A nonsteroidal estrogen is an
estrogen
Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
with a
nonsteroidal A nonsteroidal compound is a drug that is not a steroid nor a steroid derivative. Nonsteroidal anti-inflammatory drugs (NSAIDs) are distinguished from corticosteroids as a class of anti-inflammatory agents.
List of nonsteroidal steroid receptor mo ...
chemical structure
A chemical structure of a molecule is a spatial arrangement of its atoms and their chemical bonds. Its determination includes a chemist's specifying the molecular geometry and, when feasible and necessary, the electronic structure of the target m ...
.
The most well-known example is the
stilbestrol estrogen
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 ...
(DES).
Although nonsteroidal estrogens formerly had an important place in medicine, they have gradually fallen out of favor following the discovery of
toxicities associated with high-dose DES starting in the early 1970s, and are now almost never used.
On the other hand, virtually all
selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonists/antagonists (ERAAs), are a class of drugs that act on estrogen receptors (ERs). Compared to pure ER agonists–antagonists (e.g., full agonists and silent ...
s (SERMs) are nonsteroidal, with
triphenylethylene
Triphenylethylene (TPE) is the organic compound with the formula . It is a colorless solid. Synthesis and reactions
The compound is prepared in two steps from benzophenone via the intermediacy of 1,2,2-triphenylethanol. Triphenylethylene reacts ...
s like
tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...
and
clomifene
Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. It is taken by mouth.
Common side effects include pelvic pain and hot flashes. Oth ...
having been derived from DES,
and these drugs remain widely used in medicine for the treatment of
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
among other indications.
In addition to
pharmaceutical drug
Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...
s, many
xenoestrogen
Xenoestrogens are a type of xenohormone that imitates estrogen. They can be either synthetic or natural chemical compounds. Synthetic xenoestrogens include some widely used industrial compounds, such as PCBs, BPA, and phthalates, which have es ...
s, including
phytoestrogen
A phytoestrogen is a plant-derived xenoestrogen (a type of estrogen produced by organisms other than humans) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it ...
s,
mycoestrogen
Mycoestrogens are xenoestrogens produced by fungi. They are sometimes referred to as estrogenic mycotoxins. Some important mycoestrogens are zearalenone, zearalenol and zearalanol. Although all of these can be produced by various ''Fusarium'' sp ...
s, and
synthetic
Synthetic may refer to:
Science
* Synthetic biology
* Synthetic chemical or compound, produced by the process of chemical synthesis
* Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...
endocrine disruptor
Endocrine disruptors, sometimes also referred to as hormonally active agents, endocrine disrupting chemicals, or endocrine disrupting compounds are chemicals that can interfere with endocrine (or hormonal) systems. These disruptions can cause ...
s like
bisphenol A
Bisphenol A (BPA) is a chemical compound primarily used in the manufacturing of various plastics. It is a colourless solid which is Solubility, soluble in most common organic solvents, but has very poor solubility in water. BPA is produced on a ...
, are nonsteroidal substances with estrogenic activity.
Pharmacology
Nonsteroidal estrogens act as
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
s of the
estrogen receptor
Estrogen receptors (ERs) are proteins found in cell (biology), cells that function as receptor (biochemistry), receptors for the hormone estrogen (17β-estradiol). There are two main classes of ERs. The first includes the intracellular estrogen ...
s,
ERα
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the se ...
and
ERβ
Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by t ...
.
List of nonsteroidal estrogens
Synthetic
Pharmaceutical
*
Stilbestrols:
benzestrol
Benzestrol (, ) (brand names Chemestrogen, Ocestrol, Octestrol, Octoestrol, Octofollin) is a synthetic nonsteroidal estrogen of the stilbestrol group which was formerly used medically but has since been discontinued. The stilbestrol estrogens, ...
,
bifluranol,
dienestrol,
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 ...
,
dimestrol,
fosfestrol
Fosfestrol, sold under the brand name Honvan and also known as diethylstilbestrol diphosphate (DESDP), is an estrogen medication which is used in the treatment of prostate cancer in men. It is given by slow intravenous infusion once per day to o ...
,
furostilbestrol,
hexestrol
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 ...
,
mestilbol,
methestrol,
pentafluranol,
phenestrol,
terfluranol,
stilbestrol esters
*
Triphenylethylene
Triphenylethylene (TPE) is the organic compound with the formula . It is a colorless solid. Synthesis and reactions
The compound is prepared in two steps from benzophenone via the intermediacy of 1,2,2-triphenylethanol. Triphenylethylene reacts ...
s:
chlorotrianisene
Chlorotrianisene (CTA), also known as tri-''p''-anisylchloroethylene (TACE) and sold under the brand name Tace among others, is a nonsteroidal estrogen related to diethylstilbestrol (DES) which was previously used in the treatment of menopausal ...
,
desmethylchlorotrianisene,
estrobin (),
M2613,
triphenylbromoethylene,
triphenylchloroethylene,
triphenyliodoethylene,
triphenylmethylethylene
*
Secosteroid
A secosteroid () is a type of steroid with a "broken" ring. The word ''secosteroid ''derives from the Latin verb ''secare'' meaning "to cut", and 'steroid'. Secosteroids are described as a subclass of steroids under the IUPAC nomenclature. Some ...
s (open-ring steroids):
allenestrol,
allenolic acid,
bisdehydrodoisynolic acid,
carbestrol,
doisynoestrol,
doisynolic acid,
fenestrel,
methallenestril
*
Selective ERα
Estrogen receptor alpha (ERα), also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1), is one of two main types of estrogen receptor, a nuclear receptor (mainly found as a chromatin-binding protein)
that is activated by the se ...
or
ERβ
Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by t ...
agonist
An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...
s:
diarylpropionitrile,
ERB-196
ERB-196, also known as WAY-202196, is a synthetic nonsteroidal estrogen that acts as a highly selective agonist of the ERβ
Estrogen receptor beta (ERβ) also known as NR3A2 (nuclear receptor subfamily 3, group A, member 2) is one of two m ...
,
erteberel
Erteberel (, ; former developmental code name LY-500307; also known as selective estrogen receptor beta agonist-1 or SERBA-1) is a synthetic, nonsteroidal estrogen which acts as a selective ERβ agonist and was under development by Eli Lilly fo ...
,
FERb 033
FERb 033 is a synthetic, nonsteroidal estrogen that was synthesized in 2009 and is used in scientific research. It is a potent and selective ERβ agonist (Ki = 7.1 nM, EC50 = 4.8 nM), with 62-fold selectivity for the ERβ over the ERα ...
,
GTx-758,
prinaberel
Prinaberel (International Nonproprietary Name, INN, United States Adopted Name, USAN) (developmental code names ERB-041, WAY-202041) is a synthetic compound, synthetic, nonsteroidal, and highly binding selectivity, selective agonist of the estrog ...
,
propylpyrazoletriol,
WAY-166818,
WAY-214156
* Others:
2,8-dihydroxyhexahydrochrysene (2,8-DHHHC),
paroxypropione,
quadrosilan,
tetrahydrochrysene
SERMs like
tamoxifen
Tamoxifen, sold under the brand name Nolvadex among others, is a selective estrogen receptor modulator used to prevent breast cancer in women and men. It is also being studied for other types of cancer. It has been used for Albright syndrome ...
and
raloxifene can also be considered to be nonsteroidal estrogens in some
tissues.
Environmental
*
Synthetic xenoestrogens:
alkylphenols,
bisphenol
The bisphenols () are a group of industrial chemical compounds related to diphenylmethane; commonly used in the creation of plastics and epoxy resins. Most are based on two phenols, hydroxyphenyl functional groups linked by a methylene bridge. Ex ...
s (e.g.,
bisphenol A
Bisphenol A (BPA) is a chemical compound primarily used in the manufacturing of various plastics. It is a colourless solid which is Solubility, soluble in most common organic solvents, but has very poor solubility in water. BPA is produced on a ...
),
paraben
Parabens are organic compounds that are commonly used as preservatives in cosmetic and pharmaceutical products. They are esters of parahydroxybenzoic acid (also known as 4-hydroxybenzoic acid).
Chemistry
Structure and structure
Parabens a ...
s,
phthalate
Phthalates ( ), or phthalate esters, are esters of phthalic acid. They are mainly used as plasticizers, i.e., substances added to plastics to increase their flexibility, transparency, durability, and longevity. They are used primarily to soften ...
s,
polyhalogenated compounds
Natural
*
Metalloestrogens:
cadmium
Cadmium is a chemical element; it has chemical symbol, symbol Cd and atomic number 48. This soft, silvery-white metal is chemically similar to the two other stable metals in group 12 element, group 12, zinc and mercury (element), mercury. Like z ...
, others
*
Mycoestrogen
Mycoestrogens are xenoestrogens produced by fungi. They are sometimes referred to as estrogenic mycotoxins. Some important mycoestrogens are zearalenone, zearalenol and zearalanol. Although all of these can be produced by various ''Fusarium'' sp ...
s:
taleranol (β-zearalanol),
α-zearalenol,
β-zearalenol,
zearalanone,
zearalenone
Zearalenone (ZEN), also known as RAL and F-2 mycotoxin, is a potent estrogenic metabolite produced by some ''Fusarium'' and '' Gibberella'' species. Specifically, the '' Gibberella zeae'', the fungal species where zearalenone was initially detec ...
,
zeranol (α-zearalanol)
*
Phytoestrogen
A phytoestrogen is a plant-derived xenoestrogen (a type of estrogen produced by organisms other than humans) not generated within the endocrine system, but consumed by eating plants or manufactured foods. Also called a "dietary estrogen", it ...
s:
coumestrol,
daidzein
Daidzein (7-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one) is a naturally occurring compound found exclusively in soybeans and other legumes, and structurally belongs to a class of compounds known as isoflavones. Daidzein and other isoflavones a ...
,
deoxymiroestrol,
equol,
genistein
Genistein (C15H10O5) is a plant-derived, aglycone isoflavone. Genistein has the highest content of all isoflavones in soybeans and soy products, such as tempeh. As a type of phytoestrogen, genistein has estrogenic activity in vitro; consequ ...
,
miroestrol, many others
See also
*
Selective estrogen receptor modulator
Selective estrogen receptor modulators (SERMs), also known as estrogen receptor agonists/antagonists (ERAAs), are a class of drugs that act on estrogen receptors (ERs). Compared to pure ER agonists–antagonists (e.g., full agonists and silent ...
*
Nonsteroidal antiandrogen
A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens lik ...
References
Further reading
*
*
{{Estrogen receptor modulators
Estrogens
Sex hormones