Chemical compound
Hexestrol , sold under the brand name Synestrol among others, is a
nonsteroidal estrogen which was previously used for
estrogen replacement therapy and in the treatment of certain
hormone-dependent cancers as well as
gynecological disorders but is mostly no longer marketed.
[1]
[2]
[3]
[4] It has also been used in the form of
esters such as
hexestrol diacetate (brand name Sintestrol) and
hexestrol dipropionate (brand name Hexanoestrol).
[1]
[5] Hexestrol and its esters are taken
by mouth ,
held under the tongue , or via
injection into muscle .
[5]
[6]
[7]
Medical uses
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 .
[2]
Pharmacology
Pharmacodynamics
Hexestrol has approximately 302% and 234% of the
affinity of
estradiol for the
estrogen receptors (ERs)
ERα and
ERβ , respectively.
[8] The affinity of hexestrol for the ERs is said to be similar to or slightly higher than that of estradiol.
[9] Along with
diethylstilbestrol , hexestrol has been said to be one of the most
potent
estrogens known.
[10] 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 .
[5] These doses are fairly similar to those of estradiol and its esters.
[5] Hexestrol induces
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 the
liver and on
liver protein synthesis .
[12]
Pharmacokinetics
Distribution 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.
[13] Points are one animal each.
[13] With the exception of
skeletal muscle , tissues with a radioactivity concentration of less than 15% of that of the
endometrium are not shown.
[13] Hexestrol is concentrated in
target tissues such as the
uterus and
vagina due to binding to
estrogen receptors .
[14]
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.
[15]
[13]
Chemistry
Hexestrol, also known as dihydrodiethylstilbestrol, is a
synthetic
nonsteroidal estrogen of the
stilbestrol group related to
diethylstilbestrol .
[1]
[2]
Esters of hexestrol include
hexestrol diacetate ,
hexestrol dicaprylate ,
hexestrol diphosphate , and
hexestrol dipropionate .
[1]
History
Hexestrol was first described by Campbell, Dodds, and Lawson in 1938.
[16]
[11]
[17]
[18] It was isolated from the
demethylation products of
anethole .
[16]
[11]
[17]
[18]
Society and culture
Generic names
Hexestrol is the
generic name of the drug and its
INN Tooltip International Nonproprietary Name .
[1]
[2]
Brand names
Hexestrol has been marketed under a variety of brand names including Synestrol, Synoestrol, Estrifar, and Estronal, among others.
[1]
[2]
Availability
Hexestrol has mostly been discontinued and remains available in only a handful of countries.
[19]
[4] Esters of hexestrol which have been marketed include
hexestrol diacetate ,
hexestrol dicaprylate ,
hexestrol diphosphate , and
hexestrol dipropionate .
[1]
References
^
a
b
c
d
e
f
g Elks J (14 November 2014).
The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies . Springer. pp. 162–.
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 . Springer Science & Business Media. pp. 140–.
ISBN
978-94-011-4439-1 .
^ Thomas JA (12 March 1997).
Endocrine Toxicology, Second Edition . CRC Press. pp. 144–.
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 . Springer Science & Business Media. pp. 83, 85, 145, 310.
ISBN
978-94-009-8195-9 .
^ Thomas JA, Keenan EJ (6 December 2012).
Principles of Endocrine Pharmacology . Springer Science & Business Media. pp. 153–.
ISBN
978-1-4684-5036-1 .
^ Barar FS (2012).
Textbook of Pharmacology . S. Chand Publishing. pp. 348–.
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 . John Wiley & Sons. 1956. p. 40.
^
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. Retrieved 10 March 2023 .
Estrogens
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RU-16117
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