Chemical compound
Pharmaceutical compound
Hexestrol , sold under the brand nameSynestrol among others, is anonsteroidal estrogen which was previously used forestrogen replacement therapy and in the treatment of certainhormone-dependent cancers as well asgynecological disorders but is mostly no longer marketed.[ 1] [ 2] [ 3] [ 4] esters such ashexestrol diacetate (brand name Sintestrol) andhexestrol dipropionate (brand name Hexanoestrol).[ 1] [ 5] by mouth ,held under the tongue , or viainjection into muscle .[ 5] [ 6] [ 7]
Hexestrol has been used inestrogen replacement therapy , for the treatment ofbreast cancer in women andprostate cancer in men, and for the treatment of certaingynecological disorders .[ 2]
Hexestrol has approximately 302% and 234% of theaffinity ofestradiol for theestrogen receptors (ERs)ERα andERβ , respectively.[ 8] [ 9] diethylstilbestrol , hexestrol has been said to be one of the mostpotent estrogens known.[ 10] endometrial proliferation dose per cycle of different forms of hexestrol are 70 to 100 mg fororal hexestrol, 45 mg forsublingual hexestrol diacetate , and 25 mg forhexestrol dipropionate byintramuscular injection .[ 5] [ 5] mammary gland development in rodents similarly to other estrogens.[ 11]
Nonsteroidal estrogens like diethylstilbestrol, which is closely related structurally to hexestrol, are known to have dramatically disproportionate estrogenic effects in theliver and onliver protein synthesis .[ 12]
Distribution of hexestrolradioactivity inblood andtissues after asubcutaneous injection of aphysiological dose oftritium -labeled hexestrol inoil solution in five juvenile female goats.[ 13] [ 13] skeletal muscle , tissues with a radioactivity concentration of less than 15% of that of theendometrium are not shown.[ 13] target tissues such as theuterus andvagina due to binding toestrogen receptors .[ 14] Thepharmacokinetics anddistribution of hexestrol have been studied withintravenous injection ofaqueous solution in women and withsubcutaneous injection ofoil solution in female goats and sheep.[ 15] [ 13]
Hexestrol, also known as dihydrodiethylstilbestrol, is asynthetic nonsteroidal estrogen of thestilbestrol group related todiethylstilbestrol .[ 1] [ 2] Esters of hexestrol includehexestrol diacetate ,hexestrol dicaprylate ,hexestrol diphosphate , andhexestrol dipropionate .[ 1]
Hexestrol was first described by Campbell, Dodds, and Lawson in 1938.[ 16] [ 11] [ 17] [ 18] demethylation products ofanethole .[ 16] [ 11] [ 17] [ 18]
Society and culture [ edit ] Hexestrol is thegeneric name of the drug and itsINN Tooltip International Nonproprietary Name .[ 1] [ 2]
Hexestrol has been marketed under a variety of brand names including Synestrol, Synoestrol, Estrifar, and Estronal, among others.[ 1] [ 2]
Hexestrol has mostly been discontinued and remains available in only a handful of countries.[ 19] [ 4] hexestrol diacetate ,hexestrol dicaprylate ,hexestrol diphosphate , andhexestrol dipropionate .[ 1]
^a b c d e f g Elks J (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies ISBN 978-1-4757-2085-3 ^a b c d e Morton IK, Hall JM (6 December 2012).Concise Dictionary of Pharmacological Agents: Properties and Synonyms ISBN 978-94-011-4439-1 ^ Thomas JA (12 March 1997).Endocrine Toxicology, Second Edition ISBN 978-1-4398-1048-4 ^a b "Estradiol: Uses, Dosage & Side Effects" .^a b c d Horsky J, Presl J (6 December 2012).Ovarian Function and its Disorders: Diagnosis and Therapy ISBN 978-94-009-8195-9 ^ Thomas JA, Keenan EJ (6 December 2012).Principles of Endocrine Pharmacology ISBN 978-1-4684-5036-1 ^ Barar FS (2012).Textbook of Pharmacology ISBN 978-81-219-4080-1 ^ Kuiper GG, Carlsson B, Grandien K, Enmark E, Häggblad J, Nilsson S, Gustafsson JA (March 1997)."Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta" .Endocrinology .138 (3):863– 870.doi :10.1210/endo.138.3.4979 PMID 9048584 . ^ Leclercq G, Heuson JC (December 1979). "Physiological and pharmacological effects of estrogens in breast cancer".Biochimica et Biophysica Acta (BBA) - Reviews on Cancer .560 (4):427– 455.doi :10.1016/0304-419x(79)90012-x .PMID 391285 . ^ Solmssen UV (December 1945). "Synthetic estrogens and the relation between their structure and their activity".Chemical Reviews .37 (3):481– 598.doi :10.1021/cr60118a004 .PMID 21013428 . ^a b c Campbell NR, Dodds EC, Lawson W, Noble RL (1939). "Biological effects of the synthetic œstrogen hexœstrol".The Lancet .234 (6049):312– 313.doi :10.1016/S0140-6736(00)61997-9 .ISSN 0140-6736 . ^ Kuhl H (August 2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration".Climacteric .8 (Suppl 1):3– 63.doi :10.1080/13697130500148875 .PMID 16112947 .S2CID 24616324 . ^a b c d Glascock RF, Hoekstra WG (August 1959)."Selective accumulation of tritium-labelled hexoestrol by the reproductive organs of immature female goats and sheep" .The Biochemical Journal .72 (4):673– 682.doi :10.1042/bj0720673 .PMC 1196992 PMID 13828338 . ^ Jensen EV, DeSombre ER (1972). "Mechanism of action of the female sex hormones".Annual Review of Biochemistry .41 :203– 230.doi :10.1146/annurev.bi.41.070172.001223 .PMID 4563437 . ^ Folca PJ, Glascock RF, Irvine WT (October 1961). "Studies with tritium-labelled hexoestrol in advanced breast cancer. Comparison of tissue accumulation of hexoestrol with response to bilateral adrenalectomy and oophorectomy".Lancet .2 (7206):796– 798.doi :10.1016/s0140-6736(61)91088-1 .PMID 13893792 . ^a b Campbell NR, Dodds EC, Lawson W (1938)."Œstrogenic Activity of Anol; a Highly Active Phenol Isolated from the By-Products" .Nature .142 (3608): 1121.Bibcode :1938Natur.142.1121C .doi :10.1038/1421121a0 ISSN 0028-0836 .S2CID 4140616 . ^a b Medicinal Chemistry ^a b Campbell NR, Dodds EC, Lawson W (1940)."The nature of the oestrogenic substances produced during the demethylation of anethole" .Proceedings of the Royal Society of London. Series B, Biological Sciences .128 (851):253– 262.Bibcode :1940RSPSB.128..253C .doi :10.1098/rspb.1940.0009 ISSN 2053-9193 . ^ "Micromdex" . Merative. Retrieved10 March 2023 .
Estrogens
ER Tooltip Estrogen receptor agonistsSteroidal: Alfatradiol Certainandrogens /anabolic steroids (e.g.,testosterone ,testosterone esters ,methyltestosterone ,metandienone ,nandrolone esters ) (via estrogenic metabolites) Certainprogestins (e.g.,norethisterone ,noretynodrel ,etynodiol diacetate ,tibolone ) Clomestrone Cloxestradiol acetate Conjugated estriol Conjugated estrogens Epiestriol Epimestrol Esterified estrogens Estetrol † Estradiol Estradiol esters (e.g.,estradiol acetate ,estradiol benzoate ,estradiol cypionate ,estradiol enanthate ,estradiol undecylate ,estradiol valerate ,polyestradiol phosphate ,estradiol ester mixtures (Climacteron ))Estramustine phosphate Estriol Estriol esters (e.g.,estriol succinate ,polyestriol phosphate )Estrogenic substances Estrone Estrone esters Ethinylestradiol # Hydroxyestrone diacetate Mestranol Methylestradiol Moxestrol Nilestriol Prasterone (dehydroepiandrosterone; DHEA) Promestriene Quinestradol Quinestrol Progonadotropins
Antiestrogens
ER Tooltip Estrogen receptor antagonistsSERMs Tooltip selective estrogen receptor modulators /SERDs Tooltip selective estrogen receptor downregulators )Aromatase inhibitors Antigonadotropins Androgens /anabolic steroids (e.g.,testosterone ,testosterone esters ,nandrolone esters ,oxandrolone ,fluoxymesterone )D2 receptor antagonists (prolactin releasers) (e.g.,domperidone ,metoclopramide ,risperidone ,haloperidol ,chlorpromazine ,sulpiride )GnRH agonists (e.g.,leuprorelin ,goserelin )GnRH antagonists (e.g.,cetrorelix ,elagolix )Progestogens (e.g.,chlormadinone acetate ,cyproterone acetate ,gestonorone caproate ,hydroxyprogesterone caproate ,medroxyprogesterone acetate ,megestrol acetate )Others
ER Tooltip Estrogen receptor
Agonists Steroidal: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Methyl-19-methyleneandrosta-3,5-dien-17β-ol 3α-Androstanediol 3α,5α-Dihydrolevonorgestrel 3β,5α-Dihydrolevonorgestrel 3α-Hydroxytibolone 3β-Hydroxytibolone 3β-Androstanediol 4-Androstenediol 4-Androstenedione 4-Fluoroestradiol 4-Hydroxyestradiol 4-Hydroxyestrone 4-Methoxyestradiol 4-Methoxyestrone 5-Androstenediol 7-Oxo-DHEA 7α-Hydroxy-DHEA 7α-Methylestradiol 7β-Hydroxyepiandrosterone 8,9-Dehydroestradiol 8,9-Dehydroestrone 8β-VE2 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) 11β-Chloromethylestradiol 11β-Methoxyestradiol 15α-Hydroxyestradiol 16-Ketoestradiol 16-Ketoestrone 16α-Fluoroestradiol 16α-Hydroxy-DHEA 16α-Hydroxyestrone 16α-Iodoestradiol 16α-LE2 16β-Hydroxyestrone 16β,17α-Epiestriol (16β-hydroxy-17α-estradiol) 17α-Estradiol (alfatradiol )17α-Dihydroequilenin 17α-Dihydroequilin 17α-Epiestriol (16α-hydroxy-17α-estradiol) 17α-Ethynyl-3α-androstanediol 17α-Ethynyl-3β-androstanediol 17β-Dihydroequilenin 17β-Dihydroequilin 17β-Methyl-17α-dihydroequilenin Abiraterone Abiraterone acetate Alestramustine Almestrone Anabolic steroids (e.g.,testosterone andesters ,methyltestosterone ,metandienone (methandrostenolone) ,nandrolone andesters , many others; via estrogenic metabolites)Atrimustine Bolandiol Bolandiol dipropionate Butolame Clomestrone Cloxestradiol Conjugated estriol Conjugated estrogens Cyclodiol Cyclotriol DHEA DHEA-S ent -EstradiolEpiestriol (16β-epiestriol, 16β-hydroxy-17β-estradiol) Epimestrol Equilenin Equilin ERA-63 (ORG-37663) Esterified estrogens Estetrol Estradiol Estramustine Estramustine phosphate Estrapronicate Estrazinol Estriol Estrofurate Estrogenic substances Estromustine Estrone Etamestrol (eptamestrol) Ethinylandrostenediol Ethinylestradiol Ethinylestriol Ethylestradiol Etynodiol Etynodiol diacetate Hexolame Hippulin Hydroxyestrone diacetate Lynestrenol Lynestrenol phenylpropionate Mestranol Methylestradiol Moxestrol Mytatrienediol Nilestriol Norethisterone Noretynodrel Orestrate Pentolame Prodiame Prolame Promestriene RU-16117 Quinestradol Quinestrol Tibolone Xenoestrogens: Anise -related (e.g.,anethole ,anol ,dianethole ,dianol ,photoanethole )Chalconoids (e.g.,isoliquiritigenin ,phloretin ,phlorizin (phloridzin) ,wedelolactone )Coumestans (e.g.,coumestrol ,psoralidin )Flavonoids (incl.7,8-DHF ,8-prenylnaringenin ,apigenin ,baicalein ,baicalin ,biochanin A ,calycosin ,catechin ,daidzein ,daidzin ,ECG ,EGCG ,epicatechin ,equol ,formononetin ,glabrene ,glabridin ,genistein ,genistin ,glycitein ,kaempferol ,liquiritigenin ,mirificin ,myricetin ,naringenin ,penduletin ,pinocembrin ,prunetin ,puerarin ,quercetin ,tectoridin ,tectorigenin )Lavender oil Lignans (e.g.,enterodiol ,enterolactone ,nyasol (cis -hinokiresinol) )Metalloestrogens (e.g.,cadmium )Pesticides (e.g.,alternariol ,dieldrin ,endosulfan ,fenarimol ,HPTE ,methiocarb ,methoxychlor ,triclocarban ,triclosan )Phytosteroids (e.g.,digitoxin (digitalis ),diosgenin ,guggulsterone )Phytosterols (e.g.,β-sitosterol ,campesterol ,stigmasterol )Resorcylic acid lactones (e.g.,zearalanone ,α-zearalenol ,β-zearalenol ,zearalenone ,zeranol (α-zearalanol) ,taleranol (teranol, β-zearalanol) )Steroid -like (e.g.,deoxymiroestrol ,miroestrol )Stilbenoids (e.g.,resveratrol ,rhaponticin )Synthetic xenoestrogens (e.g.,alkylphenols ,bisphenols (e.g.,BPA ,BPF ,BPS ),DDT ,parabens ,PBBs ,PHBA ,phthalates ,PCBs )Others (e.g.,agnuside ,rotundifuran ) MixedSERMs Tooltip Selective estrogen receptor modulators ) Antagonists Coregulator-binding modulators: ERX-11
GPER Tooltip G protein-coupled estrogen receptor
Agonists Antagonists Unknown
