Hexestrol

Hexestrol has been used in estrogen replacement therapy, for the treatment of breast cancer in women and prostate cancer in men, and for the treatment of certain gynecological disorders.

{{Estrogen dosages for prostate cancer}}

Hexestrol has approximately 302% and 234% of the affinity of estradiol for the estrogen receptors (ERs) ERα and ERβ, respectively.{{cite journal | vauthors = Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA | title = Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta | journal = Endocrinology | volume = 138 | issue = 3 | pages = 863–870 | date = March 1997 | pmid = 9048584 | doi = 10.1210/endo.138.3.4979 | doi-access = free }} The affinity of hexestrol for the ERs is said to be similar to or slightly higher than that of estradiol.{{cite journal | vauthors = Leclercq G, Heuson JC | title = Physiological and pharmacological effects of estrogens in breast cancer | journal = Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | volume = 560 | issue = 4 | pages = 427–455 | date = December 1979 | pmid = 391285 | doi = 10.1016/0304-419x(79)90012-x }} Along with diethylstilbestrol, hexestrol has been said to be one of the most potent estrogens known.{{cite journal | vauthors = Solmssen UV | title = Synthetic estrogens and the relation between their structure and their activity | journal = Chemical Reviews | volume = 37 | issue = 3 | pages = 481–598 | date = December 1945 | pmid = 21013428 | doi = 10.1021/cr60118a004 }} The total endometrial proliferation dose per cycle of different forms of hexestrol are 70 to 100 mg for oral hexestrol, 45 mg for sublingual hexestrol diacetate, and 25 mg for hexestrol dipropionate by intramuscular injection. These doses are fairly similar to those of estradiol and its esters. Hexestrol induces mammary gland development in rodents similarly to other estrogens.

Nonsteroidal estrogens like diethylstilbestrol, which is closely related structurally to hexestrol, are known to have dramatically disproportionate estrogenic effects in the liver and on liver protein synthesis.{{cite journal | vauthors = Kuhl H | title = Pharmacology of estrogens and progestogens: influence of different routes of administration | journal = Climacteric | volume = 8 | issue = Suppl 1 | pages = 3–63 | date = August 2005 | pmid = 16112947 | doi = 10.1080/13697130500148875 | s2cid = 24616324 }}

{{Parenteral potencies and durations of nonsteroidal estrogens}}

File:Distribution of hexestrol radioactivity after a subcutaneous injection of tritiated hexestrol in oil solution in female goats.png of hexestrol radioactivity in blood and tissues after a subcutaneous injection of a physiological dose of tritium-labeled hexestrol in oil solution in five juvenile female goats.{{cite journal | vauthors = Glascock RF, Hoekstra WG | title = Selective accumulation of tritium-labelled hexoestrol by the reproductive organs of immature female goats and sheep | journal = The Biochemical Journal | volume = 72 | issue = 4 | pages = 673–682 | date = August 1959 | pmid = 13828338 | pmc = 1196992 | doi = 10.1042/bj0720673 }} Points are one animal each. With the exception of skeletal muscle, tissues with a radioactivity concentration of less than 15% of that of the endometrium are not shown. Hexestrol is concentrated in target tissues such as the uterus and vagina due to binding to estrogen receptors.{{cite journal | vauthors = Jensen EV, DeSombre ER | title = Mechanism of action of the female sex hormones | journal = Annual Review of Biochemistry | volume = 41 | pages = 203–230 | date = 1972 | pmid = 4563437 | doi = 10.1146/annurev.bi.41.070172.001223 }}]]

The pharmacokinetics and distribution of hexestrol have been studied with intravenous injection of aqueous solution in women and with subcutaneous injection of oil solution in female goats and sheep.{{cite journal | vauthors = Folca PJ, Glascock RF, Irvine WT | title = Studies with tritium-labelled hexoestrol in advanced breast cancer. Comparison of tissue accumulation of hexoestrol with response to bilateral adrenalectomy and oophorectomy | journal = Lancet | volume = 2 | issue = 7206 | pages = 796–798 | date = October 1961 | pmid = 13893792 | doi = 10.1016/s0140-6736(61)91088-1 }}

{{See also|Stilbestrol#Stilbestrol derivatives|List of estrogen esters#Hexestrol esters}}

Hexestrol, also known as dihydrodiethylstilbestrol, is a synthetic nonsteroidal estrogen of the stilbestrol group related to diethylstilbestrol. Esters of hexestrol include hexestrol diacetate, hexestrol dicaprylate, hexestrol diphosphate, and hexestrol dipropionate.

Hexestrol was first described by Campbell, Dodds, and Lawson in 1938.{{cite journal| vauthors = Campbell NR, Dodds EC, Lawson W |title=Œstrogenic Activity of Anol; a Highly Active Phenol Isolated from the By-Products|journal=Nature|volume=142|issue=3608|year=1938|pages=1121|issn=0028-0836|doi=10.1038/1421121a0|bibcode=1938Natur.142.1121C|s2cid=4140616|doi-access=free}}{{cite journal| vauthors = Campbell NR, Dodds EC, Lawson W, Noble RL |title=Biological effects of the synthetic œstrogen hexœstrol|journal=The Lancet|volume=234|issue=6049|year=1939|pages=312–313|issn=0140-6736|doi=10.1016/S0140-6736(00)61997-9}}{{cite book|title=Medicinal Chemistry|url=https://books.google.com/books?id=bpXVAAAAMAAJ|year=1956|publisher=John Wiley & Sons|page=40}}{{cite journal|vauthors=Campbell NR, Dodds EC, Lawson W|title=The nature of the oestrogenic substances produced during the demethylation of anethole|journal=Proceedings of the Royal Society of London. Series B, Biological Sciences|volume=128|issue=851|year=1940|pages=253–262|issn=2053-9193|doi=10.1098/rspb.1940.0009|bibcode=1940RSPSB.128..253C|doi-access=free}} It was isolated from the demethylation products of anethole.

Hexestrol is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}}.

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

Hexestrol has mostly been discontinued and remains available in only a handful of countries.{{cite web | title = Micromdex | url = https://www.micromedexsolutions.com/ | publisher = Merative | access-date = 10 March 2023}} Esters of hexestrol which have been marketed include hexestrol diacetate, hexestrol dicaprylate, hexestrol diphosphate, and hexestrol dipropionate.

{{Reflist}}

{{Estrogens and antiestrogens}}

{{Estrogen receptor modulators}}

Category:Abandoned drugs

Category:4-Hydroxyphenyl compounds

Category:Stilbenoids

Category:Synthetic estrogens