Estradiol cypionate (EC), sold under the brand name Depo-Estradiol among others, is an

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

medication which is used in

hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...

for

menopausal symptoms Menopause, also known as the climacteric, is the time in women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause usually occurs between the age of 47 and 54. Medical professionals often d ...

and low estrogen levels in cis women, in

for

trans women A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and so ...

, and in

hormonal birth control Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original ...

for cis women.https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/085470s015lbl.pdf It is given by injection into muscle once every 1 to 4 weeks.

Side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of estradiol cypionate include

breast tenderness Breast pain is the symptom of discomfort in either one or both breasts. Pain in both breasts is often described as ''breast tenderness'', is usually associated with the menstrual period and is not serious. Pain that involves only one part of a br ...

breast enlargement Breast enlargement is the enlargement of the breasts. It may occur naturally as in mammoplasia or may occur artificially through active intervention. Many women regard their breasts, which are female secondary sex characteristics, as important to th ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, and fluid retention. Estradiol cypionate is an

and hence is an

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

of the

estrogen receptor Estrogen receptors (ERs) are a group of proteins found inside cells. They are receptors that are activated by the hormone estrogen ( 17β-estradiol). Two classes of ER exist: nuclear estrogen receptors (ERα and ERβ), which are members of the ...

, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

s like

estradiol Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of f ...

. Estradiol cypionate is an

estrogen ester An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol. Esterification renders estradiol into a prodrug of estradiol ...

and a long-lasting

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

in the body. Because of this, it is considered to be a

natural Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are p ...

and

bioidentical Bioidentical hormone replacement therapy (BHRT), also known as bioidentical hormone therapy (BHT) or natural hormone therapy, is the use of hormones that are identical on a molecular level with endogenous hormones in hormone replacement therapy. ...

form of estrogen. Estradiol cypionate was first described as well as introduced for medical use in 1952. Along with

estradiol valerate Estradiol valerate (EV), sold for use by mouth under the brand name Progynova and Primiwal E4 and for use by injection under the brand names Delestrogen and Progynon Depot among others, is an estrogen medication. It is used in hormone therapy fo ...

, it is one of the most commonly used esters of estradiol. Estradiol cypionate has mostly been used in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

, but is also marketed in a few other countries. The medication is not available in

Europe Europe is a large peninsula conventionally considered a continent in its own right because of its great physical size and the weight of its history and traditions. Europe is also considered a Continent#Subcontinents, subcontinent of Eurasia ...

. It is not currently available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

in the United States.

Medical uses

The medical uses of estradiol cypionate are the same as those of estradiol and other estrogens. Examples of indications for the drug include

and

hormonal contraception Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The origin ...

. In regard to the latter, estradiol cypionate has been used in combination with

medroxyprogesterone acetate Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone acetate (DMPA) in injectable form and sold under the brand name Depo-Provera among others, is a hormonal medication of the progestin type. It is used as a method of bi ...

as a

combined injectable contraceptive Combined injectable contraceptives (CICs) are a form of hormonal birth control for women. They consist of monthly injections of combined formulations containing an estrogen and a progestin to prevent pregnancy. CICs are different from progestoge ...

. Along with

estradiol undecylate Estradiol undecylate (EU or E2U), also known as estradiol undecanoate and formerly sold under the brand names Delestrec and Progynon Depot 100 among others, is an estrogen (medication), estrogen medication which has been used in the treatment of ...

, and

estradiol benzoate Estradiol benzoate (EB), sold under the brand name Progynon-B among others, is an estrogen medication which is used in hormone therapy for menopausal symptoms and low estrogen levels in women, in hormone therapy for transgender women, and in the ...

, estradiol cypionate is used as a form of

high-dose estrogen High-dose estrogen (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of a progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and p ...

therapy in

feminizing hormone therapy Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a comm ...

for

transgender women A trans woman or a transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity, may experience gender dysphoria, and may transition; this process commonly includes hormone replacement therapy and som ...

. The medication has been used to induce

puberty Puberty is the process of physical changes through which a child's body matures into an adult body capable of sexual reproduction. It is initiated by hormonal signals from the brain to the gonads: the ovaries in a girl, the testes in a boy. ...

in girls with

delayed puberty Delayed puberty is when a person lacks or has incomplete development of specific sexual characteristics past the usual age of onset of puberty. The person may have no physical or hormonal signs that puberty has begun. In the United States, girls ar ...

due to

hypogonadism Hypogonadism means diminished functional activity of the gonads—the testes or the ovaries—that may result in diminished production of sex hormones. Low androgen (e.g., testosterone) levels are referred to as hypoandrogenism and low estrogen ...

. 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

such as

hot flash Hot flashes (also known as hot flushes) are a form of flushing, often caused by the changing hormone levels that are characteristic of menopause. They are typically experienced as a feeling of intense heat with sweating and rapid heartbeat, and ...

es and

vaginal atrophy Atrophic vaginitis is inflammation of the vagina as a result of tissue thinning due to not enough estrogen. Symptoms may include pain with sex, vaginal itchiness or dryness, and an urge to urinate or burning with urination. It generally does no ...

, at a dosage of 1.5 to 2 mg by intramuscular injection once a month in the treatment of female

hypoestrogenism Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiova ...

due to

, and at a dosage of 2 to 10 mg by intramuscular injection once every 1 or 2 weeks for hormone therapy in transgender women. 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.

Available forms

Estradiol cypionate is and has been available as an

oil solution An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...

for intramuscular injection provided in

vial A vial (also known as a phial or flacon) is a small glass or plastic vessel or bottle, often used to store medication as liquids, powders or capsules. They can also be used as scientific sample vessels; for instance, in autosampler devices i ...

s and

ampoule An ampoule (also ampul and ampule) is a small sealed vial which is used to contain and preserve a sample, usually a solid or liquid. Ampoules are usually made of glass. Modern ampoules are most commonly used to contain pharmaceuticals and chem ...

s at concentrations of 1, 3, and 5 mg/mL (and containing 5, 10, 15, 25, or 50 mg estradiol cypionate total). The 1 and 3 mg/mL concentrations (containing 5 and 15 mg estradiol cypionate total) have been discontinued in the

, but the 5 mg/mL concentration (containing 25 mg estradiol cypionate total) remains available. Aside from estradiol cypionate, the only other injectable estrogen formulations that remain available in the United States are

(10 mg/mL, 20 mg/mL, and 40 mg/mL in oil) and

conjugated estrogens Conjugated estrogens (CEs), or conjugated equine estrogens (CEEs), sold under the brand name Premarin among others, is an estrogen (medication), estrogen medication which is used in menopausal hormone therapy and for various other indications. ...

(25 mg/vial in solution). In addition to single-drug formulations, estradiol cypionate has been marketed in combination with

as a

microcrystalline A microcrystalline material is a crystallized substance or rock that contains small crystals visible only through microscopic examination. There is little agreement on the range of crystal sizes that should be regarded as microcrystalline, but the ...

aqueous suspension In chemistry, a suspension is a Mixture#Homogeneous and heterogeneous mixtures, heterogeneous mixture of a fluid that contains solid particles sufficiently large for sedimentation. The particles may be macroscopic, visible to the naked eye, usual ...

(brand name Lunelle) and in combination with

testosterone cypionate Testosterone cypionate, sold under the brand name Depo-Testosterone among others, is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men. It is also used in hormone therapy fo ...

as an oil solution (brand name Depo-Testadiol). Depo-Estradiol (estradiol cypionate) vials

Contraindications

Contraindication In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...

s of estrogens include

coagulation Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The mechanism o ...

problems,

cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, h ...

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Signs and symptoms Some of the sig ...

, and certain

hormone-sensitive cancer A hormone-sensitive cancer, or hormone-dependent cancer, is a type of cancer that is dependent on a hormone for growth and/or survival. Examples include breast cancer, which is dependent on estrogens like estradiol, and prostate cancer, which is ...

s such as

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

and

endometrial cancer Endometrial cancer is a cancer that arises from the endometrium (the lining of the uterus or womb). It is the result of the abnormal growth of cells that have the ability to invade or spread to other parts of the body. The first sign is most o ...

, among others.

Side effects

The

side effect In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...

s of estradiol cypionate are the same as those of estradiol. Examples of such side effects include

and enlargement,

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

bloating Abdominal bloating (or simply bloating) is a short-term disease that affects the gastrointestinal tract. Bloating is generally characterized by an excess buildup of gas, air or fluids in the stomach. A person may have feelings of tightness, press ...

edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's Tissue (biology), tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels t ...

migraine Migraine (, ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hou ...

, and

melasma Melasma (also known as chloasma faciei,James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . or the mask of pregnancy when present in pregnant women) is a tan or dark ...

High-dose estrogen High-dose estrogen (HDE) is a type of hormone therapy in which high doses of estrogens are given. When given in combination with a high dose of a progestogen, it has been referred to as pseudopregnancy. It is called this because the estrogen and p ...

therapy with estradiol cypionate injections may also cause an increased risk of

thromboembolism Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thro ...

, changes in

blood lipid Blood lipids (or blood fats) are lipids in the blood, either free or bound to other molecules. They are mostly transported in a protein capsule, and the density of the lipids and type of protein determines the fate of the particle and its influence ...

profile Profile or profiles may refer to: Art, entertainment and media Music * ''Profile'' (Jan Akkerman album), 1973 * ''Profile'' (Githead album), 2005 * ''Profile'' (Pat Donohue album), 2005 * ''Profile'' (Duke Pearson album), 1959 * '' ''Profi ...

, increased

insulin resistance Insulin resistance (IR) is a pathological condition in which cell (biology), cells fail to respond normally to the hormone insulin. Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood gluco ...

, and increased levels of

prolactin Prolactin (PRL), also known as lactotropin, is a protein best known for its role in enabling mammals to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans. Prolactin is secreted from the pit ...

Overdose

Symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality showin ...

s of estrogen overdosage may include

, increased weight, water retention,

vaginal discharge Vaginal discharge is a mixture of liquid, cells, and bacteria that lubricate and protect the vagina. This mixture is constantly produced by the cells of the vagina and cervix, and it exits the body through the vaginal opening. The composition, amou ...

heavy legs Heavy legs is a condition described as an unpleasant sensation of pain and heaviness in the lower limbs. Symptoms include legs feeling weighted, stiff, and tired. Heavy legs can be caused by a wide-ranging collection of disorders including but not ...

, and

leg cramps A cramp is a sudden, involuntary, painful skeletal muscle contraction or overshortening associated with electrical activity; while generally temporary and non-damaging, they can cause significant pain and a paralysis-like immobility of the aff ...

. These side effects can be diminished by reducing the estrogen dosage.

Interactions

Inhibitor Inhibitor or inhibition may refer to: In biology * Enzyme inhibitor, a substance that binds to an enzyme and decreases the enzyme's activity * Reuptake inhibitor, a substance that increases neurotransmission by blocking the reuptake of a neurotra ...

s and

inducer In molecular biology, an inducer is a molecule that regulates gene expression. An inducer functions in two ways; namely: *By disabling repressors. The gene is expressed because an inducer binds to the repressor. The binding of the inducer to the r ...

s of

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

may influence the

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

of estradiol and by extension circulating estradiol levels.

Pharmacology

Pharmacodynamics

Estradiol cypionate is an

estradiol ester This is a list of estrogen esters, or ester prodrugs of estrogens. It includes esters, as well as ethers, of steroidal estrogens like estradiol, estrone, and estriol and of nonsteroidal estrogens like the stilbestrols diethylstilbestrol and hex ...

, or a

. As such, it is an

, or an

of the

s. The

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

of estradiol valerate for the estrogen receptor has been reported to be 50 times less than that of estradiol, and estradiol valerate and estradiol cypionate have been found to possess similar affinity for the estrogen receptor. Both estradiol cypionate and estradiol valerate are rapidly cleaved into estradiol in the body, 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

to estradiol, and estradiol cypionate is described as a prodrug of estradiol similarly. Estradiol cypionate is of about 46% higher

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

than estradiol due to the presence of its C17β

cypionate Cypionic acid, also known as cyclopentylpropionic acid, is an aliphatic carboxylic acid with the molecular formula C8H14O2. Its salts and esters are known as cypionates or cipionates. The primary use of cypionic acid is in pharmaceutical formula ...

ester, and contains about 69% of the amount of estradiol by weight. Because estradiol cypionate is a prodrug of estradiol, it is considered to be a

and

form of estrogen.

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 Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disord ...

-containing

combined birth control pill The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: progesti ...

and found that whereas the birth control pill produced significant changes in

parameters, there were no significant

prothrombotic Thrombosis (from Ancient Greek "clotting") is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thr ...

effects of the combined injectable contraceptive on levels of

fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clo ...

, factors VII and X,

plasminogen Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...

, or the

activated prothrombin time The prothrombin time (PT) – along with its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) – is an assay for evaluating the ''extrinsic'' pathway and common pathway of coagulation. This blood test is a ...

. 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.

Pharmacokinetics

Intramuscular injection

In contrast to

oral administration Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are in ...

, which is associated with very low

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. H ...

(<10%), the bioavailability of both estradiol and estradiol esters like estradiol valerate is complete (i.e., 100%) via

intramuscular injection Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have ...

. In addition, estradiol esters like estradiol cypionate and estradiol valerate when given as an injection of

have a relatively long duration due to the formation of an intramuscular

depot Depot ( or ) may refer to: Places * Depot, Poland, a village * Depot Island, Kemp Land, Antarctica * Depot Island, Victoria Land, Antarctica * Depot Island Formation, Greenland Brands and enterprises * Maxwell Street Depot, a restaurant in ...

from which they are slowly released and absorbed. Upon intramuscular injection of estradiol cypionate in an oil solution, the solvent (i.e., oil) is absorbed, and a primary

depot is formed within the

muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

at the site of injection. In addition, a secondary depot may be formed in

adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular e ...

. The slow release of estradiol cypionate from the tissue depot is caused by the high

lipophilicity Lipophilicity (from Greek λίπος "fat" and φίλος "friendly"), refers to the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipop ...

of the estradiol ester, which in turn is due to its long fatty acid cypionic acid ester

moiety Moiety may refer to: Chemistry * Moiety (chemistry), a part or functional group of a molecule ** Moiety conservation, conservation of a subgroup in a chemical species Anthropology * Moiety (kinship), either of two groups into which a society is ...

. Estradiol cypionate is formulated for use alone and in combination with

as an oil solution, and for use in combination with medroxyprogesterone acetate as a microcrystalline aqueous suspension. Aqueous suspensions of

steroid ester A steroid ester is an ester of a steroid. They include androgen esters, estrogen esters, progestogen esters, and corticosteroid esters. Steroid esters may be naturally occurring/endogenous like DHEA sulfate or synthetic like estradiol valerate. E ...

s 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

and

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 Estradiol cypionate/medroxyprogesterone acetate (EC/MPA), sold under the brand name Cyclofem among others, is a form of combined injectable birth control. It contains estradiol cypionate (EC), an estrogen, and medroxyprogesterone acetate (MPA), a ...

(brand names Lunelle, Cyclofem) is a

containing 5 mg estradiol cypionate and 25 mg

in microcrystalline aqueous suspension for once-monthly intramuscular administration. 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.https://www.accessdata.fda.gov/drugsatfda_docs/label/2000/20874lbl.pdf

Subcutaneous injection

Estradiol cypionate in a

has been found to have equivalent effectiveness and virtually identical

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered ...

when administered by

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, ...

versus

. 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.

Chemistry

Estradiol cypionate is a

synthetic Synthetic things are composed of multiple parts, often with the implication that they are artificial. In particular, 'synthetic' may refer to: Science * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic o ...

estrane Estrane is a C18 steroid derivative, with a gonane core. ''Estrenes'' are estrane derivatives that contain a double bond, with an example being nandrolone. ''Estratrienes'' (estrins) are estrane derivatives that contain three double bonds, for i ...

steroid A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...

and the C17β cyclopentylpropionate (cypionate)

fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

. 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 enantate Estradiol enantate (EEn or E2-EN), also spelled estradiol enanthate and sold under the brand names Perlutal and Topasel among others, is an estrogen medication which is used in hormonal birth control for women. It is formulated in combination wi ...

, and

estradiol acetate Estradiol acetate (EA), sold under the brand names Femtrace, Femring, and Menoring, is an estrogen medication which is used in hormone therapy for the treatment of menopausal symptoms in women.https://www.accessdata.fda.gov/drugsatfda_docs/label/ ...

, the former two of which are C17β esters of estradiol similarly to estradiol cypionate and the latter of which is the C3

acetate An acetate is a salt (chemistry), salt formed by the combination of acetic acid with a base (e.g. Alkali metal, alkaline, Alkaline earth metal, earthy, Transition metal, metallic, nonmetallic or radical Radical (chemistry), base). "Acetate" als ...

ester of estradiol. The experimental octanol/water partition coefficient (logP) of estradiol cypionate is 6.9.

History

Estradiol cypionate was

patent A patent is a type of intellectual property that gives its owner the legal right to exclude others from making, using, or selling an invention for a limited period of time in exchange for publishing an enabling disclosure of the invention."A p ...

ed by

Upjohn The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 in Hastings, Michigan, by Dr. William E. Upjohn who was an 1875 graduate of the University of Michigan medical school. The company was originally formed to make ''friabl ...

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

.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

an countries and

Japan Japan ( ja, 日本, or , and formally , ''Nihonkoku'') is an island country in East Asia. It is situated in the northwest Pacific Ocean, and is bordered on the west by the Sea of Japan, while extending from the Sea of Okhotsk in the north ...

. The first clinical reports of estradiol cypionate were published in 1952 and thereafter. 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. Along with

(1954) and

(1933), estradiol cypionate has become one of the most commonly used esters of estradiol. When estradiol cypionate was to be combined with

as a once-a-month

injectable contraceptive Injectable birth control is a form of hormonal contraception and may refer to: * Progestogen-only injectable birth control * Combined injectable birth control Estrogen-only injectable birth control, for instance estradiol undecylate Estradiol ...

, there was a problem in that estradiol cypionate was prepared as an

while medroxyprogesterone acetate was used as a

. 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.

Society and culture

Generic names

''Estradiol cypionate'' is the generic name of the drug and its and . It is also known as ''estradiol cyclopentylpropionate'' (''ECP'').

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.

Availability

Estradiol cypionate is available in the

. It was previously marketed in

Spain , image_flag = Bandera de España.svg , image_coat = Escudo de España (mazonado).svg , national_motto = ''Plus ultra'' (Latin)(English: "Further Beyond") , national_anthem = (English: "Royal March") , i ...

and

Italy Italy ( it, Italia ), officially the Italian Republic, ) or the Republic of Italy, is a country in Southern Europe. It is located in the middle of the Mediterranean Sea, and its territory largely coincides with the homonymous geographical re ...

, but was discontinued in these countries and is no longer available in

. Estradiol cypionate has mostly been used in the United States, similarly to

, with both of these medications having been developed by

, an American

pharmaceutical company The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate sympto ...

. Besides the United States, estradiol cypionate has been marketed in

France France (), officially the French Republic ( ), is a country primarily located in Western Europe. It also comprises of Overseas France, overseas regions and territories in the Americas and the Atlantic Ocean, Atlantic, Pacific Ocean, Pac ...

Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...

, Italy, Spain, and

, among other countries. Estradiol cypionate is not available in

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...

, although it is marketed in several

veterinary Veterinary medicine is the branch of medicine that deals with the prevention, management, diagnosis, and treatment of disease, disorder, and injury in animals. Along with this, it deals with animal rearing, husbandry, breeding, research on nutri ...

formulations in this country. Estradiol cypionate is available in

Taiwan Taiwan, officially the Republic of China (ROC), is a country in East Asia, at the junction of the East and South China Seas in the northwestern Pacific Ocean, with the People's Republic of China (PRC) to the northwest, Japan to the nort ...

in combination with testosterone cypionate. It is also available as a combined injectable contraceptive in combination with

in at least 18 countries, mostly in

Latin America Latin America or * french: Amérique Latine, link=no * ht, Amerik Latin, link=no * pt, América Latina, link=no, name=a, sometimes referred to as LatAm is a large cultural region in the Americas where Romance languages — languages derived f ...

and

Southeast Asia Southeast Asia, also spelled South East Asia and South-East Asia, and also known as Southeastern Asia, South-eastern Asia or SEA, is the geographical United Nations geoscheme for Asia#South-eastern Asia, south-eastern region of Asia, consistin ...

. Estradiol cypionate/testosterone cypionate and

estradiol cypionate/medroxyprogesterone acetate Estradiol cypionate/medroxyprogesterone acetate (EC/MPA), sold under the brand name Cyclofem among others, is a form of combined injectable birth control. It contains estradiol cypionate (EC), an estrogen, and medroxyprogesterone acetate (MPA), a ...

were both formerly marketed in the United States, but have been discontinued in this country.

References

{{Estrogen receptor modulators Antigonadotropins Cypionate esters Estradiol esters Hormonal contraception Phenols Prodrugs Synthetic estrogens

Medical uses

Available forms

Contraindications

Side effects

Overdose

Interactions

Pharmacology

Pharmacodynamics

Effects on liver protein synthesis

Pharmacokinetics

Intramuscular injection

Subcutaneous injection

Chemistry

History

Society and culture

Generic names

Brand names

Availability

See also

References