Estradiol enantate (EEn or E2-EN), also spelled estradiol enanthate and sold under the brand names Perlutal and Topasel 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

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 women. It is formulated in

combination In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are th ...

with dihydroxyprogesterone acetophenide (DHPA; algestone acetophenide), a

progestin A progestogen, also referred to as a progestagen, gestagen, or gestogen, is a type of medication which produces effects similar to those of the natural product, natural female sex hormone progesterone in the body. A progestin is a ''synthetic co ...

, and is used specifically 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 ...

. Estradiol enantate is not available for medical use alone. The medication, in combination with DHPA, is given by injection into muscle once a month.

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 enantate 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 t ...

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 enantate 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 ...

. It 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 estradio ...

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 enantate was first described by 1954, and was first studied in combination with DHPA as a combined injectable contraceptive in 1964. The combination was introduced for clinical use by the mid-1970s. Estradiol enantate is not available as a standalone medication (i.e., by itself without DHPA). The combination is available 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

Hong Kong Hong Kong ( (US) or (UK); , ), officially the Hong Kong Special Administrative Region of the People's Republic of China ( abbr. Hong Kong SAR or HKSAR), is a city and special administrative region of China on the eastern Pearl River Delt ...

, and was also 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

Portugal Portugal, officially the Portuguese Republic ( pt, República Portuguesa, links=yes ), is a country whose mainland is located on the Iberian Peninsula of Southwestern Europe, and whose territory also includes the Atlantic archipelagos of ...

Medical uses

Estradiol enantate is used in combination with the progestin DHPA as a once-monthly combined injectable contraceptive for women in

and

. Estradiol enantate has been studied 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 as well. The combination of estradiol enantate and DHPA has likewise been used by transgender women for such purposes.

Available forms

The following forms of estradiol enantate are or have been available for use: * Estradiol enantate 10 mg and DHPA 150 mg (brand names Perlutal, Topasel, many others) * Estradiol enantate 5 mg and DHPA 75 mg (brand names Anafertin, Patector NF, Yectames) * Estradiol enantate 10 mg and DHPA 120 mg (brand names Unalmes, Yectuna) * Estradiol enantate 10 mg and DHPA 75 mg (brand name Ova Repos; discontinued) A 6 mg estradiol enantate and 90 mg DHPA formulation was also studied, but was never marketed. The combination of estradiol enantate and DHPA has also been studied at other doses ranging from 5 to 50 mg estradiol enantate and 75 to 200 mg DHPA. The combination of estradiol enantate and DHPA is provided in

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 estradiol enantate concentrations of 5 mg/mL and 10 mg/mL.

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

and enlargement,

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 ...

, 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 ...

. The combination of estradiol enantate and DHPA as a combined injectable contraceptive has shown no adverse effects on

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

function,

lipid metabolism Lipid metabolism is the synthesis and degradation of lipids in cells, involving the breakdown or storage of fats for energy and the synthesis of structural and functional lipids, such as those involved in the construction of cell membranes. In anim ...

, or

. A

Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...

ian

case report In medicine, a case report is a detailed report of the symptoms, signs, diagnosis, treatment, and follow-up of an individual patient. Case reports may contain a demographic profile of the patient, but usually describe an unusual or novel occurrence ...

of a

prolactinoma A prolactinoma is a tumor ( adenoma) of the pituitary gland that produces the hormone prolactin. It is the most common type of functioning pituitary tumor. Symptoms of prolactinoma are due to abnormally high levels of prolactin in the blood (hyp ...

in a

transgender woman 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 ...

treated with 10 mg estradiol enantate every 2 weeks exists.Camara, V. L., Zanardi, U. V., Glezer, A., Paraiba, D. B., Bronstein, M. D., Mendonca, B. B., & Costa, E. M. F. (2010, June). Estrogen as a Presumed Risk Factor for Prolactinoma in a Male-to-Female Transsexual Patient. Endocrine Reviews, Supplement 1, 31(3), S347–S347. https://www.endocrine.org/-/media/endocrine/files/endo-annual-meetings/endo_abstracts_2010_02.pdf#page=347Camara, V. L. (2010). Estradiol enantate First report of prolactinoma, in a transsexual. Reactions, 1311, 24. 10.2165/00128415-201013110-00077. https://link.springer.com/article/10.2165/00128415-201013110-00077 While DHPA was not mentioned in this instance, estradiol enantate is normally formulated in combination with DHPA including in Brazil.

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

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 ...

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

Interactions

Inhibitors 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 enantate 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. Estradiol enantate is of about 41% 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 enantate ester. Because estradiol enantate is a prodrug of estradiol, it is considered to be a

and

form of estrogen. The combination of 10 mg estradiol enantate and 150 mg DHPA as a once-monthly combined injectable contraceptive (which achieves levels of estradiol of around 350 pg/mL) has been found to have little to no effect on many markers of estrogen-modulated

liver protein synthesis The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

, including circulating levels of HDL and

LDL cholesterol Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall dens ...

copper Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...

ceruloplasmin Ceruloplasmin (or caeruloplasmin) is a ferroxidase enzyme that in humans is encoded by the ''CP'' gene. Ceruloplasmin is the major copper-carrying protein in the blood, and in addition plays a role in iron metabolism. It was first described in 194 ...

, total and free

cortisol Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone. It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...

corticosteroid-binding globulin Transcortin, also known as corticosteroid-binding globulin (CBG) or serpin A6, is a protein produced in the liver in animals. In humans it is encoded by the SERPINA6 gene. It is an alpha-globulin. Function This gene encodes an alpha-globulin p ...

, and

sex hormone-binding globulin Sex hormone-binding globulin (SHBG) or sex steroid-binding globulin (SSBG) is a glycoprotein that binds to androgens and estrogens. When produced by the Sertoli cells in the seminiferous tubules of the testis, it has also been called androgen ...

. However, it was found to significantly increase levels of

triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as w ...

s and to significantly decrease levels of total and free

testosterone Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testes and prostate, as well as promoting secondar ...

. In contrast to the estradiol enantate-containing combined injectable contraceptive, low-dose

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

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: progest ...

s produce highly significant changes in all of the preceding parameters. Studies in women and female

capuchin monkey The capuchin monkeys () are New World monkeys of the subfamily Cebinae. They are readily identified as the " organ grinder" monkey, and have been used in many movies and television shows. The range of capuchin monkeys includes some tropical fores ...

s have found that injections of estradiol enantate and DHPA significantly alter levels of

coagulation factor 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 ...

s.Oliva Filho, W. M., & Santos, N. da C. (1992). Efeitos na coagulação sanguinea em usuárias da associação acetofenido de dihidroxiprogesterona 150mg e enantato de estradiol 10mg como metodo anticoncepcional injetavel. Universidade de São Paulo, São Paulo. https://bdpi.usp.br/item/000736190 The clinical

ic effects of estradiol enantate and

have been compared in other studies as well.

Pharmacokinetics

When estradiol enantate is administered in 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 ...

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 ...

, a

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 ...

effect occurs, and this results in it having a long

duration of action Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for ...

. The duration of action of estradiol enantate is considerably longer than that of various other

s, such as

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 t ...

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 ...

, and

estradiol cypionate 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 estrog ...

, whereas its duration is shorter than that of

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 which has been used in the treatment of prostate cancer in men. ...

. In general, the longer the

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

chain A chain is a serial assembly of connected pieces, called links, typically made of metal, with an overall character similar to that of a rope in that it is flexible and curved in compression but linear, rigid, and load-bearing in tension. A c ...

, the more

lipophilic 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 ...

the estradiol ester, the more slowly it is released from the depot and absorbed into the circulation, and the longer its duration of action. The

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 ...

of estradiol enantate have been assessed in a number of studies. It has usually been studied in combination with DHPA. Following an

of estradiol enantate, levels of estradiol have been found to peak after 3 to 8 days. Maximal levels of estradiol after a 5 mg injection of estradiol enantate have been found to be about 163 to 209 pg/mL and after a 10 mg injection of estradiol enantate have been found to be about 283 to 445 pg/mL. However, one outlying study reported peak estradiol levels of 850 pg/mL after an intramuscular injection of 10 mg estradiol enantate in three postmenopausal women. It used

radioimmunoassay A radioimmunoassay (RIA) is an immunoassay that uses radiolabeled molecules in a stepwise formation of immune complexes. A RIA is a very sensitive in vitro assay technique used to measure concentrations of substances, usually measuring antigen conc ...

for the determinations, with no mention of chromatographic separation. Estradiol levels following an intramuscular injection of 10 mg estradiol enantate have been found to return to baseline levels of around 50 pg/mL after about 20 to 30 days. However, a

metabolic 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 ...

study found that traces of

radiolabel A radioactive tracer, radiotracer, or radioactive label is a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactive decay it can be used to explore the mechanism of chemical reactions by tr ...

ed estradiol enantate remained detectable in blood for at least 30 to 40 days and for as long as 60 days. Studies have reported that the

elimination half-life Biological half-life (also known as elimination half-life, pharmacologic half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the bl ...

of estradiol enantate after a single 10 mg intramuscular injection was 5.6 to 7.5 days. The

volume of distribution In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same c ...

of estradiol enantate has been reported to be 5.087 L. Estradiol enantate is

excreted Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after lea ...

preferentially in

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

. There were concerns about possible accumulation of estradiol enantate and consequent estrogenic overexposure with once-monthly combined injectable contraceptives containing the medication due its long

duration Duration may refer to: * The amount of time elapsed between two events * Duration (music) – an amount of time or a particular time interval, often cited as one of the fundamental aspects of music * Duration (philosophy) – a theory of time and ...

, and this may have limited the use of such combined injectable contraceptives. Subsequent clinical studies have found that there is very limited or no accumulation of estradiol enantate when it is used in once-a-month injectable contraceptives.

Chemistry

Estradiol enantate, also known as estradiol 17β-enantate or estra-1,3,5(10)-triene-3,17β-diol 17β-heptanoate, is a synthetic

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, fo ...

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 enantate (heptanoate)

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 ...

. Other common esters of estradiol used clinically include

, and

Estradiol dienantate Estradiol dienanthate (EDE), sold under the brand names Climacteron among others, is a long-acting estrogen medication which was previously used in menopausal hormone therapy for women and to suppress lactation in women. It was formulated in com ...

(component of

Climacteron Estradiol benzoate/estradiol dienanthate/testosterone enanthate benzilic acid hydrazone (EB/EDE/TEBH), sold under the brand names Climacteron, Lactimex, Lactostat, and Amenose, is an injectable combination medication of estradiol benzoate (EB), ...

), or estradiol 3,17β-dienantate, has also been used. The experimental octanol/water partition coefficient (logP) of estradiol enanthate is 6.7.

History

Estradiol enantate was first described, along with a variety of other

s, by Karl Junkmann of

Schering AG Schering AG was a research-centered German multinational pharmaceutical company headquartered in Wedding, Berlin, which operated as an independent company from 1851 to 2006. In 2006, it was bought by Bayer AG and merged to form the Bayer subs ...

in 1953. The first clinical study of estradiol enantate and DHPA as a

was conducted in 1964. The combination was marketed by the mid-1970s.

Society and culture

Generic names

''Estradiol enantate'' is the

British English British English (BrE, en-GB, or BE) is, according to Lexico, Oxford Dictionaries, "English language, English as used in Great Britain, as distinct from that used elsewhere". More narrowly, it can refer specifically to the English language in ...

generic name of the medication and its and , while ''estradiol enanthate'' is its and

American English American English, sometimes called United States English or U.S. English, is the set of variety (linguistics), varieties of the English language native to the United States. English is the Languages of the United States, most widely spoken lan ...

generic name. Its generic names in other languages are as follows: * French: ''enantate d'estradiol'' and ''estradiol enantate'' *

German German(s) may refer to: * Germany (of or related to) ** Germania (historical use) * Germans, citizens of Germany, people of German ancestry, or native speakers of the German language ** For citizens of Germany, see also German nationality law **Ge ...

: ''estradiol enantat'' *

Italian Italian(s) may refer to: * Anything of, from, or related to the people of Italy over the centuries ** Italians, an ethnic group or simply a citizen of the Italian Republic or Italian Kingdom ** Italian language, a Romance language *** Regional Ita ...

: ''estradiolo enantato'' *

Portuguese Portuguese may refer to: * anything of, from, or related to the country and nation of Portugal ** Portuguese cuisine, traditional foods ** Portuguese language, a Romance language *** Portuguese dialects, variants of the Portuguese language ** Portu ...

and

Spanish Spanish might refer to: * Items from or related to Spain: **Spaniards are a nation and ethnic group indigenous to Spain **Spanish language, spoken in Spain and many Latin American countries **Spanish cuisine Other places * Spanish, Ontario, Can ...

: ''enantato de estradiol'' and ''estradiol enantato'' Estradiol enantate is also known by its former developmental code name ''SQ-16150''. It has been referred to as ''estradiol heptanoate''.

Brand names

Estradiol enantate has been marketed under a wide variety of brand names. It has been marketed in a few different preparations, with varying doses of estradiol enantate and DHPA. These formulations all have different brand names, which include the following (^† = discontinued): * EEn 10 mg / DHPA 150 mg: Acefil, Agurin^†, Atrimon^†, Ciclomes, Ciclovar, Ciclovular, Cicnor^†, Clinomin, Cycloven, Daiva, Damix, Deprans, Deproxone, Exuna, Ginestest, Ginoplan^†, Gynomes, Horprotal, Listen, Luvonal, Neogestar, Neolutin, Nomagest, Nonestrol, Normagest, Normensil, Novular, Oterol, Ovoginal, Patector, Patectro, Perludil, Perlumes, Perlutal, Perlutale, Perlutan, Perlutin, Perlutin-Unifarma, Permisil, Preg-Less, Pregnolan, Progestrol^†, Protegin, Proter, Seguralmes, Synovular, Topasel, Unigalen, Uno-Ciclo, and Vagital. * EEn 10 mg / DHPA 120 mg: Anafertin^†, Patector NF, and Yectames. * EEn 5 mg / DHPA 75 mg: Unalmes and Yectuna. * EEn 10 mg / DHPA 75 mg: Ova Repos^†. * Unsorted: Evitas^†, Femineo^†, and Primyfar^†. The combination of EEn 10 mg and DHPA 150 mg was developed under the developmental brand name Deladroxate, but this brand name was never used commercially.

Availability

Estradiol enantate has been marketed in combination with DHPA as a

in at least 19 countries, mostly in

.
/ref> A few different preparations, with varying doses of EEn and DHPA and varying availability, have been introduced. These formulations have the following approval and availability (^† = discontinued in this country): * EEn 10 mg / DHPA 150 mg: at least 19 countries, including

Argentina Argentina (), officially the Argentine Republic ( es, link=no, República Argentina), is a country in the southern half of South America. Argentina covers an area of , making it the second-largest country in South America after Brazil, th ...

Belize Belize (; bzj, Bileez) is a Caribbean and Central American country on the northeastern coast of Central America. It is bordered by Mexico to the north, the Caribbean Sea to the east, and Guatemala to the west and south. It also shares a wate ...

Chile Chile, officially the Republic of Chile, is a country in the western part of South America. It is the southernmost country in the world, and the closest to Antarctica, occupying a long and narrow strip of land between the Andes to the east a ...

Colombia Colombia (, ; ), officially the Republic of Colombia, is a country in South America with insular regions in North America—near Nicaragua's Caribbean coast—as well as in the Pacific Ocean. The Colombian mainland is bordered by the Car ...

Costa Rica Costa Rica (, ; ; literally "Rich Coast"), officially the Republic of Costa Rica ( es, República de Costa Rica), is a country in the Central American region of North America, bordered by Nicaragua to the north, the Caribbean Sea to the no ...

, the

Dominican Republic The Dominican Republic ( ; es, República Dominicana, ) is a country located on the island of Hispaniola in the Greater Antilles archipelago of the Caribbean region. It occupies the eastern five-eighths of the island, which it shares wit ...

Ecuador Ecuador ( ; ; Quechua: ''Ikwayur''; Shuar: ''Ecuador'' or ''Ekuatur''), officially the Republic of Ecuador ( es, República del Ecuador, which literally translates as "Republic of the Equator"; Quechua: ''Ikwadur Ripuwlika''; Shuar: ''Eku ...

El Salvador El Salvador (; , meaning " The Saviour"), officially the Republic of El Salvador ( es, República de El Salvador), is a country in Central America. It is bordered on the northeast by Honduras, on the northwest by Guatemala, and on the south b ...

Guatemala Guatemala ( ; ), officially the Republic of Guatemala ( es, República de Guatemala, links=no), is a country in Central America. It is bordered to the north and west by Mexico; to the northeast by Belize and the Caribbean; to the east by H ...

Honduras Honduras, officially the Republic of Honduras, is a country in Central America. The republic of Honduras is bordered to the west by Guatemala, to the southwest by El Salvador, to the southeast by Nicaragua, to the south by the Pacific Oce ...

Mexico Mexico (Spanish: México), officially the United Mexican States, is a country in the southern portion of North America. It is bordered to the north by the United States; to the south and west by the Pacific Ocean; to the southeast by Guatema ...

Nicaragua Nicaragua (; ), officially the Republic of Nicaragua (), is the largest country in Central America, bordered by Honduras to the north, the Caribbean to the east, Costa Rica to the south, and the Pacific Ocean to the west. Managua is the cou ...

Panama Panama ( , ; es, link=no, Panamá ), officially the Republic of Panama ( es, República de Panamá), is a transcontinental country spanning the southern part of North America and the northern part of South America. It is bordered by Cos ...

Paraguay Paraguay (; ), officially the Republic of Paraguay ( es, República del Paraguay, links=no; gn, Tavakuairetã Paraguái, links=si), is a landlocked country in South America. It is bordered by Argentina to the south and southwest, Brazil to th ...

Peru , image_flag = Flag of Peru.svg , image_coat = Escudo nacional del Perú.svg , other_symbol = Great Seal of the State , other_symbol_type = Seal (emblem), National seal , national_motto = "Fi ...

^†, and

^†. * EEn 10 mg / DHPA 120 mg: at least 3 countries, including

^†,

, and

. * EEn 5 mg / DHPA 75 mg: at least 9 countries, including

, the

, and

^†. EEn is also 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 ...

in combination with

and testosterone enantate for

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 ...

use as Uni-Bol.

Usage

EEn/DHPA is the most widely used combined injectable contraceptive in Latin America. It was estimated in 1995 that EEn/DHPA was used as a combined injectable contraceptive in Latin America by at least 1 million women. However, combined injectable contraceptives like EEn/DHPA are unlikely to constitute a large proportion of total contraceptive use in the countries in which they are available.

References

{{Estrogen receptor modulators Antigonadotropins Enanthate esters Estradiol esters Hormonal contraception Phenols Prodrugs Synthetic estrogens Veterinary drugs

Medical uses

Available forms

Contraindications

Side effects

Overdose

Interactions

Pharmacology

Pharmacodynamics

Pharmacokinetics

Chemistry

History

Society and culture

Generic names

Brand names

Availability

Usage

See also

References