Estradiol cypionate

{{Main|Estradiol (medication)#Medical uses|High-dose estrogen}}

The medical uses of estradiol cypionate are the same as those of estradiol and other estrogens. Examples of indications for the drug include 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.{{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 }} 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.{{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 }}{{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 }}{{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–}}{{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–}} The medication has been used to induce puberty in girls with delayed puberty due to hypogonadism.{{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}}

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 flashes 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.{{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.}} 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.

{{Estrogen dosages for menopausal hormone therapy}}

{{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 vials and ampoules at concentrations of 1, 3, and 5 mg/mL (and containing 5, 10, 15, 25, or 50 mg estradiol cypionate total).{{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}}{{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–}} 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.{{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–}} 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).

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).

{{Available forms of estradiol}}

File:Depo-Estradiol (estradiol cypionate) vials.jpgs of Depo-Estradiol (5 mg/mL estradiol cypionate in cottonseed oil solution for use by intramuscular injection) in the United States.]]

{{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 | 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}}{{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}}{{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}}

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

The side effects of estradiol cypionate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, vomiting, bloating, edema, headache, migraine, and melasma.{{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–}}{{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}} High-dose estrogen therapy with estradiol cypionate injections may also cause an increased risk of thromboembolism, changes in blood lipid profile, increased insulin resistance, and increased levels of prolactin.

{{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 |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}} 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 |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}}

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

{{See also|Pharmacodynamics of estradiol}}

Estradiol cypionate is an estradiol ester, or a prodrug of estradiol.{{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}} As such, it is an estrogen, or an agonist of the estrogen receptors. The affinity of estradiol valerate for the estrogen receptor has been reported to be 50 times less than that of estradiol,{{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}} and estradiol valerate and estradiol cypionate have been found to possess similar affinity for the estrogen receptor.{{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}} Both estradiol cypionate and estradiol valerate are rapidly cleaved into estradiol in the body,{{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}} and estradiol valerate has been found to be unable to reach target tissues in any concentration of significance. As such, estradiol valerate is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol, and estradiol cypionate is described as a prodrug of estradiol similarly. Estradiol cypionate is of about 46% higher molecular weight than estradiol due to the presence of its C17β cypionate ester, and contains about 69% of the amount of estradiol by weight.{{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}} Because estradiol cypionate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.

{{Affinities and estrogenic potencies of estrogen esters and ethers at the estrogen receptors}}

{{Parenteral potencies and durations of steroidal estrogens}}

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, factors VII and X, plasminogen, or the activated prothrombin time.{{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}} 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.

{{See also|Pharmacokinetics of estradiol}}

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. 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 from which they are slowly released and absorbed.{{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}}{{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 }} 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. In addition, a secondary depot may be formed in adipose tissue. 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. 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. Aqueous suspensions of steroid esters generally have longer durations by intramuscular injection than oil solutions.

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). 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. This is because estradiol cypionate has a more extensive fatty acid chain and in relation to this is comparatively more lipophilic. 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).

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.{{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}}{{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 }} With this formulations, estradiol levels peak 2 to 3 days post-injection with average maximal circulating levels of about 250 pg/mL. 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.{{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}}

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. 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.

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

Estradiol cypionate is a synthetic estrane steroid and the C17β cyclopentylpropionate (cypionate) fatty acid ester of estradiol.{{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–}} It is also known as estra-1,3,5(10)-triene-3,17β-diol 17β-cyclopentylpropionate. 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.{{Cite web |title=Estradiol cypionate | C26H36O3 | ChemSpider |url=http://www.chemspider.com/Chemical-Structure.9033.html |website=www.chemspider.com}}

{{Structural properties of selected estradiol esters}}

Estradiol cypionate was patented by Upjohn in 1952, with a priority date of 1951. It was first introduced for medical use by Upjohn in 1952 under the brand name Depo-Estradiol in the United States.{{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}}{{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}}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 Subsequently, it was also marketed in other countries such as European countries and Japan. The first clinical reports of estradiol cypionate were published in 1952 and thereafter.{{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 }}{{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 }}{{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 }}{{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 }} 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.{{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 }} Along with estradiol valerate (1954){{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}} and estradiol benzoate (1933),{{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}}{{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}}{{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.}} estradiol cypionate has become one of the most commonly used esters of estradiol.

When estradiol cypionate was to be combined with medroxyprogesterone acetate as a once-a-month 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.{{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}} 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. 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.

Estradiol cypionate is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|USAN|United States Adopted Name}}. It is also known as estradiol cyclopentylpropionate (ECP).

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.

{{See also|List of estrogens available in the United States}}

Estradiol cypionate is available in the United States. It was previously marketed in Spain and Italy, but was discontinued in these countries and is no longer available in Europe. 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.{{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–}} Besides the United States, estradiol cypionate has been marketed in France, Germany, Italy, Spain, and Japan, among other countries. Estradiol cypionate for human use is not available in Canada, although it is marketed in several veterinary formulations in this country.{{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}}

Estradiol cypionate is available in Taiwan in combination with testosterone cypionate. 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.{{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}}{{Cite web|url=https://www.micromedexsolutions.com/micromedex2/librarian|title=Micromedex Products: Please Login|website=www.micromedexsolutions.com|accessdate=21 April 2023}}{{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 }}{{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}}{{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–}}{{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}} Estradiol cypionate/testosterone cypionate and estradiol cypionate/medroxyprogesterone acetate were both formerly marketed in the United States, but have been discontinued in this country.

• Estradiol cypionate/medroxyprogesterone acetate
• Estradiol cypionate/testosterone cypionate

{{Reflist}}

{{Estradiol}}

{{Estrogens and antiestrogens}}

{{Estrogen receptor modulators}}

Category:Antigonadotropins

Category:Cypionate esters

Category:Estradiol esters

Category:Hormonal contraception

Category:Hydroxyarenes

Category:Synthetic estrogens