Hexestrol, sold under the brand name Synestrol among others, is a

nonsteroidal estrogen A nonsteroidal estrogen is an estrogen with a nonsteroidal chemical structure. The most well-known example is the stilbestrol estrogen diethylstilbestrol (DES). Although nonsteroidal estrogens formerly had an important place in medicine, they ha ...

which was previously used for

estrogen 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 ...

and in the treatment of certain hormone-dependent cancers as well as gynecological disorders but is mostly no longer marketed. It has also been used in the form of

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 ...

s such as hexestrol diacetate (brand name Sintestrol) and hexestrol dipropionate (brand name Hexanoestrol). Hexestrol and its esters are taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

, held under the tongue, or via injection into muscle.

Medical uses

Hexestrol has been used in

, for the treatment of

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 ...

in women and

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, and for the treatment of certain gynecological disorders.

Pharmacology

Pharmacodynamics

Hexestrol has approximately 302% and 234% of the affinity of

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 ...

for 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) ERα and ERβ, respectively. The affinity of hexestrol for the ERs is said to be similar to or slightly higher than that of estradiol. Along with

diethylstilbestrol Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for those with ...

, hexestrol has been said to be one of the most potent

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 ac ...

s known. The total endometrial proliferation dose per cycle of different forms of hexestrol are 70 to 100 mg for

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid ** Oral administration of medicines ** Oral examination (also known as an oral exam or or ...

hexestrol, 45 mg for

sublingual Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue. The sublingual glands receive their primary ...

hexestrol diacetate, and 25 mg for hexestrol dipropionate 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 hav ...

. These doses are fairly similar to those of estradiol and its esters. Hexestrol induces

mammary gland A mammary gland is an exocrine gland in humans and other mammals that produces milk to feed young offspring. Mammals get their name from the Latin word ''mamma'', "breast". The mammary glands are arranged in organs such as the breasts in ...

development Development or developing may refer to: Arts *Development hell, when a project is stuck in development *Filmmaking, development phase, including finance and budgeting *Development (music), the process thematic material is reshaped * Photograph ...

in rodents similarly to other estrogens.

Pharmacokinetics

Distribution of hexestrol radioactivity after a subcutaneous injection of tritiated hexestrol in oil solution in female goats

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 ...

and

distribution Distribution may refer to: Mathematics * Distribution (mathematics), generalized functions used to formulate solutions of partial differential equations *Probability distribution, the probability of a particular value or value range of a vari ...

of hexestrol have been studied with

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 nutri ...

aqueous solution An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would be r ...

in women and with

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, c ...

of oil solution in female goats and sheep.

Chemistry

Hexestrol, also known as dihydrodiethylstilbestrol, 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 ...

of the stilbestrol group related to

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 ...

s of hexestrol include hexestrol diacetate,

hexestrol dicaprylate Hexestrol dicaprylate (brand name Taston), or dioctanoylhexestrol, is a synthetic, nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol that is no longer marketed. It is a long-acting ester of hexestrol. See also * Hexestr ...

hexestrol diphosphate Hexestrol diphosphate (brand names Cytostatin, Cytostesin, Pharmestrin, Retalon Aquosum) is a synthetic, nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol and used as an estrogen and antineoplastic agent in the treatm ...

, and hexestrol dipropionate.

History

Hexestrol was first described by Campbell, Dodds, and Lawson in 1938. It was isolated from the

demethylation Demethylation is the chemical process resulting in the removal of a methyl group (CH3) from a molecule. A common way of demethylation is the replacement of a methyl group by a hydrogen atom, resulting in a net loss of one carbon and two hydrogen at ...

products of

anethole Anethole (also known as anise camphor) is an organic compound that is widely used as a flavoring substance. It is a derivative of phenylpropene, a type of aromatic compound that occurs widely in nature, in essential oils. It is in the class of phe ...

Society and culture

Generic names

''Hexestrol'' is the generic name of the drug and its .

Brand names

Hexestrol has been marketed under a variety of brand names including Synestrol, Synoestrol, Estrifar, and Estronal, among others.

Availability

Hexestrol has mostly been discontinued and remains available in only a handful of countries.https://www.micromedexsolutions.com/ Esters of hexestrol which have been marketed include hexestrol diacetate,

, and hexestrol dipropionate.

References

{{Estrogen receptor modulators Abandoned drugs Phenols Stilbenoids Synthetic estrogens