Просмотр кода страницы Английская Википедия:Estradiol dipropionate

{{Английская Википедия/Панель перехода}}
{{Short description|Chemical compound}}
{{Drugbox
| Verifiedfields = 
| Watchedfields = 
| verifiedrevid = 
| IUPAC_name = [(8''R'',9''S'',13''S'',14''S'',17''S'')-13-methyl-3-propanoyloxy-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[''a'']phenanthren-17-yl] propanoate
| image = Estradiol dipropionate.svg
| width = 250px
| image2 = Estradiol dipropionate molecule ball.png
| width2 = 250px

<!--Clinical data-->
| tradename = Agofollin, Di-Ovocylin, Progynon DP, 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]]
| class = [[Estrogen (medication)|Estrogen]]; [[Estrogen ester]]

<!--Pharmacokinetic data-->
| bioavailability = {{abbr|IM|Intramuscular injection}}: High<ref name="pmid7169965">{{cite journal | vauthors = Düsterberg B, Nishino Y | title = Pharmacokinetic and pharmacological features of oestradiol valerate | journal = Maturitas | volume = 4 | issue = 4 | pages = 315–324 | date = December 1982 | pmid = 7169965 | doi = 10.1016/0378-5122(82)90064-0 }}</ref>
| protein_bound = Estradiol: ~98% (to [[human serum albumin|albumin]] and {{abbrlink|SHBG|sex hormone-binding globulin}})<ref name="pmid23375353">{{cite journal | vauthors = Stanczyk FZ, Archer DF, Bhavnani BR | title = Ethinyl estradiol and 17β-estradiol in combined oral contraceptives: pharmacokinetics, pharmacodynamics and risk assessment | journal = Contraception | volume = 87 | issue = 6 | pages = 706–727 | date = June 2013 | pmid = 23375353 | doi = 10.1016/j.contraception.2012.12.011 }}</ref><ref name="FalconeHurd2007">{{cite book| vauthors = Gupta MK, Chia SY | chapter = Ovarian hormones: structure, biosynthesis, function, mechanism of action, and laboratory diagnosis | veditors = Falcone T, Hurd WW |title=Clinical Reproductive Medicine and Surgery| chapter-url = https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA22|year=2007|publisher=Elsevier Health Sciences|isbn=978-0-323-03309-1|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]], [[benzoic acid]], and [[metabolite]]s of estradiol<ref name="OettelSchillinger2012" /><ref name="pmid16112947" />
| elimination_half-life = Unknown
| duration_of_action = {{abbr|IM|Intramuscular injection}} (5 mg): 5–8 days<ref name="KnörrKnörr-Gärtner2013" /><ref name="KnörrBeller2013" />
| excretion = [[Urine]]

<!-- Identifiers -->
| CAS_number_Ref = 
| CAS_number = 113-38-2
| CAS_supplemental = 
| ATC_prefix = G03
| ATC_suffix = CA03
| ATC_supplemental = 
| PubChem = 8225
| IUPHAR_ligand = 
| DrugBank_Ref = 
| DrugBank = 
| ChemSpiderID_Ref = 
| ChemSpiderID = 7932
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = NIG5418BXB
| KEGG = D01617
| ChEBI = 31560
| ChEMBL = 1697791
| synonyms = EDP; Estradiol dipropionate; Estradiol 3,17β-dipropionate; Estra-1,3,5(10)-triene-3,17β-diol 3,17β-dipropanoate

<!--Chemical data-->
| C=24 | H=32 | O=4
| SMILES = O=C(Oc1cc3c(cc1)[C@H]2CC[C@@]4([C@@H](OC(=O)CC)CC[C@H]4[C@@H]2CC3)C)CC
| StdInChI_Ref = 
| StdInChI = 1S/C24H32O4/c1-4-22(25)27-16-7-9-17-15(14-16)6-8-19-18(17)12-13-24(3)20(19)10-11-21(24)28-23(26)5-2/h7,9,14,18-21H,4-6,8,10-13H2,1-3H3/t18-,19-,20+,21+,24+/m1/s1
| StdInChIKey_Ref = 
| StdInChIKey = JQIYNMYZKRGDFK-RUFWAXPRSA-N
}}
<!-- Definition and medical uses -->
'''Estradiol dipropionate''' ('''EDP'''), sold under the brand names '''Agofollin''', '''Di-Ovocylin''', and '''Progynon DP''' among others, is an [[estrogen (medication)|estrogen]] medication which has been used in [[hormone replacement therapy|hormone therapy]] for [[menopausal symptoms]] and [[hypoestrogenism|low estrogen levels]] in women and in the treatment of [[gynecological disorder]]s.<ref name="NNR1949g" /><ref name="pmid13638626" /><ref name="Elks2014">{{cite book| vauthors = Elks J|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=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=PA406|date=January 2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=406–}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title= Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA206|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=206–}}</ref><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/estradiol.html|title = Estradiol: Uses, Dosage & Side Effects | work = Drugs.com }}</ref> It has also been used in [[feminizing hormone therapy]] for [[transgender women]] and in the treatment of [[prostate cancer]] in men.<ref name="pmid30861686" /><ref name="NNR1949g" /> Although widely used in the past, estradiol dipropionate has largely been discontinued and is mostly no longer available today.<ref name="pmid14388061" /><ref name="Drugs.com" /><ref name="IndexNominum2000" /> It appears to remain in use only in [[Japan]], [[North Macedonia|Macedonia]], and [[Australia]].<ref name="Drugs.com" /> Estradiol dipropionate is given by [[intramuscular injection|injection into muscle]] at intervals ranging from once or twice a week to once every week and a half to two weeks.<ref name="NNR1949g" /><ref name="HuhnstockKutscha2013" /><ref name="pmid30861686" />

<!-- Side effects and mechanism -->
[[Side effect]]s of estradiol dipropionate include [[breast tenderness]], [[breast enlargement]], [[nausea]], [[headache]], and [[water retention (medicine)|fluid retention]].<ref name="Ghosh2010">{{cite book | vauthors = McIver B, Tebben PJ, Shas P | chapter = Endocrinology | veditors = Ghosh AK |title=Mayo Clinic Internal Medicine Board Review| chapter-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> Estradiol dipropionate is an [[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 | issue = Suppl 1 | pages = 3–63 | date = August 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 }}</ref><ref name="OettelSchillinger2012" /> It is an [[estrogen ester]] and a [[prodrug]] of [[estradiol (medication)|estradiol]] in the body.<ref name="OettelSchillinger2012" /><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">{{cite book| vauthors = Oettel M, Schillinger E, Kuhnz W, Blode H, Zimmermann H | chapter = Pharmacokinetics of exogenous natural and synthetic estrogens and antiestrogens | veditors = Oettel M, Schillinger E |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen| chapter-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|page=261|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.}}</ref>

<!-- History, society, and culture -->
Estradiol dipropionate was patented in 1937<ref name="Miescher1941" /> and was introduced for medical use by 1940.<ref name="EscamillaLisserf1940" /><ref name="Shorr1940" /> It was one of the earliest estradiol esters to be used.<ref name="NNR1949g" /> Along with [[estradiol benzoate]], estradiol dipropionate was among the most widely used esters of estradiol for many years following its introduction.<ref name="pmid14388061" />

{{TOC limit|3}}

==Medical uses==
The [[medical use]]s of estradiol dipropionate are the same as those of estradiol and other estrogens.<ref name="NNR1949g">{{cite journal|title=NNR: Products Recently Accepted by the A. M. A. Council on Pharmacy and Chemistry|journal=Journal of the American Pharmaceutical Association (Practical Pharmacy Ed.)|volume=10|issue=11|year=1949|pages=692–694|issn=0095-9561|doi=10.1016/S0095-9561(16)31995-8}}</ref><ref name="pmid13638626">{{cite journal | vauthors = Swyer GI | title = The oestrogens | journal = British Medical Journal | volume = 1 | issue = 5128 | pages = 1029–1031 | date = April 1959 | pmid = 13638626 | pmc = 1993181 | doi = 10.1136/bmj.1.5128.1029 }}</ref> Estradiol dipropionate is used in [[menopausal hormone therapy|hormone therapy]] for the treatment of [[menopausal symptoms]] such as [[hot flash]]es and [[vaginal atrophy]] and in the treatment of [[hypoestrogenism]] and [[delayed puberty]] due to [[hypogonadism]] or other causes in women.<ref name="NNR1949g" /><ref name="pmid13638626" /> It is also used in [[feminizing hormone therapy]] for [[transgender women]].<ref name="pmid30861686" /> Aside from hormone therapy, estradiol dipropionate is used in the treatment of [[gynecological disorder]]s such as [[menstrual disorder]]s, [[dysfunctional uterine bleeding]], and [[breast engorgement]].<ref name="NNR1949g" /><ref name="pmid13638626" /> In addition, it is used as a form of [[high-dose estrogen]] therapy in the [[palliation|palliative]] treatment of [[prostate cancer]] in men.<ref name="NNR1949g" />

Estradiol dipropionate has typically been used at a dosage of 1 to 5&nbsp;mg once or twice per week by [[intramuscular injection]] for relevant indications.<ref name="NNR1949g" /><ref name="HuhnstockKutscha2013" /> It has been used in the treatment of menopausal symptoms at a dosage of 1 to 5&nbsp;mg initially for two to three injections and 1 to 2.5&nbsp;mg for maintenance once every 10 to 14&nbsp;days, and in the treatment of hypoestrogenism and delayed puberty at a dosage of 2.5 to 5&nbsp;mg once per week.<ref name="NNR1949g" /><ref name="AMA1977">{{cite book | chapter = Estrogens, Progestagens, Oral Contraceptives, and Ovulatory Agents | pages = 540–572 | author1 = American Medical Association. Dept. of Drugs | author2 = Council on Drugs (American Medical Association) | author3 = American Society for Clinical Pharmacology and Therapeutics | title = AMA drug evaluations | url = https://books.google.com/books?id=0h7s_rfEZgkC | date = 1 February 1977 | publisher = Publishing Sciences Group | isbn = 978-0-88416-175-2 | quote = Intramuscular: For replacement therapy, (Estradiol, Estradiol Benzoate) 0.5 to 1.5 mg two or three times weekly; (Estradiol Cypionate) 1 to 5 mg weekly for two or three weeks; (Estradiol Dipropionate) 1 to 5 mg every one to two weeks; (Estradiol Valerate) 10 to 40 mg every one to four weeks.}}</ref> As a component of [[feminizing hormone therapy]] for [[transgender women]], estradiol dipropionate has been used at dosages of 2 to 10&nbsp;mg once per week or 5 to 20&nbsp;mg once every 2&nbsp;weeks.<ref name="pmid30861686">{{cite journal | vauthors = Nakatsuka M | title = Endocrine treatment of transsexuals: assessment of cardiovascular risk factors | journal = Expert Review of Endocrinology & Metabolism | volume = 5 | issue = 3 | pages = 319–322 | date = May 2010 | pmid = 30861686 | doi = 10.1586/eem.10.18 | s2cid = 73253356 | doi-access = free }}</ref> In the treatment of prostate cancer, estradiol dipropionate has been used at a dosage of 5&nbsp;mg once per week.<ref name="NNR1949g" />

===Available forms===
{{See also|Estradiol dipropionate/hydroxyprogesterone caproate}}

Estradiol dipropionate was previously available by itself as an [[oil solution]] for intramuscular injection provided as [[vial]]s and [[ampoule]]s at concentrations of 0.1, 0.2, 0.5, 1, 2.5, and 5&nbsp;mg/mL.<ref name="NNR1949g" /><ref name="JAPA1949" /><ref name="Pamposh1968">{{cite book|title=Indian Pharmaceutical Guide|url=https://books.google.com/books?id=Ww0iAQAAIAAJ|year=1968|publisher=Pamposh Publications.}}</ref><ref name="Modell2013">{{cite book| vauthors = Modell W |title=Drugs in Current Use 1958|url=https://books.google.com/books?id=v2vwCAAAQBAJ&pg=PA51|date=21 November 2013|publisher=Springer|isbn=978-3-662-40303-7|pages=51–}}</ref><ref name="UC1952">{{cite book |title=Hospital Formulary and Compendium of Useful Information|url=https://books.google.com/books?id=t7VW3PucgboC&pg=PA49|year=1952|publisher=University of California Press|pages=49–|id=GGKEY:2UAAZRZ5LN0}}</ref> The medication has largely been discontinued, with most of these formulations no longer being available.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> Estradiol dipropionate remains available at a concentration of 1&nbsp;mg/mL in combination with 50&nbsp;mg/mL [[hydroxyprogesterone caproate]] under the brand name EP Hormone Depot (Teikoku Zoki Pharmaceutical Company) in [[Japan]].<ref name="pmid8271528">{{cite journal | vauthors = Kawamura I, Mizota T, Lacey E, Tanaka Y, Manda T, Shimomura K, Kohsaka M | title = The estrogenic and antiestrogenic activities of droloxifene in human breast cancers | journal = Japanese Journal of Pharmacology | volume = 63 | issue = 1 | pages = 27–34 | date = September 1993 | pmid = 8271528 | doi = 10.1254/jjp.63.27 | doi-access = free }}</ref><ref name="pmid9821299">{{cite journal | vauthors = Asanuma F, Yamada Y, Kawamura E, Lee K, Kobayashi H, Yamada T, Suzuki T, Kubota T | display-authors = 6 | title = Antitumor activity of paclitaxel and epirubicin in human breast carcinoma, R-27 | journal = Folia Microbiologica | volume = 43 | issue = 5 | pages = 473–474 | date = 1998 | pmid = 9821299 | doi = 10.1007/BF02820793 | s2cid = 22732235 }}</ref><ref name="pmid2137212">{{cite journal | vauthors = Noguchi M, Tajiri K, Taniya T, Kumaki T, Ashikari A, Miyazaki I | title = Influence of hormones on proliferation of ER-positive cells and ER-negative cells of human breast cancer (MCF-7) | journal = Oncology | volume = 47 | issue = 1 | pages = 19–24 | date = 1990 | pmid = 2137212 | doi = 10.1159/000226779 }}</ref><ref name="pmid2810959">{{cite journal | vauthors = Kubota T, Oka S, Utsumi T, Inoue S, Kuzuoka M, Suto A, Arisawa Y, Ishibiki K, Abe O | display-authors = 6 | title = Human breast carcinoma (ZR-75-1) serially transplanted into nude mice--with reference to estradiol dependency and sensitivity to tamoxifen | journal = The Japanese Journal of Surgery | volume = 19 | issue = 4 | pages = 446–451 | date = July 1989 | pmid = 2810959 | doi = 10.1007/BF02471626 | s2cid = 23267652 }}</ref><ref name="pmid7513682">{{cite journal | vauthors = Ueda H, Nakajima H, Hori Y, Fujita T, Nishimura M, Goto T, Okuhara M | title = FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity | journal = The Journal of Antibiotics | volume = 47 | issue = 3 | pages = 301–310 | date = March 1994 | pmid = 7513682 | doi = 10.7164/antibiotics.47.301 | doi-access = free }}</ref><ref name="pmid8360101">{{cite journal | vauthors = Hori Y, Abe Y, Nishimura M, Goto T, Okuhara M, Kohsaka M | title = R1128 substances, novel non-steroidal estrogen-receptor antagonists produced by a Streptomyces. III. Pharmacological properties and antitumor activities | journal = The Journal of Antibiotics | volume = 46 | issue = 7 | pages = 1069–1075 | date = July 1993 | pmid = 8360101 | doi = 10.7164/antibiotics.46.1055 | doi-access = free }}</ref><ref name="pmid1752778">{{cite journal | vauthors = Noguchi M, Koyasaki N, Miyazaki I, Mizukami Y | title = Effects of hormones on tumor growth and immunoreactive insulin-like growth factor-1 of estrogen receptor-positive human breast cancer (MCF-7) transplanted in nude mice | journal = Japanese Journal of Cancer Research | volume = 82 | issue = 11 | pages = 1199–1202 | date = November 1991 | pmid = 1752778 | pmc = 5918318 | doi = 10.1111/j.1349-7006.1991.tb01780.x }}</ref>

==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| vauthors = Lauritzen C | chapter = Practice of Hormone Substitution | veditors = Lauritzen C, Studd JW |title=Current Management of the Menopause| chapter-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 | vauthors = Laurtizen C | chapter = Hormone Substitution Before, During and After Menopause | pages = 67–88 | chapter-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}}</ref><ref name="Midwinter1976">{{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 = 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}}</ref>

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

The [[side effect]]s of estradiol dipropionate 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" />

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

[[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 }}</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 Pharmacologica Sinica | volume = 22 | issue = 2 | pages = 148–154 | date = February 2001 | pmid = 11741520 }}</ref>

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

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

Estradiol dipropionate 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 dipropionate is of about 41% higher [[molecular weight]] than estradiol due to the presence of its C3 and C17β [[propionic acid|propionate]] esters.<ref name="Elks2014" /><ref name="IndexNominum2000" /> Because estradiol dipropionate 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" />

{{Parenteral potencies and durations of steroidal estrogens}}

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

Compared to [[estradiol benzoate]], a related estradiol ester, estradiol dipropionate has enhanced and prolonged effects.<ref name="GreeneDorr1939" /><ref name="HuhnstockKutscha2013">{{cite book| vauthors = Huhnstock KH, Kutscha W, Dehmel H |title=Diagnose und Therapie in der Praxis|url=https://books.google.com/books?id=ZjeHBwAAQBAJ&pg=PA1053|date=12 March 2013|publisher=Springer-Verlag|isbn=978-3-642-68385-5|pages=1053–}}</ref> Whereas the [[duration of action]] of estradiol benzoate is said to be 2 to 3&nbsp;days, the duration of estradiol dipropionate has been said to be 1 to 2&nbsp;weeks.<ref name="Buchsbaum2012">{{cite book| vauthors = Quirk Jr GJ, Wendell Jr GD | chapter = The Biological Effects of Natural and Synthetic Estrogens | veditors = Buchsbaum HJ |title=The Menopause| chapter-url = https://books.google.com/books?id=z0LuBwAAQBAJ&pg=PA62|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4612-5525-3|pages=62–}}</ref> However, newer estradiol esters have longer durations than either estradiol benzoate or estradiol dipropionate; the duration of [[estradiol valerate]] has been said to be 1 to 3&nbsp;weeks, and the duration of [[estradiol cypionate]] has been said to be 3 to 4&nbsp;weeks.<ref name="Buchsbaum2012" /><ref name="HuhnstockKutscha2013" /> A single [[intramuscular injection]] of 5&nbsp;mg estradiol dipropionate has a duration of about 5 to 8&nbsp;days.<ref name="KnörrKnörr-Gärtner2013">{{cite book| vauthors = Knörr K, Knörr-Gärtner H, Beller FK, Lauritzen C |title=Lehrbuch der Geburtshilfe und Gynäkologie: Physiologie und Pathologie der Reproduktion|url=https://books.google.com/books?id=OjvMBgAAQBAJ&pg=PA508|date=8 March 2013|publisher=Springer-Verlag|isbn=978-3-662-00526-2|pages=508–}}</ref><ref name="KnörrBeller2013">{{cite book| vauthors = Knörr K, Beller FK, Lauritzen C |title=Lehrbuch der Gynäkologie|url=https://books.google.com/books?id=ACybBwAAQBAJ&pg=PA212|date=17 April 2013|publisher=Springer-Verlag|isbn=978-3-662-00942-0|pages=212–213}}</ref>

A single intramuscular injection of 50&nbsp;μg/kg estradiol dipropionate in oil in 15&nbsp;pubertal girls (about 1&nbsp;mg for a 50-kg (110-lb) girl) was found to produce peak estradiol levels of about 215&nbsp;pg/mL after 1.5&nbsp;days.<ref name="PreslHorejsi1976" /> Estradiol levels declined to about 90&nbsp;pg/mL after 4&nbsp;days.<ref name="PreslHorejsi1976" />

{{Gallery
| title=Hormone levels with estradiol dipropionate by intramuscular injection
| width=400 | height=260
| align=center
| style="font-size:small;"

| File:Estradiol levels after a single intramuscular injection of 50 μg per kg estradiol dipropionate in pubertal girls.png |  Estradiol levels after a single intramuscular injection of 50&nbsp;μg/kg estradiol dipropionate in oil in pubertal girls.<ref name="PreslHorejsi1976">{{cite journal| vauthors = Presl J, Hořejší J, Štroufová A, Herzmann J |title=Sexual maturation in girls and the development of estrogen induced gonadotropic hormone release|journal=Annales de Biologie Animale, Biochimie, et Biophysique|volume=16|issue=3|year=1976|pages=377–383|issn=0003-388X|doi=10.1051/rnd:19760314|doi-access=free}}</ref> This dose would be 1&nbsp;mg in a 50-kg (110-lb) girl.<ref name="PreslHorejsi1976" /> Source was Presl et al. (1976).<ref name="PreslHorejsi1976" />

| File:Vaginal cornification with a single intramuscular injection of different estradiol esters in women.png | [[Vagina]]l [[cornification]] with a single intramuscular injection of different estradiol esters in oil solution in women.<ref name="pmid14388061IM">{{cite journal | vauthors = Schwartz MM, Soule SD | title = Estradiol 17-beta-cyclopentylpropionate, a longacting estrogen | journal = American Journal of Obstetrics and Gynecology | volume = 70 | issue = 1 | pages = 44–50 | date = July 1955 | pmid = 14388061 | doi = 10.1016/0002-9378(55)90286-6 }}</ref> Source was Schwartz & Soule (1955).<ref name="pmid14388061IM" />
}}

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

Estradiol dipropionate, also known as estradiol 3,17β-dipropionate, is a [[synthetic compound|synthetic]] [[estrane]] [[steroid]] and a [[derivative (chemistry)|derivative]] of [[estradiol (medication)|estradiol]].<ref name="Elks2014" /><ref name="IndexNominum2000" /> It is an [[estrogen ester]]; specifically, it is the C3,17β [[dipropionate]] [[ester]] of [[estradiol (medication)|estradiol]].<ref name="Elks2014" /><ref name="IndexNominum2000" />

The experimental [[octanol/water partition coefficient]] (logP) of estradiol dipropionate is 4.9.<ref name="ChemSpider">{{Cite web|url=http://www.chemspider.com/Chemical-Structure.7932.html|title=Estradiol Dipropionate &#124; C24H32O4 | work = ChemSpider}}</ref>

{{Structural properties of selected estradiol esters}}

==History==
Estradiol dipropionate was first [[chemical synthesis|synthesized]] and [[patent]]ed in 1937.<ref name="DorrGreene1939">{{cite journal| vauthors = Dorr EM, Greene RR |title=Treatment of the menopause with estradiol dipropionate|journal=American Journal of Obstetrics and Gynecology|volume=38|issue=3|year=1939|pages=458–464|issn=0002-9378|doi=10.1016/S0002-9378(39)90763-5}}</ref><ref name="Miescher1941">{{cite patent | country = US | number = 2233025 | status = patent | title = Estradiol-17-monoesters | pubdate = 1941-02-25 | fdate = 1937-10-07 | inventor = Miescher K, Scholz C | assign1 = Ciba Pharmaceutical Products, Inc.}}</ref> It was assessed in clinical studies by 1939 and was introduced by [[Ciba Specialty Chemicals|Ciba]] as an [[oil solution]] for use by [[intramuscular injection]] under the brand name ''Di-Ovocylin'' by the same year.<ref name="DorrGreene1939" /><ref name="GreeneDorr1939">{{cite journal| vauthors = Greene RR, Dorr EM |title=Clinical use of a new estrogen|journal=Endocrinology|volume=24|issue=4|year=1939|pages=577–578|issn=0013-7227|doi=10.1210/endo-24-4-577}}</ref><ref name="EscamillaLisserf1940">{{cite journal| vauthors = Escamilla RF, Lisserf H |title=Induction of menarche and development of secondary sexual characteristics in a woman aged 34 by injections of estradiol dipropionate|journal=Endocrinology|volume=27|issue=1|year=1940|pages=153|issn=0013-7227|doi=10.1210/endo-27-1-153|quote=The estradiol dipropionate used in this case was furnished by the Ciba Co. Their trade name for this product is Di-Ovocylin.}}</ref> Other formulations such as ''Ovocyclin P'' by Ciba, ''Progynon DP'' by [[Schering AG|Schering]] and ''Dimenformon Dipropionate'' by [[Hoffman-La Roche|Roche]]-[[Organon International|Organon]] were also marketed by the early 1940s.<ref name="pmid18746057">{{cite journal | vauthors = Reilly WA | title = Estrogens: Their Use in Pediatrics | journal = California and Western Medicine | volume = 55 | issue = 5 | pages = 237–239 | date = November 1941 | pmid = 18746057 | pmc = 1634235 }}</ref><ref name="Fluhmann1944" /><ref name="Shorr1940">{{cite journal| vauthors = Shorr E |title=Effect of Concomitant Administration of Estroens and Proesterone on Vainal Smear in Man.|journal=Experimental Biology and Medicine|volume=43|issue=3|year=1940|pages=501–506|issn=1535-3702|doi=10.3181/00379727-43-11244|s2cid=75787837|quote=Grateful acknowledgment is made to Dr. Erwin Schwenk of the Schering Corporation for the estradiol benzoate (Progynon B), estradiol dipropionate (Progynon DP), progesterone (Proluton), and pregneninolone (Pranone) used in these experiments;}}</ref><ref name="pmid29646930">{{cite journal | vauthors = Macpherson AI | title = The Use of Œstrogens in Obstetrics and Gynæcology | journal = Edinburgh Medical Journal | volume = 47 | issue = 6 | pages = 406–424 | date = June 1940 | pmid = 29646930 | pmc = 5306594 }}</ref> Later in the 1940s the brand name ''Di-Ovocylin'' was changed by Ciba to ''Ovocylin Dipropionate''.<ref name="JAPA1949">{{cite journal|title=New Prescription Products|journal=Journal of the American Pharmaceutical Association (Practical Pharmacy Ed.)|volume=10|issue=4|year=1949|pages=198–206|issn=0095-9561|doi=10.1016/S0095-9561(16)31795-9}}</ref> Along with [[estradiol benzoate]], which was introduced in 1933,<ref name="Buschbeck1934">{{cite journal| vauthors = Buschbeck H |title=Neue Wege der Hormontherapie in der Gynäkologie|trans-title=New ways of hormonal therapy in gynecology|journal=Deutsche Medizinische Wochenschrift|volume=60|issue=11|year=1934|pages=389–393|issn=0012-0472|doi=10.1055/s-0028-1129842|s2cid=72668930 }}</ref> estradiol dipropionate was one of the first [[estradiol ester]]s to be introduced for medical use.<ref name="Greene1941">{{cite journal| vauthors = Greene RR |title=Endocrine Therapy for Gynecologic Disorders|journal=Medical Clinics of North America|volume=25|issue=1|year=1941|pages=155–168|issn=0025-7125|doi=10.1016/S0025-7125(16)36624-X}}</ref><ref name="Fluhmann1944">{{cite journal| vauthors = Fluhmann CF |title=Clinical Use of Extracts from the Ovaries|journal=Journal of the American Medical Association|volume=125|issue=1|year=1944|pages=1|issn=0002-9955|doi=10.1001/jama.1944.02850190003001}}</ref> Prior to the development and introduction of longer-acting estradiol esters like [[estradiol valerate]] and [[estradiol cypionate]] in the 1950s, estradiol dipropionate and estradiol benzoate were the most widely used estradiol esters.<ref name="pmid14388061">{{cite journal | vauthors = Schwartz MM, Soule SD | title = Estradiol 17-beta-cyclopentylpropionate, a longacting estrogen | journal = American Journal of Obstetrics and Gynecology | volume = 70 | issue = 1 | pages = 44–50 | date = July 1955 | pmid = 14388061 | doi = 10.1016/0002-9378(55)90286-6 }}</ref><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 = 415–424 | date = April 1980 | pmid = 7389356 | doi = 10.1016/S0010-7824(80)80018-7 }}</ref>

==Society and culture==

===Generic names===
Estradiol dipropionate is the [[generic term|generic name]] of the drug and its {{abbrlink|INNM|International Nonproprietary Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Approved Name}}.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Drugs.com" />

===Brand names===
Estradiol dipropionate has been marketed under a variety of brand names, including Agofollin, Akrofolline, Dihidrofolina "Kével", Dimenformon, Dimenformon Dipropionate, Diovocylin, Di-Ovocylin, Diprostron, Diprovex, Endofollicolina D.P., EP Hormone Depot (in combination with [[hydroxyprogesterone caproate]]), Estroici, Estronex, Follicyclin, Follicyclin P, Follikelmon Depot, Horiken-Depot, Nacyclyl, Oestradiol Galenika, Oestradiol Streuli, Orofollina, Ovacrin, Ovahormon Depot, Ovocylin, Ovocylin Dipropionate, Ovocylin P, and Progynon DP, among others.<ref name="Negwer1987">{{cite book| vauthors = Negwer M |title=Organic-chemical Drugs and Their Synonyms: (an International Survey)|url=https://books.google.com/books?id=k6fwAAAAMAAJ|year=1987|publisher=VCH Publishers|isbn=978-0-89573-552-2|page=1272}}</ref><ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Cancer1979">{{cite book|author=International Agency for Research on Cancer|title=Sex Hormones (II).|url=https://books.google.com/books?id=nrhrAAAAMAAJ|year=1979|publisher=International Agency for Research on Cancer|isbn=978-92-832-1221-8}}</ref><ref name="Lewis2008">{{cite book| vauthors = Lewis RJ |title=Hazardous Chemicals Desk Reference|url=https://books.google.com/books?id=WZeBDwAAQBAJ&pg=PA594|date=13 June 2008|publisher=John Wiley & Sons|isbn=978-0-470-18024-2|pages=594–}}</ref><ref name="Drugs.com" /> Agofollin was an [[oil solution]] of estradiol dipropionate that was previously marketed in the [[Czech Republic]] and [[Slovakia]].<ref name="Lissak2012">{{cite book| vauthors = Lissak K |title=Hormones and Brain Function|url=https://books.google.com/books?id=7wX3BwAAQBAJ&pg=PA145|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-1-4684-2007-4|pages=145–}}</ref>

===Availability===
Estradiol dipropionate has been discontinued in most countries, but remains available in [[Japan]] and [[North Macedonia|Macedonia]] alone under the brand names Ovahormon and Oestradiol Galenika and/or in combination with [[hydroxyprogesterone caproate]] under the brand name EP Hormone Depot.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> It is also marketed for use in [[veterinary medicine]] in combination with [[hydroxyprogesterone caproate]] and [[nandrolone decanoate]] under the brand name Reepair in [[Australia]].<ref name="Drugs.com" />

== See also ==
* [[Estradiol dipropionate/hydroxyprogesterone caproate]]

== References ==
{{Reflist}}

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

[[Category:Abandoned drugs]]
[[Category:Antigonadotropins]]
[[Category:Estradiol esters]]
[[Category:Hormonal antineoplastic drugs]]
[[Category:Propionate esters]]
[[Category:Synthetic estrogens]]
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