 10.1016/0010-7824(94)90034-5 }}

The combination of estradiol enantate and DHPA is provided in ampoules at estradiol enantate concentrations of 5 mg/mL and 10 mg/mL.

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

Contraindications of estrogens include coagulation problems, cardiovascular diseases, liver disease, and certain hormone-sensitive cancers such as breast cancer and endometrial cancer, among others.{{cite book| vauthors = Lauritzen C, Studd JW |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}}{{cite book | vauthors = Laurtizen C | chapter = Hormone Substitution Before, During and After Menopause | pages = 67–88 | url = https://www.kup.at/kup/pdf/4978.pdf | veditors = Fisch FH | title = Menopause – Andropause: Hormone Replacement Therapy Through the Ages | year = 2001 | publisher = Krause & Pachernegg: Gablitz | isbn = 978-3-901299-34-6}}{{cite book| vauthors = Midwinter A |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| veditors = Campbell S |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}}

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

The side effects of estradiol enantate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma.{{cite book| vauthors = Ghosh AK |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–}} The combination of estradiol enantate and DHPA as a combined injectable contraceptive has shown no adverse effects on liver function, lipid metabolism, or coagulation.

A Brazilian case report of a prolactinoma in a transgender woman treated with 10 mg estradiol enantate every 2 weeks exists.{{cite journal | vauthors = Camara VL, Zanardi UV, Glezer A, Paraiba DB, Bronstein MD, Mendonca BB, Costa EM | date = June 2010 | title = Estrogen as a Presumed Risk Factor for Prolactinoma in a Male-to-Female Transsexual Patient. | journal = Endocrine Reviews | volume = 31 | issue = 3, Supplement 1 | pages = S347 | url = https://www.endocrine.org/-/media/endocrine/files/endo-annual-meetings/endo_abstracts_2010_02.pdf#page=347 }}{{cite journal | vauthors = Camara VL | title = Estradiol enantate First report of prolactinoma, in a transsexual. | journal = Reactions | date = July 2010 | volume = 24 | issue = 1311 | pages = 24 | doi = 10.2165/00128415-201013110-00077 | s2cid = 195175382 }} While DHPA was not mentioned in this instance, estradiol enantate is normally formulated in combination with DHPA including in Brazil.

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

Symptoms of estrogen overdosage may include nausea, vomiting, bloating, increased weight, water retention, breast tenderness, vaginal discharge, heavy legs, and leg cramps.{{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 }} These side effects can be diminished by reducing the estrogen dosage.

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

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels.{{cite journal | vauthors = Cheng ZN, Shu Y, Liu ZQ, Wang LS, Ou-Yang DS, Zhou HH | title = Role of cytochrome P450 in estradiol metabolism in vitro | journal = Acta Pharmacologica Sinica | volume = 22 | issue = 2 | pages = 148–154 | date = February 2001 | pmid = 11741520 }}

File:Estradiol.svg, the active form of estradiol enantate.]]

{{See also|Pharmacodynamics of estradiol}}

Estradiol enantate is an estradiol ester, or a prodrug of estradiol. As such, it is an estrogen, or an agonist of the estrogen receptors. Estradiol enantate is of about 41% higher molecular weight than estradiol due to the presence of its C17β enantate ester. Because estradiol enantate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.

The combination of 10 mg estradiol enantate and 150 mg DHPA as a once-monthly combined injectable contraceptive (which achieves levels of estradiol of around 350 pg/mL) has been found to have little to no effect on many markers of estrogen-modulated liver protein synthesis, including circulating levels of HDL and LDL cholesterol, copper, ceruloplasmin, total and free cortisol, corticosteroid-binding globulin, and sex hormone-binding globulin.{{cite journal | vauthors = Wiemeyer JC, Vidal M, Gallardo, E | title = IX International Congress. Session 22 Long-Acting Contraception II. Abstracts. Experiences with dihydroxyprogesterone acetophenide (DHPA) 150 mg plus estradiol enanthate (E2EN) 10 mg as a once a month injectable contraceptive in Latin America | journal = Advances in Contraception | date = March 1995 | volume = 11 | pages = 54–60 | doi = 10.1007/BF02436103 | s2cid = 75854488 }}{{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 }} However, it was found to significantly increase levels of triglycerides and to significantly decrease levels of total and free testosterone. In contrast to the estradiol enantate-containing combined injectable contraceptive, low-dose ethinylestradiol-containing birth control pills produce highly significant changes in all of the preceding parameters.

Studies in women and female capuchin monkeys have found that injections of estradiol enantate and DHPA significantly alter levels of coagulation factors.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{{cite journal| vauthors = Duarte RC, Belham FS, Tavares MC |title=Risco de doenca tromboliticas apos o uso de algestona acetofenida e enantato de estradiol | trans-title = Risk of thrombolytic disease after the use of algestone acetophenide and estradiol enanthate |journal=Revista de Patologia do Tocantins | trans-journal = Journal of Pathology of Tocantins | language = pt |volume=5|issue=1|year=2018|page=17|issn=2446-6492|doi=10.20873/uft.2446-6492.2018v5n1p17|doi-access=free}}

The clinical estrogenic effects of estradiol enantate and ethinylestradiol have been compared in other studies as well.{{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 = Arzneimittel-Forschung | volume = 36 | issue = 11 | pages = 1671–1674 | date = November 1986 | pmid = 3101711 }}

{{Parenteral potencies and durations of steroidal estrogens}}

{{See also|Pharmacokinetics of estradiol}}

When estradiol enantate is administered in an oil solution by intramuscular injection, a depot effect occurs, and this results in it having a long duration of action. The duration of action of estradiol enantate is considerably longer than that of various other estradiol esters, such as estradiol benzoate and estradiol valerate, whereas its duration is shorter than that of estradiol undecylate.{{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 = 415–424 | date = April 1980 | pmid = 7389356 | doi = 10.1016/s0010-7824(80)80018-7 }}{{cite book| vauthors = Wilde PR, Coombs CF, Short AJ |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, [...]}} In general, the longer the fatty acid ester 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.{{cite journal | vauthors = Vermeulen A | title = Longacting steroid preparations | journal = Acta Clinica Belgica | volume = 30 | issue = 1 | pages = 48–55 | date = 1975 | pmid = 1231448 | doi = 10.1080/17843286.1975.11716973 }}

The pharmacokinetics of estradiol enantate have been assessed in a number of studies.{{cite journal | vauthors = Garza-Flores J | title = Pharmacokinetics of once-a-month injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 347–359 | date = April 1994 | pmid = 8013219 | doi = 10.1016/0010-7824(94)90032-9 }}{{cite journal| vauthors = Gual C, Pérez-Palacios G, Perez AE, Ruiz MR, Solis J, Cervantes A, Iramain C, Schreiber EC | display-authors = 6 |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=0010-7824|doi=10.1016/0010-7824(73)90145-5}}{{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 | display-authors = 6 | title = Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive | journal = Contraception | volume = 33 | issue = 6 | pages = 579–589 | date = June 1986 | pmid = 3769482 | doi = 10.1016/0010-7824(86)90046-6 }}{{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 = 591–598 | date = June 1988 | pmid = 3396358 | doi = 10.1016/0010-7824(88)90005-4 }}{{cite journal | vauthors = Garza-Flores J, Alba VM, Cravioto MC, Hernandez L, Perez-Palacios G, Alvarado G, Rivera R, Recio R, Bassol S | display-authors = 6 | title = Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin | journal = Contraception | volume = 39 | issue = 5 | pages = 519–529 | date = May 1989 | pmid = 2524362 | doi = 10.1016/0010-7824(89)90107-8 }} It has usually been studied in combination with DHPA. Following an intramuscular injection of estradiol enantate, levels of estradiol have been found to peak after 3 to 8 days. Maximal levels of estradiol after a 5 mg injection of estradiol enantate have been found to be about 163 to 209 pg/mL and after a 10 mg injection of estradiol enantate have been found to be about 283 to 445 pg/mL. However, one outlying study reported peak estradiol levels of 850 pg/mL after an intramuscular injection of 10 mg estradiol enantate in three postmenopausal women. It used radioimmunoassay for the determinations, with no mention of chromatographic separation. Estradiol levels following an intramuscular injection of 10 mg estradiol enantate have been found to return to baseline levels of around 50 pg/mL after about 20 to 30 days. However, a metabolic study found that traces of radiolabeled estradiol enantate remained detectable in blood for at least 30 to 40 days and for as long as 60 days. Studies have reported that the elimination half-life of estradiol enantate after a single 10 mg intramuscular injection was 5.6 to 7.5 days. The volume of distribution of estradiol enantate has been reported to be 5.087 L. Estradiol enantate is excreted preferentially in urine.{{cite journal | vauthors = Toppozada M | title = The clinical use of monthly injectable contraceptive preparations | journal = Obstetrical & Gynecological Survey | volume = 32 | issue = 6 | pages = 335–347 | date = June 1977 | pmid = 865726 | doi = 10.1097/00006254-197706000-00001 }}

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, and this may have limited the use of such combined injectable contraceptives.{{cite journal | vauthors = Sang GW | title = Pharmacodynamic effects of once-a-month combined injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 361–385 | date = April 1994 | pmid = 8013220 | doi = 10.1016/0010-7824(94)90033-7 }} 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.{{cite journal | vauthors = De Aguilar MA, Altamirano L, Leon DA, De Fung RC, Grillo AE, Gonzalez JD, Canales JR, Sanchez J, Pozuelos JL, Ramirez L, Rigionni R, Salgado JS, Torres L, Vallecillos G, Zambrano EJ, Zea C | display-authors = 6 | title = Current status of injectable hormonal contraception, with special reference to the monthly method | journal = Advances in Contraception | volume = 13 | issue = 4 | pages = 405–417 | date = December 1997 | pmid = 9404550 | doi = 10.1023/A:1006501526018 | s2cid = 19603384 }}

{{Gallery

| title=Hormone levels with estradiol enanthate by intramuscular injection

| width=300 | height=185

| align=center

| style="font-size:small;"

| Image:Estradiol levels after an intramuscular injection of different doses of estradiol enanthate in premenopausal women.png|Estradiol levels after the most recent intramuscular injection during once-monthly 5 or 10 mg estradiol enanthate and 75 or 150 mg dihydroxyprogesterone acetophenide contraception in one premenopausal woman each.{{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 | display-authors = 6 | title = Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive | journal = Contraception | volume = 33 | issue = 6 | pages = 579–589 | date = June 1986 | pmid = 3769482 | doi = 10.1016/0010-7824(86)90046-6 }} Assays were performed using radioimmunoassay. Source was Recio et al. (1986).

| Image:Estradiol levels after a single intramuscular injection of 10 mg estradiol enantate in postmenopausal women.png|Estradiol levels after a single intramuscular injection of 10 mg estradiol enanthate in three postmenopausal women.{{cite journal | vauthors = Wiemeyer JC, Fernandez M, Moguilevsky JA, Sagasta CL | title = Pharmacokinetic studies of estradiol enantate in menopausic women | journal = Arzneimittel-Forschung | volume = 36 | issue = 11 | pages = 1674–1677 | date = November 1986 | pmid = 3814225 }} Assays were performed using radioimmunoassay. Source was Wiemeyer et al. (1986).

| Image:Estradiol and prolactin levels after the last injection during therapy with estradiol enantate and dihydroxyprogesterone acetophenide in women.png|Estradiol and prolactin levels after the most recent intramuscular injection during once-monthly 10 mg estradiol enanthate and 150 mg dihydroxyprogesterone acetophenide contraception in 10 premenopausal women.{{cite journal | vauthors = Garza-Flores J, Alba VM, Cravioto MC, Hernandez L, Perez-Palacios G, Alvarado G, Rivera R, Recio R, Bassol S | display-authors = 6 | title = Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin | journal = Contraception | volume = 39 | issue = 5 | pages = 519–529 | date = May 1989 | pmid = 2524362 | doi = 10.1016/0010-7824(89)90107-8 }} Only four determinations were made: days 0, 10, 20, and 30. Assays were performed using radioimmunoassay. Source was Garza-Flores et al. (1989).

| File:Estradiol levels with estradiol enanthate and dihydroxyprogesterone acetophenide after single or repeated injections in premenopausal women.png | Simplified curves of estradiol levels after an intramuscular injection of 10 mg estradiol enanthate (E2-EN) and 150 mg dihydroxyprogesterone acetophenide (DHPA) in oil solution with single or continuous once-monthly use in women.{{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 = 591–598 | date = June 1988 | pmid = 3396358 | doi = 10.1016/0010-7824(88)90005-4 }}{{cite journal | vauthors = Garza-Flores J | title = Pharmacokinetics of once-a-month injectable contraceptives | journal = Contraception | volume = 49 | issue = 4 | pages = 347–359 | date = April 1994 | pmid = 8013219 | doi = 10.1016/0010-7824(94)90032-9 }} Source was Garza-Flores (1994).

| File:Idealized curves of estradiol levels after injection of different estradiol esters in women.png | Simplified curves of estradiol levels after injection of different estradiol esters in women. Source was Garza-Flores (1994).

}}

{{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 estrane steroid and the C17β enantate (heptanoate) fatty acid ester of estradiol. Other common esters of estradiol used clinically include estradiol benzoate, estradiol cypionate, estradiol undecylate, and estradiol valerate. Estradiol dienantate (component of Climacteron), or estradiol 3,17β-dienantate, has also been used.{{cite book | vauthors = Ginsburg ES | chapter = Androgen Replacement in Postmenopausal Women | veditors = Seifer DB, Kennard EA |title=Menopause: Endocrinology and Management |date=1999 |volume=18 |pages=209–219 |doi=10.1007/978-1-59259-246-3_13 |isbn=978-1-61737-129-5}}{{cite journal | vauthors = Greenblatt RB, Barfield WE, Jungck EC | title = The treatment of the menopause | journal = Canadian Medical Association Journal | volume = 86 | issue = 3 | pages = 113–114 | date = January 1962 | pmid = 13901504 | pmc = 1848811 }}{{cite book | vauthors = Harlow BL, Abraham ME| chapter = Depression in Menopause | chapter-url=https://books.google.com/books?id=t0zMBgAAQBAJ&pg=PT183 | title=Menopause: Endocrinology and Management | publisher=Springer Science & Business Media | date=27 July 1999 | veditors = Seifer DB, Kennard EA | pages=183– | isbn=978-1-59259-246-3 | doi=10.1007/978-1-59259-246-3_7 }}

The experimental octanol/water partition coefficient (logP) of estradiol enanthate is 6.7.{{cite web|url=http://www.chemspider.com/Chemical-Structure.19815.html|title = Estradiol enanthate | C25H36O3 | work = ChemSpider}}

{{Structural properties of selected estradiol esters}}

Estradiol enantate was first described, along with a variety of other estradiol esters, by Karl Junkmann of Schering AG in 1953.{{cite journal | vauthors = Junkmann K | 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| s2cid = 20753905 }}{{cite book | title = International Neurochemical Symposium Proceedings | url = https://books.google.com/books?id=gmhFAAAAYAAJ | year = 1954 | publisher = Academic Press | page = 453}}{{cite book | vauthors = Waelsch H | title = Biochemistry of the Developing Nervous System: Proceedings | url = https://books.google.com/books?id=55oTAQAAMAAJ | year = 1955 | publisher = Academic Press | page = 453}}{{cite book | title = Acta Cytologica | url = https://books.google.com/books?id=r2xOAQAAIAAJ | year = 1958 | publisher = International Academy of Cytology | page = 378}}{{cite journal | vauthors = Gauthier B, Le Dreff L, Aubry R | title = Hormone derivatives of long-lasting action. I. Esters of estradiol | journal = Annales Pharmaceutiques Françaises | 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.}}{{cite patent | inventor = Alter SA | title = Esters of cortical hormones, androgens, or esterogens by transesterification and alcoholysis | country=ES|number = 241206A1 | pubdate =1958-07-16 | 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°.}} The first clinical study of estradiol enantate and DHPA as a combined injectable contraceptive was conducted in 1964.{{cite journal | vauthors = Rutherford RN, Banks AL, Coburn WA | title = Deladroxate for the Prevention of Ovulation | journal = Fertility and Sterility | volume = 15 | issue = 6 | pages = 648–652 | year = 1964 | pmid = 14236841 | doi = 10.1016/s0015-0282(16)35410-3 | doi-access = free }}{{cite journal | vauthors = Taymor ML, Planck S, Yahia C | title = Ovulation Inhibition with a Long-Acting Parenteral Progestogen-Estrogen Combination | journal = Fertility and Sterility | volume = 15 | issue = 6 | pages = 653–660 | year = 1964 | pmid = 14236842 | doi = 10.1016/s0015-0282(16)35411-5 | doi-access = free }} The combination was marketed by the mid-1970s.{{cite book| vauthors = Bringer J, Hedon B |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–}}{{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 }}

Estradiol enantate is the British English 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.{{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=PA898|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=898–}}{{cite book | title = Index Nominum 2000: International Drug Directory | url = https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA405 | access-date = 20 May 2012 | year = 2000 | publisher = Taylor & Francis US | isbn = 978-3-88763-075-1 | page = 405}}{{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=PA206|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=206–}} Its generic names in other languages are as follows:

• French: enantate d'estradiol and estradiol enantate
• German: estradiol enantat
• Italian: estradiolo enantato
• Portuguese and Spanish: enantato de estradiol and estradiol enantato

Estradiol enantate is also known by its former developmental code name SQ-16150.{{cite book| vauthors = Milne GW |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–}} It has been referred to as estradiol heptanoate.{{cite web|url=https://www.drugs.com/international/estradiol.html|title = Estradiol: Uses, Dosage & Side Effects}}

Estradiol enantate has been marketed under a wide variety of brand names. It has been marketed in a few different preparations, with varying doses of estradiol enantate and DHPA. These formulations all have different brand names, which include the following (^† = discontinued):{{cite journal | vauthors = Gallo MF, Grimes DA, Lopez LM, Schulz KF, d'Arcangues C | title = Combination injectable contraceptives for contraception | journal = The Cochrane Database of Systematic Reviews | volume = 3 | pages = CD004568 | date = 2013 | pmid = 23641480 | pmc = 6513542 | doi = 10.1002/14651858.CD004568.pub3 }}

• EEn 10 mg / DHPA 150 mg: Acefil, Agurin^†, Atrimon^†, Ciclomes, Ciclovar, Ciclovular, Cicnor^†, Clinomin, Cycloven, Daiva, Damix, Deprans, Deproxone, Exuna, Ginestest, Ginoplan^†, 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^†, Protegin, Proter, Seguralmes, Synovular, Topasel, Unigalen, Uno-Ciclo, and Vagital.
• EEn 10 mg / DHPA 120 mg: Anafertin^†, Patector NF, and Yectames.
• EEn 5 mg / DHPA 75 mg: Unalmes and Yectuna.
• EEn 10 mg / DHPA 75 mg: Ova Repos^†.
• Unsorted: Evitas^†, Femineo^†, and Primyfar^†.

The combination of EEn 10 mg and DHPA 150 mg was developed under the developmental brand name Deladroxate, but this brand name was never used commercially.

File:Estradiol enanthate availability.png

Estradiol enantate has been marketed in combination with DHPA as a combined injectable contraceptive in at least 19 countries, mostly in Latin America.{{cite book| vauthors = Senanayake P, Potts M |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–}}{{cite book| vauthors = Lähteenmäki P | chapter = Intrauterine Hormone-Releasing Systems | veditors = Rabe T, Runnebaum B |title=Fertility Control — Update and Trends: Update and Trends| chapter-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= 173-184 (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).}}{{cite web|url=http://www.micromedexsolutions.com/micromedex2/librarian/|title=Micromedex Products: Please Login}}{{cite book | veditors = Sweetman SC |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/}}{{Cite web |url=https://www.drugs.com/international/algestone.html |title=Archived copy |access-date=19 September 2018 |archive-date=18 September 2018 |archive-url=https://web.archive.org/web/20180918123639/https://www.drugs.com/international/algestone.html |url-status=dead }}{{cite web|url=https://www.drugs.com/international/algestone-acetophenide.html|title=Progestin Oral, Parenteral, Vaginal Advanced Patient Information}} A few different preparations, with varying doses of EEn and DHPA and varying availability, have been introduced. These formulations have the following approval and availability (^† = discontinued in this country):

• EEn 10 mg / DHPA 150 mg: at least 19 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^†, and Spain^†.
• EEn 10 mg / DHPA 120 mg: at least 3 countries, including Brazil^†, Chile, and Paraguay.
• EEn 5 mg / DHPA 75 mg: at least 9 countries, including Costa Rica, the Dominican Republic, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, and Spain^†.

EEn is also available in Canada in combination with estradiol benzoate and testosterone enantate for veterinary use as Uni-Bol.{{cite web|url=https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=11012|title=Drug Product Database Online Query|date=25 April 2012}}

EEn/DHPA is the most widely used combined injectable contraceptive in Latin America.{{cite book | vauthors = Speroff L, Fritz MA |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–}} It was estimated in 1995 that EEn/DHPA was used as a combined injectable contraceptive in Latin America by at least 1 million women. However, combined injectable contraceptives like EEn/DHPA are unlikely to constitute a large proportion of total contraceptive use in the countries in which they are available.

• Estradiol enantate/algestone acetophenide
• Estradiol/estradiol enanthate

{{reflist|colwidth=30em}}

{{Estradiol}}

{{Estrogens and antiestrogens}}

{{Estrogen receptor modulators}}

Category:Antigonadotropins

Category:Enanthate esters

Category:Estradiol esters

Category:Hormonal contraception

Category:Hydroxyarenes

Category:Synthetic estrogens

Category:Veterinary drugs