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{{Short description|Chemical compound}} {{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] 3-cyclopentylpropanoate | image = Estradiol 17 beta-cypionate.svg | image_class = skin-invert-image | width = 250px | image2 = Estradiol cypionate molecule ball.png | width2 = 250px <!--Clinical data--> | pronounce = {{IPAc-en|ˌ|ɛ|s|t|r|ə|ˈ|d|aɪ|oʊ|l|_|s|ᵻ|ˈ|p|aɪ|oʊ|n|eɪ|t}}<br />{{respell|ES|trə|DY|ohl|_|sih|PY|oh|nate}}<ref name="Drugs.com-2">{{Cite web|url=https://www.drugs.com/estradiol.html|title=Estradiol: Uses, Dosage & Side Effects|website=Drugs.com|accessdate=21 April 2023}}</ref> | tradename = Depo-Estradiol, Depofemin, Estradep, many 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]], [[subcutaneous injection]]<ref name="pmid22078184" /> | class = [[Estrogen (medication)|Estrogen]]; [[Estrogen ester]] <!--Pharmacokinetic data--> | bioavailability = {{abbr|IM|Intramuscular injection}}: High<ref name="pmid7169965" /> | 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 |chapter-url= https://books.google.com/books?id=fOPtaEIKvcIC&pg=PA22 |title=Clinical Reproductive Medicine and Surgery |publisher=Elsevier Health Sciences |year=2007 |isbn=978-0-323-03309-1 |pages=22 }}; {{Cite book | vauthors = Arredondo F, Liu JH | chapter = Menopause | veditors = Falcone T, Hurd WW | chapter-url = https://books.google.com/books?id=YAejBQAAQBAJ&pg=PA353 |title=Clinical Reproductive Medicine and Surgery |publisher=Elsevier Health Sciences |year=2007 |isbn=978-0-323-03309-1 |pages= 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]], [[cypionic acid]], and [[metabolite]]s of estradiol<ref name="OettelSchillinger2012" /><ref name="pmid16112947" /> | elimination_half-life = {{abbr|IM|Intramuscular injection}} ([[aqueous suspension]]): 8–10 days<ref name="pmid23265980">{{Cite journal |vauthors=Thurman A, Kimble T, Hall P, Schwartz JL, Archer DF |date=June 2013 |title=Medroxyprogesterone acetate and estradiol cypionate injectable suspension (Cyclofem) monthly contraceptive injection: steady-state pharmacokinetics |journal=Contraception |volume=87 |issue=6 |pages=738–43 |doi=10.1016/j.contraception.2012.11.010 |pmid=23265980}}</ref><ref name="Lunelle-Label" /> | duration_of_action = {{abbr|IM|Intramuscular injection}} ([[oil solution|oil]]): 5 mg ≈ 11–14 days<ref name="pmid7389356">{{Cite journal |vauthors=Oriowo MA, Landgren BM, Stenström B, Diczfalusy E |date=April 1980 |title=A comparison of the pharmacokinetic properties of three estradiol esters |journal=Contraception |volume=21 |issue=4 |pages=415–24 |doi=10.1016/S0010-7824(80)80018-7 |pmid=7389356}}</ref><br />{{abbr|IM|Intramuscular injection}} ([[aqueous suspension]]): 5 mg ≈ 14–24 days<ref name="pmid23265980" /><ref name="ArunNarendra2012" /><ref name="RahimyRyan1999" /> | excretion = [[Urine]] <!-- Identifiers --> | CAS_number_Ref = | CAS_number = 313-06-4 | CAS_supplemental = | ATC_prefix = G03 | ATC_suffix = CA03 | ATC_supplemental = | PubChem = 9403 | IUPHAR_ligand = | DrugBank_Ref = | DrugBank = DB13954 | ChemSpiderID_Ref = | ChemSpiderID = 9033 | UNII = 7E1DV054LO | KEGG = D04063 | ChEBI = 34745 | ChEMBL = 1200973 | synonyms = EC; E2C; Estradiol cipionate; Estradiol cyclopentylpropionate; ECP; Estradiol 17β-cyclopentylpropionate; Estradiol 17β-cyclopentanepropionate <!--Chemical data--> | C=26 | H=36 | O=3 | SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2OC(=O)CCC4CCCC4)CCC5=C3C=CC(=C5)O | StdInChI_Ref = | StdInChI = 1S/C26H36O3/c1-26-15-14-21-20-10-8-19(27)16-18(20)7-9-22(21)23(26)11-12-24(26)29-25(28)13-6-17-4-2-3-5-17/h8,10,16-17,21-24,27H,2-7,9,11-15H2,1H3/t21-,22-,23+,24+,26+/m1/s1 | StdInChIKey_Ref = | StdInChIKey = UOACKFBJUYNSLK-XRKIENNPSA-N <!--Physical data--> | melting_point = 151 | melting_high = 152 }} <!-- Definition and medical uses --> '''Estradiol cypionate''' ('''EC'''), sold under the brand name '''Depo-Estradiol''' among others, is an [[estrogen (medication)|estrogen]] medication which is used in [[Hormone replacement therapy|hormone therapy]] for [[menopausal symptoms]] and [[hypoestrogenism|low estrogen levels]] in women, in [[Feminizing hormone therapy|hormone therapy]] for [[Trans woman|trans women]], and in [[hormonal contraception|hormonal birth control]] for women.<ref name=Depo-Estradiol-Label>{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/085470s015lbl.pdf|access-date=21 April 2023|website=accessdata.fda.gov |title=Estradiol cypionate injection, USP|year=2005}}</ref><ref name="pmid16112947" /><ref name="pmid12290848">{{Cite journal |vauthors=Newton JR, D'arcangues C, Hall PE |year=1994 |title=A review of "once-a-month" combined injectable contraceptives |journal=J Obstet Gynaecol (Lahore) |volume=4 | issue = Suppl 1 |pages=S1–34 |doi=10.3109/01443619409027641 |pmid=12290848}}</ref><ref name="BagadePawar2014">{{Cite journal |vauthors=Bagade O, Pawar V, Patel R, Patel B, Awasarkar V, Diwate S |year=2014 |title=Increasing use of long-acting reversible contraception: safe, reliable, and cost-effective birth control |url=http://www.wjpps.com/download/article/1412071798.pdf |journal=World J Pharm Pharm Sci |volume=3 |issue=10 |pages=364–392 |issn=2278-4357}}</ref> It is given by [[intramuscular injection|injection into muscle]] once every 1 to 4 weeks.<ref name="Depo-Estradiol-Label" /><ref name="pmid25220381" /> <!-- Side effects and mechanism --> [[Side effect]]s of estradiol cypionate include [[breast tenderness]], [[breast enlargement]], [[nausea]], [[headache]], and [[water retention (medicine)|fluid retention]].<ref name="Depo-Estradiol-Label" /><ref name="pmid16112947" /> Estradiol cypionate 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" /><ref name="OettelSchillinger2012" /> Estradiol cypionate is an [[estrogen ester]] and a long-lasting [[prodrug]] of [[estradiol (medication)|estradiol]] in the body.<ref name="Depo-Estradiol-Label" /><ref name="pmid16112947" /><ref name="OettelSchillinger2012">{{Cite book | vauthors = Oettel M, Schillinger E |url=https://books.google.com/books?id=wBvyCAAAQBAJ&pg=PA261 |title=Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen |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> 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="pmid17627398">{{Cite journal |vauthors=Cirigliano M |date=June 2007 |title=Bioidentical hormone therapy: a review of the evidence |journal=J Womens Health (Larchmt) |volume=16 |issue=5 |pages=600–31 |doi=10.1089/jwh.2006.0311 |pmid=17627398}}</ref><ref name="ArunNarendra2012" /> <!-- History, society, and culture --> Estradiol cypionate was first described as well as introduced for medical use in 1952.<ref name="Sittig1988" /><ref name="Publishing2013" /> Along with [[estradiol valerate]], it is one of the most commonly used esters of estradiol.<ref name="Yen1991">{{Cite book | vauthors = Yen SS |url= https://books.google.com/books?id=RN1qAAAAMAAJ |title=Reproductive endocrinology: physiology, pathophysiology, and clinical management |publisher=Saunders |year=1991 |isbn=978-0-7216-3206-3 |access-date=20 May 2012}}</ref> Estradiol cypionate has mostly been used in the [[United States]], but is also marketed in a few other countries.<ref name="IndexNominum2000">{{Cite book |url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA405 |title=Index Nominum 2000: International Drug Directory |publisher=Taylor & Francis US |year=2000 |isbn=978-3-88763-075-1 |page=405 |access-date=20 May 2012}}</ref><ref name="Drugs.com6">{{Cite web |title=Estradiol |url=https://www.drugs.com/international/estradiol.html |website=Drugs.com}}</ref><ref name="Llewellyn2011" /> The medication is not available in [[Europe]].<ref name="BruniBucciantini2017" /> It is not currently available as a [[generic drug|generic medication]] in the United States.<ref name="Drugs@FDA">{{Cite web |title=Drugs@FDA: FDA Approved Drug Products |url=http://www.accessdata.fda.gov/scripts/cder/daf/ |access-date=31 December 2017 |publisher=United States Food and Drug Administration}}</ref> {{TOC limit|3}} ==Medical uses== {{Main|Estradiol (medication)#Medical uses|High-dose estrogen}} The [[medical use]]s of estradiol cypionate are the same as those of estradiol and other estrogens. Examples of indications for the drug include [[hormone replacement therapy|hormone therapy]] and [[hormonal contraception]]. In regard to the latter, estradiol cypionate has been used in combination with [[medroxyprogesterone acetate]] as a [[combined injectable contraceptive]].<ref name="pmid12290848" /><ref name="BagadePawar2014" /><ref name="Rowlands2009">{{cite journal | vauthors = Rowlands S | title = New technologies in contraception | journal = BJOG | volume = 116 | issue = 2 | pages = 230–239 | date = January 2009 | pmid = 19076955 | doi = 10.1111/j.1471-0528.2008.01985.x | s2cid = 3415547 | url = http://wrap.warwick.ac.uk/28852/1/WRAP_Rowlands_NewtechnologiesincontraceptionBJOG2008_Uni_repos_version.pdf }}</ref> Along with [[estradiol valerate]], [[estradiol undecylate]], and [[estradiol benzoate]], estradiol cypionate is used as a form of [[high-dose estrogen]] therapy in [[feminizing hormone therapy]] for [[transgender women]].<ref name="pmid28159148">{{cite journal | vauthors = Wesp LM, Deutsch MB | title = Hormonal and Surgical Treatment Options for Transgender Women and Transfeminine Spectrum Persons | journal = The Psychiatric Clinics of North America | volume = 40 | issue = 1 | pages = 99–111 | date = March 2017 | pmid = 28159148 | doi = 10.1016/j.psc.2016.10.006 }}</ref><ref name="pmid25220381">{{cite journal | vauthors = Smith KP, Madison CM, Milne NM | title = Gonadal suppressive and cross-sex hormone therapy for gender dysphoria in adolescents and adults | journal = Pharmacotherapy | volume = 34 | issue = 12 | pages = 1282–1297 | date = December 2014 | pmid = 25220381 | doi = 10.1002/phar.1487 | s2cid = 26979177 }}</ref><ref name="EttnerMonstrey2016">{{Cite book | vauthors = Rosenthal SM | chapter = Transgender Youth: Endocrine Management | veditors = Ettner R, Monstrey S, Coleman E | chapter-url=https://books.google.com/books?id=LwszDAAAQBAJ&pg=PA216 |title=Principles of Transgender Medicine and Surgery |date=20 May 2016 |publisher=Routledge |isbn=978-1-317-51460-2 |pages=216–}}</ref><ref name="IsraelTarver2001">{{Cite book | chapter = Transgender Hormone Adiministration | vauthors = Israel GE, Tarver DE, Shaffer JD | chapter-url = https://books.google.com/books?id=IlPX6E5glDEC&pg=PA64 |title=Transgender Care: Recommended Guidelines, Practical Information, and Personal Accounts |date=1 March 2001 |publisher=Temple University Press |isbn=978-1-56639-852-7 |pages=64–}}</ref> The medication has been used to induce [[puberty]] in girls with [[delayed puberty]] due to [[hypogonadism]].<ref name="RosenfieldKiess2006">{{Cite journal | vauthors = Rosenfield RL, Kiess W, de Muinck Keizer-Schrama S |year=2006 |title=Physiologic induction of puberty in Turner syndrome with very low-dose estradiol |journal=International Congress Series |volume=1298 |pages=71–79 |doi=10.1016/j.ics.2006.07.003 |issn=0531-5131}}</ref><ref name="BruniBucciantini2017" /> Estradiol cypionate is usually used at a dosage of 1 to 5 mg by intramuscular injection every 3 to 4 weeks in the treatment of [[menopausal symptoms]] such as [[hot flash]]es and [[vaginal atrophy]], at a dosage of 1.5 to 2 mg by intramuscular injection once a month in the treatment of female [[hypoestrogenism]] due to [[hypogonadism]], and at a dosage of 2 to 10 mg by intramuscular injection once every 1 or 2 weeks for hormone therapy in transgender women.<ref name="Depo-Estradiol-Label" /><ref name="pmid25220381" /><ref name="EttnerMonstrey2016" /><ref name="pmid28159148" /><ref name="AMA1977">{{Cite book | author1 = American Medical Association. Dept. of Drugs |url=https://books.google.com/books?id=0h7s_rfEZgkC |title=AMA drug evaluations | author2 = Council on Drugs (American Medical Association) | author3 = American Society for Clinical Pharmacology and Therapeutics |date=1 February 1977 |publisher=Publishing Sciences Group |isbn=978-0-88416-175-2 |pages=540–572 |chapter=Estrogens, Progestagens, Oral Contraceptives, and Ovulatory Agents |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> The doses used to induce puberty in girls are 0.2 to 2.5 mg per month, gradually increased over a period of 4 years.<ref name="RosenfieldKiess2006" /><ref name="BruniBucciantini2017" /> {{Estrogen dosages for menopausal hormone therapy}} ===Available forms=== {{See also|Estradiol cypionate/medroxyprogesterone acetate|Estradiol cypionate/testosterone cypionate}} Estradiol cypionate is and has been available as an [[oil solution]] for intramuscular injection provided in [[vial]]s and [[ampoule]]s at concentrations of 1, 3, and 5 mg/mL (and containing 5, 10, 15, 25, or 50 mg estradiol cypionate total).<ref name="Drugs@FDA" /><ref name="Pharmaceutical">{{Cite book | vauthors = Kleemann A, Engel J, Kutscher B, Reichert D |url=https://books.google.com/books?id=fO2IAwAAQBAJ&pg=PA1167 |title=Pharmaceutical Substances: Syntheses, Patents and Applications of the most relevant APIs | edition = 5th | date = 2014 |publisher=Thieme |isbn=978-3-13-179525-0 |pages=1167–1174}}</ref><ref name="Becker2001f">{{Cite book | chapter = Endocrine Drugs and Values | veditors = Becker KL | chapter-url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA2153 |title=Principles and Practice of Endocrinology and Metabolism |publisher=Lippincott Williams & Wilkins |year=2001 |isbn=978-0-7817-1750-2 |pages=2153–}}</ref> The 1 and 3 mg/mL concentrations (containing 5 and 15 mg estradiol cypionate total) have been discontinued in the [[United States]], but the 5 mg/mL concentration (containing 25 mg estradiol cypionate total) remains available.<ref name="Drugs@FDA" /><ref name="Administration2011">{{Cite book | author = Food and Drug Administration |url=https://books.google.com/books?id=JDZ4DAAAQBAJ&pg=PR586 |title=Approved Drug Products with Therapeutic Equivalence Evaluations - FDA Orange Book | edition = 31st |publisher=DrugPatentWatch.com |year=2011 |isbn=978-1-934899-81-6 |pages=586–}}</ref> Aside from estradiol cypionate, the only other injectable estrogen formulations that remain available in the United States are [[estradiol valerate]] (10 mg/mL, 20 mg/mL, and 40 mg/mL in oil) and [[conjugated estrogens]] (25 mg/vial in solution).<ref name="Drugs@FDA" /> In addition to single-drug formulations, estradiol cypionate has been marketed in combination with [[medroxyprogesterone acetate]] as a [[microcrystalline]] [[aqueous suspension]] (brand name Lunelle) and in combination with [[testosterone cypionate]] as an oil solution (brand name Depo-Testadiol).<ref name="Drugs@FDA" /> {{Available forms of estradiol}} [[File:Depo-Estradiol (estradiol cypionate) vials.jpg|thumb|left|300px|5-mL [[vial]]s of Depo-Estradiol (5 mg/mL estradiol cypionate in [[cottonseed oil]] [[oil solution|solution]] for use by [[intramuscular injection]]) in the [[United States]].<ref name="Depo-Estradiol-Label" />]] ==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 | chapter-url = https://books.google.com/books?id=WD7S7677xUUC&pg=PA95 |title=Current Management of the Menopause |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 | veditors = Fisch FH |title=Menopause – Andropause: Hormone Replacement Therapy Through the Ages |publisher=Krause & Pachernegg: Gablitz |year=2001 |isbn=978-3-901299-34-6 |pages=67–88 |chapter-url=https://www.kup.at/kup/pdf/4978.pdf}}</ref><ref name="Midwinter1976">{{Cite book | vauthors = Midwinter A |chapter= Contraindications to estrogen therapy and management of the menopausal syndrome in these cases | 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 |publisher=MTP Press Limited |year=1976 |isbn=978-94-011-6167-1 |pages=377–382 |doi=10.1007/978-94-011-6165-7_33}}</ref> ==Side effects== {{Main|Estradiol (medication)#Side effects}} The [[side effect]]s of estradiol cypionate are the same as those of estradiol. Examples of such side effects include [[breast tenderness]] and [[breast enlargement|enlargement]], [[nausea]], [[vomiting]], [[bloating]], [[edema]], [[headache]], [[migraine]], and [[melasma]].<ref name="Ghosh2010">{{Cite book | vauthors = McLiver B, Tebben PJ, Shah P | chapter = Endocrinology | veditors = Ghosh AK |chapter-url=https://books.google.com/books?id=LS65jBzoD40C&pg=PA222 |title=Mayo Clinic Internal Medicine Board Review |date=23 September 2010 |publisher=OUP USA |isbn=978-0-19-975569-1 |pages=222–}}</ref><ref name="pmid26684553">{{Cite journal |vauthors=Bishop BM |date=December 2015 |title=Pharmacotherapy Considerations in the Management of Transgender Patients: A Brief Review |journal=Pharmacotherapy |volume=35 |issue=12 |pages=1130–9 |doi=10.1002/phar.1668 |pmid=26684553 |s2cid=37001563}}</ref> [[High-dose estrogen]] therapy with estradiol cypionate injections may also cause an increased risk of [[thromboembolism]], changes in [[blood lipids|blood lipid]] [[lipid profile|profile]], increased [[insulin resistance]], and increased levels of [[prolactin]].<ref name="pmid26684553" /> ==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 |date=September 1990 |title=Clinical use of oestrogens and progestogens |journal=Maturitas |volume=12 |issue=3 |pages=199–214 |doi=10.1016/0378-5122(90)90004-P |pmid=2215269}}</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 |date=February 2001 |title=Role of cytochrome P450 in estradiol metabolism in vitro |journal=Acta Pharmacol. Sin. |volume=22 |issue=2 |pages=148–54 |pmid=11741520}}</ref> ==Pharmacology== [[File:Estradiol.svg|class=skin-invert-image|thumb|right|225px|[[Estradiol (medication)|Estradiol]], the [[active metabolite|active form]] of estradiol cypionate.]] ===Pharmacodynamics=== {{See also|Pharmacodynamics of estradiol}} Estradiol cypionate is an [[estradiol ester]], or a [[prodrug]] of [[estradiol (medication)|estradiol]].<ref name="pmid16112947">{{Cite journal |vauthors=Kuhl H |year=2005 |title=Pharmacology of estrogens and progestogens: influence of different routes of administration |url=http://hormonebalance.org/images/documents/Kuhl%2005%20%20Pharm%20Estro%20Progest%20Climacteric_1313155660.pdf |journal=Climacteric |volume=8 | issue = Suppl 1 |pages=3–63 |doi=10.1080/13697130500148875 |pmid=16112947 |s2cid=24616324}}</ref><ref name="OettelSchillinger2012" /> As such, it is an [[estrogen (medication)|estrogen]], or an [[agonist]] of the [[estrogen receptor]]s.<ref name="pmid16112947" /><ref name="OettelSchillinger2012" /> The [[affinity (pharmacology)|affinity]] of estradiol valerate for the estrogen receptor has been reported to be 50 times less than that of estradiol,<ref name="pmid7169965">{{Cite journal |vauthors=Düsterberg B, Nishino Y |date=December 1982 |title=Pharmacokinetic and pharmacological features of oestradiol valerate |journal=Maturitas |volume=4 |issue=4 |pages=315–24 |doi=10.1016/0378-5122(82)90064-0 |pmid=7169965}}</ref> and estradiol valerate and estradiol cypionate have been found to possess similar affinity for the estrogen receptor.<ref name="pmid10764660">{{Cite journal |vauthors=Dubey RK, Jackson EK, Gillespie DG, Zacharia LC, Imthurn B, Keller PJ |year=2000 |title=Clinically used estrogens differentially inhibit human aortic smooth muscle cell growth and mitogen-activated protein kinase activity |journal=Arterioscler. Thromb. Vasc. Biol. |volume=20 |issue=4 |pages=964–72 |doi=10.1161/01.atv.20.4.964 |pmid=10764660 |doi-access=free}}</ref> Both estradiol cypionate and estradiol valerate are rapidly cleaved into estradiol in the body,<ref name="pmid16112947" /><ref name="pmid2909371">{{Cite journal |vauthors=MacLusky NJ, Larner JM, Hochberg RB |date=January 1989 |title=Actions of an estradiol-17-fatty acid ester in estrogen target tissues of the rat: comparison with other C-17 metabolites and a pharmacological C-17 ester |journal=Endocrinology |volume=124 |issue=1 |pages=318–24 |doi=10.1210/endo-124-1-318 |pmid=2909371}}</ref> and estradiol valerate has been found to be unable to reach target tissues in any concentration of significance.<ref name="pmid7169965" /> As such, estradiol valerate is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a [[prodrug]] to estradiol,<ref name="pmid7169965" /> and estradiol cypionate is described as a prodrug of estradiol similarly.<ref name="OettelSchillinger2012" /> Estradiol cypionate is of about 46% higher [[molecular weight]] than estradiol due to the presence of its C17β [[cypionic acid|cypionate]] ester, and contains about 69% of the amount of estradiol by weight.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="BruniBucciantini2017">{{Cite book | vauthors = Bruni V, Bucciantini S, Ambroggio S | chapter = From Primary Hypergonadotropic Amenorrhea to "POI": Aetiology and Therapy | title = Frontiers in Gynecological Endocrinology: Pediatric and Adolescent Gynecological Endocrinology | volume = 4 |year=2017 |isbn=978-3-319-41431-7 |series=ISGE Series |pages=67–109 | publisher = Springer |doi=10.1007/978-3-319-41433-1_7 |issn=2197-8735}}</ref> Because estradiol cypionate 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="pmid17627398" /><ref name="ArunNarendra2012" /> {{Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors}} {{Parenteral potencies and durations of steroidal estrogens}} ====Effects on liver protein synthesis==== A study compared the combination of 5 mg estradiol cypionate and 25 mg medroxyprogesterone acetate as a combined injectable contraceptive (which has been associated with peak estradiol levels of around 300 pg/mL) with an [[ethinylestradiol]]-containing [[combined birth control pill]] and found that whereas the birth control pill produced significant changes in [[coagulation]] parameters, there were no significant [[prothrombotic]] effects of the combined injectable contraceptive on levels of [[fibrinogen]], [[factor VII|factors VII]] and [[factor X|X]], [[plasminogen]], or the [[activated prothrombin time]].<ref name="pmid11091987">{{Cite journal |vauthors=Kaunitz AM |date=December 2000 |title=Injectable contraception. New and existing options |journal=Obstet. Gynecol. Clin. North Am. |volume=27 |issue=4 |pages=741–80 |doi=10.1016/S0889-8545(05)70171-6 |pmid=11091987}}</ref> As such, it appears that similarly to depot medroxyprogesterone acetate, combined injectable contraceptives with 5 mg estradiol cypionate and 25 mg medroxyprogesterone acetate have less or no procoagulant effect relative to combined birth control pills.<ref name="pmid11091987" /> ===Pharmacokinetics=== {{See also|Pharmacokinetics of estradiol}} ====Intramuscular injection==== In contrast to [[oral administration]], which is associated with very low [[bioavailability]] (<10%), the bioavailability of both estradiol and estradiol esters like estradiol valerate is complete (i.e., 100%) via [[intramuscular injection]].<ref name="pmid7169965" /><ref name="pmid16112947" /> In addition, estradiol esters like estradiol cypionate and estradiol valerate when given as an injection of [[oil solution]] or [[microcrystalline]] [[aqueous suspension]] have a relatively long duration due to the formation of an intramuscular [[depot injection|depot]] from which they are slowly released and absorbed.<ref name="pmid7169965" /><ref name="Sriram">{{Cite book | vauthors = Sriram D, Yogiswari P | chapter = Steroids | chapter-url=https://books.google.com/books?id=9HSoZrcBRl0C&pg=PA427 |title=Medicinal Chemistry |publisher=Pearson Education India |year=2007 |isbn=978-81-317-0031-0 |page=427 |access-date=20 May 2012}}</ref><ref name="CrabbéArcher1983">{{cite journal | vauthors = Crabbé P, Archer S, Benagiano G, Diczfalusy E, Djerassi C, Fried J, Higuchi T | title = Long-acting contraceptive agents: design of the WHO Chemical Synthesis Programme | journal = Steroids | volume = 41 | issue = 3 | pages = 243–253 | date = March 1983 | pmid = 6658872 | doi = 10.1016/0039-128X(83)90095-8 | s2cid = 12896179 }}</ref> Upon intramuscular injection of estradiol cypionate in an oil solution, the solvent (i.e., oil) is absorbed, and a primary [[microcrystalline]] depot is formed within the [[muscle]] at the site of injection.<ref name="pmid16112947" /> In addition, a secondary depot may be formed in [[adipose tissue]].<ref name="pmid16112947" /> The slow release of estradiol cypionate from the tissue depot is caused by the high [[lipophilicity]] of the estradiol ester, which in turn is due to its long fatty acid cypionic acid ester [[moiety (chemistry)|moiety]].<ref name="pmid7169965" /> Estradiol cypionate is formulated for use alone and in combination with [[testosterone cypionate]] as an oil solution, and for use in combination with medroxyprogesterone acetate as a microcrystalline aqueous suspension.<ref name="Drugs@FDA" /><ref name="Pharmaceutical" /><ref name="Becker2001f" /><ref name="Administration2011" /> Aqueous suspensions of [[steroid ester]]s generally have longer durations by intramuscular injection than oil solutions.<ref name="CrabbéArcher1983" /> A single intramuscular injection of 5 mg estradiol cypionate has been found to result in peak circulating concentrations of 338 pg/mL estradiol and 145 pg/mL estrone, which occurred at about 4 and 5 days post-injection, respectively (see right table).<ref name="pmid7389356" /> Compared to two other commonly used estradiol esters (which were also assessed in the study), estradiol cypionate had the longest duration, at approximately 11 days, whereas [[estradiol benzoate]] and [[estradiol valerate]] were found to last for 4 to 5 days and 7 to 8 days, respectively.<ref name="pmid7389356" /> This is because estradiol cypionate has a more extensive fatty acid chain and in relation to this is comparatively more lipophilic.<ref name="pmid16112947" /> For a given estradiol ester, the longer or more extensive the fatty acid chain is, the more lipophilic, longer-lasting, and more uniform/plateau-like the resultant levels of estradiol are as well as the lower the peak/maximal levels are (and hence less spike-like).<ref name="pmid16112947" /> [[Estradiol cypionate/medroxyprogesterone acetate]] (brand names Lunelle, Cyclofem) is a [[combined injectable contraceptive]] containing 5 mg estradiol cypionate and 25 mg [[medroxyprogesterone acetate]] in microcrystalline aqueous suspension for once-monthly intramuscular administration.<ref name="ArunNarendra2012">{{Cite book | vauthors = Seth S, Nagrath A, Deoghare R | chapter = Injectable Contraceptives till Date | veditors = Arun N, Narendra M, Shikha S | chapter-url=https://books.google.com/books?id=AS3UBAAAQBAJ&pg=PA416 |title=Progress in Obstetrics and Gynecology--3 |date=15 December 2012 |publisher=Jaypee Brothers Medical Publishers Pvt. Ltd. |isbn=978-93-5090-575-3 |pages=416–419}}</ref><ref name="RahimyRyan1999">{{cite journal | vauthors = Rahimy MH, Ryan KK, Hopkins NK | title = Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): steady-state pharmacokinetics of MPA and E2 in surgically sterile women | journal = Contraception | volume = 60 | issue = 4 | pages = 209–214 | date = October 1999 | pmid = 10640167 | doi = 10.1016/S0010-7824(99)00086-4 }}</ref> With this formulations, estradiol levels peak 2 to 3 days post-injection with average maximal circulating levels of about 250 pg/mL.<ref name="pmid23265980" /><ref name="ArunNarendra2012" /><ref name="RahimyRyan1999" /> The elimination half-life of estradiol with these formulations is 8.4 to 10.1 days, and circulating estradiol levels return to a baseline of about 50 pg/mL approximately 14 to 24 days post-injection.<ref name="pmid23265980" /><ref name="ArunNarendra2012" /><ref name="RahimyRyan1999" /><ref name=Lunelle-Label>{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20874lbl.pdf|access-date=21 April 2023|website=accessdata.fda.gov |title=LUNELLE' Monthly Contraceptive Injection|year=2000}}</ref> <div class="skin-invert-image">{{Gallery | title=Hormone levels with estradiol cypionate by intramuscular injection | width=300 | height=210 | align=center | style="font-size:small;" | File:Estradiol levels after a single subcutaneous or intramuscular injection of 5 mg estradiol cypionate.png | Estradiol levels after subcutaneous (s.c.) or intramuscular (i.m.) injection of 5 mg estradiol cypionate in aqueous suspension.<ref name="pmid22078184">{{Cite journal |vauthors=Sierra-Ramírez JA, Lara-Ricalde R, Lujan M, Velázquez-Ramírez N, Godínez-Victoria M, Hernádez-Munguía IA, Padilla A, Garza-Flores J |year=2011 |title=Comparative pharmacokinetics and pharmacodynamics after subcutaneous and intramuscular administration of medroxyprogesterone acetate (25 mg) and estradiol cypionate (5 mg) |journal=Contraception |volume=84 |issue=6 |pages=565–70 |doi=10.1016/j.contraception.2011.03.014 |pmid=22078184}}</ref> Assays were performed using [[ELISA|enzyme immunoassay]].<ref name="pmid22078184" /> Source was Sierra-Ramírez et al. (2011).<ref name="pmid22078184" /> | File:Estradiol levels at steady state with intramuscular injections of 5 mg estradiol cypionate per month in premenopausal women.png | Estradiol levels at steady state (after the 3rd injection) with intramuscular injections of aqueous suspensions of 5 mg estradiol cypionate per month in premenopausal women.<ref name="pmid10640167">{{Cite journal |vauthors=Rahimy MH, Ryan KK, Hopkins NK |date=October 1999 |title=Lunelle monthly contraceptive injection (medroxyprogesterone acetate and estradiol cypionate injectable suspension): steady-state pharmacokinetics of MPA and E2 in surgically sterile women |journal=Contraception |volume=60 |issue=4 |pages=209–14 |doi=10.1016/S0010-7824(99)00086-4 |pmid=10640167}}</ref><ref name="pmid23265980" /> Assays were performed using [[ELISA|enzyme immunoassay]] and {{abbrlink|LC-MS/MS|liquid chromatography–tandem mass spectrometry}}.<ref name="pmid10640167" /><ref name="pmid23265980" /> Sources were Rahimy et al. (1999) and Thurman et al. (2013).<ref name="pmid10640167" /><ref name="pmid23265980" /> | File:Estradiol levels after a single intramuscular injection of 1.0 to 2.0-mg estradiol cypionate in hypogonadal girls.png | Estradiol levels after a single intramuscular injection of 1.0 to 2.0 mg (average 1.67 mg) of estradiol cypionate in oil (Depo-Estradiol) in hypogonadal girls.<ref name="pmid4742538">{{Cite journal |vauthors=Rosenfield RL, Fang VS, Dupon C, Kim MH, Refetoff S |date=October 1973 |title=The effects of low doses of depot estradiol and testosterone in teenagers with ovarian failure and Turner's syndrome |journal=J. Clin. Endocrinol. Metab. |volume=37 |issue=4 |pages=574–80 |doi=10.1210/jcem-37-4-574 |pmid=4742538}}</ref><ref name="pmid4370903">{{Cite journal |vauthors=Rosenfield RL, Fang VS |date=December 1974 |title=The effects of prolonged physiologic estradiol therapy on the maturation of hypogonadal teen-agers |journal=J Pediatr |volume=85 |issue=6 |pages=830–7 |doi=10.1016/s0022-3476(74)80355-0 |pmid=4370903}}</ref> Assays were performed using [[radioimmunoassay]] with [[chromatographic separation]].<ref name="pmid4742538" /><ref name="pmid4370903" /> Sources were Rosenfield et al. (1973, 1974).<ref name="pmid4742538" /><ref name="pmid4370903" /> | File:Estradiol levels after a single 5 mg intramuscular injection of estradiol esters.png | Estradiol levels after single intramuscular injections of 5 mg of different estradiol esters in oil in premenopausal women.<ref name="pmid7389356" /> Assays were performed using [[radioimmunoassay]] with [[chromatographic separation]].<ref name="pmid7389356" /> Source was Oriowo et al. (1980).<ref name="pmid7389356" /> | 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 oil solution in women.<ref name="pmid8013219">{{Cite journal |vauthors=Garza-Flores J |date=April 1994 |title=Pharmacokinetics of once-a-month injectable contraceptives |journal=Contraception |volume=49 |issue=4 |pages=347–59 |doi=10.1016/0010-7824(94)90032-9 |pmid=8013219}}</ref> Source was Garza-Flores (1994).<ref name="pmid8013219" /> | File:Estradiol cypionate levels after a single intramuscular injection of 5 mg microcrystalline estradiol cypionate in aqueous suspension in women.png | Estradiol cypionate levels after a single injection of 5 mg microcrystalline estradiol cypionate in aqueous suspension in women.<ref name="pmid30947128">{{Cite journal |vauthors=Martins RS, Antunes NJ, Comerlatti G, Caraccio G, Moreno RA, Frecentese F, Caliendo G, De Nucci G |date=June 2019 |title=Quantification of estradiol cypionate in plasma by liquid chromatography coupled with tandem mass spectrometry: Application in a pharmacokinetic study in healthy female volunteers |journal=J Pharm Biomed Anal |volume=170 |pages=273–278 |doi=10.1016/j.jpba.2019.03.053 |pmid=30947128 |s2cid=96433789}}</ref> Assays were performed using {{abbrlink|LC-MS/MS|liquid chromatography–tandem mass spectrometry}}. Source was Martins et al. (2019).<ref name="pmid30947128" /> | 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="pmid14388061">{{Cite journal |vauthors=Schwartz MM, Soule SD |date=July 1955 |title=Estradiol 17-beta-cyclopentylpropionate, a long-acting estrogen |journal=Am. J. Obstet. Gynecol. |volume=70 |issue=1 |pages=44–50 |doi=10.1016/0002-9378(55)90286-6 |pmid=14388061}}</ref> Source was Schwartz & Soule (1955).<ref name="pmid14388061" /> }}</div> ====Subcutaneous injection==== Estradiol cypionate in a [[microcrystalline]] [[aqueous suspension]] has been found to have equivalent effectiveness and virtually identical [[pharmacokinetics]] when administered by [[subcutaneous injection]] versus [[intramuscular injection]].<ref name="pmid22078184" /> However, subcutaneous injection is considered to be easier and less painful relative to intramuscular injection, and for these reasons, may result in comparatively greater satisfaction and compliance.<ref name="pmid22078184" /> ==Chemistry== {{See also|Estrogen ester|List of estrogen esters#Estradiol esters}} Estradiol cypionate is a [[synthetic compound|synthetic]] [[estrane]] [[steroid]] and the C17β [[cypionic acid|cyclopentylpropionate]] (cypionate) [[fatty acid]] [[ester]] of [[estradiol (medication)|estradiol]].<ref name="Elks2014">{{Cite book | vauthors = Elks J |url= https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA898 |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies |date=14 November 2014 |publisher=Springer |isbn=978-1-4757-2085-3 |pages=898–}}</ref><ref name="IndexNominum2000" /> It is also known as estra-1,3,5(10)-triene-3,17β-diol 17β-cyclopentylpropionate.<ref name="Elks2014" /><ref name="IndexNominum2000" /> Other common esters of estradiol in use include [[estradiol valerate]], [[estradiol enantate]], and [[estradiol acetate]], the former two of which are C17β esters of estradiol similarly to estradiol cypionate and the latter of which is the C3 [[acetate]] ester of estradiol. The experimental [[octanol/water partition coefficient]] (logP) of estradiol cypionate is 6.9.<ref name="ChemSpider">{{Cite web |title=Estradiol cypionate | C26H36O3 | ChemSpider |url=http://www.chemspider.com/Chemical-Structure.9033.html |website=www.chemspider.com}}</ref> {{Structural properties of selected estradiol esters}} ==History== Estradiol cypionate was [[patent]]ed by [[Upjohn]] in 1952, with a priority date of 1951.<ref name="Pharmaceutical" /> It was first introduced for medical use by Upjohn in 1952 under the brand name Depo-Estradiol in the [[United States]].<ref name="Sittig1988">{{Cite book | vauthors = Sittig M |url=https://books.google.com/books?id=X2EyLsG4bcUC&pg=PA576 |title=Pharmaceutical Manufacturing Encyclopedia |date=1 January 1988 |publisher=William Andrew |isbn=978-0-8155-1144-1 |pages=575–576 |access-date=20 May 2012}}</ref><ref name="Publishing2013">{{Cite book | author = William Andrew Publishing |url=https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1476 |title=Pharmaceutical Manufacturing Encyclopedia| edition = 3rd |date=22 October 2013 |publisher=Elsevier |isbn=978-0-8155-1856-3 |pages=1476–1477}}</ref><ref name="US2611773">Ott, A. C. (1952). U.S. Patent No. 2,611,773. Washington, DC: U.S. Patent and Trademark Office. https://patents.google.com/patent/US2611773A/en</ref> Subsequently, it was also marketed in other countries such as [[Europe]]an countries and [[Japan]].<ref name="Pharmaceutical" /><ref name="Publishing2013" /><ref name="IndexNominum2000" /> The first clinical reports of estradiol cypionate were published in 1952 and thereafter.<ref name="pmid13000121">{{cite journal | vauthors = Shearman AM, Vogel M, Mcgavack TH | title = Responses of the vaginal epithelium of postmenopausal women to single doses of estrogens | journal = Journal of Gerontology | volume = 7 | issue = 4 | pages = 549–554 | date = October 1952 | pmid = 13000121 | doi = 10.1093/geronj/7.4.549 }}</ref><ref name="pmid13057994">{{cite journal | vauthors = Shearman AM, Mcgavack TH | title = A comparison of the influence of alpha-estradiol dipropionate and of estradiol cyclopentylpropionate on the vaginal mucosa of nonmenstruating and irregularly menstruating women | journal = American Journal of Obstetrics and Gynecology | volume = 66 | issue = 1 | pages = 178–181 | date = July 1953 | pmid = 13057994 | doi = 10.1016/0002-9378(53)90300-7 }}</ref><ref name="pmid13096552">{{cite journal | vauthors = Robinson WW | title = Estradiol cyclopentylpropionate: a new, long-acting, injectable estrogen | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 13 | issue = 10 | pages = 1279–1280 | date = October 1953 | pmid = 13096552 | doi = 10.1210/jcem-13-10-1279 }}</ref><ref name="pmid13072193">{{cite journal | vauthors = Soule SD, Yanow M | title = Estradiol 17-cyclopentyl-propionate | journal = Missouri Medicine | volume = 50 | issue = 5 | pages = 345–346 | date = May 1953 | pmid = 13072193 }}</ref><ref name="pmid14388061" /> It was initially known as ''estradiol cyclopentylpropionate'' (''ECP''), and did not become known as ''estradiol cypionate'' until over a decade later in the mid-to-late 1960s.<ref name="pmid13057994" /><ref name="pmid13096552" /><ref name="pmid5643482">{{cite journal | vauthors = Coutinho EM, Carlos de Souza J | title = Conception control by monthly injections of medroxyprogesterone suspension and long-acting oestrogen | journal = Journal of Reproduction and Fertility | volume = 15 | issue = 2 | pages = 209–214 | date = March 1968 | pmid = 5643482 | doi = 10.1530/jrf.0.0150209 | doi-access = free }}</ref> Along with [[estradiol valerate]] (1954)<ref name="Publishing2013" /><ref name="Duetsch1969">{{Cite book | vauthors = Duetsch LL |url=https://books.google.com/books?id=4vdsAAAAMAAJ |title=Research and development, market power, and patent policy in ethical drugs |publisher=University of Wisconsin--Madison |year=1969 |page=95}}</ref> and [[estradiol benzoate]] (1933),<ref name="Kaufman1933">{{Cite journal | vauthors = Kaufman C |year=1933 |title=Die Behandlung der Amenorrhöe mit Hohen Dosen der Ovarialhormone |journal=Klinische Wochenschrift |volume=12 |issue=40 |pages=1557–1562 |doi=10.1007/BF01765673 |issn=0023-2173 |s2cid=25856898}}</ref><ref name="Buschbeck1934">{{Cite journal | vauthors = Buschbeck H |year=2009 |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 |pages=389–393 |doi=10.1055/s-0028-1129842 |s2cid=72668930 |issn=0012-0472}}</ref><ref name="Biskind1935">{{Cite journal | vauthors = Biskind MS |year=1935 |title=Commercial Glandular Products |journal=Journal of the American Medical Association |volume=105 |issue=9 |pages=667 |doi=10.1001/jama.1935.92760350007009a |issn=0002-9955 |quote=Progynon-B, Schering Corporation: This is crystalline hydroxyestrin benzoate obtained by hydrogenation of theelin and subsequent conversion to the benzoate. [...] Progynon-B is marketed in ampules containing 1 cc. of a sesame oil solution of hydroxyestrin benzoate of either 2,500, 5,000, 10,000 or 50,000 international units.}}</ref> estradiol cypionate has become one of the most commonly used esters of estradiol.<ref name="Yen1991" /> When estradiol cypionate was to be combined with [[medroxyprogesterone acetate]] as a once-a-month [[combined injectable contraceptive|injectable contraceptive]], there was a problem in that estradiol cypionate was prepared as an [[oil solution]] while medroxyprogesterone acetate was used as a [[microcrystalline]] [[aqueous suspension]].<ref name="GoldzieherGoldzieher1994">{{Cite book | vauthors = Goldzieher JW, Goldzieher JW, Fotherby K |url=https://books.google.com/books?id=bJRsAAAAMAAJ |title=Pharmacology of the contraceptive steroids |publisher=Raven Press |year=1994 |isbn=978-0-7817-0097-9 |page=164}}</ref> This issue was resolved by switching to a microcrystalline aqueous suspension in the case of estradiol cypionate, allowing it to be combined with medroxyprogesterone acetate in a single suspension.<ref name="GoldzieherGoldzieher1994" /> As a result, single-drug preparations of estradiol cypionate are oil solutions, while the combination of estradiol cypionate and medroxyprogesterone acetate are microcrystalline aqueous suspensions.<ref name="GoldzieherGoldzieher1994" /> ==Society and culture== ===Generic names=== ''Estradiol cypionate'' is the [[generic term|generic name]] of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|USAN|United States Adopted Name}}.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Drugs.com6" /> It is also known as ''estradiol cyclopentylpropionate'' (''ECP'').<ref name="pmid13057994" /><ref name="pmid13096552" /> ===Brand names=== Estradiol cypionate has been marketed under the brand names Cicloestradiolo, D-Est, depGynogen, Depo-Estradiol, Depoestra, Depofemin, Depogen, Dura-Estrin, E-Cypionate, E-Ionate, Estradep, Estro-Cyp, Estrofem, Estroject, Estromed-PA, Estronol, Femovirin, Neoginon Depositum, Oestradiol-Retard, Pertradiol, Spendepiol, and T-E Cypionate, among others.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="Publishing2013" /><ref name="Drugs.com6" /> ===Availability=== {{See also|List of estrogens available in the United States}} Estradiol cypionate is available in the [[United States]].<ref name="Drugs@FDA" /><ref name="Drugs.com6" /><ref name="BruniBucciantini2017" /> It was previously marketed in [[Spain]] and [[Italy]], but was discontinued in these countries and is no longer available in [[Europe]].<ref name="IndexNominum2000" /><ref name="BruniBucciantini2017" /> Estradiol cypionate has mostly been used in the United States, similarly to [[testosterone cypionate]], with both of these medications having been developed by [[Upjohn]], an American [[pharmaceutical company]].<ref name="IndexNominum2000" /><ref name="Llewellyn2011">{{Cite book | vauthors = Llewellyn W |url=https://books.google.com/books?id=afKLA-6wW0oC&pg=PT426 |title=Anabolics |publisher=Molecular Nutrition Llc |year=2011 |isbn=978-0-9828280-1-4 |pages=426–}}</ref> Besides the United States, estradiol cypionate has been marketed in [[France]], [[Germany]], Italy, Spain, and [[Japan]], among other countries.<ref name="Pharmaceutical" /><ref name="Publishing2013" /><ref name="IndexNominum2000" /> Estradiol cypionate for human use is not available in [[Canada]], although it is marketed in several [[veterinary medicine|veterinary]] formulations in this country.<ref name="HealthCanada2012">{{cite web | title=Drug Product Database online query | website=Health Canada | date=25 April 2012 | url=https://health-products.canada.ca/dpd-bdpp/ | access-date=19 August 2022}}</ref> Estradiol cypionate is available in [[Taiwan]] in combination with testosterone cypionate.<ref name="Drugs.com6" /> It is also available as a combined injectable contraceptive in combination with [[medroxyprogesterone acetate]] in at least 18 countries, mostly in [[Latin America]] and [[Southeast Asia]].<ref name="Martindale">{{Cite book |title=Martindale: The Complete Drug Reference |publisher=Pharmaceutical Press |year=2009 |isbn=978-0-85369-840-1 | veditors = Sweetman SC |edition=36th |location=London |page=2082 |chapter=Sex hormones and their modulators}}</ref><ref name="Micromedex">{{Cite web|url=https://www.micromedexsolutions.com/micromedex2/librarian|title=Micromedex Products: Please Login|website=www.micromedexsolutions.com|accessdate=21 April 2023}}</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 |url=https://monographs.iarc.fr/wp-content/uploads/2018/06/mono72.pdf |title=Hormonal Contraception and Post-menopausal Hormonal Therapy |date=1 January 1999 |publisher=IARC |isbn=978-92-832-1272-0 |page=65 |access-date=24 February 2019 |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 |url-status=dead }}</ref><ref name="BagadePawar2014" /><ref name="Sen2008">{{Cite book | vauthors = Senanayake P, Potts M | chapter = Hormonal Contraception | chapter-url=https://books.google.com/books?id=7dDKBQAAQBAJ&pg=PA51 |title=Atlas of Contraception | edition = Second |date=2008 |publisher=CRC Press |isbn=9780203347324 |page=51 |language=en |archive-url=https://web.archive.org/web/20170102080305/https://books.google.ca/books?id=7dDKBQAAQBAJ&pg=PA51 |archive-date=2017-01-02 |url-status=live}}</ref><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 |url=https://books.google.com/books?id=aGDU5xibtNgC&pg=PA431 |title=Combined Estrogen-progestogen Contraceptives and Combined Estrogen-progestogen Menopausal Therapy|publisher=World Health Organization |year=2007 |isbn=978-92-832-1291-1 |pages=431–}}</ref><ref name="pmid8666089">{{Cite journal |vauthors=Klitsch M |date=1995 |title=Still waiting for the contraceptive revolution |journal=Fam Plann Perspect |volume=27 |issue=6 |pages=246–53 |doi=10.2307/2136177 |jstor=2136177 |pmid=8666089 |s2cid=38860459}}</ref> [[Estradiol cypionate/testosterone cypionate]] and [[estradiol cypionate/medroxyprogesterone acetate]] were both formerly marketed in the United States, but have been discontinued in this country.<ref name="Drugs@FDA" /> ==See also== * [[Estradiol cypionate/medroxyprogesterone acetate]] * [[Estradiol cypionate/testosterone cypionate]] ==References== {{Reflist}} {{Estradiol}} {{Estrogens and antiestrogens}} {{Estrogen receptor modulators}} [[Category:Antigonadotropins]] [[Category:Cypionate esters]] [[Category:Estradiol esters]] [[Category:Hormonal contraception]] [[Category:Hydroxyarenes]] [[Category:Synthetic estrogens]]
Estradiol cypionate
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