Hexestrol, sold under the brand name Synestrol among others, is a nonsteroidal estrogen 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 cancer A hormone-sensitive cancer, or hormone-dependent cancer, is a type of cancer that is dependent on a hormone for growth and/or survival. Examples include breast cancer, which is dependent on estrogens like estradiol, and prostate cancer, which is ...

s as well as gynecological disorders but is mostly no longer marketed. It has also been used in the form of esters such as

hexestrol diacetate Hexestrol diacetate (JAN) (brand names Retalon Lingual, Robal, Sintestrol, Sintofolin) is a synthetic, nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol. It is an ester of hexestrol, and was discovered in 1939. See al ...

(brand name Sintestrol) and

hexestrol dipropionate Hexestrol dipropionate (brand name Hexanoestrol, Retalon Oleosum), or hexestrol dipropanoate, is a synthetic, nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol. It is an ester of hexestrol, and has been known since at l ...

(brand name Hexanoestrol). Hexestrol and its esters are taken by mouth, held under the tongue, or via

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 ...

Medical uses

Hexestrol has been used in

, for the treatment of breast cancer 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 sur ...

in men, and for the treatment of certain gynecological disorders.

Pharmacology

Pharmacodynamics

Hexestrol has approximately 302% and 234% of the

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 Partn ...

of estradiol for the estrogen receptors (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, hexestrol has been said to be one of the most potent estrogens known. The total

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 ...

dose per cycle of different forms of hexestrol are 70 to 100 mg for oral 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 prima ...

, and 25 mg for

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 ...

. These doses are fairly similar to those of estradiol and its esters. Hexestrol induces mammary gland development 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 re ...

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, ...

oil solution An oil is any nonpolar chemical substance that is composed primarily of hydrocarbons and is hydrophobic (does not mix with water) & lipophilic (mixes with other oils). Oils are usually flammable and surface active. Most oils are unsaturated ...

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 o ...

nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol. Esters of hexestrol include

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 Organic compound#Synthetic compounds, synthetic, nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol and used as an estrogen and ...

, and

History

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

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

, and

References

{{Estrogen receptor modulators Abandoned drugs Phenols Stilbenoids Synthetic estrogens