Estradiol benzoate (EB), sold under the brand name Progynon-B 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 a ...

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 treatment of gynecological disorders. It is also used in the treatment of

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that su ...

in men. Estradiol benzoate is used in

veterinary medicine 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 ...

as well. When used clinically, the medication is given by

injection into muscle 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 l ...

usually two to three times per week.

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 benzoate 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 b ...

, breast enlargement,

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 resul ...

, and fluid retention. Estradiol benzoate 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, 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 o ...

. 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 estrad ...

and a prodrug of

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 ...

and bioidentical form of estrogen. Estradiol benzoate was discovered in 1933 and was introduced for medical use that same year. It was the first estradiol ester to be discovered or marketed, and was one of the first estrogens to be used in medicine. Along with estradiol dipropionate, estradiol benzoate was among the most widely used esters of estradiol for many years following its introduction. However, in the 1950s, longer-acting estradiol esters that necessitated less frequent injections, such as estradiol valerate and estradiol cypionate, were developed, and have since largely superseded estradiol benzoate. Nonetheless, estradiol benzoate remains widely available throughout the world. It is not available for medical use 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 U.S. state, states, a Washington, D.C., federal district, five ma ...

, but is available in this country for use in veterinary medicine.

Medical uses

The

medical use Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care practice ...

s of estradiol benzoate are the same as those of estradiol and other estrogens. Estradiol benzoate is used in hormone therapy for the treatment of menopausal symptoms such as hot flashes 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 ...

and in the treatment of hypoestrogenism and delayed puberty 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 est ...

or other causes in women. It is also used in hormone therapy for transgender women. Aside from hormone therapy, estradiol benzoate is used in the treatment of gynecological disorders such as menstrual disorders, dysfunctional uterine bleeding, and

breast engorgement Breast engorgement occurs in the mammary glands due to expansion and pressure exerted by the synthesis and storage of breast milk. It is also a main factor in altering the ability of the infant to latch-on. Engorgement changes the shape and cu ...

. In addition, it 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 the palliative treatment of

in men. Estradiol benzoate has a relatively short

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

, and is administered by

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 ...

usually two to three times per week. It is used in the treatment of menopausal symptoms at a dosage of 1 to 1.66 mg initially and 0.33 to 1 mg for maintenance two times per week, and in the treatment of hypoestrogenism and delayed puberty at a dosage of 1.66 mg two to three times per week. The dosage used in hormone therapy for transgender women is 0.5 to 1.5 mg two to three times per week. In the treatment of prostate cancer, estradiol benzoate is used at a dosage of 1.66 mg three times per week (for a total of 5 mg per week).

Available forms

Estradiol benzoate is and has been available as an

oil solution An oil is any nonpolar chemical substance A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent C ...

for intramuscular injection provided as

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 ...

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 ch ...

s at concentrations of 0.167, 0.2, 0.33, 1, 1.67, 2, 5, 10, 20, and 25 mg/mL. It is also available as a microcrystalline

aqueous suspension In chemistry, a suspension is a heterogeneous mixture of a fluid that contains solid particles sufficiently large for sedimentation. The particles may be visible to the naked eye, usually must be larger than one micrometer, and will eventually s ...

for intramuscular injection under the brand name Agofollin Depot.

Sistocyclin Estradiol benzoate/progesterone (EB/P4), sold under the brand names Duogynon and Sistocyclin among others, is a combination medication of estradiol benzoate (EB), an estrogen, and progesterone (P4), a progestogen. It has been formulated both a ...

was the brand name of a product containing 10 mg microcrystalline estradiol benzoate and 200 mg microcrystalline

progesterone Progesterone (P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

in an aqueous suspension. Follivirin (and previously Femandren M) is the brand name of a product containing 2.5 mg microcrystalline estradiol benzoate and 25 to 50 mg microcrystalline testosterone isobutyrate in aqueous suspension. A vaginal tablet formulation containing 0.125 mg estradiol benzoate and 10 mg monalazone sodium (a vaginal disinfectant and spermicidal

contraceptive Birth control, also known as contraception, anticonception, and fertility control, is the use of methods or devices to prevent unwanted pregnancy. Birth control has been used since ancient times, but effective and safe methods of birth cont ...

) has been marketed under the brand name Malun 25. Estradiol benzoate was also formerly available as 50 and 100 mg pellets for

subcutaneous implantation In medicine, a subcutaneous implant, or subcutaneous pellet, is an implant that is delivered under the skin into the subcutaneous tissue by surgery or injection and is used to deliver a drug for a long period of time. Examples of drugs that ca ...

and as a 2 mg/g ointment.

Contraindications

Contraindication In medicine, a contraindication is a condition (a situation or factor) 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 reas ...

s of estrogens include coagulation 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, ...

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 s ...

, and certain hormone-sensitive cancers 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 ...

and endometrial cancer, 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 benzoate are the same as those of estradiol. Examples of such side effects include

and enlargement,

, bloating,

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. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...

, and melasma.

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 showi ...

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 nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

, bloating, increased weight, water retention,

, vaginal discharge, heavy legs, 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 inducers of

cytochrome P450 Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compo ...

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 c ...

of estradiol and by extension circulating estradiol levels.

Pharmacology

Pharmacodynamics

Estradiol benzoate is an estradiol ester, or a prodrug of

. As such, it is an

, or an

of the estrogen receptors. Estradiol benzoate has very low affinity for the ERs, on the order of 100-fold less than that of estradiol. As such, estradiol benzoate is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol. Estradiol benzoate is of about 38% 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 C3

benzoate Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoi ...

ester. Because estradiol benzoate is a prodrug of estradiol, it is considered to be a

and bioidentical form of estrogen.

Estrogenic potency

In the case of intramuscular injections of either estradiol benzoate or estradiol valerate in oil solution, the maturation dosage for the

vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hy ...

l epithelium is 5 to 7 mg once per week and the

endometrial The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...

proliferation Proliferation may refer to: Weapons *Nuclear proliferation, the spread of nuclear weapons, material, and technology *Chemical weapon proliferation, the spread of chemical weapons, material, and technology * Small arms proliferation, the spread of ...

dosage is 7 to 10 mg once per week. The total endometrial proliferation dosage of estradiol benzoate in oil solution by intramuscular injection over 14 days is 25 to 35 mg. The full

endometrial transformation Decidualization is a process that results in significant changes to cells of the endometrium in preparation for, and during, pregnancy. This includes morphological and functional changes (the decidual reaction) to endometrial stromal cells (ESCs), ...

dosage of

estradiol benzoate/progesterone Estradiol benzoate/progesterone (EB/P4), sold under the brand names Duogynon and Sistocyclin among others, is a combination medication of estradiol benzoate (EB), an estrogen, and progesterone (P4), a progestogen. It has been formulated both as ...

in oil solution is 1 to 2 mg estradiol benzoate and 20 to 25 mg progesterone by intramuscular injection daily for 10 to 14 days, whereas the full endometrial transformation dosage of estradiol benzoate/progesterone in microcrystalline aqueous suspension is a single intramuscular injection of 10 mg estradiol benzoate and 200 mg progesterone. For comparison, the full endometrial transformation dosage of estradiol valerate and hydroxyprogesterone caproate in oil solution (brand name

Gravibinon Estradiol valerate/hydroxyprogesterone caproate (EV/OHPC), sold under the brand names Gravibinon and Injectable No. 1 (or Chinese Injectable No. 1) among others, is a combined estrogen and progestogen medication which is used in the treatment of ...

) is a single intramuscular injection of 10 mg estradiol valerate and 250 to 375 mg hydroxyprogesterone caproate. Endometrial transformation normally occurs during the

luteal phase The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is ...

of the

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that make pregnancy possible. The ovarian cycle controls the production and release of eg ...

; it is induced by endogenous progesterone following adequate priming by endogenous estradiol. The decidua (

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...

-type endometrium) induction dosage of estradiol benzoate/progesterone in oil solution is 2 to 5 mg estradiol benzoate and 20 to 100 mg progesterone by intramuscular injection daily for 5 to 7 weeks, whereas the decidua induction dosage of estradiol benzoate/progesterone in microcrystalline aqueous suspension is 10 to 20 mg estradiol benzoate and 200 to 250 mg progesterone in microcrystalline aqueous suspension by intramuscular injection once per week for about 6 weeks. For comparison, the decidua induction dosage of estradiol valerate and hydroxyprogesterone caproate in oil solution is about the same as that of microcrystalline estradiol benzoate/progesterone in aqueous suspension. The decidua induction dosages of estrogen and progestogen combinations are pseudopregnancy dosages.

Pharmacokinetics

Following administration, estradiol benzoate acts as a prodrug of estradiol via cleavage by

esterase An esterase is a hydrolase enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis. A wide range of different esterases exist that differ in their substrate specificity, their protein structure ...

s into estradiol and the natural

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, ...

benzoic acid. This cleavage occurs not only in the

liver 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 ...

, but also in the

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...

and in tissues. Esters of estradiol like estradiol benzoate are readily hydrolyzed to estradiol, but have an extended duration when administered in via

intramuscular 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 ...

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, co ...

due to a depot effect afforded by their

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 ...

and consequent 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 lipo ...

. A long-lasting local tissue depot is formed by the injection that slowly releases estradiol benzoate into the circulation.

Intramuscular injection

=Oil solution

= The

of estradiol benzoate in oil solution by intramuscular injection at typical clinical doses (e.g., 0.33–1.66 mg) is said to be 2 to 3 days. A single dose of 2.5 mg estradiol benzoate in oil solution by intramuscular injection was found to produce plasma estradiol levels of greater than 400 pg/mL, measured 24 hours post-injection, in a group of patients with minimal baseline levels of estradiol (due to GnRH analogue therapy with

triptorelin Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is ...

). The elimination half-life of estradiol benzoate in oil solution by intramuscular injection has been reported to be 48 to 120 hours (2 to 5 days). A single intramuscular injection of 5 mg estradiol benzoate in oil solution has been found to result in peak circulating concentrations of 940 pg/mL estradiol and 343 pg/mL estrone, which occurred at about 2 days post-injection. Compared to two other commonly used estradiol esters, estradiol benzoate had the shortest duration, at approximately 4 to 5 days, whereas estradiol valerate and estradiol cypionate were found to last for 7 to 8 days and 11 days, respectively. This is because estradiol benzoate has a shorter and less bulky

chain A chain is a wikt:series#Noun, 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 (physics), compression but line (g ...

, and in relation to this, is comparatively less lipophilic. For a given estradiol ester, the shorter or less bulky the fatty acid chain is, the less lipophilic, shorter-lasting, and less uniform/plateau-like the resultant levels of estradiol are as well as the higher (and hence more spike-like) the peak/maximal levels are. Daily intramuscular injections of 1 mg estradiol benzoate in oil solution have been found to produce estradiol

excretion 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 afte ...

rates almost double those of the normal

. This is in accordance with known production rates of estradiol in women (e.g., 300 µg/day in the luteal phase).

=Aqueous suspension

= Microcrystalline estradiol benzoate in

(brand names Agofollin Depot and Ovocyclin M alone and Follivirin in combination with testosterone isobutyrate) has been found to have a longer

than

amorphous In condensed matter physics and materials science, an amorphous solid (or non-crystalline solid, glassy solid) is a solid that lacks the long-range order that is characteristic of a crystal. Etymology The term comes from the Greek language ...

estradiol benzoate in oil solution when administered via intramuscular injection. Whereas the duration of a single intramuscular injection of estradiol benzoate in oil solution is 6 days, the duration of a single intramuscular injection of microcrystalline estradiol benzoate in aqueous suspension is 16 to 21 days. Its duration also surpasses that of estradiol valerate and estradiol cypionate. The duration of microcrystalline aqueous suspensions administered by intramuscular injection is dependent both on

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', '' molar concentration'', '' number concentration'' ...

and on crystal size.

Other routes

The duration of estradiol benzoate is not prolonged if it is administered directly into the

circulation Circulation may refer to: Science and technology * Atmospheric circulation, the large-scale movement of air * Circulation (physics), the path integral of the fluid velocity around a closed curve in a fluid flow field * Circulatory system, a bio ...

via intravenous injection, in contrast to intramuscular injection. Estradiol benzoate is active with oral and sublingual administration, similarly to estradiol valerate and estradiol acetate. However, it is not marketed in any formulation for use by these routes. Oral estradiol benzoate has been reported to possess about one-third to half the potency of intramuscular injection of estradiol benzoate. This level of oral potency has been described as remarkably high. The sublingual potency of estradiol benzoate is similar to that of estradiol. A study found that the total dose of estradiol benzoate needed for

endometrial proliferation The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The functional layer ...

in women was 60 to 140 mg, relative to 60 to 180 mg for estradiol. Both estradiol and estradiol benzoate has a persistence of estrogenic effect with single administration of one day.

Subcutaneous implant In medicine, a subcutaneous implant, or subcutaneous pellet, is an implant that is delivered under the skin into the subcutaneous tissue by surgery or injection and is used to deliver a drug for a long period of time. Examples of drugs that can ...

ation of crystalline estradiol benzoate pellets has been studied, but no estradiol benzoate pellet implants have been marketed.

Chemistry

Estradiol benzoate 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

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 ...

and the C3

(benzenecarboxylate)

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 ...

. It is also known as estradiol 3-benzoate or as estra-1,3,5(10)-triene-3,17β-diol 3-benzoate. Two estradiol esters that are related to estradiol benzoate are estradiol dipropionate, the C3,17β dipropionate ester of estradiol, and estradiol acetate, the C3 acetate ester of estradiol. The experimental octanol/water partition coefficient (logP) of estradiol benzoate is 4.7.

History

Estradiol benzoate was one of the first estrogens to be developed and marketed. In 1932,

Adolf Butenandt Adolf Friedrich Johann Butenandt (; 24 March 1903 – 18 January 1995) was a German biochemist. He was awarded the Nobel Prize in Chemistry in 1939 for his "work on sex hormones." He initially rejected the award in accordance with government p ...

described

estrone benzoate Estrone benzoate, or estrone 3-benzoate, is a synthetic estrogen and estrogen ester – specifically, the C3 benzoate ester of estrone – which was first reported in 1932 and was never marketed. It led to the development in 1933 of the more ...

and reported that it had a prolonged

. Schwenk and Hildebrant at Schering discovered estradiol via reduction of estrone in 1933, and they proceeded to synthesize estradiol benzoate from estradiol the same year. Estradiol benzoate 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 sufficiency of disclosure, enabling disclo ...

ed by Schering in 1933 and was introduced in an

for use by

under the brand name ''Progynon B'' that year as well. By 1936, multiple formulations of estradiol benzoate in oil solution had been marketed, including under the brand names ''Progynon B'' by Schering, ''Dimenformon Benzoate'' by Roche-

Organon The ''Organon'' ( grc, Ὄργανον, meaning "instrument, tool, organ") is the standard collection of Aristotle's six works on logical analysis and dialectic. The name ''Organon'' was given by Aristotle's followers, the Peripatetics. The si ...

, and ''Oestroform B'' by British Drug Houses. By the early 1940s, ''Ben-Ovocylin'' had been introduced by Ciba as well. In the late 1940s, the brand name ''Ben-Ovocylin'' was changed by Ciba to ''Ovocylin Benzoate''. Following their introduction, estradiol benzoate and estradiol dipropionate were the most widely used esters of estradiol for many years. However, estradiol valerate and estradiol cypionate, which are longer-acting esters that require less frequent administration, were developed and introduced in the 1950s, and have since largely superseded estradiol benzoate and estradiol dipropionate.

Society and culture

Generic names

''Estradiol benzoate'' is the generic name of the drug and its , , and , while ''oestradiol benzoate'' was formerly its .

Brand names

The major brand name of estradiol benzoate is Progynon-B. It has also been sold under a variety of other brand names including Agofollin Depot, Ben-Ovocylin, Benzhormovarine, Benzoestrofol, Benzofoline, Benzo-Ginestryl, Benzo-Ginoestril, Benzo-Gynoestryl, Benzoate d'oestradiol P.A. Intervet, Benztrone, Benztrone Pabyrn, Diffollisterol, Di-Folliculine, Dimenformon, Dimenformon Benzoate, Dimenformone, Diogyn B, EBZ, Eston-B, Estradiolo Amsa, Femestrone, Follicormon, Follidrin, Graafina, Gynecormone, Gynecormone Gouttes, Gynformone, Metroval, Hidroestron, Hormogynon, Oestradiol Benzoat, Oestradiol-Benzoat Intervet, Oestradiol-K Streuli, Oestradiolium Benzoicum, Oestraform, Ostrin, Ovahormon Benzoate, Ovasterol-B, Ovex, Ovocyclin Benzoate, Ovocyclin M, Primogyn B, Primogyn B Oleosum, Primogyn I, Progynon Benzoate, Recthormone, Oestradiol, Reglovar, Solestro, and Unistradiol, among others.

Availability

Estradiol benzoate is 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 subcontinent of Eurasia and it is located enti ...

and in other parts of the world. It was previously available for medical use in the

, but is no longer marketed in this country. However, it is approved and marketed in the United States for

veterinary use 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 nut ...

as a subdermal implant both alone and in combination with the androgen/

anabolic steroid Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects t ...

trenbolone acetate (brand names Celerin and Synovex, respectively). Outside of the United States, estradiol benzoate is also marketed in combination with progesterone for use as an intramuscular injection. Microcrystalline estradiol benzoate in

is available in the

Czech Republic The Czech Republic, or simply Czechia, is a landlocked country in Central Europe. Historically known as Bohemia, it is bordered by Austria to the south, Germany to the west, Poland to the northeast, and Slovakia to the southeast. Th ...

and

Slovakia Slovakia (; sk, Slovensko ), officially the Slovak Republic ( sk, Slovenská republika, links=no ), is a landlocked country in Central Europe. It is bordered by Poland to the north, Ukraine to the east, Hungary to the south, Austria to the ...

alone under the brand name Agofollin Depot and in combination with microcrystalline testosterone isobutyrate under the brand name Folivirin.

Research

Estradiol benzoate has been studied in combination with norethisterone enanthate as a once-a-month

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 progesto ...

, but ultimately did not complete development for this indication.Goldsmith, A., & Toppozada, M. (1983). Long-acting contraception. pp. 94-95 https://www.popline.org/node/423289

References

{{Estrogen receptor modulators Antigonadotropins Benzoate esters Estradiol esters Hormonal antineoplastic drugs Hormonal contraception Prodrugs Secondary alcohols Synthetic estrogens Veterinary drugs