Equilin 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 synt ...

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 ...

sex hormone Sex hormones, also known as sex steroids, gonadocorticoids and gonadal steroids, are steroid hormones that interact with vertebrate steroid hormone receptors. The sex hormones include the androgens, estrogens, and progestogens. Their effects ar ...

found in

horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million y ...

s as well as a

medication A medication (also called medicament, medicine, pharmaceutical drug, 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 medical field and re ...

. It is one of the estrogens present in the estrogen

mixture In chemistry, a mixture is a material made up of two or more different chemical substances which are not chemically bonded. A mixture is the physical combination of two or more substances in which the identities are retained and are mixed in the ...

s known as

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. ...

(CEEs; brand name Premarin) and

esterified estrogens Esterified estrogens (EEs), sold under the brand names Estratab and Menest among others, is an estrogen medication which is used hormone therapy for menopausal symptoms and low sex hormone levels in women, to treat breast cancer in both women ...

(EEs; Estratab, Menest). CEEs is the most commonly used form of estrogen in

hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal ...

(HRT) 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 ...

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 ...

Estrone sulfate Estrone sulfate, also known as E1S, E1SO4 and estrone 3-sulfate, is a natural, endogenous steroid and an estrogen ester and conjugate. In addition to its role as a natural hormone, estrone sulfate is used as a medication, for instance in menop ...

is the major estrogen in CEEs (about 50%) while

equilin sulfate Equilin is a naturally occurring estrogen sex hormone found in horses as well as a medication. It is one of the estrogens present in the estrogen mixtures known as conjugated estrogens (CEEs; brand name Premarin) and esterified estrogens (EEs; E ...

is the second major estrogen in the formulation, present as about 25% of the total.

Pharmacology

Pharmacodynamics

Equilin is an estrogen, or 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 ...

s (ERs), the

ERα Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein) that is activated by the sex ...

and

ERβ Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by ...

. In terms of

relative binding affinity In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-ligand binding, the ligand is usually a mole ...

for the ERs, equilin has about 13% and 49% of that of estradiol for the ERα and ERβ, respectively. Analogously to the reversible transformation of

estrone Estrone (E1), also spelled oestrone, is a steroid, a weak estrogen, and a minor female sex hormone. It is one of three major endogenous estrogens, the others being estradiol and estriol. Estrone, as well as the other estrogens, are synthesized ...

into

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 ...

17β-hydroxysteroid dehydrogenase A hydroxysteroid is a molecule derived from a steroid with a hydrogen replaced with a hydroxy group. When the hydroxy group is specifically at the C3 position, hydroxysteroids are referred to as sterols, with an example being cholesterol. See ...

, equilin can be converted into the more potent estrogen

17β-dihydroequilin 17β-Dihydroequilin is a naturally occurring estrogen sex hormone found in horses as well as a medication. As the C3 sulfate ester sodium salt, it is a minor constituent (1.7%) of conjugated estrogens (CEEs; brand name Premarin). However, as equ ...

in the body. This estrogen has about 113% and 108% of the relative binding affinities of estradiol for the ERα and ERβ, respectively. Equilin is present in CEEs in the form of

, which itself is inactive and acts as a

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 ...

of equilin via

steroid sulfatase Steroid sulfatase (STS), or steryl-sulfatase (EC 3.1.6.2), formerly known as arylsulfatase C, is a sulfatase enzyme involved in the metabolism of steroids. It is encoded by the ''STS'' gene. Reactions This enzyme catalysis, catalyses the follow ...

. Similarly to

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 ...

estrogens like

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 ...

, equilin and CEEs have disproportionate effects in certain tissues such as the

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 ...

and

uterus The uterus (from Latin ''uterus'', plural ''uteri'') or womb () is the organ in the reproductive system of most female mammals, including humans that accommodates the embryonic and fetal development of one or more embryos until birth. The uter ...

relative to

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. ...

human estrogens like estradiol and estrone. Because of their disproportionate potency in the liver, equilin and CEEs have relatively increased effects on

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 is ...

compared to estradiol. A dosage of 0.25 mg/day equilin sulfate is equivalent to 0.625 mg/day CEEs in terms of relief from

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. At a dosage of 0.625 mg/day equilin sulfate, the increases in circulating levels of

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-bi ...

(SHBG),

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 pro ...

, and

angiotensinogen Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adren ...

were 1.5 to 8 times those observed with

estrone sulfate Estrone sulfate, also known as E1S, E1SO4 and estrone 3-sulfate, is a natural, endogenous steroid and an estrogen ester and conjugate. In addition to its role as a natural hormone, estrone sulfate is used as a medication, for instance in menop ...

. Equilin has about 42% of the relative potency of CEEs in 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 hymen ...

and 80% of the relative potency of CEEs in the

, while its more active form, 17β-dihydroequilin, has about 83% of the relative potency of CEEs in the vagina and 200% of the relative potency of CEEs in the uterus.

Pharmacokinetics

Equilin has about 8% of the

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 ...

for SHBG, relative to 12% in the case of

. In terms of

plasma protein binding Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse or diffuse th ...

, it is bound 26% to SHBG and 13% to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

. The metabolic clearance rates of equilin and equilin sulfate are 2,640 L/day/m² and 175 L/day/m², respectively. In accordance, the

biological 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 equilin sulfate is substantially longer than that of equilin. Equilin is converted into

in the

and in other tissues. Equilin and 17β-dihydroequilin can also be transformed into

equilenin Equilenin, also known as 6,8-didehydroestrone, as well as estra-1,3,5(10),6,8-pentaen-3-ol-17-one, is a naturally occurring steroidal estrogen obtained from the urine of pregnant mares. It is used as one of the components in conjugated estroge ...

and 17β-dihydroequilenin. Equilin 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 ...

in the form of

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucur ...

conjugates.

Chemistry

Equilin, also known as δ⁷-estrone or as 7-dehydroestrone, as well as estra-1,3,5(10),7-tetraen-3-ol-17-one, is a

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 an analogue of

. In terms of

chemical structure A chemical structure determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target molecule or other solid. Molecular geometry refers to the spatial arrangement of at ...

and

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

, equilin is to

(δ⁷-17β-estradiol) as estrone is to

References

{{Estrogen receptor modulators Sterols Phenols Estranes Estrogens Human drug metabolites Ketones Prodrugs