Estradiol stearate (E2-17-St), also known as estradiol octadecanoate and sold under the brand name Depofollan, is a

naturally occurring A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical ...

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

and 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 ...

– specifically, the C17β stearate

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

estradiol Estradiol (E2), also called oestrogen, oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of female reproductive cycles such as estrous and menstrual cycles. Estradiol is responsible ...

. It occurs in the body as a very long-lasting

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

and

prohormone A prohormone is a committed precursor of a hormone consisting of peptide hormones synthesized together that has a minimal hormonal effect by itself because of its expression-suppressing structure, often created by protein folding and binding addit ...

of estradiol. The compound is one of the components that collectively constitute lipoidal estradiol, another of which is estradiol palmitate. It is extremely

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

and

hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...

. Estradiol stearate has no

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 Pa ...

for the

estrogen receptor Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...

, requiring

transformation Transformation may refer to: Science and mathematics In biology and medicine * Metamorphosis, the biological process of changing physical form after birth or hatching * Malignant transformation, the process of cells becoming cancerous * Trans ...

into estradiol via

esterase In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

s for its estrogenic activity. The compound does not bind to

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 is called androgen-binding prot ...

α-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome ...

, instead being transported by

lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

s such as

high-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...

and

low-density lipoprotein 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 density ...

. Estradiol stearate has a prolonged duration of action relative to estradiol regardless of whether it is given by

intravenous injection Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

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 (medicine), bolus into the subcutis, the layer of skin directly below the dermis and ...

. This is in contrast to short-chain fatty acid esters of estradiol, 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 the ...

, which do not show a prolonged duration with intravenous injection. When administered by intravenous injection in rodents, estradiol stearate has a greatly increased

terminal half-life Biological half-life (elimination half-life, pharmacological 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 blood plasma. ...

relative to estradiol (6 hours vs. 2 minutes). Estradiol stearate also had a half-life that was 60% longer than that of estradiol arachidonate, despite similar ester chain lengths. In contrast to the long-chain esters, the half-lives of short-chain estradiol esters such as

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. It is taken by mouth once daily or given as a vagin ...

and estradiol hexanoate were the same as that of estradiol. As such, whereas short-chain estradiol esters are rapidly

hydrolyzed Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolysi ...

, long-chain estradiol esters like estradiol stearate are resistant to

metabolism Metabolism (, from ''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 cellular processes; the co ...

. Thus, the prolongation of effect of short-chain estradiol esters is purely due to their increased

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

and slow release from the injected depot, whereas the prolonged duration of long-chain estradiol esters is due both to this property and to their resistance to metabolism. Estradiol stearate is susceptible to

first-pass metabolism The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism at a specific location in the body which leads to a reduction in the concentration of the active drug before it reaches the ...

in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

, and hence has much greater potency by subcutaneous injection than by

oral administration Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. In addition to its

endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...

role, estradiol stearate was previously available as a

pharmaceutical drug Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...

for use via

depot Depot may refer to: Places * Depot, Poland, a village * Depot Glacier (disambiguation) * Depot Island (disambiguation) * Depot Nunatak * Depot Peak Brands and enterprises * Maxwell Street Depot, a restaurant in Chicago, United States * Of ...

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

. The medication was introduced between 1938 and 1941 under the brand name Depofollan. It has been used to treat

prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...

. Estradiol stearate is a long-acting estrogen and is said to have been the first long-acting estrogen used in medicine, although it was never widely employed. It was reported to have a duration of more than one month. The medication was provided 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) and lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturat ...

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 containing 15 mg estradiol stearate. It was manufactured by Chinoin, a Hungarian

pharmaceutical company The pharmaceutical industry is a Medicine, medical industry that discovers, develops, produces, and markets pharmaceutical goods such as medications and medical devices. Medications are then administered to (or Self-medicate, self-administered b ...

. The compound was studied by Karl Miescher in 1938 and 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 discl ...

ed by Miescher and Chinoin in 1939 and 1941, respectively. A similar clinically used long-acting estradiol ester is

estradiol undecylate Estradiol undecylate (EU, EUn, 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 ...

, which has 11

carbon Carbon () is a chemical element; it has chemical symbol, symbol C and atomic number 6. It is nonmetallic and tetravalence, tetravalent—meaning that its atoms are able to form up to four covalent bonds due to its valence shell exhibiting 4 ...

atom Atoms are the basic particles of the chemical elements. An atom consists of a atomic nucleus, nucleus of protons and generally neutrons, surrounded by an electromagnetically bound swarm of electrons. The chemical elements are distinguished fr ...

s instead of the 18 carbon atoms in estradiol stearate.

References

{{Estrogen receptor modulators Abandoned drugs Estradiol esters Stearate esters

See also

References