Etynodiol diacetate, or ethynodiol diacetate, sold under the brand name Ovulen among others, is 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 female sex hormone progesterone in the body. A progestin is a '' synthetic'' progestogen. ...

medication which is used in

birth control pills Oral contraceptives, abbreviated OCPs, also known as birth control pills, are medications taken by mouth for the purpose of birth control. The introduction of the birth control pill ("the Pill") in 1960 revolutionized the options for contraception, ...

. The medication is available only in combination with an

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 ...

. It is taken

by mouth 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 ...

. Etynodiol diacetate is a progestin, or a

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

progestogen Progestogens, also sometimes written progestins, progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestoge ...

, and hence is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

progesterone receptor The progesterone receptor (PR), also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the steroid hormone progesterone. In humans, PR is encoded by a single ''PGR'' gene resi ...

, 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 ...

of progestogens like

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 ...

. It has weak

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

ic and

ic activity and no other important

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

activity. The medication is a

prodrug A prodrug is a pharmacologically inactive 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 ...

norethisterone Norethisterone, also known as norethindrone and sold under the brand name Norlutin among others, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medicatio ...

in the body, with

etynodiol Etynodiol, or ethynodiol, is a steroidal progestin of the 19-nortestosterone group which was never marketed. A diacylated derivative, etynodiol diacetate, is used as a hormonal contraceptive. ''Etynodiol'' is sometimes used as a synonym for ''e ...

occurring as an intermediate. Etynodiol, a related compound, was discovered in 1954, and etynodiol diacetate was introduced for medical use in 1965. The combination ethynodiol with mestranol (Ovulen) was approved for medical use in the United States in 1966. The combination ethinylestradiol with ethynodiol (Demulen) was approved for medical use in the United States in 1970. In 2021, the combination with

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

was the 276th most commonly prescribed medication in the United States, with more than 800,000 prescriptions.

Medical uses

Etynodiol diacetate is used in combination with an

such as ethinylestradiol or mestranol in

combined oral contraceptives 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 Oral administration, taken orally by women. It is the oral form of combi ...

for women for the prevention of pregnancy.

Side effects

Pharmacology

Etynodiol diacetate is virtually inactive in terms of

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

and

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...

s and acts as a rapidly converted

, with

occurring as an intermediate. Upon

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 ...

and during

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 ...

, etynodiol diacetate is rapidly converted by

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 into etynodiol, which is followed by oxygenation of the C3

hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

to produce norethisterone. In addition to its progestogenic activity, etynodiol diacetate has weak

ic activity, and, unlike most progestins but similarly to norethisterone and noretynodrel, also has some

ic activity. 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 describing how the body affects a specific su ...

of etynodiol diacetate have been reviewed.

Chemistry

Etynodiol diacetate, also known as 3β-hydroxy-17α-ethynyl-19-nortestosterone 3β,17β-diaceate, 3β-hydroxynorethisterone 3β,17β-diacetate, or 17α-ethynylestr-4-ene-3β,17β-diol 3β,17β-diacetate, 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 an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

and a

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

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

. It is specifically a derivative of

19-nortestosterone Nandrolone, also known as 19-nortestosterone, is an endogenous androgen. It is also an anabolic steroid (AAS) which is medically used in the form of esters such as nandrolone decanoate (brand name Deca-Durabolin) and nandrolone phenylpropionat ...

and 17α-ethynyltestosterone, or of

(17α-ethynyl-19-nortestosterone), in which the C3

ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

group A group is a number of persons or things that are located, gathered, or classed together. Groups of people * Cultural group, a group whose members share the same cultural identity * Ethnic group, a group whose members share the same ethnic iden ...

has been dehydrogenated into a C3β

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

group and

acetate An acetate is a salt formed by the combination of acetic acid with a base (e.g. alkaline, earthy, metallic, nonmetallic, or radical base). "Acetate" also describes the conjugate base or ion (specifically, the negatively charged ion called ...

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 ...

s have been attached at the C3β and C17β positions. Etynodiol diacetate is the 3β,17β- diacetate

(17α-ethynylestr-4-ene-3β,17β-diol).

Synthesis

Chemical syntheses of etynodiol diacetate have been published. Reduction of

(1) affords the 3,17-diol. The 3β-hydroxy compound is the desired product; since reactions at C3 do not show nearly the

stereoselectivity In chemistry, stereoselectivity is the property of a chemical reaction in which a single reactant forms an unequal mixture of stereoisomers during a non- stereospecific creation of a new stereocenter or during a non-stereospecific transformation ...

as those at C17 by virtue of the relative lack of stereo-directing proximate substituents, the formation of the desired isomer is engendered by use of a bulky reducing agent, lithium tri-tert-butoxyaluminum hydride. Acetylation of the 3β,17β-diol affords etynodiol diacetate (3).

History

Etynodiol Etynodiol, or ethynodiol, is a steroidal progestin of the 19-nortestosterone group which was never marketed. A diacylated derivative, etynodiol diacetate, is used as a hormonal contraceptive. ''Etynodiol'' is sometimes used as a synonym for ''e ...

was first synthesized in 1954, via reduction of

, and etynodiol diacetate was introduced for medical use in 1965.

Society and culture

Generic names

Etynodiol diacetate is the generic name of the drug (the of its free alcohol form is etynodiol), while ethynodiol diacetate is its , , and . It is also known by its former developmental code names CB-8080 and SC-11800.

Brand names

Etynodiol diacetate is or has been marketed under brand names including Conova, Continuin, Demulen, Femulen, Kelnor, Lo-Malmorede, Luteonorm, Luto-Metrodiol, Malmorede, Metrodiol, Ovulen, Soluna, Zovia, and others.

Availability

Etynodiol diacetate is marketed in only a few countries, including the United States, Canada, Argentina, and Oman.

References

{{DEFAULTSORT:Etynodiol Diacetate Acetate esters Ethynyl compounds Anabolic–androgenic steroids Combination drugs Drugs developed by Merck Estranes Prodrugs Progestogen esters Progestogens Synthetic estrogens